26671 IPR008248 Members of this group are response regulators involved in chemoreceptor modification. In bacterial chemotaxis, cellular movement is directed in response to chemical gradients. Transmembrane chemoreceptors that sense the stimuli are coupled (via a coupling protein, CheW) with a signal transduction histidine kinase (CheA). CheA phosphorylates response regulators CheB and CheY. Phosphorylated CheY binds to FliM, a component of the flagellar motor switch complex, and modulates the direction of flagellar rotation[MEDLINE:99160447]. Response regulator CheB (receptor modification enzyme, protein-glutamate methylesterase) modulates the signaling output of the chemotaxis receptors through control of the level of chemoreceptor methylation [MEDLINE:99160447]. Specific glutamyl residues in the transmembrane chemoreceptor cytoplasmic domain are methylated by methyltransferase CheR to form gamma-carboxyl glutamyl methyl esters. These esters can be hydrolyzed by methylesterase CheB. Receptor modification resets the signaling states of receptors, allowing for responses to changes in concentration of the chemical stimuli irrespective of their absolute concentrations [MEDLINE:99160447].

Response regulators of the microbial two-component signal transduction systems typically consist of an N-terminal CheY-like receiver domain and a C-terminal output (usually DNA-binding) domain [MEDLINE:20439986],\ [MEDLINE:21300007]. In members of this group, the output domain is an enzymatic domain, protein-glutamate methylesterase (demethylase, EC: 3.1.1.61). In response to an environmental stimulus, a phosphoryl group is transferred from the His residue of a signal transduction histidine kinase to an Asp residue in the CheY-like receiver domain of the cognate response regulator. Phosphorylation of the receiver domain induces conformational changes that activate an associated output domain. Phosphorylation-induced conformational changes in the response regulator molecule have been demonstrated in direct structural studies [MEDLINE:21841389]. In members of this group, phosphorylation of receiver domain activates the methylesterase [MEDLINE:90008896], resulting in the subsequent demethylation of the chemoreceptors.

For additional information please see [MEDLINE:98105092], [MEDLINE:98434376], [MEDLINE:22289338], [MEDLINE:98362584], [MEDLINE:94032299].\ \ \N \N \N 26670 IPR008247

Members of this group are response regulators containing CheY-like receiver and HTH (helix-turn-helix) DNA-binding domains (cognate sensor kinases are in PIRSF:PIRSF002842.

\ \ \N \N \N 26669 IPR008246 Members of this group are response regulators containing CheY-like receiver and LytTR DNA-binding domains. Many of them have been experimentally characterised, e.g., Pseudomonas aeruginosa AlgR, a regulator of alginate biosynthesis and pathogenesis of cystic fibrosis [MEDLINE:91317733]; Clostridium perfringens VirR, a regulator of virulence factors [MEDLINE:94179094], [MEDLINE:22255069]; regulators of bacteriocin biosynthesis of the AgrA/ComE family, and others. Members of this group of transcriptional regulators control the genes involved in biosynthesis of extracellular polysaccharides and bacteriocins, expression of exoproteins, including toxins, fimbriation, and quorum sensing [MEDLINE:22030819].

Response regulators of the microbial two-component signal transduction systems typically consist of an N-terminal CheY-like receiver domain and a C-terminal output (usually DNA-binding) domain. In response to an environmental stimulus, a phosphoryl group is transferred from the His residue of sensor histidine kinase to an Asp residue in the CheY-like receiver domain of the cognate response regulator [MEDLINE:20439986], [MEDLINE:21300007]. Phosphorylation of the receiver domain induces conformational changes that activate an associated output domain, which in turn triggers the response. Phosphorylation-induced conformational changes in response regulators have been demonstrated in direct structural studies [MEDLINE:21841389].

DNA-binding properties, as well as recognised DNA sequence motifs, have been directly demonstrated for many members of this family, firmly establishing the LytTR as a DNA-binding domain [MEDLINE:22255069], [MEDLINE:22030819], [MEDLINE:99377133].

The predicted secondary structure of the LytTR domain is not similar to any protein with known three-dimensional structure, indicating that it comprises a novel type of a DNA-binding domain [MEDLINE:22030819]. In addition to response regulators, the LytTR domain is found in combination with MHYT, PAS and other sensor domains [MEDLINE:22030819].

For additional information please see [MEDLINE:22267103], [MEDLINE:94032299].\ \N \N \N 26662 IPR008239 Chorismate mutase (CM; EC: 5.4.99.5) catalyses the reaction at the branch point of the biosynthetic pathway leading to the three aromatic amino acids, phenylalanine, tryptophan and tyrosine (chorismic acid is the last common intermediate, and CM leads to the L-phenylalanine/L-tyrosine branch). It is part of the shikimate pathway, which is present only in bacteria, fungi and plants. Members of this family are stand-alone versions of a chorismate mutase domain of the AroQ class (prokaryotic type), and have an all-helical structure.

The three types of CM are AroQ class, prokaryotic type, AroQ class, eukaryotic type (IPR008238.\ \N \N \N 26668 IPR008245 This bifunctional enzyme contains two catalytic domains (chorismate mutase and 3-deoxy-D-arabino-heptulosonate 7-phosphate (DAHP) synthase). Chorismate mutase (CM; EC: 5.4.99.5) catalyses the rearrangement of chorismate to prephenate, the reaction at the branch point of the biosynthetic pathway leading to the three aromatic amino acids, phenylalanine, tryptophan and tyrosine (chorismic acid is the last common intermediate, and CM leads to the L-phenylalanine/L-tyrosine branch). The chorismate mutase domain of this protein belongs to the AroQ class (Prokaryotic type), and has an all-helical structure. There are stand-alone versions of this domain (e.g., IPR008239.\ \N \N \N 26667 IPR008244 The bifunctional T-protein (TyrA), which plays a central role in tyrosine biosynthesis, contains two catalytic domains (chorismate mutase and prephenate dehydrogenase). It is part of the shikimate pathway, which is present only in bacteria, fungi and plants. It is feedback inhibited by tyrosine. Chorismate mutase (CM; EC: 5.4.99.5) catalyses the rearrangement of chorismate to prephenate, the reaction at the branch point of the biosynthetic pathway leading to the three aromatic amino acids, phenylalanine, tryptophan and tyrosine (chorismic acid is the last common intermediate, and CM leads to the L-phenylalanine/L-tyrosine branch). The chorismate mutase domain of this protein belongs to the AroQ class (Prokaryotic type), and has an all-helical structure. There are stand-alone versions of this domain (e.g., IPR008239.\ \N \N \N 26666 IPR008243 Chorismate mutase (CM; EC: 5.4.99.5) catalyses the reaction at the branch point of the biosynthetic pathway leading to the three aromatic amino acids, phenylalanine, tryptophan and tyrosine (chorismic acid is the last common intermediate, and CM leads to the L-phenylalanine/L-tyrosine branch). It is part of the shikimate pathway, which is present only in bacteria, fungi and plants. Members of this family are stand-alone chorismate mutase domains of the AroH class. They are monofunctional, homotrimeric, nonallosteric enzymes and are not regulated by the end-product aromatic amino acids.

The three types of CM are AroQ class, Prokaryotic type (e.g., IPR008239.\ \N \N \N 26665 IPR008242 The bifunctional P-protein, which plays a central role in phenylalanine biosynthesis, contains two catalytic domains (chorismate mutase and prephenate dehydratase) and a regulatory domain (ACT). It is part of the shikimate pathway, which is present only in bacteria, fungi, and plants. Chorismate mutase (CM; EC: 5.4.99.5) catalyses the rearrangement of chorismate to prephenate, the reaction at the branch point of the biosynthetic pathway leading to the three aromatic amino acids, phenylalanine, tryptophan and tyrosine (chorismic acid is the last common intermediate, and CM leads to the L-phenylalanine/L-tyrosine branch). The chorismate mutase domain of this protein belongs to the AroQ class (Prokaryotic type) [MEDLINE:21419612] and has an all-helical structure. There are stand-alone versions of this domain (e.g., IPR008239.\ \N \N \N 26664 IPR008241 Isochorismate pyruvate-lyase (IPL; PchB) catalyses the second reaction in the pyochelin biosynthetic pathway of Pseudomonas aeruginosa, conversion of isochorismate to salicylate plus pyruvate (following the initial PchA-dependent conversion of chorismate to isochorismate) [MEDLINE:96086939]. This enzyme can also carry out the chorismate mutase (CM) reaction, but with a low catalytic efficiency. It is unlikely that PchB plays a significant role in aromatic amino acid biosynthesis. This enzyme is a stand-alone version of a chorismate mutase domain of the AroQ class.

The three types of CM are AroQ class, Prokaryotic type (e.g., IPR008239.\ \N \N \N 26663 IPR008240 Chorismate mutase (CM; EC: 5.4.99.5) catalyses the reaction at the branch point of the biosynthetic pathway leading to the three aromatic amino acids, phenylalanine, tryptophan and tyrosine (chorismic acid is the last common intermediate, and CM leads to the L-phenylalanine/L-tyrosine branch). It is part of the shikimate pathway, which is present only in bacteria, fungi and plants. Members of this family contain a chorismate mutase domain of the AroQ class (Prokaryotic type) that has an all-helical structure.

The three types of CM are AroQ class, Prokaryotic type (e.g., IPR008239.\ \N \N \N 26661 IPR008238 Chorismate mutase (CM; EC: 5.4.99.5) catalyses the reaction at the branch point of the biosynthetic pathway leading to the three aromatic amino acids, phenylalanine, tryptophan and tyrosine (chorismic acid is the last common intermediate, and CM leads to the L-phenylalanine/L-tyrosine branch). It is part of the shikimate pathway, which is present only in bacteria, fungi and plants. Members of this family contain a chorismate mutase domain of the AroQ class (eukaryotic type) and have an all-helical structure. The monomer consists of a catalytic and a regulatory domain covalently linked by a loop, which functions as a molecular hinge. They are monofunctional, allosteric enzymes and are subject to allosteric inhibition by tyrosine and activation by tryptophan.

The three types of CM are AroQ class, prokaryotic type (e.g., IPR008239.\ \N \N \N 26660 IPR008237 This enzyme catalyses a step in phenylalanine biosynthesis. It contains a prephenate dehydratase domain and a regulatory domain (ACT). It is part of the shikimate pathway, which is present only in bacteria, fungi and plants. Prephenate dehydratase (PDT; EC: 4.2.1.51) converts prephenate to phenylpyruvate. It can also be fused to a chorismate mutase domain in the bifunctional P-protein (IPR008242.\ \N \N \N 26659 IPR008236 This enzyme catalyses a step in tyrosine biosynthesis. It contains a prephenate dehydrogenase domain (PDH) and a regulatory domain (ACT). It is part of the shikimate pathway, which is present only in bacteria, fungi and plants. Prephenate dehydrogenase (PDH) (EC: 1.3.1.12) catalyses oxidative decarboxylation of prephenate to 4-hydroxyphenylpyruvate. Many of the proteins containing this domain are able to use the alternative intermediates of tyrosine biosynthesis, prephenate or L-arogenate, as substrates, thus containing both prephenate dehydrogenase and arogenate dehydrogenase activities (arogenate dehydrogenase (EC: 1.3.1.43) catalyses oxidative decarboxylation of arogenate into tyrosine). Therefore, they are also called cyclohexadienyl dehydrogenases. Prephenate dehydrogenases/arogenate dehydrogenases fall into two classes: sensitive or insensitive to feedback inhibition by L-tyrosine. Members of this family are predicted to be feedback inhibition-sensitive versions, with the ACT domain responsible for this end-product inhibition. In Escherichia coli P-protein (IPR008242.\ \N \N \N 26655 IPR008232 Pro-EMAP II and its relatives consist of a tRNA-binding OB-fold structure flanked by lysine-rich regions. After proteolytic cleavage, the EMAP II polypeptide acts as a cytokine, presumably mediated by the N-terminal portion of the tRNA-binding region [MEDLINE:20418079]. Pro-EMAP II (ARC1p in yeast) forms a complex with aminoacyl-tRNA synthtases and acts as a general tRNA-binding cofactor, thus increasing the catalytic efficiency of the complex [MEDLINE:21101987].\ \N \N \N 26658 IPR008235 Members of this group catalyse a step in tyrosine biosynthesis in the shikimate pathway, which is present only in bacteria, fungi, and plants. Many of them are able to use the alternative intermediates of tyrosine biosynthesis, prephenate or L-arogenate as substrates, thus containing both prephenate dehydrogenase and arogenate dehydrogenase activities. Therefore, they are also called cyclohexadienyl dehydrogenases. Prephenate dehydrogenase (PDH) (EC: 1.3.1.12) catalyses oxidative decarboxylation of prephenate to 4-hydroxyphenylpyruvate. Arogenate dehydrogenase (EC: 1.3.1.43) catalyses oxidative decarboxylation of arogenate into tyrosine.

Prephenate dehydrogenases/arogenate dehydrogenases fall into two classes: sensitive or insensitive to feedback inhibition by L-tyrosine. Members of this family represent stand-alone versions of the PDH domain lacking the regulatory domain ACT and are therefore predicted to be not sensitive to this feedback inhibition. In Escherichia coli P-protein (IPR008242.\ \N \N \N 26657 IPR008234 These enzymes contain two catalytic domains: 4-diphosphocytidyl-2-methyl-D-erythritol synthase domain (IspD homolog) and 2C-methyl-D-erythritol 2,4-cyclodiphosphate synthase domain (IspF homolog). They catalyse steps 3 (EC: 2.7.7.60) and 5 (EC: 4.6.1.12) in the alternative (non-mevalonate) pathway of terpenoid biosynthesis. The stand-alone versions of the corresponding domains are in IPR008233.\ \N \N \N 26656 IPR008233 4-diphosphocytidyl-2-methyl-D-erythritol synthase is the third step in the alternative (non-mevalonate) pathway of terpenoid biosynthesis: the formation of 4-diphosphocytidyl-2C-methyl-D-erythritol from CTP and 2C-methyl-D-erythritol 4-phosphate [MEDLINE:98427948]. They are a subgroup of cytidyltransferases. This family contains a stand-alone version of 4-diphosphocytidyl-2-methyl-D-erythritol synthase (EC: 2.7.7.60). In various bacterial genomes, orthologues of the Escherichia coli ispD (ygbP) gene (IPR008233.\ \N \N \N 26651 IPR008228 There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function.\ \N \N \N 26652 IPR008229 All mature tRNAs contain a terminal CCA sequence essential for function [MEDLINE:98062413]. CCA-adding enzyme ensures that each tRNA contains a terminal CCA, either by de novo addition or by repair of a damaged end [MEDLINE:21476390]. CCA-adding enzyme of this group is a class I nucleotidyltransferase unrelated, except at the active site, to class II CCA-adding enzymes (PIRSF:PIRSF000813.\ \N \N \N 26653 IPR008230 Structural characterisation of the Haemophilus influenzae member of this group revealed an / hydrolase (Rossmann) fold. Sequence analysis revealed the presence of three motifs common to sequences related to L-2-haloacid dehalogenase (HAD) [MEDLINE:95055742]. The first aspartate of the motif DxDx(T/V) forms a phosphoaspartate intermediate with the substrate [MEDLINE:98269064]. A loosely-defined second motif contains a serine or threonine. The third motif, KX(18-30)(G/S)(D/S)xxx(D/N), also contributes to the active site. The enzyme, a homotetramer, contains four active sites, each at the subunit-subunit interface. Partial biochemical characterisation indicates phosphatase activity, with the preferred substrate being a terminal phosphate attached to an open chain or planar ring of a small molecule. The enzyme is likely magnesium dependent and, based on operon structure, proposed to be a sugar phosphatase.\ \N \N \N 26654 IPR008231 The CsaA protein is required for SecA-mediated translocation of a subset of proteins [MEDLINE:20277939], [MEDLINE:20121741]. CsaA and its relatives are typified by the presence of little more than a tRNA-binding motif that adopts an OB-fold. The Aquifex aeolicus member, Trbp111, has been demonstrated to bind tRNA, likely in a structure-specific manner [MEDLINE:99298198].\ \N \N \N 26648 IPR008225 There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function.\ \N \N \N 26649 IPR008226 There is currently no experimental data for members of this group. However, they are homologues of the endonuclease domain of the dsRNA-specific ribonuclease III. While retaining the features that contribute to dimerisation, members lack several charged active-site residues, including (using the numbering for Aquifex aeolicus RNase III) E40 (A) and D107 (T) [MEDLINE:21605734]. It is not clear if these substitutions preclude catalytic function.\ \N \N \N 26650 IPR008227 There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function.\ \N \N \N 26647 IPR008224 Methionyl-tRNA synthetase (methionine--tRNA ligase; MetRS) covalently links methionine to its cognate tRNA [MEDLINE:21589219]. MetRS of the dimer-forming class contain a tRNA-binding domain at the C-terminal end, which is missing in proteins belonging to PIRSF:PIRSF036369.\ \N \N \N 26643 IPR008220 Homoserine acetyltransferase (homoserine transacetylase; EC: 2.3.1.31) catalyses the first step unique to methionine biosynthesis, converting L-homoserine to O-acetyl-L-homoserine using acetyl-CoA as an acetyl group donor [MEDLINE:20374530].\ \N \N \N 26644 IPR008221 Urease (urea amidohydrolase, EC: 3.5.1.5) catalyses the hydrolysis of urea to form ammonia and carbamate. The subunit composition of urease from different sources varies [MEDLINE:96035699], but each holoenzyme consists of four structural domains [MEDLINE:95273988]: three structural domains and a nickel-binding catalytic domain common to amidohydrolases [MEDLINE:97290007]. Urease is unique among nickel metalloenzymes in that it catalyses a hydrolysis rather than a redox reaction. In Klebsiella aerogenes, the domains are found in an subunit (with the C-terminal two-thirds representing the catalytic domain and the N-terminal one-third representing one of the structural domains; PIRSF:PIRSF001226This group represents the gamma-- type.

\ \N \N \N 26646 IPR008223 Urease (urea amidohydrolase, EC: 3.5.1.5) catalyses the hydrolysis of urea to form ammonia and carbamate. The subunit composition of urease from different sources varies [MEDLINE:96035699], but each holoenzyme consists of four structural domains [MEDLINE:95273988]: three structural domains and a nickel-binding catalytic domain common to amidohydrolases [MEDLINE:97290007]. Urease is unique among nickel metalloenzymes in that it catalyses a hydrolysis rather than a redox reaction. In Klebsiella aerogenes, the domains are found in an

subunit (with the C-terminal two-thirds representing the catalytic domain and the N-terminal one-third representing one of the structural domains; PIRSF:PIRSF001226This group represents the fused gamma/

organization typified by the Helicobacter pylori

subunit.

\ \N \N \N 26645 IPR008222 Urease (urea amidohydrolase, EC: 3.5.1.5) catalyses the hydrolysis of urea to form ammonia and carbamate. The subunit composition of urease from different sources varies [MEDLINE:96035699], but each holoenzyme consists of four structural domains [MEDLINE:95273988]: three structural domains and a nickel-binding catalytic domain common to amidohydrolases [MEDLINE:97290007]. Urease is unique among nickel metalloenzymes in that it catalyses a hydrolysis rather than a redox reaction. In Klebsiella aerogenes, the domains are found in an

subunit (with the C-terminal two-thirds representing the catalytic domain and the N-terminal one-third representing one of the structural domains; PIRSF:PIRSF001226This group represents standalone

subunits.

\ \N \N \N 26642 IPR008219 Proline can be oxidized to glutamate via a two-step process. Proline dehydrogenase (proline oxidase) performs the first step. The second step is performed by delta-1-pyrroline 5-carboxylate dehydrogenase (EC: 1.5.1.12), which is often linked to proline dehydrogenase (EC: 1.5.99.8) in bifunctional bacterial enzymes such as PutA (PIRSF:PIRSF000197). The enzymes in this group are predicted to have proline dehydrogenase (PDH) function only, and in this respect are similar to yeast Put1p and other mitochondrial PDHs.\ \N \N \N 26640 IPR008217

Proteins in this family are possible integral membrane proteins. The family includes Ccc1 protein from Saccharomyces cerevisiae (P47818) that may have arole in regulating calcium levels [MEDLINE:95028150].

\ \ \N \N \N 26641 IPR008218

Synonym(s): ATP synthase, bacterial Ca2+/Mg2+ ATPase, chloroplast ATPase, coupling factors (F0,F1 and CF1), F0F1-ATPase, F1-ATPase, F1F0H+-ATPase, H+-ATPase, H+-translocating ATPase, H+-transporting ATPase, mitochondrial ATPase, proton-ATP.

\ \

The H(+)-transporting two-sector ATPase (EC: 3.6.3.14) is a component\ of the cytoplasmic membrane of eubacteria, the inner membrane of mitochondria,\ and the thylakoid membrane of chloroplasts. The ATPase complex is composed of\ an oligomeric transmembrane sector, called CF(0) which is composed of nine subunits, A, B, C, D, E, F, G, F6 and 8 ( or A6L), and a catalytic core, called coupling factor CF(1). The former acts as a proton channel; the latter is composed of five subunits, , , gamma, delta and epsilon.

\ \

The F1-ATPase has been shown to be a rotary motor in which the central g-subunit rotates inside the cylinder made of\ a3b3 subunits. At low ATP concentrations, the motor rotates in discrete 120 degree steps, consistent with sequential ATP hydrolysis on\ the three b-subunits. The mechanism of stepping is unknown. Using high-speed imaging it has been shown that the 120 degree step consists of two substeps of about 90 degrees and 30 degrees, each taking only a fraction of a millisecond. ATP binding drives the 90 degree substep, and the 30 degree substep is probably driven by release of a hydrolysis product. The two substeps are separated by two reactions of about 1 ms, which\ together occupy most of the ATP hydrolysis cycle. This scheme probably applies to rotation at full speed (~130 revolutions per\ second at saturating ATP) down to occasional stepping at nanomolar ATP concentrations, and supports the binding-change model\ for ATP synthesis by reverse rotation of F1-ATPase [MEDLINE:21206300].

\ \ \ \ \ \ \

This family also includes the 14 kDa subunit from vATPases [MEDLINE:96269411] and archaebacterial H+-transporting two-sector ATPase, F subunit [MEDLINE:96324968].

\ \ hydrogen-translocating V-type ATPase activity ; GO:0000260 proton-transporting ATP synthase complex (sensu Eukarya) ; GO:0005753 ATP synthesis coupled proton transport ; GO:0015986 26639 IPR008216

Tachykinins [MEDLINE:88208276], [MEDLINE:90201634], [MEDLINE:92375028] are a group of biologically active peptides which exciteneurons, evoke behavioral responses, are potent vasodilatators, and contract\ (directly or indirectly) many smooth muscles. This family includes the precursors that are enzymatically converted to their mature forms. Tachykinins are from ten to twelve residues long.

\ \ \ \N \N tachykinin signaling pathway ; GO:0007217 26638 IPR008215 Tachykinins [MEDLINE:88208276], [MEDLINE:90201634], [MEDLINE:92375028] are a group of biologically active peptides which exciteneurons, evoke behavioral responses, are potent vasodilatators and contract\ (directly or indirectly) many smooth muscles. This family includes many other peptides. Tachykinins, like most other active peptides, are synthesized as larger protein precursors, protachykinins, that are enzymatically converted to their mature forms. Tachykinins are from ten to twelve residues long.\ \ \N \N tachykinin signaling pathway ; GO:0007217 26637 IPR008214

The phycobilisome linker polypeptide determines the state of aggregation and the location of the disc-shaped phycobiliprotein units within the phycobilisome and modulates their spectroscopic properties in order to mediate a directed and optimal energy transfer. The phycobilisome is a hemidiscoidal structure that is composed of two distinct substructures, a core complex (that contains the phycobiliproteins) and a number of rods radiating from the core. The N-terminal domain of the petH gene product from Anabaena sp. PCC 7119 shows homology to the CpcD phycobilisome linker polypeptide [MEDLINE:93344523].

\ \N phycobilisome ; GO:0030089 \N 26631 IPR008208

This domain is present at the N-terminus in proteins which undergo autophosphorylation. The group includes, the gliding motility regulatory protein from Myxococcus xanthus and a number of bacterial chemotaxis proteins.

\ signal transducer activity ; GO:0004871 \N signal transduction ; GO:0007165 26632 IPR008209 Phosphoenolpyruvate carboxykinase (GTP) (EC: 4.1.1.32) (PEPCK) [MEDLINE:90237025] catalyzesthe formation of phosphoenolpyruvate by decarboxylation of oxaloacetate while\ hydrolyzing GTP:\

\
GTP + oxaloacetate = GDP + phosphoenolpyruvate + CO₂\

\ This is a rate limiting step in gluconeogenesis (the biosynthesis of\ glucose). In vertebrates there are two isozymes: a cytosolic form whose\ activity is affected by hormones regulating this metabolic process (such as\ glucagon, or insulin) and a mitochondrial form.\ An essential cysteine residue has been proposed [MEDLINE:89079663] to be implicated in the\ catalytic mechanism; this residue is located in the central part of PEPCK.\ \ GTP binding activity ; GO:0005525 \N gluconeogenesis ; GO:0006094 26636 IPR008213 The phycobilisome linker polypeptide determines the state of aggregation and the location of the disc-shaped phycobiliprotein units within the phycobilisome and modulates their spectroscopic properties in order to mediate a directed and optimal energy transfer. The phycobilisome is a hemidiscoidal structure that is composed of two distinct substructures, a core complex (that contains the phycobiliproteins) and a number of rods radiating from the core. The N-terminal domain of the petH gene product from Anabaena sp. PCC 7119 shows homology to the CpcD phycobilisome linker polypeptide [MEDLINE:93344523].\ \N phycobilisome ; GO:0030089 \N 26635 IPR008212 Laminin is thought to mediate the attachment, migration and organisation of cells into tissues during embryonic development by interacting with other extracellular matrix components [MEDLINE:90368768].\ \N extracellular matrix ; GO:0005578 \N 26634 IPR008211 Laminin is thought to mediate the attachment, migration and organisation of cells into tissues during embryonic development by interacting with other extracellular matrix components [MEDLINE:90368768].\ \N extracellular matrix ; GO:0005578 \N 26633 IPR008210

This N-terminal domain identifies phosphoenolpyruvate carboxykinase (GTP) (EC: 4.1.1.32) and phosphoenolpyruvate carboxykinase (ATP) (EC: 4.1.1.49) (PEPCK) [MEDLINE:90237025] which catalyse the formation of phosphoenolpyruvate by decarboxylation of oxaloacetate while hydrolyzing either ATP or GTP.

\ GTP binding activity ; GO:0005525 \N gluconeogenesis ; GO:0006094 26629 IPR008206

This entry represents a C-terminal region of prokaryotic proteins that are related to pcrB. Staphylococcus aureus chromosomal gene pcrA encodes a protein with significant similarity (40% identity) to two Escherichia coli helicases: the helicase II encoded by the uvrD gene and the Rep helicase. PcrB gene seems to belong to an operon containing at least one other gene, pcrBA, downstream from pcrB [MEDLINE:94049679]. The PcrB proteins often contain an FMN binding site although the function of these proteins is still unknown.

\ \N \N \N 26630 IPR008207 This domain is present at the N-terminus in proteins which undergo autophosphorylation. The group includes, the gliding motility regulatory protein from Myxococcus xanthus and a number of bacterial chemotaxis proteins.\ \N \N \N 26628 IPR008205

This family contains prokaryotic proteins that are related to pcrB. Staphylococcus aureus chromosomal gene pcrA encodes a protein with significant similarity (40% identity) to two Escherichia coli helicases: the helicase II encoded by the uvrD gene and the Rep helicase. PcrB gene seems to belong to an operon containing at least one other gene, pcrBA, downstream from pcrB [MEDLINE:94049679]. The PcrB proteins often contain an FMN binding site although the function of these proteins is still unknown.

\ \N \N \N 26627 IPR008204

This entry represents a group of short archaebacterial proteins of unknown function. This N-terminal region specifically identifies the majority of the sequences from Archaeoglobus fulgidus with several being clustered together in the genome.

\ \N \N \N 26625 IPR008202

This entry describes archaebacterial proteins of unknown function.

\ \N \N \N 26626 IPR008203 This family includes short archaebacterial proteins ofunknown function. Archaeoglobus fulgidus has twelve\ copies of this protein, with several being clustered\ together in the genome.\ \ \N \N \N 26624 IPR008201

This entry describes archaebacterial proteins of unknown function.

\ \N \N \N 26622 IPR008199

Neuromedin U (NmU) [MEDLINE:89191980], [MEDLINE:93087774] is a vertebrate peptide which stimulates uterine smooth muscle contraction and causes selective vasoconstriction. Like most other active peptides, it is proteolytically processed from a larger precursor protein. The mature peptides are 8 (NmU-8) to 25 (NmU-25) residues long and C-terminally amidated.

The sequence of the C-terminal extremity of NmU is extremely well conserved.

\ \ \N \N regulation of smooth muscle contraction ; GO:0006940 26623 IPR008200

The sequence of the C-terminal extremity of NmU is extremely well conserved.

\ \ \ \N \N regulation of smooth muscle contraction ; GO:0006940 26621 IPR008198

A group of proteins containing 8 characteristically-spaced cysteineresidues, which are involved in disulphide bond formation, have been\ termed '4-disulphide core' proteins [MEDLINE:82196900]. While the pattern of conserved \ cysteines suggests that the sequences may adopt a similar fold, the\ overall degree of sequence similarity is low (e.g. a few Pro and Gly\ residues are reasonably well conserved, as is the polar/acidic nature of\ residues between the third and fourth Cys, but otherwise there is little \ sequence conservation). The group of sequences that share this pattern\ include whey acidic protein (WAP) [MEDLINE:82196900]; elafin (an elastase-specific \ inhibitor from human skin) [MEDLINE:90368643]; WDNM1 protein (which is involved in the\ metastatic potential of adenocarcinomas in rats [MEDLINE:88310901]; Kallmann syndrome\ protein [MEDLINE:92005720]; and caltrin-like protein II from guinea pig [MEDLINE:90216715] (which inhibits calcium transport into spermatozoa).

\ \ \ \N \N \N 26620 IPR008197

\ \ \N \N \N 26619 IPR008196

Ribosomes are the particles that catalyze mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites [MEDLINE:21196157], [MEDLINE:21185928]. About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to - the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits.

Many of ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilize its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organize and stabilize the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome [MEDLINE:21185928], [MEDLINE:20566949].

\ \ \

A number of eukaryotic and archaebacterial ribosomal proteins belong to the L34e\ family. These include vertebrate L34, mosquito L31 [MEDLINE:94325361], plant L34 [MEDLINE:94355650], yeast putative ribosomal protein YIL052c and archaebacterial L34e.This C-terminal region identifies the vertebrate sequences.

\ \ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 26618 IPR008195

\ \ \

A number of eukaryotic and archaebacterial ribosomal proteins belong to the L34e\ family. These include, vertebrate L34, mosquito L31 [MEDLINE:94325361], plant L34 [MEDLINE:94355650],\ yeast putative ribosomal protein YIL052c and archaebacterial L34e.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 26617 IPR008194

In eukaryotes, there are three different forms of DNA-dependent RNA polymerases (EC: 2.7.7.6) transcribing different sets of genes. Each class of RNA polymerase is \ an assemblage of ten to twelve different polypeptides. In archaebacteria, there is \ generally a single form of RNA polymerase which also consists of an oligomeric assemblage \ of 10 to 13 polypeptides. Small subunits of about 13 to 16 kDa are found in all three\ types of eukaryotic polymerases. This entry identifies a group of archaeal proteins.

\ \ \ DNA-directed RNA polymerase activity ; GO:0003899 \N transcription ; GO:0006350 26613 IPR008190

Several uncharacterized proteins have been shown to share regions of similarities, including Escherichia coli hypotheticalprotein yraL, and HI1654, the corresponding Haemophilus influenzae protein; Bacillus subtilis hypothetical protein\ yabC; Helicobacter pylori hypothetical protein HP0552; Mycoplasma genitalium and pneumoniae hypothetical\ protein MG056; Mycobacterium tuberculosis hypothetical protein MtCI237.19; and Synechocystis strain PCC\ 6803 hypothetical protein sll0818. These are proteins of about 30 to 34 kDa. This region represents the C-terminal domain of a sub-set of these proteins.

\ \ \ molecular_function unknown ; GO:0005554 \N \N 26616 IPR008193 In eukaryotes, there are three different forms of DNA-dependent RNA polymerases (EC: 2.7.7.6) transcribing different sets of genes. Each class of RNA polymerase is \ an assemblage of ten to twelve different polypeptides. In archaebacteria, there is \ generally a single form of RNA polymerase which also consists of an oligomeric assemblage \ of 10 to 13 polypeptides. Small subunits of about 13 to 16 kDa are found in all three\ types of eukaryotic polymerases. Subunits that belong to this family include, Saccharomyces cerevisiae RPC19 subunit from RNA polymerases I and III [MEDLINE:91332053], Saccharomyces cerevisiae RPB11 subunit from RNA polymerase II \ [MEDLINE:93283931], mammalian RPB11 (gene POLR2K) from \ RNA polymerase II, Caenorhabditis elegans hypothetical protein F58A4.9, Methanococcus \ jannaschii RNA polymerase subunit L (gene rpoL) and Sulfolobus acidocaldarius \ RNA polymerase subunit L (gene rpoL).\ \ DNA-directed RNA polymerase activity ; GO:0003899 \N transcription ; GO:0006350 26615 IPR008192

This C-terminal domain is found in a number of proteins which have predicted RNA-binding activity. These include the Staphylococcus aureus nuclease (SNase) homologues and the Drosophila melanogaster tudor protein. The function of this domain is unknown.

\ \N \N \N 26614 IPR008191 There are multiple copies of this domain in the Drosophila melanogaster tudor protein and ithas been identified in several RNA-binding proteins [MEDLINE:97200561]. Although the\ function of this domain is unknown, in Drosophila melanogaster the tudor protein is required\ during oogenesis for the formation of primordial germ cells and for normal\ abdominal segmentation [MEDLINE:97157029].\ \ \N \N \N 26610 IPR008187 The human immunodeficiency virus type 1 Vpu protein acts in the degradation of CD4 in the endoplasmic reticulum and in the enhancement of virion release from the plasma membrane of infected cells [MEDLINE:95156576].\ \N \N viral release ; GO:0019076 26611 IPR008188

This domain is the N-terminal transmembrane region from the human immunodeficiency virus type 1 Vpu protein. Vpu acts in the degradation of CD4 in the endoplasmic reticulum and in the enhancement of virion release from the plasma membrane of infected cells [MEDLINE:95156576].

\ \N \N \N 26612 IPR008189 Several uncharacterized proteins have been shown to share regions of similarities, including Escherichia coli hypotheticalprotein yraL, and HI1654, the corresponding Haemophilus influenzae protein; Bacillus subtilis hypothetical protein\ yabC; Helicobacter pylori hypothetical protein HP0552; Mycoplasma genitalium and pneumoniae hypothetical\ protein MG056; Mycobacterium tuberculosis hypothetical protein MtCI237.19; and Synechocystis strain PCC\ 6803 hypothetical protein sll0818. These are proteins of about 30 to 34 kDa.\ \ molecular_function unknown ; GO:0005554 \N \N 26609 IPR008186

This N-terminal domain identifies Dnase I like proteins belonging to the endonuclease/exonuclease/phosphatase family.

\ \N \N \N 26608 IPR008185

Deoxyribonuclease I (DNase I) (EC: 3.1.21.1) [MEDLINE:86230916] is a vertebrate enzyme which catalyzes the endonucleolytic cleavage of double-stranded DNA to 5'- phosphodinucleotide and 5'-phosphooligonucleotide end-products. DNase I is an enzyme involved in DNA degradation; it is normally secreted outside of the cell but seems to be able to gain access to the nucleus where it is involved in cell death by apoptosis [MEDLINE:93154344].

As shown in the following schematic representation, DNase I is a glycoprotein of about 260 residues with two conserved disulfide bonds.\

\ +-+ +--------+\ | | | |\ xxxxxxxxxxxxxxxxx#xxxxxxCxCxxxxx#xxxxxxxxxCxxxxxxxxCxxxxxxxxxxxxx\ \ \ 'C': conserved cysteine involved in a disulfide bond.\ '#': active site residue.\

DNase I has a pH-optimum around 7.5 and requires calcium and magnesium for full activity. It causes single strand nicks in duplex DNA. A proton acceptor-donor chain composed of an histidine and a glutamic acid produce a nucleophilic hydroxyl ion from water, which cleaves the 3'-P-O bond [MEDLINE:88175075].

DNase I forms a 1:1 complex with G-actin, resulting in the inhibition of DNase activity and loss of the ability of G-actin to polymerise into fibres [MEDLINE:90370087].

DNase I has been used in the treatment of lung problems in patients with cystic fibrosis: here it acts by degrading DNA found in purulent lung secretions, reducing their viscosity and making it easier for the patient to breathe [MEDLINE:91067672].

The sequence of DNase I is evolutionary related to that of human muscle-specific DNase-like protein and human proteins DHP1 and DHP2. However, the first disulfide bond of DNase I is not conserved in these proteins.

\ \ deoxyribonuclease activity ; GO:0004536 \N DNA catabolism ; GO:0006308 26606 IPR008183

Aldose 1-epimerase (EC: 5.1.3.3) (mutarotase) is the enzyme responsible for the anomeric interconversion of D-glucose and other aldoses between their - and -forms.

The sequence of mutarotase from two bacteria, Acinetobacter calcoaceticus and Streptococcus thermophilus is available [MEDLINE:90299833]. It has also been shown that, on the basis of extensive sequence similarities, a mutarotase domain seems to be present in the C-terminal half of the fungal GAL10 protein which encodes, in the N-terminal part, UDP-glucose 4-epimerase.

The best conserved region in the sequence of mutarotase is centered around a conserved histidine residue which may be involved in the catalytic mechanism.

\ \ \N \N \N 26607 IPR008184

Aldose 1-epimerase (EC: 5.1.3.3) (mutarotase) is the enzyme responsible for the anomeric interconversion of D-glucose and other aldoses between their - and -forms.

The sequence of mutarotase from two bacteria, Acinetobacter calcoaceticus and Streptococcus thermophilus is available [MEDLINE:90299833]. It has also been shown that, on the basis of extensive sequence similarities, a mutarotase domain seem to be present in the C-terminal half of the fungal GAL10 protein which encodes, in the N-terminal part, for UDP-glucose 4-epimerase.

The best conserved region in the sequence of mutarotase is centred around a conserved histidine residue which may be involved in the catalytic mechanism.

\ \ \ aldose 1-epimerase activity ; GO:0004034 \N galactose metabolism ; GO:0006012 26605 IPR008182

Synonym(s): dUTP diphosphatase, Deoxyuridine-triphosphatase

The essential enzyme dUTP pyrophosphatase (EC: 3.6.1.23) is specific for dUTP and is critical for the fidelity of DNA replication and repair. dUTPase hydrolyzes dUTP to dUMP and pyrophosphate, simultaneously reducing dUTP levels and providing the dUMP for dTTP biosynthesis. dUTPase decreases the intracellular concentration of dUPT so that uracil cannot be incorporated into DNA [MEDLINE:96398696].

The crystal structure of human dUTPase reveals that each subunit of the dUTPase trimer folds into an eight-stranded jelly-roll barrel, with the C-terminal strands interchanged among the subunits. The structure is similar to that of the Escherichia coli enzyme, despite low sequence homology between the two enzymes [MEDLINE:96398696].

Some retroviruses encode dUTPases. Retroviral dUTPase is synthesised as part of POL polyprotein that contains; an aspartyl protease, a reverse transcriptase, dUTPase and RNase H.

\ \ \ \N \N \N 26604 IPR008181

Synonym(s): dUTP diphosphatase, Deoxyuridine-triphosphatase.

The essential enzyme dUTP pyrophosphatase (EC: 3.6.1.23) is specific for dUTP and is\ critical for the fidelity of DNA replication and repair. dUTPase hydrolyzes dUTP to dUMP\ and pyrophosphate, simultaneously reducing dUTP levels and providing the dUMP for\ dTTP biosynthesis. dUTPase decreases the intracellular concentration of dUPT so that\ uracil cannot be incorporated into DNA [PUB00005269].

\ \

The crystal structure of human dUTPase reveals that each subunit of the dUTPase trimer\ folds into an eight-stranded jelly-roll barrel, with the C-terminal strands\ interchanged among the subunits. The structure is similar to that of the Escherichia coli\ enzyme, despite low sequence homology between the two enzymes [PUB00005269].

\ \

Other enzymes like deoxycytidine triphosphate deaminase (dCTP) (EC: 3.5.4.13) that\ specifically bind uridine also belong to this group suggesting that the signature may\ recognise a putative uridine-binding motif.

\ \

Some retroviruses encode dUTPases. Retroviral dUTPase is synthesised as part of POL\ polyprotein that contains; an aspartyl protease, a reverse transcriptase, dUTPase and\ RNase H.

\ \ hydrolase activity ; GO:0016787 \N dUTP metabolism ; GO:0046080 26602 IPR008179

Phosphoribosyl-ATP pyrophosphatase, EC: 3.6.1.31 catalyses the second step in the histidine biosynthetic pathway:

\
5-phosphoribosyl-ATP + H2O = 5-phosphoribosyl-AMP + PPi

\ \ The Neurospora crassa enzyme also catalyzes the reactions of histidinol dehydrogenase (EC: 1.1.1.23) and phosphoribosyl-AMP cyclohydrolase (EC: 3.5.4.19).

\ \ \ phosphoribosyl-ATP pyrophosphatase activity ; GO:0004636 \N histidine biosynthesis ; GO:0000105 26603 IPR008180

Synonym(s): dUTP diphosphatase, Deoxyuridine-triphosphatase

Other enzymes like deoxycytidine triphosphate deaminase (dCTP) (EC: 3.5.4.13) that specifically bind uridine also belong to this group suggesting that the signature may recognise a putative uridine-binding motif.

Some retroviruses encode dUTPases. Retroviral dUTPase is synthesised as part of POL polyprotein that contains; an aspartyl protease, a reverse transcriptase, dUTPase and RNase H.

\ \ \N \N dUTP metabolism ; GO:0046080 26601 IPR008178

Phosphoribosyl-ATP pyrophosphatase, EC: 3.6.1.31 catalyses the second step in the histidine biosynthetic pathway while phosphoribosyl-AMP cyclohydrolase EC: 3.5.4.19 catalyses the third step. This domain is found in both of these enzymes.

\ \ phosphoribosyl-ATP pyrophosphatase activity ; GO:0004636 \N histidine biosynthesis ; GO:0000105 26600 IPR008177

Thionins are small plant proteins that are toxic to animal cells. The proteins belong to a functionally related family, which includes -\ and -thionins from wheat and barley, and gamma-purothionins. Gamma-\ purothionin inhibits protein translation in cell-free systems. It is a single polypeptide chain of 47 amino acids and contains 4 disulphide bridges [MEDLINE:91099329]. The folded structure is characterised by a well-defined 3-stranded anti-parallel -sheet and a short -helix [MEDLINE:93136169]. Three disulphide bridges are located in the hydrophobic core between the helix\ and sheet, forming a cysteine-stabilised -helical motif. This \ structure differs from that of the plant - and - thionins, but\ is analogous to scorpion toxins and insect defensins.

\ \ \ \N \N \N 26599 IPR008176

The following small plant proteins are evolutionary related:

Gamma-thionins from Triticum aestivum (wheat) endosperm (gamma-purothionins) and Hordeum vulgare (barley, gamma-hordothionins) which are toxic to animal cells and inhibit protein synthesis in cell free systems [MEDLINE:93136169].
A flower-specific thionin (FST) from tobacco [MEDLINE:92357021].
Antifungal proteins (AFP) from the seeds of Brassicaceae species such as radish, mustard, turnip and Arabidopsis thaliana\ \ \ \ [MEDLINE:93138130].
Inhibitors of insect -amylases from sorghum [MEDLINE:91138737].
Probable protease inhibitor P322 from potato.
A germination-related protein from cowpea [MEDLINE:91355865].
Anther-specific protein SF18 from sunflower. SF18 is a protein that contains a gamma-thionin domain at its N-terminus and a proline-rich C-terminal domain.
Soybean sulfur-rich protein SE60 [MEDLINE:94105312].
Vicia faba antibacterial peptides fabatin-1 and -2.

In their mature form, these proteins generally consist of about 45 to 50 amino-acid residues. As shown in the following schematic representation, these peptides contain eight conserved cysteines involved in disulfide bonds.

\
          +-------------------------------------------+\
          |          +-------------------+            |\
          |          |                   |            |\
        xxCxxxxxxxxxxCxxxxxCxxxCxxxxxxxxxCxxxxxxCxCxxxC\
                           |   |                | |\
                           +---|----------------+ |\
                               +------------------+\
\
'C': conserved cysteine involved in a disulfide bond.\

The folded structure of Gamma-purothionin is characterised by a well-defined 3-stranded anti-parallel -sheet and a short -helix [MEDLINE:93136169]. Three disulphide bridges are located in the hydrophobic core between the helix and sheet, forming a cysteine-stabilised -helical motif. This structure differs from that of the plant - and - thionins, but is analogous to scorpion toxins and insect defensins.

\ \ \N \N \N 26598 IPR008175

Galanin is a peptide hormone that controls various biological activities [MEDLINE:91257299]. Galanin-like immuno-reactivity has been found in the central and peripheral nervous systems of mammals, with high concentrations demonstrated in discrete regions of the central nervous system, including the median eminence, hypothalamus, arcuate nucleus, septum, neuro-intermediate lobe of the pituitary, and the spinal cord. Its localisation within neurosecretory granules suggests that galanin may function as a neurotransmitter, and it has been shown to coexist with a variety of other peptide and amine neurotransmitters within individual neurons [MEDLINE:88124976].

Although the precise physiological role of galanin is uncertain, it has a number of pharmacological properties: it stimulates food intake, when injected into the third ventricle of rats; it increases levels of plasma growth hormone and prolactin, and decreases dopamine levels in the median eminence [MEDLINE:88124976]; and infusion into humans results in hyperglycemia and glucose intolerance, and inhibits pancreatic release of insulin, somatostatin and pancreatic peptide. Galanin also modulates smooth muscle contractility within the gastro-intestinal and genito-urinary tracts, all such activities suggesting that the hormone may play an important role in the nervous modulation of endocrine and smooth muscle function [MEDLINE:88124976].

This family represents the 124 amino acid precursor protein to galanin. The precursor includes a signal peptide, galanin (29 amino acids), and a 60-amino acid galanin mRNA-associated peptide. In the precursor, galanin includes a C-terminal glycine and is flanked on each side by dibasic tryptic cleavage sites. The deduced amino acid sequence of rat galanin is 90% similar to porcine galanin, with all three amino acid differences in the C-terminal heptapeptide. The predicted galanin mRNA-associated peptide includes a 35-amino acid sequence that is 78% similar to the previously reported porcine analogue. This sequence is set off by a single basic tryptic cleavage site and includes a 17-amino acid region that is nearly identical to the porcine counterpart. The high interspecies conservation suggests a biological role for this putative peptide.

\ \ \ hormone activity ; GO:0005179 extracellular ; GO:0005576 \N 26594 IPR008171

This domain is found in phosphate regulatory proteins including PhoU. The exact nature of this regulation is not well understood [MEDLINE:94042841].

\ \N \N \N 26595 IPR008172

These sequences are functionally identified as members of the adenylate cyclase family EC: 4.6.1.1, which catalyses the conversion of ATP to 3',5'-cyclic AMP and pyrophosphate.

The protein CyaB from Aeromonas hydrophila is a second adenylyl cyclase from that species, as demonstrated by complementation in Escherichia coli and by assay of the enzymatic properties of purified recombinant protein [MEDLINE:98317271]. It has no detectable homology to any other protein of known function, and has several unusual properties, including an optimal temperature of 65 degrees and an optimal pH of 9.5. A cluster of uncharacterised archaeal homologs may be orthologous and serve (under certain circumstances) to produce the regulatory metabolite cyclic AMP (cAMP).

\ \ \ \N \N \N 26597 IPR008174

Galanin is a 29 amino acid peptide processed from a larger precursor protein. Except in human, galanin is C-terminally amidated. Its sequence is highly conserved and the first 14 residues are identical in all currently known sequences.

\ \ \ hormone activity ; GO:0005179 extracellular ; GO:0005576 \N 26596 IPR008173

These sequences are functionally identified as members of the adenylate cyclase family EC: 4.6.1.1, which catalyses the conversion of ATP to 3',5'-cyclic AMP and pyrophosphate.

\ \ \N \N \N 26593 IPR008170

This family contains phosphate regulatory proteins including PhoU. The exact nature of this regulation is not well understood [MEDLINE:94042841].

\ \N \N \N 26592 IPR008169 Cytochrome c (cytC) proteins can be defined as electron-transfer proteins having one or several haem c groups, bound to the protein by one or, more generally, two thioether bonds involving sulphydryl groups of cysteine \ residues. The fifth haem iron ligand is always provided by a histidine \ residue. CytC possess a wide range of properties and function in a large \ number of different redox processes PUB00006083. \

Ambler PUB00006083 recognised four classes of cytC.

Class I includes the low-spin soluble cytC of mitochondria and bacteria, with the haem-attachment site towards the N-terminus, and the sixth ligand provided by a methionine residue about 40 residues further on towards the C-terminus. On the basis of sequence similarity, class I cytC were further subdivided into five classes, IA to IE. Class IC, 'split--band' cyt C, possess a widened or split -band of lowered absorptivity. This class includes dihaem cyt C4 and monohaem cyt C6 (cyt C-553) and cyt C-554.

The 3D structures of Chlamydomonas reinhardtii cyt C6 [MEDLINE:95349073] and Desulfovibrio \ vulgaris cyt C-553 [MEDLINE:91185321] have been determined. The proteins consist of 4 -helices; three 'core' helices form a 'basket' around the haem group, with one haem edge exposed to the solvent.

\ \ electron transporter activity ; GO:0005489 \N electron transport ; GO:0006118 26587 IPR008164 This short repeat of unknown function is found in multiple copies in several Caenorhabditis elegans proteins. The repeat is five residues long and consists of XGLTT where X can be any amino acid.\ \N \N \N 26588 IPR008165

This domain is associated with a short repeat of unknown function and is found in multiple copies in several Caenorhabditis elegans proteins. The repeat is five residues long and consists of XGLTT where X can be any amino acid.

\ \N \N \N 26589 IPR008166

This family contains Caenorhabditis elegans proteins of unknown function.

\ molecular_function unknown ; GO:0005554 \N \N 26590 IPR008167

These sequences are exclusively Caenorhabditis elegans proteins of unknown function.

\ \N \N \N 26591 IPR008168 Cytochrome c (cytC) proteins can be defined as electron-transfer proteins having one or several haem c groups, bound to the protein by one or, more generally, two thioether bonds involving sulphydryl groups of cysteine \ residues. The fifth haem iron ligand is always provided by a histidine \ residue. CytC possess a wide range of properties and function in a large \ number of different redox processes PUB00006083. \

Ambler PUB00006083 recognised four classes of cytC.

\ \ electron transporter activity ; GO:0005489 \N electron transport ; GO:0006118 26586 IPR008163

Inorganic pyrophosphatase (EC: 3.6.1.1) (PPase) [MEDLINE:90254161], [MEDLINE:92367227] is the enzyme responsible for the hydrolysis of pyrophosphate (PPi) which is formed principally as the product of the many biosynthetic reactions that utilize ATP. All known PPases require the presence of divalent metal cations, with magnesium conferring the highest activity. Among other residues, a lysine has been postulated to be part of or close to the active site. PPases have been sequenced from bacteria such as Escherichia coli (homohexamer), thermophilic bacteria PS-3 and Thermus thermophilus, and from the archaebacteria Thermoplasma acidophilum.

The sequences of PPases share some regions of similarities, among which is a region that contains three conserved aspartates that are involved in the binding of cations.

\ \ pyrophosphatase activity ; GO:0016462 membrane ; GO:0016020 metabolism ; GO:0008152 26582 IPR008159

This family is the protein translocase SEC61 complex gamma subunit of the archaeal and eukaryotic type. It does not hit bacterial SecE proteins. Sec61 is required for protein translocation in the endoplasmic reticulum. It is a heterotrimeric complex composed of , and gamma subunits.

\ protein translocase activity ; GO:0015450 membrane ; GO:0016020 protein transport ; GO:0015031 26583 IPR008160 Members of this family belong to the collagen superfamily [MEDLINE:94059583].Collagens are generally extracellular structural proteins\ involved in formation of connective tissue structure.\ The sequence is predominantly repeats of the G-X-Y and the polypeptide chains\ form a triple helix. The first position of the repeat is\ glycine, the second and third positions can be any residue\ but are frequently proline and hydroxyproline. Collagens\ are post-translationally modified by proline hydroxylase\ to form the hydroxyproline residues. Defective\ hydroxylation is the cause of scurvy.\

Some members of the collagen superfamily are not involved\ in connective tissue structure but share the same triple\ helical structure.

\ \ \N \N \N 26584 IPR008161

Members of this family belong to the collagen superfamily [MEDLINE:94059583]. Collagens are generally extracellular structural proteinsinvolved in formation of connective tissue structure. The sequence is predominantly repeats of the G-X-Y and the polypeptide chains\ form a triple helix. The first position of the repeat is\ glycine, the second and third positions can be any residue\ but are frequently proline and hydroxyproline. Collagens\ are post-translationally modified by proline hydroxylase\ to form the hydroxyproline residues. Defective\ hydroxylation is the cause of scurvy.

Some members of the collagen superfamily are not involved\ in connective tissue structure but share the same triple\ helical structure.

\ \ \N \N \N 26585 IPR008162

Inorganic pyrophosphatase (EC: 3.6.1.1) (PPase) [MEDLINE:90254161], [MEDLINE:92367227] is the enzyme responsible for the hydrolysis of pyrophosphate (PPi) which is formed principally as the product of the many biosynthetic reactions that utilize ATP. All known PPases require the presence of divalent metal cations, with magnesium conferring the highest activity. Among other residues, a lysine has been postulated to be part of or close to the active site. PPases have been sequenced from bacteria such as Escherichia coli (homohexamer), thermophilic bacteria PS-3 and Thermus thermophilus, from the archaebacteria Thermoplasma acidophilum, from fungi (homodimer), from a plant, and from bovine retina. In yeast, a mitochondrial isoform of PPase has been characterized which seems to be involved in energy production and whose activity is stimulated by uncouplers of ATP synthesis.

The sequences of PPases share some regions of similarities, among which is a region that contains three conserved aspartates that are involved in the binding of cations.

\ \ pyrophosphatase activity ; GO:0016462 membrane ; GO:0016020 metabolism ; GO:0008152 26581 IPR008158

\ protein translocase activity ; GO:0015450 membrane ; GO:0016020 protein transport ; GO:0015031 26580 IPR008155

Amyloidogenic glycoprotein (A4 protein or APP) is an integral, glycosylated membrane brain protein [MEDLINE:88296437], [MEDLINE:94188932]. APP is associated with Alzheimer's disease (AD). This responsibility stems from the fact that a small peptide (of 43 residues), called the amyloid protein, which is part of the sequence of A4, is the major constituent of amyloid deposits in AD and in Down's syndrome. As shown in the schematic representation below, the amyloid protein both precedes and forms part of the unique transmembrane region of A4.

\ +----------------------------------------xxxxxxx-------------+\ | Extracellular XXXXXXX Cytoplasmic |\ +------------------------------------BBBBBBBBxxx-------------+\ \ 'X': Transmembrane region.\ 'B': Position of the amyloid

protein in A4.\

The exact function of A4 protein is not yet known, but it has been suggested that it mediates cell-cell interactions [MEDLINE:93133829], [MEDLINE:93145954].

\ \ \N \N \N 26579 IPR008154

protein in A4.\

The exact function of A4 protein is not yet known, but it has been suggested that it mediates cell-cell interactions [MEDLINE:93133829], [MEDLINE:93145954].

\ \ \N \N \N 26577 IPR008152

Adaptins are components of the adaptor complexes which link clathrin toreceptors in coated vesicles. Clathrin-associated protein complexes are\ believed to interact with the cytoplasmic tails of membrane proteins,\ leading to their selection and concentration. Gamma-adaptin is a subunit\ of the golgi adaptor. Alpha adaptin is a heterotetramer which regulates clathrin-bud formation. The carboxyl-terminal appendage of the subunit regulates translocation of endocytic accessory proteins to the bud site. This ig-fold domain is found in , and gamma adaptins.

\ \ \N \N \N 26578 IPR008153

\ \ \ \N \N \N 26576 IPR008151

Phytoene dehydrogenase (phytoene desaturase) is an enzyme of carotenoidbiosynthesis that converts phytoene into zeta-carotene via the symmetrical\ introduction of two double bonds at the C-11 and C-11' positions of phytoene.\ The sequence of phytoene dehydrogenase from bacteria (gene crtI or carC) and\ fungi (gene AL-1) are not related to that from cyanobacteria and plants but are\ evolutionary related [MEDLINE:90368827] to that of another enzyme of carotenoid biosynthesis,\ methoxyneurosporene dehydrogenase (gene crtD).\ There are two glycine-rich conserved regions, both of which probably play a\ role in the binding of either FAD or NAD. The first conserved region is in the\ N-terminal section while the second one is in the C-terminal section.

\ \ \N \N \N 26575 IPR008150

\ \ oxidoreductase activity ; GO:0016491 \N biosynthesis ; GO:0009058 26574 IPR008149

Deoxyribodipyrimidine photolyase (EC: 4.1.99.3) (DNA photolyase) [MEDLINE:91128595] is a DNA repair enzyme. It binds to UV-damaged DNA containing pyrimidine dimers and, upon absorbing a near-UV photon (300 to 500 nm), breaks the cyclobutane ring joining the two pyrimidines of the dimer. DNA photolyase is an enzyme that requires two choromophore-cofactors for its activity: a reduced FADH2 and either 5,10-methenyltetrahydrofolate (5,10-MTFH) or an oxidized 8-hydroxy-5- deazaflavin (8-HDF) derivative (F420). The folate or deazaflavin chromophore appears to function as an antenna, while the FADH2 chromophore is thought to be responsible for electron transfer. On the basis of sequence similarities [MEDLINE:95112825] DNA photolyases can be grouped into two classes.

The second class contains\ enzymes from Myxococcus xanthus, methanogenic archaebacteria, insects, fish\ and marsupial mammals. It is not yet known what second cofactor is bound to\ class 2 enzymes. There are a number of conserved sequence regions in all known class 2 DNA\ photolyases, especially in the C-terminal part.

\ \

This entry represents the C-terminal part of the DNA photolyase FAD binding domain.

\ \ deoxyribodipyrimidine photolyase activity ; GO:0003904 \N DNA repair ; GO:0006281 26573 IPR008148

\ \ deoxyribodipyrimidine photolyase activity ; GO:0003904 \N DNA repair ; GO:0006281 26570 IPR008145

This entry represents a domain found in guanylate kinase (EC: 2.7.4.8) and in L-type calcium channel.

Guanylate kinase (EC: 2.7.4.8) (GK) [MEDLINE:92235848] catalyzes the ATP-dependent phosphorylation of GMP into GDP.\ It is essential for recycling GMP and indirectly, cGMP. In prokaryotes (such as Escherichia coli), lower eukaryotes\ (such as yeast) and in vertebrates, GK is a highly conserved monomeric protein of about 200 amino acids. GK\ has been shown [MEDLINE:92154676], [MEDLINE:93238695], [MEDLINE:93032124] to be structurally similar to protein A57R (or SalG2R)\ from various strains of Vaccinia virus.

L-type calcium channnels are formed from different -1 subunit isoforms\ that determine the pharmacological properties of the channel, since they\ form the drug binding domain. Other properties, such as gating voltage-dependence, G protein modulation and kinase susceptibility, are influenced \ by -2, delta and subunits.

\ \ \ \N \N \N 26572 IPR008147

Glutamine synthetase (EC: 6.3.1.2) (GS) [MEDLINE:88295737] plays an essential role in the metabolism of nitrogen by catalyzing the condensation of glutamate and ammonia to form glutamine.

There seem to be three different classes of GS [MEDLINE:93219414], [MEDLINE:90133971], [MEDLINE:94365840]:\

Class I enzymes (GSI) are specific to prokaryotes, and are oligomers of 12 identical subunits. The activity of GSI-type enzyme is controlled by the adenylation of a tyrosine residue. The adenylated enzyme is inactive (see IPR001637).
Class II enzymes (GSII) are found in eukaryotes and in bacteria belonging to the Rhizobiaceae, Frankiaceae, and Streptomycetaceae families (these bacteria have also a class-I GS). GSII are octamer of identical subunits. Plants have two or more isozymes of GSII, one of the isozymes is translocated into the chloroplast.
Class III enzymes (GSIII) has, currently, only been found in Bacteroides fragilis and in Butyrivibrio fibrisolvens. It is a hexamer of identical chains. It is much larger (about 700 amino acids) than the GSI (450 to 470 amino acids) or GSII (350 to 420 amino acids) enzymes.

While the three classes of GS's are clearly structurally related, the sequence similarities are not so extensive.

\ \ glutamate-ammonia ligase activity ; GO:0004356 \N nitrogen fixation ; GO:0009399 26571 IPR008146

Glutamine synthetase (EC: 6.3.1.2) (GS) [MEDLINE:88295737] plays an essential role in the metabolism of nitrogen by catalyzing the condensation of glutamate and ammonia to form glutamine.

There seem to be three different classes of GS [MEDLINE:93219414], [MEDLINE:90133971], [MEDLINE:94365840]:\

Class I enzymes (GSI) are specific to prokaryotes, and are oligomers of 12 identical subunits. The activity of GSI-type enzyme is controlled by the adenylation of a tyrosine residue. The adenylated enzyme is inactive (see IPR001637).
Class II enzymes (GSII) are found in eukaryotes and in bacteria belonging to the Rhizobiaceae, Frankiaceae, and Streptomycetaceae families (these bacteria have also a class-I GS). GSII are octamer of identical subunits. Plants have two or more isozymes of GSII, one of the isozymes is translocated into the chloroplast.
Class III enzymes (GSIII) has, currently, only been found in Bacteroides fragilis and in Butyrivibrio fibrisolvens. It is a hexamer of identical chains. It is much larger (about 700 amino acids) than the GSI (450 to 470 amino acids) or GSII (350 to 420 amino acids) enzymes.

While the three classes of GS's are clearly structurally related, the sequence similarities are not so extensive.

\ \ \ glutamate-ammonia ligase activity ; GO:0004356 \N nitrogen fixation ; GO:0009399 26569 IPR008144

Guanylate kinase (EC: 2.7.4.8) (GK) [MEDLINE:92235848] catalyzes the ATP-dependent phosphorylation of GMP into GDP.It is essential for recycling GMP and indirectly, cGMP. In prokaryotes (such as Escherichia coli), lower eukaryotes\ (such as yeast) and in vertebrates, GK is a highly conserved monomeric protein of about 200 amino acids. GK\ has been shown [MEDLINE:92154676], [MEDLINE:93238695], [MEDLINE:93032124] to be structurally similar to protein A57R (or SalG2R)\ from various strains of Vaccinia virus.

Proteins containing one or more copies of the DHR domain, an SH3 domain as well as a C-terminal GK-like\ domain, are collectively termed MAGUKs (membrane-associated guanylate kinase homologs) [MEDLINE:94206852], and\ include Drosophila lethal(1)discs large-1 tumor suppressor protein (gene dlg1); mammalian tight junction\ protein Zo-1; a family of mammalian synaptic proteins that seem to interact with the cytoplasmic tail of\ NMDA receptor subunits (SAP90/PSD-95, CHAPSYN-110/PSD-93, SAP97/DLG1 and SAP102); vertebrate 55 kD erythrocyte\ membrane protein (p55); C. elegans protein lin-2; rat protein CASK; and human proteins DLG2 and DLG3. There is\ an ATP-binding site (P-loop) in the N-terminal section of GK, which is not conserved in the GK-like domain of\ the above proteins. However these proteins retain the residues known, in GK, to be involved in the binding of\ GMP.

\ \ \N \N \N 26568 IPR008143

Alanine dehydrogenases (EC: 1.4.1.1) and pyridine nucleotide transhydrogenase (EC: 1.6.1.1) have beenshown to share regions of similarity [MEDLINE:93176150]. Alanine dehydrogenase catalyzes the NAD-dependent\ reversible reductive amination of pyruvate into alanine. Pyridine nucleotide transhydrogenase catalyzes\ the reduction of NADP⁺ to NADPH with the concomitant oxidation of NADH to NAD⁺. This enzyme is located\ in the plasma membrane of prokaryotes and in the inner membrane of the mitochondria of eukaryotes. The\ transhydrogenation between NADH and NADP is coupled with the translocation of a proton across the\ membrane. In prokaryotes the enzyme is composed of two different subunits, an chain (gene pntA)\ and a chain (gene pntB), while in eukaryotes it is a single chain protein. The sequence of alanine\ dehydrogenase from several bacterial species are related with those of the subunit of bacterial\ pyridine nucleotide transhydrogenase and of the N-terminal half of the eukaryotic enzyme. The two most\ conserved regions correspond respectively to the N-terminal extremity of these proteins and to a central\ glycine-rich region which is part of the NAD(H)-binding site.

This is a C-terminal domain of alanine dehydrogenases (EC: 1.4.1.1). This domain is also found in the lysine 2-oxoglutarate reductases.

\ \ oxidoreductase activity ; GO:0016491 \N electron transport ; GO:0006118 26567 IPR008142

Alanine dehydrogenases (EC: 1.4.1.1) and pyridine nucleotide transhydrogenase (EC: 1.6.1.1) have beenshown to share regions of similarity [MEDLINE:93176150]. Alanine dehydrogenase catalyzes the NAD-dependent\ reversible reductive amination of pyruvate into alanine. Pyridine nucleotide transhydrogenase catalyzes\ the reduction of NADP⁺ to NADPH with the concomitant oxidation of NADH to NAD⁺. This enzyme is located\ in the plasma membrane of prokaryotes and in the inner membrane of the mitochondria of eukaryotes. The\ transhydrogenation between NADH and NADP is coupled with the translocation of a proton across the\ membrane. In prokaryotes the enzyme is composed of two different subunits, an chain (gene pntA)\ and a chain (gene pntB), while in eukaryotes it is a single chain protein. The sequence of alanine\ dehydrogenase from several bacterial species are related with those of the subunit of bacterial\ pyridine nucleotide transhydrogenase and of the N-terminal half of the eukaryotic enzyme. The two most\ conserved regions correspond respectively to the N-terminal extremity of these proteins, represented in this entry, and to a central\ glycine-rich region which is part of the NAD(H)-binding site.

\ \ oxidoreductase activity ; GO:0016491 \N electron transport ; GO:0006118 26566 IPR008141 Alanine dehydrogenases (EC: 1.4.1.1) and pyridine nucleotide transhydrogenase (EC: 1.6.1.1) have beenshown to share regions of similarity [MEDLINE:93176150]. Alanine dehydrogenase catalyzes the NAD-dependent\ reversible reductive amination of pyruvate into alanine. Pyridine nucleotide transhydrogenase catalyzes\ the reduction of NADP⁺ to NADPH with the concomitant oxidation of NADH to NAD⁺. This enzyme is located\ in the plasma membrane of prokaryotes and in the inner membrane of the mitochondria of eukaryotes. The\ transhydrogenation between NADH and NADP is coupled with the translocation of a proton across the\ membrane. In prokaryotes the enzyme is composed of two different subunits, an

chain (gene pntA)\ and a

chain (gene pntB), while in eukaryotes it is a single chain protein. The sequence of alanine\ dehydrogenase from several bacterial species are related with those of the

subunit of bacterial\ pyridine nucleotide transhydrogenase and of the N-terminal half of the eukaryotic enzyme. The two most\ conserved regions correspond respectively to the N-terminal extremity of these proteins and to a central\ glycine-rich region which is part of the NAD(H)-binding site.\ \ alanine dehydrogenase activity ; GO:0000286 \N electron transport ; GO:0006118 26562 IPR008137 Saposins are small lysosomal proteins that serve as activators of variouslysosomal lipid-degrading enzymes [MEDLINE:96048294]. They probably act by isolating the\ lipid substrate from the membrane surroundings, thus making it more \ accessible to the soluble degradative enzymes. All mammalian saposins\ are synthesized as a single precursor molecule (prosaposin) which contains\ four Saposin-B domains, yielding the active saposins after proteolytic\ cleavage, and two Saposin-A domains that are removed in the activation\ reaction. \ The Saposin-B domains also occur in other \ proteins, many of them active in the lysis of membranes [MEDLINE:94272336], [MEDLINE:97021725].\

Pulmonary surfactant consists of 90% lipid and 10% protein. There are 4 surfactant associated proteins, two collagenous, carbohydrate-binding glycoproteins (SP-A and SP-D), and two small hydrophobic proteins (SP-B and SP-C). Pulmonary surfactant proteins are involved in respiration, and promote alveolar stability by lowering the surface tension at the air-liquid interface in the peripheral air spaces. Surfactant protein B increases the collapse pressure of palmitic acid. It acts as a homodimer.

\ \ \N \N respiratory gaseous exchange ; GO:0007585 26565 IPR008140

Saposins are small lysosomal proteins that serve as activators of variouslysosomal lipid-degrading enzymes [MEDLINE:96048294]. They probably act by isolating the\ lipid substrate from the membrane surroundings, thus making it more \ accessible to the soluble degradative enzymes. All mammalian saposins\ are synthesized as a single precursor molecule (prosaposin) which contains\ four Saposin B domains, yielding the active saposins after proteolytic\ cleavage, and two Saposin-A domains that are removed in the activation\ reaction. \ The Saposin B domains also occur in other \ proteins, many of them active in the lysis of membranes [MEDLINE:94272336], [MEDLINE:97021725].

\ \ \N \N \N 26564 IPR008139 Saposins are small lysosomal proteins that serve as activators of variouslysosomal lipid-degrading enzymes [MEDLINE:96048294]. They probably act by isolating the\ lipid substrate from the membrane surroundings, thus making it more \ accessible to the soluble degradative enzymes. All mammalian saposins\ are synthesized as a single precursor molecule (prosaposin) which contains\ four Saposin B domains, yielding the active saposins after proteolytic\ cleavage, and two Saposin-A domains that are removed in the activation\ reaction. \ The Saposin B domains also occur in other \ proteins, many of them active in the lysis of membranes [MEDLINE:94272336], [MEDLINE:97021725].

The 3D-structure of NK-lysin has recently been determined [MEDLINE:97475218] and found to\ be very different from the one predicted in [MEDLINE:96048294].\ A group of plant aspartic proteases related to cyprosin. These proteins\ have a peculiar SAP-B domain where the two halves are 'swapped' [MEDLINE:95334819].

\ \ \N \N \N 26563 IPR008138 Saposins are small lysosomal proteins that serve as activators of variouslysosomal lipid-degrading enzymes [MEDLINE:96048294]. They probably act by isolating the\ lipid substrate from the membrane surroundings, thus making it more \ accessible to the soluble degradative enzymes. All mammalian saposins\ are synthesized as a single precursor molecule (prosaposin) which contains\ four Saposin-B domains, yielding the active saposins after proteolytic\ cleavage, and two Saposin-A domains that are removed in the activation\ reaction. \ The Saposin-B domains also occur in other \ proteins, many of them active in the lysis of membranes [MEDLINE:94272336], [MEDLINE:97021725].\ \ \ \N \N \N 26561 IPR008136 CinA is the first gene in the competence-inducible (cin) operon, and is thought to be specifically required at some stage in the process of transformation [MEDLINE:95264922]. This is a C-terminal region of putative competence-damaged proteins from the cin operon.\ \N \N \N 26560 IPR008135 CinA is the first gene in the competence-inducible (cin) operon, and is thought to be specifically required at some stage in the process of transformation [MEDLINE:95264922]. This family consists of putative competence-damaged proteins from the cin operon.\ \N \N \N 26559 IPR008134

Serotonin (5-hydroxytryptamine, 5-HT) is widely distributed in both the central and peripheral nervous system, where it acts as a neurotransmitterand neuromodulator [MEDLINE:21860512]. It has been implicated in several aspects of brain\ function, including regulation of affective states, ingestive behavior and\ addiction. 5-HT can activate a number of different receptor subtypes that\ produce diverse neuronal responses, principally through activation of\ G-protein-mediated signalling pathways. Signalling through the 5-HT3\ receptor (5-HT3R) differs, since this subtype belongs to the ligand-gated\ ion channel (LGIC) superfamily, which also includes the inhibitory\ gamma-aminobutyric acid type A and glycine receptors, and excitatory\ nicotinic acetylcholine receptors (nAChR) [MEDLINE:21258146]. 5-HT3 receptor function has\ been implicated in a variety of neural processes, including pain perception,\ emesis, anxiety and drug abuse.

\ \

Like the other members of the LGIC superfamily, the 5HT3R exhibits a high\ degree of sequence similarity, and therefore putative structural similarity,\ with nAChRs [MEDLINE:99150336]. Thus, functional 5HT3Rs comprise a pentamer: the ion channel\ is formed at the centre of a rosette formed between five homologous\ subunits. Two classes of 5-HT3R subunit are currently known, termed 5-HT3A\ and 5-HT3B. Whilst homomeric pentamers of 5-HT3A form functional receptors,\ heteromeric assemblies display channel conductances, cation permeabilities\ and current-voltage relationships typical of characterised neuronal 5-HT3 \ channels [MEDLINE:99133928].

\ \

The proposed topology of 5-HT3R subunits comprises four putative\ transmembrane (TM) domains (designated M1-4); a large extracellular \ N-terminal region (~200 amino acids); and a variable cytoplasmic loop \ between M3 and M4. The M2 domains from each subunit are thought to form the \ channel pore. The agonist binding site is formed by the N terminus,\ which, on binding, induces a conformational change in the channel pore, a\ process often referred to as "gating" [MEDLINE:20286564]. Opening of the pore allows cation\ flux through the neuronal membrane and depolarises the membrane potential.\ Thus, 5-HT3Rs may be thought of as excitatory receptors [MEDLINE:99334497].

\ \

Whilst it was initially thought that 5-HT3Rs comprised a homopentamer of subunits, the channel conductance and permeability to anions was\ different in homomeric receptors from that observed in native channels. More\ recently, another 5-HT3 receptor subunit, 5-HT3B, was identified and cloned\ from a human brain cDNA library [MEDLINE:99133928]. This subunit was unable to form\ functional channels when expressed alone in oocytes, but produced functional\ receptors when injected with 5-HT3A into the same cell. It is thought that\ 5HT3B contributes towards tissue-specific functional changes in\ 5-HT3-mediated signalling [MEDLINE:99452976].

\ \ \N \N \N 26558 IPR008133

\ \

Cloning of the 5-HT3A subunit from a neuroblastoma expression library was\ reported in 1991 [MEDLINE:92022603]. Whilst recombinant expression of 5-HT3A yields\ functional receptors, the channel conductance and permeability to cations\ are different from that observed for native receptors [MEDLINE:99133928]. Alternative exon\ splicing gives rise to two isoforms of 5-HT3A, termed 5-HT3AS and 5-HT3AL\ for short and long variants, respectively. The 5-HT3RA subunit is widely\ expressed throughout the peripheral and central nervous systems, including\ several regions of the brain.

\ \ \N \N \N 26557 IPR008132

\ \

\ \ \N \N \N 26556 IPR008131

The E3B 14.5 kDa was first identified in human adenovirus type 5. It is an integral membrane protein oriented with its C terminus in the cytoplasm. It functions to down-regulate the epidermal growth factor receptor and prevent tumour necrosis factor cytolysis. It achieves this through the interaction with E3 10.4 kDa protein [MEDLINE:98147801], [MEDLINE:92148953].

\ \N \N \N 26555 IPR008130

Glycine is a majory inhibitory neurotransmitter (NT) in the adult vertebratecentral nervous system (CNS). Glycinergic synapses have a well-established\ role in the processing of motor and sensory information that controls\ movement, vision and audition [MEDLINE:21289562]. This action of glycine is mediated\ through its interaction with the glycine receptor (GlyR): an intrinsic\ chloride channel is opened in reponse to agonist binding. The subsequent\ influx of anions prevents membrane depolarisation and neuronal firing\ induced by exitatory NTs. Strychnine acts as a competitive antagonist of\ glycine binding, thereby reducing the activity of inhibitory neurones.\ Poisoning with strychnine is characterised by over-excitation, muscle spasms\ and convulsions. Whilst glycine is the principal physiological agonsist at\ GlyRs, taurine and -alanine also behave as agonists [MEDLINE:21330237]. Compounds that\ modulate GlyR activity include zinc, some alcohols and anaesthetics,\ picrotoxin, cocaine and some anticonvulsants. GlyRs were thought for some\ time to be localised exclusively in the brain stem and spinal cord, but have\ since been found to be expressed more widely, including the cochlear nuclei,\ cerebellar cortex and forebrain [MEDLINE:21258146].\

GlyRs belong to the ligand-gated ion channel family, which also includes the\ inhibitory gamma-aminobutyric acid type A (GABAA) and excitatory nicotinic\ acetylcholine (nACh) and serotonin type 3 (5-HT3) receptors [MEDLINE:99342756].\ Affinity-purified GlyR was found to contain two glycosylated membrane\ proteins of 48kDa and 56kDa, corresponding to and subunits,\ respectively. Four genes encoding subunits have been identified (GLRA1\ to 4), together with a single polypeptide (GLRB). The heterogeneity of subunits is further increased by alternative exon splicing, yielding\ two isoforms of GLRA1 to 3 [MEDLINE:21258146]. The characteristics of different GlyR\ subtypes, therefore, can be largely explained by their GLRA content.\

GlyRs are generally believed to adopt a pentameric structure in vivo: five\ subunits assemble to form a ring structure with a central pore. Typically, a\ stoichiometry of 3:2 (:) is observed [MEDLINE:21330237]. GlyR subunits share a\ high overall level of sequence similarity both with themselves and with the\ subunits of the GABAA and nACh receptors. Four highly conserved segments\ have been proposed to correspond to transmembrane (TM) helices (TM1-4), \ the second of which is thought to contribute to the pore wall [MEDLINE:21258146]. A long \ extracellular N-terminal segment preceeds TM1 and a long cytoplasmic loop \ links TM3 and 4. Short cytoplasmic and extracellular loops join TM1-2 and\ TM2-3, respectively, and a short C-terminal sequence follows TM4. Studies\ using radiolabelled strychnine have shown the subunit to be\ responsible for ligand binding, the critical residues for this interaction \ lying within the N-terminal domain. The subunit plays a structural\ role, contributing one of its TM domains to the pore wall as well as playing\ a putative role in postsynaptic clustering of the receptor.\

In several mammalian species, defects in glycinergic transmission are\ associated with complex motor disorders. Mutations in the gene encoding\ GLRA1 give rise to hyperplexia, or startle disease [MEDLINE:92359997]. This is\ characterised by muscular spasms in response to unexpected light or noise\ stimuli, similar to the symptoms of sublethal doses of strychnine. The\ mutations result in amino acid substitutions within the TM1-2 and TM3-4\ loops, suggesting that these regions are involved in the transduction of\ ligand binding into channel activation.\

\ \

GLRA3 is expressed in the\ cerebellum, olfactory bulb and hippocampus. GLRA3 trancripts, together with\ GLRA1, predominate in the postnatal CNS, replacing GLRA2, which is more\ abundant in embryonic and neonatal neurones.

\ \ \ glycine-gated chloride channel activity ; GO:0016934 membrane ; GO:0016020 chloride transport ; GO:0006821 26554 IPR008129

\ \

In humans, the GLRA2 gene is located on chromosome Xp22.2-22.1 [MEDLINE:98337669]. In situ\ hybridisation studies have shown GLRA2 to be expressed in the hippocampus,\ cerebral cortex and thalamus. GLRA2 trancripts predominate in the neonatal\ and embyonic CNS, and are replaced postnatally by those of GLRA1 and, to a\ lesser extent, GLRA3.

\ \ glycine-gated chloride channel activity ; GO:0016934 membrane ; GO:0016020 chloride transport ; GO:0006821 26553 IPR008128

\ \

In humans, the 1 gene is located on chromosome 5p32 [MEDLINE:22032705]. In situ\ hybridisation studies have shown GLRA1 to be expressed in the spinal cord,\ brain stem and colliculi. GLRA1 trancripts, together with GLRA3, predominate\ in the postnatal CNS, replacing GLRA2, which is more abundant in embryonic\ and neonatal neurones.

\ \ \ glycine-gated chloride channel activity ; GO:0016934 membrane ; GO:0016020 chloride transport ; GO:0006821 26552 IPR008127

\ \

\ \ glycine-gated chloride channel activity ; GO:0016934 membrane ; GO:0016020 chloride transport ; GO:0006821 26551 IPR008126

The genus Yersinia contains just three species: Yersinia enterocolita, Yersinia pestis, and Yersinia pseudotuberculosis [MEDLINE:96330998]. Although the three use different routes to \ infect their host, each targets the lymphoid tissue for invasion, and all \ have developed specific systems to evade host immune cells [MEDLINE:96330998]. PYV, a major \ virulence plasmid common to all members of this family, harbours the genes\ necessary for type III secretion in the host and the exotoxins translocated \ by them. \

One of the proteins encoded within this plasmid is the Yersinia YadA \ non-fimbrial adhesin, a moiety that facilitates cell interaction between \ the host and pathogen [MEDLINE:93366454]. Mutational studies indicate that this protein\ allows intimate attachment and subsequent uptake by host macrophages of the \ bacterial cell. Synergistic mechanisms by two other PYV-encoded proteins,\ YopH and YopE, inhibit the action of YadA. Electron microscopy of the \ mature YadA adhesins suggest that they form distinct "lollipop" shaped \ structures on the cell surface [MEDLINE:20532493]. This is a trait shared by the adhesins\ of another pathogen, namely Moraxella catarrhalis UspA1 and UspA2 [MEDLINE:20532493]. \

The YadA protein itself exists as a homotrimer of 45kDa subunits, anchored \ in the outer bacterial membrane by its C-terminus [MEDLINE:21438348]. The lollipop's \ globular head is formed by the N-terminus in the extracellular space. A\ Yersinia bacterial cell thus coated with YadA can bind a number of host cell \ macromolecules, including collagen, laminin, mucus and fibronectin, \ enhancing its capacity for infection.

\ \ \ cell adhesion molecule activity ; GO:0005194 membrane ; GO:0016020 \N 26550 IPR008125

A small number of bacterial pathogens are implicated in urinary tractinfections (UTIs), amongst the most frequent infections in the developed\ world. The commonest bacterium isolated from UTI is Escherichia coli, with \ streptococcal and staphylococcal species coming a close second [MEDLINE:21622578]. Virulent \ microbes that colonise the human urinary tract usually possess sets of\ virulence factors specific to the host environment [MEDLINE:21622578]. The most common are\ adhesins, molecules that allow an infection to become established; well-\ characterised E.coli type I pili are a good example.\

Aside from adhesins, other UTI-specific virulence moieties include: toxins, \ such as Cnf1 and hemolysin, and host biocides that act against other\ microbes competing for the same niche [MEDLINE:21622578]. Streptothricin, an antibiotic \ synthesised and secreted by some Gram-negative pathogens, is an example of \ the latter [MEDLINE:21622578]; the antibiotic also has a toxic effect on host cells. The\ biocide is synthesised in a five-step process in the bacterial cytoplasm,\ and secreted to the cell exterior via the general secretory pathway\ [MEDLINE:21622578].\

The last step in the synthesis process is the acetyl co-enzyme A-dependent \ acetylation of the streptothricin molecule to the mature antibiotic. This is \ catalysed by the streptothricin acetyltransferase protein, located adjacent \ to the inner face of the cytoplasmic membrane [MEDLINE:21622578]. Homologues of the\ original gene found in Streptomyces spp. have been found in Bacillus \ subtilis and Staphylococcus spp., as well as Escherichia coli [MEDLINE:21622578]. More recently, \ the streptothricin biosynthesis enzymes were shown to be related to those\ that carry out non-ribosomal peptide bond formation.

\ \ transferase activity, transferring acyl groups ; GO:0016746 \N metabolism ; GO:0008152 26548 IPR008123

Activator protein-2 (AP-2) transcription factors constitute a family ofclosely related and evolutionarily conserved proteins that bind to the DNA \ consensus sequence GCCNNNGGC and stimulate target gene transcription\ [MEDLINE:91184621], [MEDLINE:91149909].\ Four different isoforms of AP-2 have been identifed in mammals, termed AP-2 , , gamma and delta. Each family member shares a common structure, \ possessing a proline/glutamine-rich domain in the N-terminal region, which \ is responsible for transcriptional activation [MEDLINE:91184621], and a helix-span-helix\ domain in the C-terminal region, which mediates dimerisation and site-specific DNA binding [MEDLINE:91149909].\

The AP-2 family have been shown to be critical regulators of gene expression\ during embryogenesis. They regulate the development of facial prominence and\ limb buds, and are essential for cranial closure and development of the lens\ [MEDLINE:20578883]; they have also been implicated in tumorigenesis. AP-2 protein \ expression levels have been found to affect cell transformation, tumour \ growth and metastasis, and may predict survival in some types of cancer\ [MEDLINE:98298171], [MEDLINE:20320202]\

\ \

AP-2 gamma was originally isolated from murine carcinoma cells [MEDLINE:96404130]. The \ gene was found to be expressed in several embryonic areas whose development \ can be affected by retinoids, such as the forebrain, face and limb buds [MEDLINE:96404130].\ A human homologue has also been identified. The protein was initially termed\ AP-2.2, but has since been reclassified as AP-2 gamma.

\ \ \ transcription factor activity ; GO:0003700 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 26549 IPR008124

A small number of bacterial pathogens are implicated in urinary tractinfections (UTIs), amongst the most frequent infections in the developed\ world. The commonest bacterium isolated from UTI is Escherichia coli, with \ streptococcal and staphylococcal species coming a close second [MEDLINE:21622578]. Virulent \ microbes that colonise the human urinary tract usually possess sets of\ virulence factors specific to the host environment [MEDLINE:21622578]. The most common are\ adhesins, molecules that allow an infection to become established; well-characterised E.coli type I pili are a good example.\

\ \ plasminogen activator activity ; GO:0008243 \N \N 26547 IPR008122

\ \

AP-2 was originally isolated by cDNA screening of a human genomic \ library [MEDLINE:96038090]. The protein was designated AP-2 on the basis of its high \ sequence similarity to AP-2 , its site-specific DNA binding, and its\ ability to stimulate transcription [MEDLINE:96038090]. Defects in AP-2 have been shown\ to cause Char syndrome, an autosomal dominant trait characterised by patent\ ductus arteriosus, facial dysmorphism and hand anomalies.

\ \ transcription factor activity ; GO:0003700 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 26546 IPR008121

\ \

AP-2 was initially isolated from human HeLa cells [MEDLINE:87301729]. The protein was\ shown to bind to enhancer regions of the SV40 and human metallothionein IIA \ promoters, and to stimulate RNA synthesis [MEDLINE:87301729]. AP-2 gene knockout in \ mice causes neural-tube defects during embryogenesis, leading to craniofacial\ abnormalities and anencephaly [MEDLINE:96208648]. In humans, deletion of chromosome 6\ region 6p24-p25, which includes the AP-2 gene, is associated with\ microphthalmia, corneal clouding and a number of other dysmorphic features, \ including hypertelorism, micrognathia, dysplastic ears, thin limbs, and \ congenital cardiac defects.

\ \ \ transcription factor activity ; GO:0003700 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 26545 IPR008120

Toxoplasma gondii is an obligate intracellular apicomplexan protozoan parasite, with a complex lifestyle involving varied hosts [MEDLINE:21165808]. It has two \ phases of growth: an intestinal phase in feline hosts, and an extra-intestinal phase in other mammals. Oocysts from infected cats develop \ into tachyzoites, and eventually, bradyzoites and zoitocysts in the \ extraintestinal host [MEDLINE:21165808]. Transmission of the parasite occurs through \ contact with infected cats or raw/undercooked meat; in immunocompromised \ individuals, it can cause severe and often lethal toxoplasmosis. Acute \ infection in healthy humans can sometimes also cause tissue damage [MEDLINE:21165808].\

The protozoan utilises a variety of secretory and antigenic proteins to \ invade a host and gain access to the intracellular environment [MEDLINE:21165808]. These \ originate from distinct organelles in the T. gondii cell termed micronemes, \ rhoptries, and dense granules. They are released at specific times during \ invasion to ensure the proteins are allocated to their correct target \ destinations [MEDLINE:21165808]. \ Dense granule antigens (GRAs) are released from the T.gondii tachyzoite\ while still encapsulated in a host vacuole.

Gra7, one of these moieties, is\ believed to be secreted by the parasite during the late phase of intra-\ vacuolar habitation [MEDLINE:98226168]. Studies utilising immunogold labelling have\ localised Gra7 to the parasitophorous vacuolar membrane, and the network \ tubules formed by the Gra2/4/6 complex [MEDLINE:98226168]. It has been suggested that \ dense granule antigens stimulate humoral immunity in the host [MEDLINE:98226168]. A homologue of Gra7 is found in Neospora caninum.\

\ \ \ \N extracellular ; GO:0005576 \N 26544 IPR008119

Gra6, one of these moieties, is\ associated with the parasitophorous vacuole [MEDLINE:99426474]. It\ possesses a hydrophobic\ central region flanked by two hydrophilic domains, and is present as a\ single copy gene in the T.gondii genome [MEDLINE:99426474]. Gra6\ shares a similar function\ with Gra2, in that it is rapidly targeted to a network of membranous tubules\ that connect with the vacuolar membrane [MEDLINE:99426474]. Indeed,\ these two proteins,\ together with Gra4, form a multimeric complex that stabilises the parasite\ within the vacuole.

\ \ \ \N \N \N 26543 IPR008118

Gra2, one of these moieties, is\ rapidly targeted to a network of membranous tubules that connect with the\ vacuolar membrane [MEDLINE:93211457]. A recent study into the exact mechanism of Gra2\ secretion has revealed that the secondary structure of the protein plays a\ major role in its targeting and release from the apical pole of the \ parasitic cell [MEDLINE:98330441]. Two amphipathic -helical regions ensure not only\ that association of Gra2 with the host vacuole membrane takes place, but \ also that it is correctly targeted to the cell posterior, where stabilising\ networks of tubules form and hold the cell steady in the vacuole.

\ \ \N extracellular ; GO:0005576 \N 26541 IPR008116

The sequence-specific single-strand DNA-binding protein (SSDP) family isthought to be involved in transciption regulation. SSDP specifically binds\ single-stranded pyrimidine-rich mirror repeat elements commonly found in\ promoter regions, and is believed to regulate -2(I) collagen [MEDLINE:98198381]. It\ has been identified as a target for unbalanced translocations and deletions\ in acute myelogenous leukemia cells, implying a role as a tumour suppressor\ gene. It is expressed in spleen, lymph node, peripheral blood, bone\ marrow, thymus and foetal liver. Family members have been identified in\ chicken, human, rat, mouse and Drosophila. The highest sequence identity is\ observed in the first 100 N-terminal residues, which contains a tryptophan-rich region in its centre. The C-terminus is more viariable, with glycine/\ proline-rich low complexity regions.

\ \ \ transcription regulator activity ; GO:0030528 \N \N 26542 IPR008117

Toxoplasma gondii is an obligate intracellular apicomplexan protozoan parasite, with a complex lifestyle involving varied hosts [MEDLINE:20097145]. It has two \ phases of growth: an intestinal phase in feline hosts, and an extra-intestinal phase in other mammals. Oocysts from infected cats develop \ into tachyzoites, and eventually, bradyzoites and zoitocysts in the \ extraintestinal host [MEDLINE:20097145]. Transmission of the parasite occurs through \ contact with infected cats or raw/undercooked meat; in immunocompromised \ individuals, it can cause severe and often lethal toxoplasmosis. Acute \ infection in healthy humans can sometimes also cause tissue damage [MEDLINE:20097145].\

MIC1, a protein secreted from the microneme, is a 456-residue moiety\ involved in host cell recognition by the parasite [MEDLINE:21165808]. The protein is\ released from the apical pole of T. gondii during infection, and attaches to\ host-specific receptors [MEDLINE:21165808]. Recent studies have demonstrated that Mic1 is\ a lactose-binding lectin, and utilises this to enhance its binding to host\ endothelial cells [MEDLINE:21165808]. A homologue of Mic1 found in Neospora caninum \ interacts with sulphated host cell-surface glycosaminoglycans.

\ \ \ \N \N \N 26540 IPR008115

Septins constitute a eukaryotic family of guanine nucleotide-binding proteins.Members of the family were first identified by genetic screening for \ Saccharomyces cerevisiae mutants defective in cytokinesis [MEDLINE:74111208]. Temperature-sensitive mutations in four genes, CDC3, CDC10, CDC11 and CDC12, were found\ to cause cell-cycle arrest and defects in bud growth and cytokinesis. The\ protein products of these genes localise at the division plane between\ mother and daughter cells, indicating a role in mother-daughter separation\ during cytokinesis [MEDLINE:88065507]. Members of the family were therefore termed septins\ to reflect their role in septation and cell division. The identification of\ septin homologues in higher eukaryotes, which localise to the cleavage\ furrow in dividing cells, supports an orthologous function in cytokinesis.\ Septins have since been identified in most eukaryotes, except plants [MEDLINE:20266293].\

Septins are approximately 40-50 kDa in molecular mass, and typically comprise\ a conserved central core domain (more than 35% sequence identity between mammalian\ and yeast homologues) flanked by more divergent N- and C-termini. Most\ septins possess a P-loop motif in their N-terminal domain (which is\ characteristic of GTP-binding proteins), and a predicted C-terminal coiled-coil domain [MEDLINE:99412523].\

A number of septin interaction partners have been identified in yeast, \ many of which are components of the budding site selection machinery, kinase\ cascades or of the ubiquitination pathway. It has been proposed that septins may act as a scaffold that provides an interaction \ matrix for other proteins [MEDLINE:20266293], [MEDLINE:99412523]. In mammals, septins have been shown to \ regulate vesicle dynamics [MEDLINE:21939136]. Mammalian septins have also been implicated\ in a variety of other cellular processes, including apoptosis, carcinogenesis\ and neurodegeneration [MEDLINE:97347241].

\ \

Cloning of a novel human cDNA, whose protein product shared a high degree of\ sequence similarity with Saccharomyces cerevisiae CDC10, was reported in\ 1994. This protein was termed hCDC10 and is also known as septin 7.\

\ \ \ GTP binding activity ; GO:0005525 \N cell cycle ; GO:0007049 26539 IPR008114

\ \

Northern blotting studies indicate that septin 3 expression\ is high in the brain but undetectable in other tissues, suggesting that the\ protein is primarily neuronal.

\ \ \ GTP binding activity ; GO:0005525 \N cell cycle ; GO:0007049 26538 IPR008113

\ \

Septin 2, also termed NEDD5, was originally cloned in mice. Orthologues\ from several other species have also been identified. Micro-injection of \ cells with an anti-septin 2 antibody blocks cytokinesis, giving rise to \ binucleated cells.

\ \ \ GTP binding activity ; GO:0005525 \N cell cycle ; GO:0007049 26536 IPR008111

RNA-binding motif protein 8 (RBM8) contains a putative RNA-binding domain known as an RNA recognition motif (RRM). The RRM motif is found in numerous\ RNA-binding proteins, including heterogenous nuclear ribonucleoproteins\ (hnRNPs), and proteins implicated in regulation of alternative splicing. The\ RRM is a 90-residue domain that binds single-stranded RNA; the structure\ consists of four -stands and two -helices arranged in an / sandwich, with a third helix present in some cases during RNA binding [MEDLINE:94119674].\ Three-dimensional modelling of the RBM8 RRM domain indicates that the\ sequences fold into an RNA-binding domain, forming a hydrophobic core\ between a -sheet and two helices.\

The human RBM8A protein is ubiquitously expressed; the protein is localised\ predominantly in the cell nucleus and diffused throughout the cytoplasm\ [MEDLINE:20469404]. It preferentially associates with mRNAs produced by splicing, including\ both nuclear mRNAs and newly exported cytoplasmic mRNAs. Evidence suggests\ the protein remains associated with spliced mRNAs as a tag to indicate the\ position of spliced introns. Human RBM8A protein specicially binds to MAGOH,\ the human homologue of Drosophila mago nashi, a protein required for normal\ germ plasm development in the Drosophila embryo [MEDLINE:20130124]; a similar association\ occurs with the Drosophila RBM8 protein, Tsunagi [MEDLINE:21549073].\

The RBM8A and RBM8B protein sequences contain a putative bipartate nuclear\ localisation signal [MEDLINE:91121518] at the N-terminus, as well a stretch of glycine\ residues. In addition, the RRM contained within RBM8A and RBM8B contains \ one set of the two consensus nucleic acid-binding motifs, RNP-1 and RNP-2,\ characteristic of heterogeneous nuclear ribonucleoprotein (hnRNP).

\ \ \ RNA binding activity ; GO:0003723 cytoplasm ; GO:0005737 RNA processing ; GO:0006396 26535 IPR008110

Periodontal disease in humans is a major health problem in the developed world, and is caused by a number of specialised pathogens that inhabit \ the oral cavity. Amongst the bacterial species culturable from periodontal \ lesions are the streptococcal microbes Streptococcus mutans and S treptococcus sobrinus, and \ the Gram-negative anaerobe Porphyromonas (Bacteroides) gingivalis [MEDLINE:88169488]. The\ latter bacterium has been implicated as the causative agent of peridontitis,\ pulpal infections and tonsillar abcesses [MEDLINE:88169488].\

Adherence by Porphyromonas gingivalis to the periodontal surface is mediated by its \ major virulence factor fimbriae [MEDLINE:91099990]. This differs from other pathogenic \ Gram-negative bacterial polymeric Type I and IV fimbriae/pili in that it is \ much more simplified, consisting of only a monomeric fimbrillin repeating \ subunit, Fma1/FimA. Fma1/FimA has a molecular weight of 43kDa, and can \ exhibit antigenic diversity in different Porphyromonas gingivalis strains \ [MEDLINE:91099990]. Unusually, this form of fimbrillin possesses a far longer leader \ peptide compared to the fimbrial subunits of other bacteria [MEDLINE:91099990]. It has been \ hypothesised that this allows for the maturation of the preprotein during \ secretion [MEDLINE:91099990].\

Recently, a study into the different antigenic types of P. gingivalis\ fimbrillin classified them into five distinct groups, depending on their \ gene sequences [MEDLINE:21614934]. Investigations into the functional differences of\ each type revealed that in the majority of peridontitis cases, bacterial\ strains possessing the type II Fma1/FimA were the most prevalent [MEDLINE:21614934]; in\ healthy adults, type I strains were the most common. This has implications \ for particular strains that are associated with periodontal disease.\

\ \ \ structural molecule activity ; GO:0005198 \N \N 26537 IPR008112

G-protein-coupled receptors, GPCRs, constitute a vast protein family that encompasses a wide range of functions (including various autocrine, paracrine and endocrine processes). They show considerable diversity at the sequence level, on the basis of which they can be separated into distinct groups. We use the term clan to describe the GPCRs, as they embrace a group of families for which there are indications of evolutionary relationship, but between which there is no statistically significant similarity in sequence [MEDLINE:94224751]. The currently known clan members include the rhodopsin-like GPCRs, the secretin-like GPCRs, the cAMP receptors, the fungal mating pheromone receptors, and the metabotropic glutamate receptor family. There is a specialized database for GPCRs: http://www.gpcr.org/7tm/.

The rhodopsin-like GPCRs themselves represent a widespread protein family that includes hormone, neurotransmitter and light receptors, all of which transduce extracellular signals through interaction with guanine nucleotide-binding (G) proteins. Although their activating ligands vary widely in structure and character, the amino acid sequences of the receptors are very similar and are believed to adopt a common structural framework comprising 7\ transmembrane (TM) helices [MEDLINE:90262152], [MEDLINE:88139292], [MEDLINE:93234436].

Relaxin has diverse actions in the reproductive tract and in other tissues\ during pregnancy [MEDLINE:22207966]. Although binding sites for relaxin have been found in\ reproductive tissue, the nature of the receptor was previously unknown.\ Recently, two orphan GPCRs, LGR7 and LGR8, have been identified as receptors\ for the hormone. These two receptors contain large extracellular N-termini\ with leucine-rich repeat regions, and are structurally similar to the\ gonadotropin and thyrotropin receptors. LGR7 is expressed in the brain,\ kidney, testis, placenta, uterus, ovary, adrenal gland, prostate, skin and\ heart, while LGR8 is expressed mainly in the brain, kidney, muscle, testis,\ thyroid, uterus, peripheral blood cells and bone marrow. Upon binding to\ LGR7 or 8, relaxin stimulates a dose-dependent increase in cyclic AMP\ production, indicating coupling of the receptors to Gs proteins.

\ \ G-protein coupled receptor activity ; GO:0004930 membrane ; GO:0016020 signal transduction ; GO:0007165 26534 IPR008109

Receptors for adenine nucleotides are collectively termed P2 purinoceptors. \ They can be further subdivided into two structural classes: P2X receptors \ are ligand-gated ion channels, while P2Y receptors are G protein-coupled \ receptors. P2Y receptors have also been identified that are selective for \ uridine (rather than adenine) nucleotides. \

P2Y13 is a high affinity receptor for ADP. It is expressed at highest levels\ in the brain and a number of immune tissues, particularly the spleen.\ Upon activation by ADP, the receptor couples to Gi proteins to inhibit\ adenylyl cyclase activity and activate MAP kinases [MEDLINE:21959234].

\ \ \ purinergic nucleotide receptor activity, G-protein coupled ; GO:0045028 membrane ; GO:0016020 G-protein coupled receptor protein signaling pathway ; GO:0007186 26532 IPR008107

Mycoplasma species are unique amongst bacteria in having very small genomesand lacking cell walls, and are wholly dependent on their host for survival,\ be it in a symbiotic or pathogenic lifestyle [MEDLINE:97432062]. Some virulent species can\ quickly adapt to new environments, and utilise a number of cell surface\ moieties to attach to target cells. Although the most common form of\ Mycoplasma pathogenesis is respiratory infection, some strains have also\ been implicated in bacterial vaginosis and rheumatoid arthritis [MEDLINE:97432062].\

An outer membrane lipoprotein, designated P48 on account of its 48kDa \ molecular weight, was purified from Mycoplasma fermetans [MEDLINE:97079268]. It was found\ to be a potent differentiation/activation factor of human monocytes, and \ possesses both immunomodulatory and haematopoietic differentiation \ activities [MEDLINE:97079268], [MEDLINE:99387038]. This is believed to aid the bacterium by recruiting human\ blood cells to the point of infection, and altering them to allow \ intracellular invasion by Mycoplasma [MEDLINE:99387038]. Similar species also use the\ P48 lipoprotein to invade host cells of sheep and cattle, causing contagious \ agalactia [MEDLINE:99387038].\

Recently, recombinant studies on the Mycoplasma agalactiae P48 major surface protein\ have shown that changing key elements at the genetic level decreases the \ immunomodulatory effects of the gene product [MEDLINE:20166444]. This may lead to a novel \ vaccine for Mycoplasma infections.

\ \ \ \N \N \N 26533 IPR008108

Some Gram-negative animal enteropathogens express a specialised secretion system to directly "inject" exotoxins into the cytoplasm of host cells. \ Dubbed the type III secretion system, it is of specific interest to \ researchers, as the components of such a system are only expressed in \ pathogenic strains [MEDLINE:20471859]. The system is composed of structural proteins and \ exotoxin effectors; these are often encoded on large virulence plasmids or \ on the bacterial chromosome itself [MEDLINE:20471859]. \

The Shigella flexneri invasion plasmid antigen (ipa) genes are found on such \ a plasmid, and are arranged into an operon. Directly upstream of this operon \ is another cluster of type III genes, termed ipgD, E and F [MEDLINE:93239268]. Deletion \ mutational studies of all three genes showed they were essential for \ virulence in S.flexneri, and that IpgD is secreted by the type III needle \ to the outside of the bacterial cell [MEDLINE:93239268]. Further analysis of the ipg operon\ confirmed that the IpgD gene product is chaperoned by the IpgE protein while \ in the bacterial cytoplasm [MEDLINE:20485604]. \

More recently, a large study into the spread of the ipa/mxi/ipg\ pathogenicity islands through their relevant plasmid has revealed that \ homologues exist in many different Shigella strains, as well as \ enteroinvasive E.coli and Salmonella spp. [MEDLINE:21437637]. There is evidence that the \ genes were acquired from Shigella through lateral transfer, like most of the\ other type III secretion system virulence plasmids.

\ \ \ \N \N \N 26531 IPR008106

The pathogenic neisseriae are a small group of virulent bacteria that initiate infection at the human host mucosal membranes [MEDLINE:21112216]. They are Gram-negative cocci and usually exist in pairs. Neisseria gonorrhoeae is passed through \ sexual transmission and can cause renal failure in extreme cases. The more\ extreme Neisseria meningitidis is a usually commensal nasopharynx microbe that \ causes meningococcemia and acute bacterial meningitis, especially in young \ children and teenagers [MEDLINE:21112216]. There are several serogroups, of which types \ A, B and C are the most virulent. Despite recent advances in vaccinology, \ this pathogen is highly important to research and still poorly understood [MEDLINE:21112216].\

N. meningitidis has many virulence factors, its major determinant being a \ antiphagocytic polysaccharide capsule that allows the bacterium to evade \ the host immune response [MEDLINE:21605978]. Vaccines based on this polysaccharide have \ proven effective against serogroups A and C meningococci, but serogroup B\ still does not possess an efficient vaccine, and causes the most severe \ form of meningitis [MEDLINE:21605978]. It is believed that a conjugate protein vaccine \ derived from published neisserial genome sequences, rather than one based \ on polysaccharide, will be the best way of eradicating this disease [MEDLINE:21605978].\

The focus on novel vaccine targets for N. meningitidis has shifted to the \ adhesins the bacterium secretes to colonise host mucosal epithelia before a\ serious infection takes hold [MEDLINE:20487752]. Interaction of these adhesion molecules\ with their cognate host receptors allows bacterial entry to the epithelium,\ intracellular transport across the host cell, and exit into the bloodstream\ on the other side [MEDLINE:20487752]. Following publication of the complete genome sequence\ of an N. meningitidis serogroup B strain [MEDLINE:20175755], several new adhesins have been \ identified, including one identical to MafB from N. gonorrhoreae.

\ \ \ \N \N \N 26530 IPR008105

Chemokines are proteins that have important physiological and patho-physiological roles in a wide range of acute and chronic inflammatory processes [MEDLINE:21428943]. Chemokines exert their biological effects by binding to cell surface receptors. Their sequences are similar and are characterised by a 4-cysteine motif: the family can be divided according to whether the first 2\ Cys residues are adjacent (the C-C family), separated by an intervening residue (the C-x-C family), have only one of the first two Cys residues (C chemokines), or contain both cysteines, separated by three\ intervening residues (C-x3-C chemokines).

\ \

Chemokine receptors belong to a superfamily of serpentine proteins that signal\ through coupled heterotrimeric G proteins. At least eighteen chemokine receptors have been cloned so far including, six CXC, 10 CC, one CX3C and one XC receptor. Although each of these receptors binds only a single class of chemokines they can bind several members of the\ same class with high affinity.

Lymphotactin is the only known member of the C\ chemokine family. It has closest similarity to the C-C chemokines, but\ contains only the second and fourth of the conserved cysteine residues. The\ chemokine is produced by certain subsets of T cells and natural killer cells,\ and is also chemotactic for these cell types [MEDLINE:95064019].

\ \ \ chemokine activity ; GO:0008009 extracellular ; GO:0005576 immune response ; GO:0006955 26529 IPR008104

Legionella pneumophila, the causative agent of Legionnaire's disease, is afacultative intracellular microbe that commonly infects human lung \ monocytes and macrophages and causes pneumonia [MEDLINE:93350346]. It is water-borne and \ highly virulent, relying on several specific pathogenic factors to invade \ and infect the alveolar tissue. However, once grown to stationary phase in \ culture, the pathogen spontaneously converts to an avirulent state [MEDLINE:93350346]. \

The major virulence factor expressed by Legionella pneumophila is the \ macrophage infectivity potentiator (Mip) [MEDLINE:89173328]. Site-directed mutagenesis\ studies of this protein in vitro severely impaired the intracellular\ infection of human macrophages by L.pneumophila, causing it to lose\ its potent antigenic activity [MEDLINE:89173328]. Further studies into the enzymatic \ activity of Mip have revealed that it plays a similar role to eukaryotic\ FK506-binding proteins. In vivo, it acts as a peptidyl-prolyl-cis/trans-\ isomerase (PPIase) on oligopeptides [MEDLINE:92349965], although it is unclear whether this\ forms part of the virulence process. Substitution of Asp142 of the mature \ protein by Leu severely reduces the PPIase activity of Mip [MEDLINE:94283864].\

The structure of Mip has been resolved to 2.41A by X-ray crystallography [MEDLINE:21415765],\ revealing the virulence factor to exist as a homodimer. Each monomer \ consists of an N-terminal dimerisation module, a long central connecting -helix and a conserved PPIase domain at the C terminus.

\ \ peptidyl-prolyl cis-trans isomerase activity ; GO:0003755 membrane ; GO:0016020 \N 26528 IPR008103

The metastasis suppressor gene KiSS-1 encodes a number of RFamide-related \ peptides, the largest of which, metastin, contains 54 amino acids.\ An orphan G protein-coupled receptor, GPR54, has been identified as a \ receptor for these peptides [MEDLINE:21279176]. GPR54 is highly expressed in placenta, \ pituitary, pancreas and spinal cord. Binding of KiSS-1-encoded peptides\ to the receptor results in coupling to the Gq pathway, stimulating calcium\ mobilisation, phosphatidylinositol hydrolysis, arachidonic acid release, \ ERK and p38 MAP kinase phosphorylation and stress fibre formation. It also\ inhibits cell proliferation. The distribution of GPR54, together with \ the finding that administration of KiSS-1 peptides in rat stimulates \ oxytocin secretion, suggests a role in regulation of endocrine function.

\ \ \N \N \N 26527 IPR008102

Histamine is distributed within mast cells in all peripheral tissues and\ is a well-characterised mediator of inflammation and allergy. It also\ regulates release of gastric acid from parietal cells in the gastric mucosa.\ A fourth member of the histamine receptor family, HH4R, has been identified\ that is expressed primarily in cells and tissues of the immune system, \ including: peripheral blood leukocytes, bone marrow, spleen and thymus \ [MEDLINE:21106318]. This expression pattern suggests that the receptor may represent a\ novel therapeutic target for the regulation of immune function, particularly\ in allergy and asthma. Binding of histamine to HH4R appears to result in\ inhibition of forskolin-stimulated cAMP accumulation through coupling to Gi\ proteins. The receptor has also been found to have a relatively high \ level of constitutive activity.\

\ \ \ rhodopsin-like receptor activity ; GO:0001584 membrane ; GO:0016020 G-protein coupled receptor protein signaling pathway ; GO:0007186 26526 IPR008101

Neurotransmitter ligand-gated ion channels are transmembrane receptor-ion channel complexes that open transiently upon binding of specific ligands, allowing rapid transmission of signals at chemical synapses [MEDLINE:92084670], [MEDLINE:91108470].

Of the five families known, four have been shown to form a sequence-related superfamily. These are the gamma-aminobutyric acid type A (GABA-A), nicotinic acetylcholine, glycine and the serotonin 5HT3 receptors. The ionotropic glutamate receptors (IPR001320) have a distinct primary structure.

However, all these receptors possess a pentameric structure (made up of varying subunits), surrounding a central pore. Each of these subunits contains a large extracellular N-terminal ligand-binding region; 3 hydrophobic transmembrane domains; a large intracellular region; and a fourth hydrophobic domain [MEDLINE:92084670], [MEDLINE:91108470].

\ \

Gamma-aminobutyric acid type A (GABAA) receptors are members of the neurotransmitter ligand-gated ion channels: they mediate neuronal inhibition on\ binding GABA. The effects of GABA on GABAA receptors are modulated by a range\ of therapeutically important drugs, including barbiturates, anaesthetics and\ benzodiazepines (BZs) [MEDLINE:96122225]. The BZs are a diverse range of compounds,\ including widely prescribed drugs, such as librium and valium, and their\ interaction with GABAA receptors provides the most potent pharmacological\ means of distinguishing different GABAA receptor subtypes.

\ GABAA receptors are pentameric membrane proteins that operate GABA-gated\ chloride channels [MEDLINE:21179859]. Eight types of receptor subunit have been cloned,\ with multiple subtypes within some classes: 1-6, 1-4, gamma 1-4,\ delta, epsilon, pi, rho 1-3 and theta [MEDLINE:98317658], [MEDLINE:99380615]. Subunits are typically 50-60kDa\ in size and comprise a long N-terminal extracellular domain, containing\ a putative signal peptide and a disulphide-bonded structural loop; 4\ putative transmembrane (TM) domains; and a large cytoplasmic loop connecting\ the third and fourth TM domains. Amongst family members, the large\ cytoplasmic loop displays the most divergence in terms of primary structure,\ the TM domains showing the highest level of sequence conservation [MEDLINE:89181956].

Identification and characterisation of the theta subunit was first reported\ in 1999 [MEDLINE:89181956]. Cloning of the full-length cDNA was performed using a human\ whole-brain library, yielding a deduced open reading frame of 627 amino\ acids. This polypeptide was found to be most similar to the 1 subunit\ with regard to sequence identity, and was able to co-assemble with 2, 1 and gamma 1 subunits, yielding heteromeric assemblies with a 4-fold\ increase in sensitivity towards GABA. Furthermore, theta mRNA was found \ to have a unique spatial distribution, with significant expression within\ monoaminergic neurons of both human and monkey brain.

\ \ GABA-A receptor activity ; GO:0004890 membrane ; GO:0016020 ion transport ; GO:0006811 26525 IPR008100

\ \

The existence of a pi subunit was first reported in 1997, where it was\ detected in a number of human and rat tissues. The subunit shares 30-40%\ amino acid identity with other members of the GABAA receptor subunit family.\ The polypeptide is found in several peripheral tissues, including the\ uterus, where its function appears to be related to tissue contractility: pi\ subunits can co-assemble with other GABAA receptor subunits to form\ recombinant receptors with altered sensitivity to pregnenalone [MEDLINE:97326112].

\ \ \ GABA-A receptor activity ; GO:0004890 membrane ; GO:0016020 ion transport ; GO:0006811 26524 IPR008099

\ \

The epsilon subunit was first identified in 1997. Northern blot analysis of several human\ brain tissues showed that epsilon transcripts were relatively enriched in\ amygdala and thalamus, compared to whole brain, and particularly abundant in\ the subthalmic nucleus. Heteromeric recombinant receptors containing the\ epsilon subunit were found to be insenstitive to the potentiating effects of\ anaesthetic agents [MEDLINE:97192095].

\ \ \ GABA-A receptor activity ; GO:0004890 membrane ; GO:0016020 ion transport ; GO:0006811 26523 IPR008098

\ \

Delta cDNA was first reported in rat, mouse and humans [MEDLINE:96122225]. Delta mRNA\ was found to be present in regions of the brain that were low in gamma 2, \ and insensitivity towards "classical" BZs was observed in receptors\ containing the delta subunit. Furthermore, delta subunits are thought to \ preferentially pair with the 6 polypeptides over other subtypes, and are often found in place of gamma subunits. \

\ \ \ GABA-A receptor activity ; GO:0004890 membrane ; GO:0016020 ion transport ; GO:0006811 26522 IPR008097

\ \

The only C-x3-C chemokine identified to date is\ fractalkine, a transmembrane (TM) molecule containing a chemokine domain on\ an extended mucin-like stalk [MEDLINE:97177111]. The membrane-bound form of fractalkine can\ be induced on endothelial cells in response to inflammation, and promotes\ adhesion of monocytes and T lymphocytes. The chemokine can also be released\ in a soluble form, which causes chemotaxis of monocytes and T cells.

\ \ chemokine activity ; GO:0008009 membrane ; GO:0016020 immune response ; GO:0006955 26521 IPR008096

T cell-dependent immune processes require cell-surface interactions thatmediate the initiation, modulation and the ultimate course of the response.\ The specificity of T cell recognition is determined by the engagement of the\ T cell receptor (TCR) on T cells with cognate peptide-MHC complexes \ presented by antigen presenting cells (APCs). Additional signals are\ required to sustain and enhance T cell activity, the most important of which\ is provided by the engagement of CD28 on T cells with its ligands B7-1\ (CD80) and B7-2 (CD86). By contrast, the interaction of B7 isoforms\ with cytotoxic T lymphocyte-associated molecule-4 CTLA-4, a CD28 homologue \ receptor on T cells (31% identity), provides inhibitory signals required\ for down-regulation of the response, while it may also prevent T cell \ activation by weak TCR signals\ [MEDLINE:91341416], [MEDLINE:98263348], [MEDLINE:20508109], [MEDLINE:21831269], [MEDLINE:21665932].\

Unlike CD28, which is not expressed on resting T cells, CTLA-4 is not \ detected on the cell surface until 24 hours after activation. In fact, T\ cell activation leads to both increased CTLA4 gene expression and\ trafficking of CTLA4 protein to the cell surface. In addition, CTLA-4\ exhibits an affinity for the B7 isoforms that is 10 to 100 times that for\ CD28. Covalent dimerisation of CTLA4 is required for its high binding\ avidity, but each monomeric subunit also contains a binding site for CD80\ and CD86. It is likely that CTLA-4 directly competes with CD28 for binding\ B7 and also directs the assembly of inhibitory signalling complexes that\ lead to quiescence or anergy. Thus the balance between the opposing signals \ elicited by CD28 and CTLA-4 is central to the regulation of T cell\ responsiveness and homeostasis. One mechanism by which CTLA-4 may perform\ this function is by regulating cell-cycle progression; by contrast with \ CD28, which down-regulates the cell-cycle inhibitor p27kip1, CTLA-4 \ prevents this degradation\ [MEDLINE:98263348], [MEDLINE:20508109], [MEDLINE:21665932].\

Sequence comparison between human CTLA-4 and CD28 proteins suggests they are\ homologous, with the highest of degree of similarity being in the juxta-\ membrane and cytoplasmic regions. In addition, the cytoplasmic domains\ of human and murine CTLA-4 are identical, suggesting that this region has\ important functional properties [MEDLINE:91341416].\

Typically, activation of T cells by TCR-engaging peptide-MHC is dramatically \ enhanced by interaction of the CD28 co-stimulatory receptor with its ligands \ CD80 (B7-1) and CD86 (B7-2) on the APC surface. Interestingly, CTLA-4 is \ transported from intracellular stores toward the region of the cell surface \ receiving activation signals. This suggests that binding of CD28 to its \ ligand may occur primarily at the centre of the mature immunological synapse, \ and that CTLA-4 may be transported to this site under certain circumstances\ to block or reverse this effect.\

\ \ \ \N membrane ; GO:0016020 immune response ; GO:0006955 26520 IPR008095

Class II transactivator (CIITA) determines the level, cell type specificity,inducibility and extinction of MHC-II expression. CIITA is also the \ obligatory mediator of INF-gamma inducible MHC-II expression. Thus control\ of MHC-II expression is ultimately dependent on the control of expression\ of the CIITA gene itself. Defective CIITA has been shown to be responsible\ for one class of base lymphocyte syndrome (BLS). BLS is an often fatal \ genetic defect, characterised by severe immunodeficiency as a result of \ failure to express MHC class II genes. Expression of CIITA is controlled by\ four independent CIITA promoters, leading to CIITA transcripts with four \ distinct first exons. The individual promoters are used in an alternative\ and tissue-specific manner. CIITA promoter (CIITA-P)I is the promoter used\ in dentritic cells; CIITA-PII is expressed at insignificant levels and is \ as yet functionally poorly understood; CIITA-PIII is constitutively\ expressed in B lymphocytes and can drive CIITA expression after INF-gamma\ stimulation in a number of different cell types, including endothelial cells\ and fibroblasts; and CIITA-PIV is the principal INF-gamma-inducible promoter.\ The cellular and temporal diversity in MHC class II expression is thus \ regulated via the different usage of the CIITA promoters\ [MEDLINE:97327562], [MEDLINE:98263345], [MEDLINE:20270031], [MEDLINE:21636492], [MEDLINE:21653196], [MEDLINE:21681688].\

CIITA contains four domains: acidic (A), proline-serine-threonine-rich (PST), \ GTP-binding (GBD), and leucine-rich repeat (LRR). All of these are required\ to activate the MHC class II promoter. The acidic transcriptional activation\ domain interacts with TAFII32. Recruitment of the coactivator protein CBP by\ the acidic domain has also been shown to lead to synergistic activation of\ MHC class II promoters and the repression of the interleukin-4 promoter. The\ PST domain is essential for CIITA function, but its exact role remains \ unknown. The central region containing the GTP-binding and LXXLL motifs \ plays an important role in CIITA self-association. This region interacts \ with itself, the N-terminal domain of CIITA (A/PST) and C-terminal LRR. In \ addition to their role in CIITA self-association, which is generally \ necessary for the association of the protein with the import machinery, both\ GBD (where GTP binding is believed to cause a conformational change \ compatible with nuclear translocation) and LRR domains have been shown to\ play important roles in the nuclear localisation of CIITA. Human CIITA appears to contain a NLS. Export of a protein depends \ on the presence of a specific export signal (NES). NESs are short leucine-\ rich motifs - in CIITA, they have the consensus LXXXLXXLXL, and are\ localised in the N- and C-terminal regions\ [MEDLINE:21332099], [MEDLINE:21402925], [MEDLINE:21653196].\

Numerous in vitro and functional studies have implicated CIITA in multiple\ steps of the transcriptional activation process: e.g., (i) it may facilitate\ chromatin remodelling, as it interacts with histone acetyltransferases;\ moreover, it has intrinsic acetyltransferase activity; (ii) it interacts\ with the general transcription factors TFIIB, HTAFII32 and HTAFI70, implying\ that it may recruit the transcriptional apparatus directly; (iii) it\ interacts with TFIIH and P-TEFb, and may therefore enhance promoter\ clearance and transcription elongation. \

\ \ \ \ transcription regulator activity ; GO:0030528 \N regulation of transcription ; GO:0045449 26519 IPR008094

Zona occludens (ZO), or tight junctions (TJ), are specialised membrane domains found at the most apical region of polarised epithelial and endothelial cells that create a primary barrier, preventing paracellular \ transport of solutes, and restricting the lateral diffusion of membrane \ lipids and proteins, thus maintaining cellular polarity [MEDLINE:98311639]. Under freeze-fracture electron microscopy, TJs appear as a network of continuous \ anastomosing intramembranous strands. These strands consist mainly of \ claudins and occludin (IPR005417), which are transmembrane proteins that polymerise \ within plasma membranes to form fibrils [MEDLINE:21181410].

\ \ \

The claudin protein family is encoded by at least 17 human genes, with many homologues cloned from other species. Tissue distribution patterns for the claudin family members are distinct. Claudin-1 and -2, for example, are expressed at high levels in the liver and kidney, whereas claudin-3 mRNA is detected mainly in the lung and liver [MEDLINE:98311639], [MEDLINE:99110921]. This suggests that multiple claudin family members may be involved in tight junction strand formation in a tissue-dependent manner.

\ \

Hydropathy analysis suggests that all claudins share a common transmembrane (TM) topology. Each family member is predicted to possess four TM domains with intracellular N and C termini. Although their C-terminal cytoplasmic domain sequences vary, most claudin family members share a common motif of -Y-V in this region. This has been postulated as a possible binding motif for PDZ domains of other tight junction-associated membrane proteins, such as ZO-1 (IPR005417/>).

Human and mouse isoforms of claudin-15 have been cloned. Claudin-15 shares\ ~25-45% overall similarity with other claudin family members at the amino\ acid level, displaying highest similarity to claudin-10.\

\ \ \ structural molecule activity ; GO:0005198 membrane ; GO:0016020 \N 26516 IPR008091

Iron is essential for growth in both bacteria and mammals. Controlling the amount of free iron in solution is often used as a tactic by hosts to limit \ invasion of pathogenic microbes; binding iron tightly within protein \ molecules can accomplish this. Such iron-protein complexes include haem in \ blood, lactoferrin in tears/saliva, and transferrin in blood plasma. Some \ bacteria express surface receptors to capture eukaryotic iron-binding \ compounds, while others have evolved siderophores (enterobactins) to \ scavenge iron from iron-binding host proteins [MEDLINE:94335702]. \

Most high-affinity systems for iron uptake in Gram-negative bacteria are thought to employ periplasmic-binding-protein-dependent transport. In Escherichia coli, FepB is a periplasmic protein required for uptake of iron complexed to its endogenously-synthesized siderophore enterobactin (Ent) [MEDLINE:96004464].

\ \

The control of such siderophore gene expression in Escherichia coli is under \ the regulation of the negative repressor protein FUR [MEDLINE:99144129]. When complexed \ with Fe2+, it down-regulates the transcription not only of the siderophore \ genes, but also of the moieties that release Fe2+ ions bound to the hydrox-amate enterobactin proteins in the microbial cytoplasm [MEDLINE:99144129]. One of these\ codes for FhuD, a ferric hydroxymate binding protein located in the\ bacterial periplasm [MEDLINE:87279948], [MEDLINE:96099304]. Homologues of the FhuD gene, first described in Escherichia coli, have been found in other Gram-negative pathogens, such as Yersinia\ pestis and Salmonella spp., as well as in the plant microbe Rhizobium \ leguminosarum [MEDLINE:87279948], [MEDLINE:96099304].\

Recent mutational studies have shown the FhuD gene to be an essential and \ integral part of the ferric hydroxymate ABC transport system in E.coli [MEDLINE:22041847]. \ Mutants lacking the Fhu operon were unable to utilise ferrichrome as an iron \ source, and showed a lower level of virulence than the wild type bacteria [MEDLINE:22041847].\

The structure of E.coli FhuD complexed to gallichrome has been resolved to \ 1.90A using X-ray crystallography [MEDLINE:20207044]. The iron component is held in a \ shallow binding pocket between two domains separated by a long central -helix [MEDLINE:20207044]. This constitutes a novel fold, and is not found in any \ other periplasmic binding protein.

\ \ \ iron ion transporter activity ; GO:0005381 \N high affinity iron ion transport ; GO:0006827 26518 IPR008093

Antigen (Ag) recognition by the T cell receptor (TCR) induces activation ofT lymphocytes. However, TCR-mediated signals alone are insufficient for\ efficient T cell activation, and additional co-stimulatory signals are \ required. One of the most important surface molecules that delivers \ co-stimulatory signals for T cells is CD28. The human T lymphocyte Ag CD28 \ (Tp44) is a homodimeric 90kDa glycoprotein expressed on the surface of the\ majority of human peripheral T cells and lymphocytes. Stimulation of CD4+ T\ cells in the absence of CD28 co-signalling causes impaired proliferation, \ reduced cytokine production and altered generation of helper T cell subsets.\ Co-stimulation via CD28 promotes T cell viability, clonal expansion,\ cytokine production and effector functions, while also regulating apoptosis\ of activated T cells, suggesting its importance in regulating long-term T \ cell survival [MEDLINE:90293482], [MEDLINE:90217534], [MEDLINE:21555167], [MEDLINE:21555161].\

Ligands for CD28 and the structurally related CTLA-4 (CD152) are the\ molecules B7.1 (CD80) and B7.2 (CD86). B7.1 and B7.2 are expressed on\ professional antigen presenting cells (APCs) and their expression is up-regulated during an immune response. Ligation of CD28 by its natural ligands\ results in tyrosine phosphorylation at a YMNM motif within its cytoplasmic\ tail. The phosphorylated motif subsequently interacts with the Src homology\ 2 domain in the p85 regulatory subunit of P13K, activating the p110 \ catalytic subunit. One of the P13K-dependent downstream targets, resulting \ from the antibody cross-linking of CD28, is the phoshporylation and \ activation of Akt (or PKB). Constitutively active Akt is able to substitute\ for CD28 signals, and stimulates IL-2 production when introduced into mature\ CD28-deficient cells. Another molecule affected by CD28 stimulation is the\ proto-oncogene Vav, which acts as a guanine-nucleotide exchange factor for\ Rac and CDC42, allowing these molecules to switch from the inactive GDP-\ bound state to the active GTP-bound state [MEDLINE:21881743], [MEDLINE:21686212].\

Another interesting feature of CD28, is its ability to induce expression of\ PDE7, a cAMP phosphodiesterase, thus reducing cellular cAMP levels. cAMP has\ been reported to affect nearly every pathway important for lymphocyte\ activation, leading to inhibition of T cell proliferation. Specifically,\ increased intracellular cAMP has been implicated in the induction of T cell\ anergy, a non-responsive state that occurs after T cells are stimulated\ through TCR/CD3 in the absence of co-stimulation. This can have therapeutic \ implications, in that blockage of CD28 co-stimulation can be profoundly\ immunosuppressive, preventing induction of pathogenic T cell responses in\ autoimmune disease models, and allowing for prolonged acceptance of \ allografts in models of organ transplantation [MEDLINE:21686212]. \

Finally, CD28 co-stimulation directly controls T cell cycle progression by \ down-regulating the cdk inhibitor p27kip1, which actually integrates\ mitogenic MEK and P13K-dependent signals from both TCR and CD28 [MEDLINE:21881743].\

\ \ \ \N membrane ; GO:0016020 immune response ; GO:0006955 26517 IPR008092

The DAP3 (death associated protein 3) family appear to be positive mediatorsof apoptosis. Human DAP3 mediates inteferon-gamma-induced cell death [MEDLINE:96070931], \ and also mediates the effects of Fas and TNF-. The proteins are \ ubiquitously expressed and are localised to the mitochondrial matrix [MEDLINE:96070931], [MEDLINE:20472653].\

DAP3 contains a potential P-loop motif, suggesting that it might be an\ ATP/GTP-binding protein. Mutations in the P-loop region of human DAP3 do \ not affect the overall stability of the protein, but do however reduce its\ apoptopic effects by more than 2-fold [MEDLINE:99107752]. By contrast, mutations in the murine DAP3\ P-loop motif do abolish the pro-apoptopic effects.

\ \ \ \N small ribosomal subunit ; GO:0015935 apoptosis ; GO:0006915 26515 IPR008090

The control of such siderophore gene expression in Escherichia coli is under \ the regulation of the negative repressor protein FUR [MEDLINE:99144129]. When complexed \ with Fe2+, it down-regulates the transcription not only of the siderophore \ genes, but also of the moieties that release Fe2+ ions bound to the hydrox-\ amate enterobactin proteins in the microbial cytoplasm [MEDLINE:99144129]. An example of \ the latter is FhuF from the Gram-negative microbes Yersinia pestis, \ Salmonella typhi, and Escherichia coli [MEDLINE:99144129]. In conjunction with the \ siderophore system, this gene has been demonstrated to be essential for \ growth and virulence in pathogenic enterobacteria [MEDLINE:99144129].\

\ FhuF is a member of the [2Fe-2S] ferric iron reductase family. However,\ in place of the symmetrical tetrahedral arrangement at the ferric iron\ binding site, an unusual Cys-Cys C-terminal group distorts the site in this\ protein [MEDLINE:99255563]. This property makes FhuF inherently unstable, and another set\ of regulatory genes, designated "suf", is thought to maintain its activity\ in the cytoplasm.\

\ \ \ ferric iron binding activity ; GO:0008199 \N \N 26514 IPR008089

Carbohydrates are used for a wide variety of functions in animals, plants and microbes. As well as providing the main energy source for most organisms,\ carbohydrates are ideally suited for molecular recognition [MEDLINE:21563371]. For example, \ the stereochemistry of each hydroxyl substituent in a simple six-carbon six-oxygen pyranose ring can be varied to give up to 10 different molecules.\ An organism's ability to change and control the stereochemistry of moieties\ like glucose and galactose is, therefore, important.\

Epimerases or "dehydratases", enzymes that catalyse these changes in \ carbohydrates, exist in both prokaryotes and eukaryotes. The processes they \ arbitrate are known as "epimerisation" and are involved in many metabolic \ pathways [MEDLINE:98345984]. For example, the UDP-galactose epimerase in Arabidopsis \ thaliana mediates the reversible epimerisation of UDP-galactose, and is \ considered essential for this reason, providing a secondary growth \ metabolite to glucose [MEDLINE:98345984]. \

Bacterial homologues of the mouse-ear cress epimerase are involved in the \ synthesis of extracellular polysaccharide capsule components, as well as \ metabolic pathways [MEDLINE:98261501]. For this reason, they are considered virulence \ factors if present in a pathogenic strain. Vibrio vulnificus, the causative\ agent of septicemia and infectious disease from contaminated seafood, relies \ on a thick polysaccharide capsule to evade host immune cells [MEDLINE:98261501]. Epimerase\ deletion mutants were unable to infect a mouse model, suggesting that the\ gene is essential for bacterial virulence. Deletion studies with other\ capsular pathogens, like Staphylococcus aureus, have shown that the\ epimerase enzyme is needed for capsule polysaccharide formation and,\ ultimately, virulence.\

\ \ \ racemase and epimerase activity, acting on carbohydrates and derivatives ; GO:0016857 \N carbohydrate metabolism ; GO:0005975 26513 IPR008088

Giardia lamblia is a protozoan parasite of numerous mammals, including humans [MEDLINE:21325898]. It belongs to the phylum Sarcomastigophora, and is amongst the \ most primitive eukaryotes identified to date. It is the main causative agent\ of global protozoan diarrhoea, and severe infection can cause giardiasis.\ G.lamblia exists as either trophozoites that live in the small intestine of\ the host and cause the disease symptoms, or cysts that are passed in the\ faeces of the host and infect the next host through contaminated water or\ food [MEDLINE:21325898]. \

Trophozoites exhibit antigenic variation to evade the host immune system, \ expressing a number of virulence factors to aid adherence and invasion of \ the small intestine endothelium [MEDLINE:95357276]. The molecular basis for its antigenic \ variation has been well characterised, and it is believed that its \ phenotypic heretogeneity arises from sexual reproduction [MEDLINE:95357276]. One of the\ major virulence factors of G.lamblia is giardin, an antigen expressed \ as several variants on the trophozoite surface [MEDLINE:94105103]. Alpha giardin is the \ predominant immunotypic giardin present, although and gamma giardin \ have also been identified [MEDLINE:94105103]. \

A recent study on the biochemical properties of giardin has\ identified the protein as an annexin, a eukaryotic protein widely conserved\ amongst plants and animals. Purified giardin associates with \ multimellar phosphatidyl serine-containing vesicles in a Ca2+-dependent\ manner, and has very low sequence similarity with human annexin XIX [MEDLINE:99237240].\

\ \ \ calcium-dependent phospholipid binding activity ; GO:0005544 \N cytoskeleton organization and biogenesis ; GO:0007010 26512 IPR008087

AIRE (AutoImmune REgulator) is the predicted protein responsible for a rare autosomal recessively inherited disease termed APECED. APECED, also \ called Autoimmune Polyglandular Syndrome type I (APS 1), is the only \ described autoimmune disease with established monogenic background, being \ localised outside the major histocompatibility complex region. It is \ characterised by the presence of two of the three major clinical entities, \ chronic mucocutaneus candidiasis, hypoparathyroidism and Addison's disease. \ Other immunologically mediated phenotypes, including insulin-dependent \ diabetes mellitus (IDDM), gonadal failure, chronic gastritis, vitiligo, \ autoimmune thyroid disease, enamel hypoplasia, and alopecia may also \ be present. Immunologically, APECED patients have deficient T cell \ responses towards Candida antigens, and clinical symptoms both within and \ outside the endocrine system, mainly as a result of autoimmunity against \ organ-specific autoantigens [MEDLINE:98061087], [MEDLINE:99160890].\

AIRE has motifs suggestive of a transcriptional regulator protein. It \ harbours two zinc fingers of the plant homodomain (PHD) type. A putative DNA-\ binding domain, termed SAND, as well as four nuclear receptor binding LXXLL \ motifs, an inverted LXXLL domain, and a variant of the latter (FXXLL), hint \ that this protein functions as a transcription coactivator. Furthermore, a \ highly conserved N-terminal 100-amino acid domain in AIRE shows significant\ similarity to the homogeneously staining (HSR) domain of Sp100 and Sp140 \ proteins, which has been shown to function as a dimerisation domain in\ several Sp-100 related proteins \ [MEDLINE:99160890], [MEDLINE:99225312], [MEDLINE:21538881].\

AIRE has a dual subcellular location. It is not only expressed in multiple \ immunologically relevant tissues, such as the thymus, spleen, lymph nodes \ and bone marrow, but it has also been detected in various other tissues, \ such as kidney, testis, adrenal glands, liver and ovary, suggesting that \ APECED proteins might also have a function outside the immune system. \ However, AIRE is not expressed in the target organs of autoimmune\ destruction. At the subcellular level, AIRE can be found in the cell nucleus \ in a speckled pattern in domains resembling promyeolocytic leukaemia nuclear \ bodies, also known as ND10, nuclear dots or potential oncogenic domains \ associated with the AIRE homologous nuclear proteins Sp100, Sp140, and Lysp100. \ The nuclear localisation of AIRE, in keeping with its predicted protein \ domains, suggest that it may regulate the mechanisms involved in the\ induction and maintenance of immune tolerance.\

\ \ \ translation regulator activity ; GO:0045182 cytoplasm ; GO:0005737 humoral immune response ; GO:0006959 26511 IPR008086

Antistasin is a 15-kDa protein found in the salivary glands of the Mexicanleech, Haementeria officinalis; it is an anticoagulant that functions by\ inhibiting factor Xa. The protein contains 119 residues, with an \ unusually high cysteine content (20 residues in all), and exhibits a 2-fold\ internal repeated structure. Four isoforms of antistasin have been\ identified in leech salivary gland extracts; partial sequence analysis \ indicates that these isoforms differ only by 1 or 2 amino acid residues [MEDLINE:88273105].\

Ghilanten is an anticoagulant-antimetastatic protein of the haematophagous\ leech, Haementeria ghilianii. Like antistasin, it contains 119 amino acids,\ with 20 cysteines, and a heparin-binding consensus motif at its C-terminus.\ Arginine-34 is the residue involved in the active-site inhibition of trypsin\ and Factor Xa [MEDLINE:90165947].\

The 3D structure of antistasin has been determined to 1.9A resolution by\ X-ray crystallography [MEDLINE:97459903]. The structure reveals a novel protein fold\ comprising two similar domains, which can be divided into two similarly \ sized subdomains, with different relative orientations. Thus, the domain\ shapes differ, the N-terminal domain being wedge-shaped and the C-terminal\ domain flat [MEDLINE:97459903]. Docking studies suggest that it is differences in domain\ shape that enable the N-terminal domain to bind and inhibit factor Xa,\ rather than the C-terminal domain, despite very similar active sites. A \ putative exosite binding region is evident in the N-terminal domain\ (residues 15-17), which is likely to interact with a cluster of positively\ charged residues on the factor Xa surface (Arg222/Lys223/Lys224), explaining\ the specificity and inhibitory potency of antistasin towards factor Xa.\

\ \ \ anticoagulant activity ; GO:0008435 \N \N 26510 IPR008085

The TSP1 (thrombospondin 1) repeat was first identified in thethrombospondin protein, where it is repeated 3 times [MEDLINE:90028727]. The domain is \ ~60 amino acid residues in length and is characterised by a highly \ conserved W-S-X-W motif and six cysteine residues. TSP1 repeats have \ been identified in a number of proteins including: the complement pathway\ proteins properdin, C6, C7, C8A, C8B and C9; extracellular matrix proteins,\ including mindin, ADAMTS and F-spondin; Plasmodium TRAP proteins; and G \ protein-coupled receptors, such as the brain-specific angiogenesis \ inhibitors. The domains have a number of functions, including effects \ on cell attachment, motility, proliferation, the activities of extracellular\ proteases, and inhibition of angiogenesis, contributing to vascular \ homeostasis. A study of the structure of properdin indicates that the \ TSP1 repeat contains two amphipathic turn regions and a hydrophilic -strand [MEDLINE:91329374].\

\ \ \ \N \N \N 26509 IPR008083

The CD34 group of monoclonal antibodies recognises CD34 (also termed CD34antigen), a 105-120kDa cell surface glycoprotein, which is selectively \ expressed by human myeloid and lymphoid progenitor cells, including \ the haemopoietic stem cell. The protein is also expressed on vascular\ endothelial cells. Here, it is concentrated on the surface of the inter-digitating processes, suggesting a possible involvement in cell interactions\ or adhesion, by mediating the attachment of stem cells to the bone marrow \ extracellular matrix, or directly to stromal cells. The restricted pattern\ of expression of CD34 in haemopoiesis suggests that it may have a \ significant function in the earliest stages of blood cell differentiation \ in the bone marrow [MEDLINE:90293044], [MEDLINE:91223042].\

CD34 is a phosphoprotein shown to be activated by protein kinase C (PKC) in\ a developmental stage-specific manner. Analysis of the human CD34 sequence\ reveals that the protein appears to be a type I transmembrane (TM) molecule.\ The predicted internal portion of the protein appears to retain basic amino \ acid residues adjacent to Ser residues, presenting at least two potential\ target sites for PKC phosphorylation. In addition, there are two other \ consensus motifs that correspond to potential target sites for \ Ca+/calmodulin-dependent kinase and/or protease activated kinase I [MEDLINE:90293044].\

The protein is not strongly similar to other known proteins, but some weak\ similarities do exist: e.g., to the S+T region (a region rich in potential\ O-linked carbohydrate attachment sites), the TM domain and cytoplasmic \ domain of cell surface proteins such as leukosialin, a major sialoglyco-protein of rat and human leukocytes; to the N-terminal glycosylated region\ of CD45 (the leukocyte common antigen); and to groups of interrelated\ proteins involved in cell adhesion or the regulation of complement.\

A homologue of human CD34 is expressed in mouse. The amino acid sequences\ only diverge significantly at their N-termini, which are predicted to be \ highly glycosylated and whose functions are probably modulated by \ carbohydrate. The observed pattern of expression of the murine CD34 gene\ is consistent with that of the human antigen. That CD34 is also highly\ expressed outside haematopoiesis, by vascular endothelial cells and by \ fibroblasts in differentiated tissue, suggests a role common to a variety\ of cell types. Concentration of CD34 on the interdigitating membrane\ projections of adjacent capillary endothelial cells has strengthened the\ idea that it functions in the control of events leading to cell-cell or\ cell-matrix adhesion, which role could be modulated by variation in its\ levels of glycosylation. The conservation between the human and mouse\ cysteine-rich domain in the extracellular part of the protein, and the\ exceptionally high conservation of the cytoplasmic domain, imply that the\ protein is more than a carrier for either carbohydrate or negatively charged\ terminal sialic acid residues (a role postulated for leukosialin/sialophorin).\ The highly conserved domain may serve to provide an internal signal of \ external contact with a ligand.\

\ \ \ \N membrane ; GO:0016020 cell adhesion ; GO:0007155 26508 IPR008081

Cytoplasmic fragile X mental retardation protein (FMRP) interacting proteinbelongs to a highly conserved but, as yet, functionally uncharacterised\ family. Absence of FMRP is responsible for pathologic manifestations in \ Fragile X Syndrome, the most frequent cause of inherited mental retardation\ [MEDLINE:99380159]. FMRP is an RNA-binding protein that may have a role in local protein\ translation at neuronal dendrites and in dendritic spine maturation [MEDLINE:99380159].\ CYFIP1 and CYFIP2, which share a high level of sequence identity, have \ recently been identified as cytoplasmic FMRP interacting proteins [MEDLINE:99380159].\ CYFIP2 interacts with FMRP-related proteins FXR1P/2P, while CYFIP1 interacts\ exclusively with FMRP. The FMRP-CYFIP interaction involves the domain of\ FMRP that also mediates homo- and heteromerisation, suggesting competition\ between the various interaction partners. CYFIP1 also interacts with the \ small GTPase Rac1 implicated in development and maintenance of neuronal\ structures. CYFIP1/2 are both present in synaptosomal extracts [MEDLINE:99380159]. \

PIR121 (121F-specific p53 inducible RNA) is another functionally\ uncharacterised member of this family. The PIR121 gene maps to human\ chromosome 5q34, a region frequently translocated in acute myeloid leukaemia\ but not known to be amplified or deleted in solid tumours. Interaction\ between PIR121 and FMRP has been demonstrated, and hence PIR121 has also \ been termed CYFIP2 (Cytoplasmic FMRP Interacting Protein 2) [MEDLINE:99380159], [MEDLINE:98427792].\

Shyc (Selective HYbridizing Clone) is a cytoplasmic protein of unknown \ function, expressed in the developing and embryonic nervous system. The\ protein has also been designated CYFIP1 due to the high sequence identity\ (98.7%) to its human orthologue. The CYFIP orthologues in Caenorhabditis\ elegans and Drosophila melanogaster share about 51% and 67% sequence \ identity with the human proteins, respectively [MEDLINE:99380159]. The high level of\ conservation manifest throughout the entire CYFIP sequence between various\ orthologues suggests a number of functionally/structurally important domains.

\ \ \N \N \N 26507 IPR008080

Fish allergies are common in Europe, particularly among male children and \ young adults. Children allergic to fish react variably to different species.\ Cod is among the most common offenders, while salmon is the one best\ tolerated. The allergy-eliciting protein has been isolated from the white\ muscle albumin. It is a parvalbumin, designated Allergen M. Parvalbumins are\ calcium (Ca)-binding proteins of low molecular weight. Like many other \ Ca-binding proteins, they belong to the EF-hand family characterised by\ helix-loop-helix (HLH) binding motifs (two helices pack together at an angle\ of ~90 degrees, separated by a loop region where calcium binds). In the \ parvalbumin HLH structural motif, calcium is coordinated through one \ carbonyl oxygen atom and the oxygen-containing side-chains of 5 amino acid\ residues, or 4 residues and a water molecule\ [MEDLINE:75198151], [MEDLINE:89380285], [MEDLINE:97002034].\

Initially, parvalbumins were detected in relatively high amounts in lower\ vertebrate white muscle, where they were thought to be important for fibre\ relaxation. They were subsequently found, although in lesser amounts, in the\ fast twitch skeletal muscles of higher vertebrates, as well as in a variety\ of non-muscle tissues, including testis, endocrine glands, skin and specific\ neurons. There are two distinct phylogenetic lineages: and . Most\ muscles contain parvalbumin of only or origin. Cod parvalbumin \ belongs to the -lineage and shares significant similarity with \ parvalbumin of other fish species [MEDLINE:75198151], [MEDLINE:97002034].\

Allergen M contains 113 residues, is a homogenous acidic protein and belongs\ to a group of muscle sarcoplasmic proteins. It carries the major allergenic\ determinants associated with cod sensitivity, which is dependent directly on\ the linear structure rather than on the molecular conformation. The \ allergenic activity of allergen M resides in particular epitopes found in\ three loops: AB (~13-33), CD (~48-64) and EF (~80-103). It has an N-acetyl\ terminal amino acid residue and includes 1 residue of glucose attached to \ the conserved N-terminal cysteine, and 1 residue each of tyrosine, \ tryptophan and arginine - the arginine is believed to play a key role in \ maintaining the tertiary structure. Mutation of the last conserved\ coordinating residue of the Ca-binding loop (E101D-motif 4) has also been\ shown to have a significant impact on the ability of the mutant to obtain\ the sevenfold coordination preferred by Ca2+.\

\ \ \ calcium ion binding activity ; GO:0005509 \N \N 26506 IPR008079

Ca2+ ions are unique in that they not only carry charge but they are also the most widely used of diffusible second messengers. Voltage-dependent Ca2+ channels (VDCC) are a family of molecules\ that allow cells to couple electrical activity to intracellular Ca2+ signalling. The opening and closing of\ these channels by depolarizing stimuli, such as action potentials, allows Ca2+ ions to enter neurons\ down a steep electrochemical gradient, producing transient intracellular Ca2+ signals. Many of the\ processes that occur in neurons, including transmitter release, gene transcription and metabolism are\ controlled by Ca2+ influx occurring simultaneously at different cellular locales.

\ \

Voltage-gated calcium channels\ are classified as T, L, N, P, Q and R, and are distinguished by their\ sensitivity to pharmacological blocks, single-channel conductance kinetics,\ and voltage-dependence. On the basis of their voltage activation\ properties, the voltage-gated calcium classes can be further divided into\ two broad groups: the low (T-type) and high (L, N, P, Q and R-type)\ threshold-activated channels PUB00010557.

There are\ four distinct subunits: -1, -2, -3 and -4; and the\ magnitude of the shift in the voltage-dependence of activation of change to membrane\ potentials varies with the particular subtype PUB00010557.

Beta-3 subunits are most abundant in the brain, but are also present in\ aorta, trachea, lung, heart, skeletal muscle and pancreatic islets, where\ they play a role in the regulation of insulin secretion [MEDLINE:93155194]. The -3\ subunits regulate the activation (opening) and inactivation (closing)\ kinetics through phosphorylation and dephosphorylation. However, it is noted\ that no single channel is dependent on the -3 subunit.

\ \ \ voltage-gated calcium channel activity ; GO:0005245 \N calcium ion transport ; GO:0006816 26504 IPR008077

The secretin-like GPCRs include secretin [MEDLINE:91266890], calcitonin [MEDLINE:92054591], parathyroid hormone/parathyroid hormone-related peptides [MEDLINE:92054592] and vasoactive intestinal peptide [MEDLINE:92232309], all of which activate adenylyl cyclase and the phosphatidyl-inositol-calcium pathway. The amino acid sequences of the receptors contain high proportions of hydrophobic residues grouped into 7 domains, in a manner reminiscent of the rhodopsins and other receptors believed to interact with G-proteins. However, while a similar 3D framework has been proposed to account for this, there is no significant sequence identity between these families: the secretin-like receptors thus bear their own unique '7TM' signature.

Three human secretin-like GPCRs that are expressed specifically in the\ brain, and appear to have a role in the inhibition of angiogenesis, have\ been identified and named BAI (brain-specific angiogenesis inhibitor) 1-3\ [MEDLINE:98054121]. In addition to the characteristic 7 TM domains, the BAIs also have a\ large extracellular domain containing a number of thrombospondin type 1 \ repeats - these have been shown to inhibit in vivo angiogenesis induced by\ bFGF in rat cornea. BAI1 has been found to be transcriptionally \ regulated by p53 and is absent in many glioblastoma cell lines, suggesting\ that it may play an important role in suppression of the disease.\

\ \ \ brain-specific angiogenesis inhibitor activity ; GO:0016527 membrane ; GO:0016020 G-protein coupled receptor protein signaling pathway ; GO:0007186 26505 IPR008078

The rhodopsin-like GPCRs themselves represent a widespread protein family that includes hormone, neurotransmitter and light receptors, all of which transduce extracellular signals through interaction with guanine nucleotide-binding (G) proteins. Although their activating ligands vary widely in structure and character, the amino acid sequences of the receptors are very similar and are believed to adopt a common structural framework comprising 7transmembrane (TM) helices [MEDLINE:90262152], [MEDLINE:88139292], [MEDLINE:93234436].

A novel member of the secretin-like family of GPCRs has been cloned and\ named Ig-hepta, due to the presence of two immunoglobulin-like repeats\ in its large extracellular domain. The receptor is expressed\ predominantly in the lung, this expression being strongly induce\ postnatally. Biochemical analysis indicates that Ig-hepta is heavily\ glycosylated and exists as a disulphide-linked dimer. The receptor appears\ to be localised in alveolar walls of the lungs and intercalated cells of the\ kidney collecting ducts, suggesting a role in regulation of acid-base\ balance [MEDLINE:99321930].\

\ \ \ \N \N \N 26503 IPR008076

Cyanase, an enzyme found in bacteria and plants, catalyses the reactionof cyanate with bicarbonate to produce ammonia and carbon dioxide, allowing\ the host organisms to overcome the toxicity of environmental cyanate [MEDLINE:87280031].\ \

The cyanate lyase monomer is composed of two domains: an N-terminal domain\ that shows structural similarity to the DNA-binding -helix bundle\ motif, and a C-terminal domain that has an 'open fold' that shows no \ structural similarity to other proteins [MEDLINE:87280031].\

The enzyme is active as a homodecamer of 17kDa subunits, and displays\ half-site binding of substrates or substrate analogues. The dimer structure\ reveals the C-terminal domains to be intertwined; the decamer is formed\ from a pentamer of these dimers. The active site of the enzyme is located\ between dimers and comprises residues from four adjacent subunits\ of the homodecamer.\

Synonym(s): cyanase lyase, cyanase hydrolase

\ \ \ hydro-lyase activity ; GO:0016836 \N metabolism ; GO:0008152 26502 IPR008075

Lipocalin-1 is a memberof the lipocalin superfamily produced by a number of secretory glands and\ tissues [MEDLINE:20513987]. The biological relevance of the many possible activities of\ Lcn-1 has still to be established, but its main function appears to be\ scavenging of lipophilic, potentially harmful molecules, providing a\ protection factor for cells and tissues [MEDLINE:21283009]. \

Beyond its interaction with Lcn-1, the precise physiological function of\ lipocalin-1 interacting membrane receptor (LIMR) is unknown. It could be\ involved in the detoxification of the ligands bound to Lcn-1, either\ transferring the ligand into the cell, or acting as a detoxification\ protein itself, with possible enzymatic activity similar to the membrane-associated enzymes involved in lipid molecule modification [MEDLINE:93015903]. \

Currently, there is only limited data available concerning the identity of \ lipocalin receptors. While there is clear evidence for a specific receptor\ for plasma retinol binding protein (RBP), there is only indirect evidence of\ receptors for alpha1-microglobulin (A1M), major urinary protein (MUP), -lactoglobulin, glycodelin, insecticyanin, alpha1-acid glycoprotein \ (AGP) and odorant binding protein (OBP). There is no consensus in the\ mechanism of interaction between lipocalins and their receptors. Lipocalin\ receptors have been found to act via carbohydrate binding and protein-protein interactions. With the exception of megalin, an apparent endocytic\ receptor for several soluble macromolecules including some lipocalins, no\ specific lipocalin receptor has so far been fully characterised.\

Synonym(s): Lcn-1, tear lipocalin, von Ebners gland protein

\ \ \ \N \N \N 26501 IPR008074

Potassium channels are the most diverse group of the ion channel family[MEDLINE:92126332], [MEDLINE:91348257]. They are important in shaping the action potential, and in neuronal excitability and plasticity [MEDLINE:88189348]. The potassium channel family is\ composed of several functionally distinct isoforms, which can be broadly\ separated into 2 groups [MEDLINE:90059914]: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.

These are all highly similar proteins, with only small amino acid\ changes causing the diversity of the voltage-dependent gating mechanism,\ channel conductance and toxin binding properties. Each type of K⁺ channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; and others are regulated by GTP-binding proteins or\ other second messengers [MEDLINE:88122563]. In eukaryotic cells, K⁺ channels\ are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes [MEDLINE:92235098]. In prokaryotic cells, they play a role in the\ maintenance of ionic homeostasis [MEDLINE:21114513].

All K⁺ channels discovered so far possess a core of subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has\ been termed the K⁺ selectivity sequence.\ In families that contain one P-domain, four subunits assemble to form a selective pathway for K⁺ across the membrane.\ However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of subunits or association with auxillary cytoplasmic subunits. K⁺ channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains.\ The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K⁺ channels; and three types of calcium (Ca)-activated K⁺ channels (BK, IK and SK)\ [MEDLINE:21114513], PUB00009384. The 2TM domain family comprises inward-rectifying K⁺ \ channels. In addition, there are K⁺ channel -subunits that possess two P-domains. These are usually highly regulated K⁺ selective leak channels.

TRAAK (TWIK-related arachidonic acid-stimulated K+ channel) is a member of\ the 2P-domain K+ channel family, and is expressed mainly in the brain and\ placenta. It is strongly activated by unsaturated fatty acids, such as\ oleate and linoleate. An alternative way of activating TRAAK channels is the\ application of stretch to the cell membrane, for example, by means of cell\ swelling, shear stress or negative pressure PUB00009384.

\ \ potassium channel activity ; GO:0005267 membrane ; GO:0016020 potassium ion transport ; GO:0006813 26500 IPR008073

The TASK (TWIK-related acid-sensitive K+ channel) family contains five\ members (TASK1-5), which share no more than 54% amino acid identity. These\ form functional K+ channels in various cell types and encode background\ K+ channels, thereby helping to set the resting membrane potential. All\ members are very sensitive to variations in extracellular pH in the\ physiological range, changing from fully-open to closed in approximately\ 0.5pH units around pH7.4. Thus, they may well constitute biological sensors\ of external pH variations.\

TASK-5 is expressed in the pancreas, liver, kidney, lung, ovary, testis and\ heart. It requires another as yet unidentified partner subunit to form \ functional channels in the plasma membrane, or it may form a channel in an\ intracellular organelle PUB00009384.

\ \ \ potassium channel activity ; GO:0005267 membrane ; GO:0016020 potassium ion transport ; GO:0006813 26498 IPR008071

The cytochrome P450 enzymes constitute a superfamily of haem-thiolate proteins. P450 enzymes usually act as terminal oxidases in multicomponentelectron transfer chains, called P450-containing monooxygenase systems and are involved\ in metabolism of a plethora of both exogenous and endogenous compounds. P450-containing\ monooxygenase systems primarily fall into two major classes: bacterial/mitochondrial\ (type I), and microsomal (type II). All P450 enzymes can be categorised into two\ main groups, the so-called B- and E-classes: P450 proteins of prokaryotic 3-component\ systems and fungal P450nor (CYP55) belong to the B-class; all other known P450 proteins\ from distinct systems are of the E-class [MEDLINE:93135827].

\ \

The CYP2 family comprises 15 subfamilies (A-H, J-N, P and Q). Six of these subfamilies are non-mammalian: 2H derives\ from chicken; 2K, 2M, 2N and 2P are from fish; 2L is from lobster; and 2Q\ from Xenopus [MEDLINE:20493204]. Several CYP2J1 isoforms have been reported, including rabbit\ CYP2J1; human CYP2J2; rat 2J3 and 2J4; mouse 2J5, 2J6, 2J7, 2J8 and 2J9; and\ rat CYP2J10. The metabolic activities of CYP2J2, 2J3, 2J4 and 2J5 have\ been characterised; all isoforms are active toward arachidonic acid, forming\ metabolites believed to be important for cellular functions. In addition,\ CYP2J4 is active in the biosynthesis of retinoic acid from retinal.\

\ \ \ oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen ; GO:0016712 \N electron transport ; GO:0006118 26499 IPR008072

\ \

Enzymes of the CYP3 family constitute major mammalian, especially human,\ forms involved in the metabolism of foreign compounds. There is\ considerable structural variety in the known substrates of CYP3A enzymes and\ it is difficult to categorise such diverse substrate specificity. Although a\ number of 3A substrates are also metabolised by other P450s, such as 2D6 and\ 2C isozymes, the site of metabolism is often different and N-dealkylation is\ a common feature of 3A mediated metabolism. One means of rationalising the\ apparent lack of similarity in 3A substrates can be achieved by molecular\ modelling of the relevant enzymes. It appears that a highly conserved\ asparagine residue may be strategically placed in the 3A binding site such\ that hydrogen-bonding interactions with known substrates enable orientation\ for oxygenation in the relevant positions. In general, the CYP3A\ subfamily mediates detoxifying metabolism of exogenous substrates, but a\ number of activating pathways, such as detoxifying carcinogens by additional\ metabolism in alternative, non-activating positions, have been demonstrated.\

\ \

The CYP2 family comprises 15 subfamilies (A-H, J-N, P and Q). Six of these subfamilies are non-mammalian: 2H derives\ from chicken; 2K, 2M, 2N and 2P are from fish; 2L is from lobster; and 2Q\ from Xenopus [MEDLINE:93135827]. The first five (A-E) are present in mammalian liver, but\ in differing amounts and with different inducibilities. These five \ subfamilies show varied substrate specificities, with some degree of \ overlap. There is growing evidence for the involvement of 2E in the \ activation of carcinogens and other toxic chemicals, although isozymes\ in this subfamily also exhibit detoxifying metabolic pathways. In addition\ to oxygenations, 2E is able to carry out reductive dehalogenation reactions\ under low oxygen conditions, and this usually gives rise to cytotoxic\ species. The different 2E orthologues are highly similar across species,\ resulting in the sole designation CYP2E1.\

Although highly similar in terms of amino acid sequence, it is possible that\ a number of key residue changes between mammalian 2E proteins may explain\ some of the known species differences in substrate metabolism. Site-directed\ mutagenesis of a threonine residue (Thr-301) in 2E1 has indicated that the\ rate of metabolism of substrates can be altered by changing this residue,\ and it is likely that the electronic properties of certain key atoms in the\ substrate are also relevant to metabolism.

\ \ oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen ; GO:0016712 \N electron transport ; GO:0006118 26494 IPR008067

\ \

The CYP2 family comprises 15 subfamilies (A-H, J-N, P and Q). Six of these subfamilies are non-mammalian: 2H derives\ from chicken; 2K, 2M, 2N and 2P are from fish; 2L is from lobster; and 2Q\ from Xenopus [MEDLINE:97057932]. The first five (A-E) are present in mammalian liver, but\ in differing amounts and with different inducibilities. These five \ subfamilies show varied substrate specificities, with some degree of \ overlap. The 2D subfamily is generally regarded as being involved in \ detoxifying pathways of metabolism. There is considerable interest in the\ 2D subfamilies, due to the fact that about 30% of all currently-used\ drugs are metabolised in man by the 2D6 orthologue. As the constitutive\ levels of 2D6 are low (1-2% of human hepatic P450 complement) and the enzyme\ is non-inducible, any defect in 2D6-dependent metabolism may have serious\ consequences with respect to an undesirable accumulation of pharmaceutical\ agents, leading to potential toxicity and possible adverse drug reactions.

\ \

The CYP2 family comprises 15 subfamilies (A-H, J-N, P and Q). Six of these subfamilies are non-mammalian: 2H derives\ from chicken; 2K, 2M, 2N and 2P are from fish; 2L is from lobster; and 2Q\ from Xenopus [MEDLINE:96062494]. The first five (A-E) are present in mammalian liver, but\ in differing amounts and with different inducibilities. These five \ subfamilies show varied substrate specificities, with some degree of \ overlap, particularly between the 2B and 2C subfamilies. Although primarily\ associated with detoxification, 2B has been also linked with toxic effects\ produced by generation of reactive oxygen species (ROS) via a mechanism\ known as futile cycling in rodent. The likelihood of toxic activation\ mediated by 2B is minimal in man, as the relevant orthologue is poorly\ expressed in human liver and is only associated with the toxicity of a very\ small number of carcinogens and cytotoxic agents.

\ \

CYP1 enzymes mainly metabolise exogenous substrates and are found in \ mammalia (1A, 1B), bony fishes (1A), sharks, skates, rays (1A) and birds\ (1A). CYP1A contains five proteins, namely, CYP1A1, 1A2, 1A3, 1A4 and 1A5.\ CYP1A1 and CYP1A2 have been found in all classes of the animal kingdom [MEDLINE:93135827];\ the proteins are highly similar between mammalian species (human and rat\ CYP1A1 are 80% identical) and CYP1A1 and CYP1A2 are themselves closely\ related. CYP1 family members are closely associated with the metabolic\ activation of pro-carcinogens and mutagens. The mechanisms of activation\ have been extensively studied, and are known to involve 'bay-region' \ epoxidation in conformationally hindered positions, often followed by a \ second epoxidation step on the subsequent 'bay-region' diol to give rise to\ electrophilic diol epoxides capable of interacting covalently with DNA. This\ causes mutagenesis and utimately, carcinogenesis. Clearly, the CYP1 family\ has a role in toxic activation, but it may also possess important endogenous\ functions, in addition to mediating several detoxifying pathways.\

Neuropeptide FF (together with neuropeptides AF and SF, which are derivedfrom the same precursor) belongs to a family of neuropeptides containing an \ RF-amide motif at their C-termini [MEDLINE:21225177]. Neuropeptide FF is found at high\ concentrations in the posterior pituitary, spinal cord, hypothalamus and \ medulla, and is believed to be involved in pain modulation, opioid tolerance,\ cardiovascular regulation, memory and neuroendocrine regulation.\

\ \ \ neuropeptide hormone activity ; GO:0005184 \N \N 26491 IPR008064

Like all apoptotic cell death, T cell receptor (TCR)-mediated death can bedivided into two phases: an inductive phase and an effector phase. The \ effector phase includes a sequence of steps that are common to apoptosis in\ many cell types, which, if not interrupted, will lead to cell death. The\ induction phase, which often requires the expression of new genes, consists\ of a set of signals that activate the effector phase. Outside the thymus,\ most, if not all, of the TCR-mediated apoptosis of mature T cells (sometimes\ referred to as activation-induced cell death (AICD)) is induced through the\ surface antigen Fas pathway: activation through the TCR induces expression\ of the Fas (CD95) ligand (FasL); the expression of FasL on either a\ neighbouring cell, or on the Fas-bearing cell, induces trimerisation of Fas,\ which then initiates a signal-transduction cascade, leading to apoptosis of \ the Fas-bearing cell. This commitment stage requires the activation of key\ death-inducing enzymes, termed caspases, which act by cleaving proteins that\ are essential for cell survival and proliferation\ [MEDLINE:21617179], [MEDLINE:21287301]. However what\ happens to FasL itself remains unknown. It is possible that it is cleaved\ from the effector cells and internalised into the target cells; it may be\ downregulated in the effector cells; or it may be phagocytosed by the target\ cells.\

Fas is also known to be essential in the death of hyperactivated peripheral\ CD4+ cells: in the absence of Fas, mature peripheral T cells do not die, but\ the activated cells continue to proliferate, producing cytokines that lead\ to grossly enlarged lymph nodes and spleen. Defects in the Fas-FasL system\ are associated with various disease syndromes. Mice with non-functional Fas\ or FasL display characteristics of lymphoproliferative disorder, such as \ lymphadenopathy, splenomegaly, and elevated secretion of IgM and IgG. These\ mice also secrete anti-DNA autoantibodies and rheumatoid factor [MEDLINE:95127560].\

FasL is a 40kDa type II membrane protein belonging to the tumour necrosis\ factor (TNF) family. It is expressed on activated lymphocytes, NK cells,\ platelets, certain immune-privileged cells and some tumour cells\ [MEDLINE:21617179], [MEDLINE:95127560].\ Human and mouse FasL induce apoptosis in cells expressing either mouse or\ human Fas with the same specificity. Although the amino acid sequence of\ FasL is highly conserved between human and mouse, the similarity between\ human and murine Fas is much less pronounced. Greater conservation of the\ ligand than the receptor is also observed in other members of the TNF family.\ By comparison with other TNF family members, FasL has a long N-terminal \ intracellular region rich in proline residues, which is known to bind to \ the SH3 domain. SH3 domains play important roles in mediating specific\ protein-protein interactions, specifically in the cytoskeleton.\

\ \ \ tumor necrosis factor receptor ligand activity ; GO:0005164 membrane ; GO:0016020 signal transduction ; GO:0007165 26490 IPR008063

Like all apoptotic cell death, T cell receptor (TCR)-mediated death can bedivided into two phases: an inductive phase and an effector phase. The \ effector phase includes a sequence of steps that are common to apoptosis in\ many cell types, which, if not interrupted, will lead to cell death. The\ induction phase, which often requires the expression of new genes, consists\ of a set of signals that activate the effector phase. Outside the thymus,\ most, if not all, of the TCR-mediated apoptosis of mature T cells (sometimes\ referred to as activation-induced cell death (AICD)) is induced through the\ surface antigen Fas pathway: activation through the TCR induces expression\ of the Fas (CD95) ligand (FasL); the expression of FasL on either a\ neighbouring cell, or on the Fas-bearing cell, induces trimerisation of Fas,\ which then initiates a signal-transduction cascade, leading to apoptosis of \ the Fas-bearing cell. This commitment stage requires the activation of key\ death-inducing enzymes, termed caspases, which act by cleaving proteins that \ are essential for cell survival and proliferation\ [MEDLINE:21617179], [MEDLINE:21287301].\

Fas is also known to be essential in the death of hyperactivated peripheral\ CD4+ cells: in the absence of Fas, mature peripheral T cells do not die, but\ the activated cells continue to proliferate, producing cytokines that lead\ to grossly enlarged lymph nodes and spleen. Fas belongs to the tumour\ necrosis factor receptor (TNFR) family of cysteine-rich type I membrane\ receptors; its ligand (FasL) is expressed on activated lymphocytes, NK cells,\ platelets, certain immune-privileged cells and some tumour cells [MEDLINE:21617179], [MEDLINE:21287301].\

Defects in the Fas-FasL system are associated with various disease syndromes.\ Mice with non-functional Fas or FasL display characteristics of lympho-proliferative disorder, such as lymphadenopathy, splenomegaly, and elevated \ secretion of IgM and IgG. These mice also secrete anti-DNA autoantibodies\ and rheumatoid factor [MEDLINE:21287301].\

\ \ \ transmembrane receptor activity ; GO:0004888 membrane ; GO:0016020 signal transduction ; GO:0007165 26488 IPR008061

Inwardly-rectifying K⁺ channels (Kir) are the principal class of two-TM domain K⁺ channels. They are characterised by the property of inward-rectification, which is described as the ability to allow large inward currents and smaller outward currents. Inwardly rectifying potassium channels (Kir) are responsible for regulating diverse processes including: cellular excitability, vascular tone, heart rate, renal salt flow, and insulin release [MEDLINE:99200398]. To date, around twenty members of this superfamily have been cloned, which can be grouped into six families by sequence similarity, and these are designated Kir1.x-6.x [MEDLINE:96059035], [MEDLINE:99379911].

Cloned Kir channel cDNAs encode proteins of between ~370-500 residues, both N- and C-termini are thought to be cytoplasmic, and the N-terminus lacks a signal sequence. Kir channel subunits possess only 2TM domains linked with a P-domain. Thus, Kir channels share similarity with the fifth and sixth domains, and P-domain of the other families. It is thought that four Kir subunits assemble to form a tetrameric channel complex, which may be hetero- or homomeric [MEDLINE:99200398].

Potassium channels are the most diverse group of the ion channel family\ [MEDLINE:92126332], [MEDLINE:91348257]. They are important in shaping the action potential, and in neuronal excitability and plasticity [MEDLINE:88189348]. The potassium channel family is\ composed of several functionally distinct isoforms, which can be broadly\ separated into 2 groups [MEDLINE:90059914]: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.

Kir5 channels are significantly expressed in kidney, pancreas and thyroid\ gland, suggesting that they may be involved in the regulation of fluid and\ pH balance.

\ \ inward rectifier potassium channel activity ; GO:0005242 membrane ; GO:0016020 potassium ion transport ; GO:0006813 26489 IPR008062

The KCNJ13 gene encodes a Kir7 subunit that is predominantly expressed\ in the brain. It is also present in intestinal epithelial cells, thyroid\ follicular cells, spinal cord, kidney and stomach PUB00009384\ in the regulation of the ion-transporting functions of these specialised\ cells. The unique properties of Kir7 make it a strong candidate for the low-\ conductance K+ channel that is coupled to Na+K+-ATPase by recycling K+ [MEDLINE:99386663].\

\ \ \ inward rectifier potassium channel activity ; GO:0005242 membrane ; GO:0016020 potassium ion transport ; GO:0006813 26486 IPR008059

\ \

GABAA receptors are characterised by their sensitivity\ towards a selective antagonist, bicuculline. A second type of ionotropic\ GABA receptor has been identified that is insensitive to bicuculline and\ classical GABAA modulators but has an enhanced affinity for GABA. This\ receptor was found to be composed principally of rho subunits and was termed\ 'GABAC' in recognition of its altered pharmacology [MEDLINE:85111717]. Despite this\ distinction, rho subunits are generally considered to be part of the GABAA\ family of receptor proteins due to similarities in sequence and topology.\

Whilst early studies supported the view that rho subunits assembled to form\ a homopentamer, it has been shown that a mutant rho 1 protein is able to\ coassemble with GABAA gamma 2 subunits as well as the glycine receptor subunit. Rho subunit mRNA occurs prominently in both human and rat\ retina [MEDLINE:98317658], each subunit showing a characteristic pattern of spatial\ expression. In rat retina, rho 1 mRNA has been detected only in bipolar\ cells, whereas rho 2 transcripts have been detected in both bipolar and\ ganglion cells. In retinal tissues, expression of rho 3 mRNA is exclusive to\ ganglion cells. Reverse transcriptase PCR (RT-PCR) and in situ\ hybridisation have shown rho transcripts also to be present in other regions\ of the brain, specifically those involved in visual signal processing, such\ as the superior colliculus and visual cortex.\

\ \ \ GABA-A receptor activity ; GO:0004890 membrane ; GO:0016020 ion transport ; GO:0006811 26487 IPR008060

\ \

\ \ glycine-gated chloride channel activity ; GO:0016934 membrane ; GO:0016020 chloride transport ; GO:0006821 26485 IPR008058

\ \

\ \ \ GABA-A receptor activity ; GO:0004890 membrane ; GO:0016020 ion transport ; GO:0006811 26484 IPR008057

\ \

\ \ \ GABA-A receptor activity ; GO:0004890 membrane ; GO:0016020 ion transport ; GO:0006811 26482 IPR008055

Neurotensin is a 13-residue peptide transmitter, sharing significantsimilarity in its 6 C-terminal amino acid residues with several other\ neuropeptides, including neuromedin N (which is derived from the same\ precursor). This C-terminal region is responsible for the full biological\ activity, the N-terminal portion having a modulatory role. \

Neurotensin is distributed throughout the central nervous system, with\ highest levels in the hypothalamus, amygdala and nucleus accumbens. It\ induces a variety of effects, including: analgesia, hypothermia and \ increased locomotor activity. It is also involved in regulation of dopamine\ pathways. In the periphery, neurotensin is found in endocrine cells of the\ small intestine, where it leads to secretion and smooth muscle contraction\ [MEDLINE:21670954]. The neurotensin/neuromedin N precursor can also be processed to\ produce large 125-138 amino acid peptides with the neurotensin or neuromedin\ N sequence at their C-terminus. These large peptides appear to be less\ potent than their smaller counterparts, but are also less sensitive to \ degradation and may represent endogenous, long-lasting activators in a\ number of pathophysiological situations.

\ \ neuropeptide hormone activity ; GO:0005184 extracellular ; GO:0005576 \N 26483 IPR008056

Major histocompatibility complex (MHC) class I molecules present antigenic peptides to CD8 T cells. The majority of peptides found associated with \ class I molecules are derived from nuclear and cytosolic proteins, and they \ are generated largely by the proteasome complex. These peptides are \ transported from cytosol into the lumen of the endoplasmic reticulum \ (ER) by a peptide transporter, which is known as the transporter associated \ with antigen processing (TAP). TAP is a trimeric complex consisting of \ TAP1, TAP2 and tapasin (TAP-A). TAP1 and TAP2 are required for peptide \ transport. Tapasin, which actually serves as a docking site on the TAP \ complex specific for interaction with class I MHC molecules, is essential \ for peptide loading (up to four MHC class I-tapasin complexes have been\ found to bind to each TAP molecule). However, since the exact mechanisms of\ tapasin functions are still unknown, it has also been speculated that\ tapasin may regulate the MHC class I release from the ER rather than \ directly loading peptides onto MHC class I molecules \ [MEDLINE:97385168], [MEDLINE:97419259], [MEDLINE:99185086], [MEDLINE:99310121].\

In studies of the interaction between MHC class I and TAP, it was found that \ TAP1, but not TAP2, is required for the association of TAP with class I \ molecules. Because tapasin is essential for the association of MHC class I \ to TAP, tapasin may directly interact with TAP1. Thus the predicted order of \ interaction between different molecules in the TAP complex is TAP2 to TAP1, \ TAP1 to tapasin, and tapasin to MHC class I molecules. Thus, by these linked \ events, the translocation and loading of peptides rapidly and efficiently\ proceed in the same microenvironment [MEDLINE:97385168], [MEDLINE:20102660].\

Tapasin is a type I transmembrane (TM) glycoprotein with a double lysine\ motif that is thought to be involved with mediating the retrieval of \ proteins back from the cis-Golgi, thus maintaining membrane proteins in the\ ER [MEDLINE:97419259]. It is encoded by an MHC-linked gene and is a member of the\ immunoglobulin superfamily. Binding to TAP is mediated by the C-terminal\ region, whereas its N-terminal 50 residues constitute the key element that\ converts the MHC class I molecules and TAP weak interactions into a stable\ complex [MEDLINE:99185086], [MEDLINE:99310121].\

\ \ \ \N membrane ; GO:0016020 antigen processing, endogenous antigen via MHC class I ; GO:0019885 26481 IPR008054

Voltage-dependent sodium channels are transmembrane (TM) proteinsresponsible for the depolarising phase of the action potential in most\ electrically excitable cells [MEDLINE:92279233]. They may exist in 3 states [MEDLINE:92359997]: the\ resting state, where the channel is closed; the activated state, where the\ channel is open; and the inactivated state, where the channel is closed\ and refractory to opening. Several different structurally and functionally\ distinct isoforms are found in mammals, coded for by a multigene family, these being responsible for the different types of sodium ion currents\ found in excitable tissues.\

The structure of sodium channels is based on 4 internal repeats of a 6-helix\ bundle [MEDLINE:85061498] (in which 5 of the membrane-spanning segments are hydrophobic and\ the other is positively charged), forming a 24-helical bundle. The charged\ segments are believed to be localised within clusters formed by their 5 \ hydrophobic neighbours: it is postulated that the charged domain may be the\ voltage sensor region, possibly moving outward on depolarisation, causing a\ conformational change. This model, proposed by Noda et al. [MEDLINE:85061498], contrasts\ with that of Sato and Matsumoto [MEDLINE:92359997], in which the TM segments are juxtaposed\ octagonally. The basic structural motif (the 6-helix bundle) is also found \ in potassium and calcium channel subunits.\

\ \

The gene SCN8A encodes the voltage-gated Na+ channel 8 subunit and is\ strongly expressed in Purkinje cells. Sodium currents are known to generate\ the rising phase and the prolonged plateau phase of cerebellar purkinje cell\ action potentials. Experiments in mice with mutated SCN8A subunits suggest\ its involvement in the persistent sodium current responsible for the\ prolonged plateau phase [MEDLINE:97338144]. The SCN8A gene is abundantly expressed\ throughout the CNS and in the spinal cord. Mutations in mouse SCN8A result\ in a number of neurological disorders, including paralysis, ataxia and\ dystonia [MEDLINE:98363707].\

\ \ \ \N \N \N 26480 IPR008053

\ \

The SCN5A gene encodes the NaH1 channel and is expressed in cardiac muscle,\ foetal skeletal muscle and denervated adult skeletal muscle. Mutations\ in the SCN5A gene affect the function of NaH1 channels in the heart and are\ one of the three causes of Long QT syndrome, an inherited cardiac arrhythmia\ that can cause abrupt loss of consciousness, seizures and sudden death [MEDLINE:95196273]; \ it is also associated with Brugada syndrome [MEDLINE:99286852] and conduction system\ disease [MEDLINE:99400546].\

\ \ \ voltage-gated sodium channel activity ; GO:0005248 membrane ; GO:0016020 sodium ion transport ; GO:0006814 26479 IPR008052

\ \

The SCN4A gene belongs to the Nav1 family, which also includes SCN1A, SCN2A,\ SCN3A, SCN5A and SCN8A. This family is typically expressed in the brain,\ spinal cord, skeletal muscle, cardiac muscle and peripheral neurons [MEDLINE:91236179].\ Mutations in SCN4A are associated with hyperkalaemic periodic paralysis,\ paramyotonia congenita and a diverse group of disorders collectively known\ as potassium-aggravated myotonia. These are characterised by skeletal muscle\ hyperexcitability or muscle weakness, which is exacerbated by exposure to\ cold temperature [MEDLINE:20066743].\

\ \ \ voltage-gated sodium channel activity ; GO:0005248 membrane ; GO:0016020 sodium ion transport ; GO:0006814 26478 IPR008051

\ \

The SCN1A gene encodes the NaB1 channel and is particularly expressed in\ the brain, but is also found in a variety of other tissues, ranging from the\ retina to the olfactory bulb. Epilepsy, a disorder of neuronal\ hyperexcitability, has been associated with altered kinetics of SCN1A, as\ well as delayed inactivation of SCN2A [MEDLINE:21630138].

\ \ \ voltage-gated sodium channel activity ; GO:0005248 membrane ; GO:0016020 sodium ion transport ; GO:0006814 26475 IPR008048

Mini-chromosome maintenance (MCM) proteins are a family of eukaryoticreplication factors required for the initiation of DNA replication. All\ eukaryotes contain six orthologous MCM proteins, designated MCM2-7. Studies \ in Xenopus eggs have showed them to form hexamers, where each class is\ present in equal stoichiometry [MEDLINE:97357318]. The initiation of DNA synthesis in\ eukaryotes requires the binding of origin recognition complex (ORC) - a\ complex of six subunits - to the autonomously replicating sequences (ARS)\ of replication origins [MEDLINE:94171703], the recruitment of CDC6 and binding of the MCM\ protein complex to the ARS to form the prereplicative complex (pre-RC) [MEDLINE:97078759].\ DNA synthesis is subsequently initiated by the activation of pre-RC by CDC7\ and CDC28 protein kinases [MEDLINE:96155611].\

MCM proteins associate with chromatin during G1 phase and dissociate again\ during S phase, remaining unbound until the end of mitosis [MEDLINE:97474311]. Periodic\ chromatin association of the MCM complex ensures that DNA synthesis from \ replication origins is initiated only once during the cell cycle, avoiding\ over-replication of parts of the genome. Elongation of replication forks \ away from individual replication origins results in displacement of the\ MCM-containing complex from chromatin. Budding yeast MCM proteins are\ translocated in and out of the nucleus during each cell cycle. However,\ fission yeast MCMs, like those in metazoans, are constitutively nuclear.\

The six classes of MCM protein together share a conserved 200 amino acid \ residue domain, while sequences within the same class show more extensive\ similarity outside this region. The conserved central domain is similar to\ the A motif of the Walker-type NTP-binding domain; it also shares similarity\ with ATPase domains of prokaryotic NtrC-related transcription regulators.\ The ATP-binding motif is thought to mediate ATP-dependent opening of double-stranded DNA at replication origins. In addition to the central region, MCM2,\ 4, 6 and 7 contain a zinc-finger-type motif thought to have a role in\ mediating protein-protein interactions [MEDLINE:98138613]. Moreover, a conserved -helical structure in the C-terminal region has been noted; this comprises a\ conserved heptad repeat and a putative four-helix bundle. Most of the MCM\ proteins contain acidic regions, or alternately repeated clusters of acidic\ and basic residues.\

\ \

The human MCM5 gene has been localised to chromosome region 22q13.1-q13.2. \ It has been shown that MCM5 protein containing mutations of R732/K734 fails\ to form complexes with other MCM proteins in vivo, suggesting that these two\ residues are important for protein-protein interactions. MCM5 directly \ interacts with the Stat1 protein (signal transducer and activator of transcription) to enhance Stat1-mediated transcription activation [MEDLINE:21145793].\

\ \ \ ATP binding activity ; GO:0005524 nucleus ; GO:0005634 DNA replication initiation ; GO:0006270 26477 IPR008050

\ \

In addition to its role as a replication factor, the MCM7 protein has DNA\ helicase activity when complexed as a hexamer (containing two molecules each\ of MCM4, MCM6 and MCM7), suggesting that this complex is involved in the\ initiation of DNA replication as a DNA-unwinding enzyme. The human MCM7 gene\ has been localised to chromosome 7q21.3-q22.1. Increased expression of MCM7\ RNA and protein in MYCN-amplified neuroblastoma tumour and cell lines has\ been reported [MEDLINE:21849884]. Furthermore, The MCM7 protein has been shown to form\ complexes with the retinoblastoma protein [MEDLINE:98226547]. These findings suggest MCM7-\ directed DNA replication contributes to neoplastic transformation.

\ \ \ ATP binding activity ; GO:0005524 nucleus ; GO:0005634 DNA replication initiation ; GO:0006270 26476 IPR008049

\ \

In addition to its role as a replication factor, the MCM6 protein has DNA\ helicase activity when complexed as a hexamer (containing two molecules each\ of MCM4, MCM6 and MCM7), suggesting that this complex is involved in the\ initiation of DNA replication as a DNA-unwinding enzyme. Xenopus MCM6\ exists in two forms, maternal and zygotic, suggesting that specific\ forms of MCM6 may be used at different developmental stages.\

\ \ \ ATP binding activity ; GO:0005524 nucleus ; GO:0005634 DNA replication initiation ; GO:0006270 26473 IPR008046

\ \

Members of the MCM3 class have been isolated from a number of organisms. \ Human MCM3 was first described as a protein associated with DNA polymerase -primase [MEDLINE:92195806], although subsequent analysis failed to show a direct\ interaction between the them. The gene encoding human MCM3 has been\ localised to chromosome 6p21.1-p12 [MEDLINE:20241692]. In S.cerevisiae, MCM3 is a phospho-\ protein that exists in multiple isoforms; distinct isoforms can be detected\ at specific stages of the cell cycle. MCM3 has been implicated in limb \ development in Xenopus; identification of maternal and zygotic proteins \ suggests that specific forms may be used at different developmental stages.\ The MCM3 protein contains a nuclear localisation signal, which is necessary for its translocation into the nucleus.\

\ \ \ ATP binding activity ; GO:0005524 nucleus ; GO:0005634 DNA replication initiation ; GO:0006270 26474 IPR008047

\ \

MCM4 is thought to play a pivotal role in ensuring DNA replication occurs\ only once per cell cycle. Phosphorylation of MCM4 dramatically reduces its\ affinity for chromatin - it has been proposed that this cell cycle-dependent\ phosphorylation is the mechanism that inactivates the MCM complex from late\ S phase through mitosis, thus preventing illegitimate DNA replication during that period of the cell cycle [MEDLINE:97057222].\

\ \ \ ATP binding activity ; GO:0005524 nucleus ; GO:0005634 DNA replication initiation ; GO:0006270 26468 IPR008041

The Carlavirus (apple stem pitting virus) endopeptidase is a member of the C23 family. It is thought to playa role in the post-translational cleavage of the high molecular weight primary translation products of the virus.

\ \ \N \N viral life cycle ; GO:0016032 26469 IPR008042

Pao retrotransposon peptidase is a member of the A17 peptidase family.

\ \N \N \N 26470 IPR008043

The noncapsid protein expressed from ORF-206 of turnip yellow mosaic virus (TYMV) is autocatalytically processed by apapain-like protease, producing N-terminal 150-kDa and C-terminal 70-kDa proteins. The Tymovirus endopeptidase\ is a member of the C21 peptidase family. The original transcipt is a polyprotein containing several viral proteins.

\ \ RNA-directed RNA polymerase activity ; GO:0003968 \N viral life cycle ; GO:0016032 26471 IPR008044

At least one of the members of this family, the Pal protein from the pneumococcalbacteriophage Dp-1 O03979 has been shown to be an\ N-acetylmuramoyl-L-alanine amidase [MEDLINE:84264376]. According to the known modular\ structure of this and other peptidoglycan hydrolases from the pneumococcal system, the active site\ should reside in the N-terminal domain whereas the C-terminal domain binds to the choline residues\ of the cell wall teichoic acids [MEDLINE:98025469], [MEDLINE:88124951].

\ \ bacteriolytic toxin activity ; GO:0015642 extracellular ; GO:0005576 \N 26472 IPR008045

\ \

In addition to its role in initiation of DNA replication, MCM2 is able to\ inhibit the MCM4,6,7 helicase. Studies on murine MCM2 indicate that its\ C-terminus is required for interaction with MCM4, as well as for inhibition\ of the DNA helicase activity of the MCM4,6,7 complex. The N-terminal region,\ which contains an H3-binding domain and a region required for nuclear \ localisation, is required for the phosphorylation by CDC7 kinase.\

\ \ \ ATP binding activity ; GO:0005524 nucleus ; GO:0005634 DNA replication initiation ; GO:0006270 26466 IPR008039

Although archaeal flagella appear superficially similar to those of bacteria, they are quitedistinct [MEDLINE:21147832]. In several archaea, the flagellin genes are followed immediately by the\ flagellar accessory genes flaCDEFGHIJ. The gene products may have a role in translocation,\ secretion, or assembly of the flagellum. FlaC is a protein whose exact role is unknown but it has\ been shown to be membrane-associated (by immuno-blotting fractionated cells)\ [MEDLINE:21574152].

\ \ \N flagellum (sensu Eukarya) ; GO:0009434 \N 26467 IPR008040

This domain is found at the N terminus of the hydantoinase/oxoprolinase IPR002821 family.

\ \N \N \N 26461 IPR008034

Delta-lysin is a 26 amino acid, hemolytic peptide toxin secreted by Staphylococcus aureus. It is thought that delta-toxin forms an amphipathichelix upon binding to lipid bilayers [MEDLINE:22195408]. The precise mode of action of delta-lysis is\ unclear.

\ \ toxin activity ; GO:0015070 \N \N 26462 IPR008035

Iron (II)/2-oxoglutarate (2-OG)-dependent oxygenases catalyse oxidative reactions in a rangeof metabolic processes. Proline 3-hydroxylase hydroxylates proline at position 3, the first of a\ 2-OG oxygenase catalysing oxidation of a free -amino acid. The structure contains conserved\ motifs present in other 2-OG oxygenases including a jelly roll strand core and residues binding iron\ and 2-oxoglutarate, consistent with divergent evolution within the extended family. The structure\ differs significantly from many other 2-OG oxygenases in possessing a discrete C-terminal helical\ domain.

\ \ \N \N \N 26463 IPR008036

Mu-conotoxins are a family of peptides from the venoms of predatory cone snails. Mu-conotoxins are peptide inhibitors of voltage-sensitive sodium channels,preferentially in skeletal muscle. Conotoxin gm9a, a putative 27-residue polypeptide encoded by Conus gloriamaris,\ has been shown to adopt an inhibitory cystine knot motif constrained by three\ disulfide bonds\ [MEDLINE:22128859], [MEDLINE:22301917].

\ \ sodium channel inhibitor activity ; GO:0019871 extracellular ; GO:0005576 \N 26464 IPR008037

A 155-kDa proteinase inhibitor, pacifastin, from plasma of the freshwater crayfish, Pacifastacus leniusculus, was found to becomposed of two covalently linked subunits. The two subunits are encoded by two different mRNAs.The heavy chain of pacifastin (105 kDa) is related to transferrins, containing three transferrin lobes, two of which seem to\ be active for iron binding. The light chain of pacifastin (44 kDa) is the inhibitory subunit, and has nine cysteine-rich inhibitory domains\ that are homologous to each other. Structures of members of this family show that they are comprised of a triple-stranded\ antiparallel -sheet connected by three disulfide bridges, which defines this as a novel family of\ serine protease inhibitors [MEDLINE:97338078].

\ \ protease inhibitor activity ; GO:0030414 \N \N 26465 IPR008038

Archaeal flagellins are initially synthesized as preflagellins with a short, positively charged leader peptide, which is cleaved prior to theincorporation of the mature flagellins into the filament [MEDLINE:21932510].

\ \ \N \N \N 26454 IPR008027

The UQCRX/QCR9 protein is the 9/10 subunit of complex III, and is a protein of about 7kDa. Deletion of QCR9 results in the inability of Saccharomyces cerevisiae to grow on a fermentable carbon\ source [MEDLINE:93182539]. The protein is part of the mitchondrial respiratory chain.

\ \ ubiquinol-cytochrome c reductase activity ; GO:0008121 mitochondrial membrane ; GO:0005740 oxidative phosphorylation, ubiquinone to cytochrome c ; GO:0006122 26455 IPR008028

Sarcolipin is a 31 amino acid integral membrane protein that regulates Ca-ATPase activity inskeletal muscle [MEDLINE:21639966].

\ \ enzyme regulator activity ; GO:0030234 membrane ; GO:0016020 \N 26456 IPR008029

Endonuclease I is a junction-resolving enzyme encoded by bacteriophage T7, that selectively binds and cleavesfour-way Holliday DNA junctions [MEDLINE:22088303]. The structure of the enzyme shows that it forms a symmetric homodimer arranged in two well-separated domains. Each domain, however,\ is composed of elements from both subunits, and amino acid side chains from both protomers contribute to the active site [MEDLINE:20577277].

\ \ deoxyribonuclease IV (phage T4-induced) activity ; GO:0008833 \N viral life cycle ; GO:0016032 26457 IPR008030

NmrA is a negative transcriptional regulator involved in the post-translational modification of thetranscription factor AreA. NmrA is part of a system controlling nitrogen metabolite repression in\ fungi [MEDLINE:21583329]. This family only contains a few sequences as iteration results in significant\ matches to other Rossmann fold families.

\ \ transcriptional repressor activity ; GO:0016564 \N regulation of nitrogen utilization ; GO:0006808 26458 IPR008031

Monomethylamine methyltransferase of the archaebacterium Methanosarcina barkeri contains a novel amino acid, pyrrolysine, encoded by the termination codon UAG [MEDLINE:22117215]. The structure of the enzyme reveals a homohexamer comprised of individualsubunits with a TIM barrel fold. MtmB initiates the metabolism of monomethylamine by catalysing the transfer of the methyl group from monomethylamine to the corrinoid cofactor of MtmC.

\ \ methyltransferase activity ; GO:0008168 \N \N 26459 IPR008032

This is a domain of unknown function found in archaebacterial proteins. The domain has been solved via structuralgenomics techniques and comprises of segregated helical and anti-parallel sheet regions.

\ \ \N \N \N 26460 IPR008033

The filamentous bacteriophages are flexible rods about 1 to 2 microns long and 6 nm in diameter, with a helical shell of protein subunitssurrounding a DNA core. The approximately 50-residue coat protein subunit is largely -helix and the axis of the -helix\ makes a small angle with the axis of the virion. The protein shell can be considered in three sections: the outer surface, occupied by the\ N-terminal region of the subunit, rich in acidic residues that interact with the surrounding solvent and give the virion a low isoelectric\ point; the interior of the shell, including a 19-residue stretch of apolar side-chains, where protein subunits interact mainly with each\ other; and the inner surface, occupied by the C-terminal region of the subunit, rich in basic residues that interact with the DNA core.

This is a family of class I phage major coat protein Gp8 or B which is a baseplate structural protein. The coat protein is largely -helix with a slight\ curve [MEDLINE:94118269].

\ \ \N viral capsid ; GO:0019028 \N 26445 IPR008018

The phage head-tail attachment protein is required for the joining of phage heads and tails at thelast step of morphogenesis [MEDLINE:22078221].

\ \ \N \N \N 26446 IPR008019

Apolipoprotein C-II (ApoC-II) is the major activator of lipoprotein lipase, a key enzyme in theregulation of triglyceride levels in human serum\ [MEDLINE:20363536].

\ \ \N \N \N 26447 IPR008020

The major coat protein in the capsid of filamentous bacteriophage forms a helical assembly of about7000 identical protomers, with each protomer comprised of 46 amino acids, after the cleavage of the\ signal peptide. Each protomer forms a slightly curved helix that combines to form a tubular structure\ that encapsulates the viral DNA [MEDLINE:20133149].

\ \ structural molecule activity ; GO:0005198 viral capsid ; GO:0019028 \N 26448 IPR008021

Coat protein A, also known as attachment protein, is necessary for adsorption of the virion onto the F-pilus of the host cell.

\ \N \N \N 26449 IPR008022

DicB is part of the dic operon, which resides on cryptic prophage Kim. Under normalconditions, expression of dicB is actively repressed. When expression is induced, however, cell\ division rapidly ceases, and this division block is dependent on MinC with which it interacts\ [MEDLINE:21999256].

\ \ \N \N \N 26450 IPR008023

This is a family of proteins of unknown function.

\ \N \N \N 26451 IPR008024

This domain consists of two transmembrane helices and a conserved linking section.

\ \N \N \N 26452 IPR008025

Contractility of vascular smooth muscle depends on phosphorylation of myosin light chains, andis modulated by hormonal control of myosin phosphatase activity. Signaling pathways activate\ kinases such as PKC or Rho-dependent kinases that phosphorylate the myosin phosphatase inhibitor\ protein called CPI-17. Phosphorylation of CPI-17 at Thr-38 enhances its inhibitory potency\ 1000-fold, creating a molecular switch for regulating contraction [MEDLINE:21592567].

\ \ \N \N \N 26453 IPR008026

US12 is a key factor in the evasion of cellular immune response against HSV-infected cells.Specific inhibition of the transporter associated with antigen processing (TAP) by US12 prevents\ peptide transport into the endoplasmic reticulum and subsequent loading of major histocompatibility\ complex (MHC) class I molecules [MEDLINE:99452710]. US12 is comprised of three helices and is\ associated with cellular membranes [MEDLINE:99452710].

\ \ \N \N viral-host defense evasion ; GO:0019049 26434 IPR008007

Peptidase family M42 contains glutamyl aminopeptidases. For members of this family predicted metal ligands occur in thesame order in the sequence: H, D, E, D/E, H; and active site residues in the\ motifs HXD and EE.

\ \ \N \N \N 26435 IPR008008

This is a short conserved region found in some transposons.

\ \N \N \N 26436 IPR008009

This alignment represents the conserved core region of a ~90 residue repeat found in severalhaemagglutinins and other cell surface proteins. Sequence similarities to Hyalin (IPR003410) protein families.

\ \ \N \N \N 26437 IPR008010

This family of eukaryotic membrane proteins includes the putative receptor for human cytomegalovirus gH. The cellular function of this familyremains unknown.

\ \ \N \N \N 26438 IPR008011

This family of short proteins includes proteins from the NADH-ubiquinone oxidoreductasecomplex I. The family includes the B14 subunit from bovine NADH-ubiquinone oxidoreductase B14 subunit Q02366. All the members of this family are predicted to be\ components of complex I. The family has been named LYR after a highly conserved tripeptide motif\ close to the N terminus of these proteins.

\ \ \N \N \N 26439 IPR008012

UMP1 is a short-lived chaperone present in the precursor form of the 20S proteasome andabsent in the mature complex. UMP1 is required for the correct assembly and enzymatic activation\ of the proteasome. UMP1 seems to be degraded by the proteasome upon its formation.

\ \ \N \N \N 26440 IPR008013

GATA transcription factors mediate cell differentiation in a diverse range of tissues. Mutationsare often associated with certain congenital human\ disorders. The six classical vertebrate GATA proteins, GATA-1 to GATA-6, are highly\ homologous and have two tandem zinc fingers. The classical GATA transcription factors function as\ transcription activators. In lower metazoans GATA proteins carry a single canonical zinc finger. This\ family represents the N-terminal domain of the family of GATA transcription activators.

\ \ \N \N \N 26441 IPR008014

Glycogen synthase kinase-3 (GSK-3) sequentially phosphorylates four serine residues onglycogen synthase (GS), in the sequence SxxxSxxxSxxx-SxxxS(p), by recognising and\ phosphorylating the first serine in the sequence motif SxxxS(P) (where S(p) represents a\ phosphoserine). Interaction of GSK-3 with a peptide derived from GSK-3 binding protein\ prevents GSK-3 interaction with Axin. This interaction thereby inhibits the Axin-dependent\ phosphorylation of -catenin by GSK-3 [MEDLINE:21605727].

\ \ \N \N \N 26442 IPR008015

GMP-PDE delta subunit was originally identified as a fourth subunit of rod-specific cGMPphosphodiesterase (PDE) (EC: 3.1.4.35). The precise function of PDE delta\ subunit in the rod specific GMP-PDE complex is unclear. In addition, PDE delta subunit is not\ confined to photoreceptor cells but is widely distributed in different tissues. PDE delta subunit is\ thought to be a specific soluble transport factor for certain prenylated proteins and Arl2-GTP a\ regulator of PDE-mediated transport [MEDLINE:21977290].

\ \ \N \N \N 26443 IPR008016

The head-tail connector of bacteriophage 29 is composed of 12 36 kDasubunits with 12 fold symmetry. It is the central component of a rotary motor that packages the\ genomic dsDNA into pre-formed proheads. This motor consists of the head-tail connector,\ surrounded by a 29-encoded, 174-base, RNA and a viral ATPase protein [MEDLINE:99108736].

\ \ \N \N \N 26444 IPR008017

Delta atracotoxin produces potentially fatal neurotoxic symptoms in primates by slowing theinactivation of voltage-gated sodium channels [MEDLINE:98046100]. The structure of atracotoxin\ comprises a core region containing a triple-stranded a thumb-like extension protruding from\ the region and a C-terminal helix. The region contains a cystine knot motif, a feature seen in other neurotoxic\ polypeptides [MEDLINE:98046100].

\ \ \N \N \N 26418 IPR007991

This family consists of several eukaryotic proteins which are homologous to the Saccharomyces cerevisiae RRN3 protein. RRN3 is one of the RRN genes specifically required for the transcription of rDNA by RNA polymerase I (Pol I) in the S. cerevisiae\ \ \ [MEDLINE:96324404] RNA polymerase I complex within the nucleolus.\ In mammalian cells, the phosphorylation state of Rrn3 regulates rDNA transcription by determining the steady-state\ concentration of the Rrn3 [MEDLINE:22128885].

\ \ \N \N \N 26419 IPR007992

This family consists of several eukaryotic succinate dehydrogenase [ubiquinone] cytochrome Bsmall subunit, mitochondrial precursor (CybS) proteins. SDHD encodes the small subunit (cybS) of\ cytochrome b in succinate-ubiquinone oxidoreductase (mitochondrial complex II). Mitochondrial\ complex II is involved in the Krebs cycle and in the aerobic electron transport chain. It contains four\ proteins. The catalytic core consists of a flavoprotein and an iron-sulfur protein; these proteins are\ anchored to the mitochondrial inner membrane by the large subunit of cytochrome b (cybL) and\ cybS, which together comprise the heme-protein cytochrome b. Mutations in the SDHD gene can\ lead to hereditary paraganglioma, characterised by the development of benign, vascularised tumours\ in the head and neck [MEDLINE:20126372].

\ \ \N \N \N 26420 IPR007993

This family contains several uncharacterised plant proteins of unknown function, mostly fromArabidopsis thaliana.

\ \ \N \N \N 26421 IPR007994

This family contains several uncharacterised humanproteins. The function of this family is unknown, however, the family member FKSG56 is a\ hepatocellular carcinoma-associated antigen.

\ \ \N \N \N 26422 IPR007995

This family consists of several uncharacterised Streptomyces proteins as well as one fromMycobacterium tuberculosis. The function of these proteins is\ unknown.

\ \ \N \N \N 26431 IPR008004

This family consists of several uncharacterised plant proteins of unknown function.

\ \N \N \N 26432 IPR008005

This family consists of several uncharacterised nucleopolyhedrovirus proteins of unknownfunction.

\ \ \N \N \N 26433 IPR008006

Peptidase family M26 contains IgA1-specific metalloendopeptidases. The active site residues for members of this family occur in the motifHEXXH.

\ \ \N \N \N 26429 IPR008002

This family consists of several herpesvirus proteins of unknown function.

\ \N \N \N 26430 IPR008003

This family contains several bacteriophage proteins. Three of the proteins in thisfamily have been labelled putative cro repressor proteins.

\ \ \N \N \N 26427 IPR008000

This family consists of several uncharacterised bacterial proteins of unknown function.

\ \N \N \N 26428 IPR008001

Colony stimulating factor 1 (CSF-1) is a homodimeric polypeptide growth factor whoseprimary function is to regulate the survival, proliferation, differentiation, and function of cells of the\ mononuclear phagocytic lineage. This lineage includes mononuclear phagocytic precursors, blood\ monocytes, tissue macrophages, osteoclasts, and microglia of the brain, all of which possess cell\ surface receptors for CSF-1. The protein has also been linked with male fertility [MEDLINE:21895447]\ and mutations in the Csf-1 gene have been found to cause osteopetrosis and failure of tooth eruption\ [MEDLINE:22294966].

\ \ \N \N \N 26424 IPR007997

This family consists of several plant mitochondrial proteins of unknown function.

\ \N \N \N 26425 IPR007998

This family consists of several eukaryotic proteins of unknown function.

\ \N \N \N 26426 IPR007999

This family consists of several uncharacterised Drosophila melanogaster proteins of unknown function.

\ \N \N \N 26423 IPR007996

This family consists of several uncharacterised Calicivirus proteins of unknown function.

\ \N \N \N 26416 IPR007989

This family consists of several uncharacterised Arabidopsisthaliana proteins of unknown function.

\ \ \N \N \N 26417 IPR007990

This family consists of seminal vesicle autoantigen and prolactin-inducible (PIP) proteins.Seminal vesicle autoantigen (SVA) is specifically present in the seminal plasma of mice. This 19 kDa secretory glycoprotein suppresses the motility of\ spermatozoa by interacting with phospholipid. PIP has several known functions. In saliva, this\ protein plays a role in host defence by binding to microorganisms such as Streptococcus. PIP is an\ aspartyl proteinase and it acts as a factor capable of suppressing T-cell apoptosis through its\ interaction with CD4 [MEDLINE:21092791].

\ \ \N \N \N 26411 IPR007984

The poxvirus DNA-directed RNA polymerase (EC: 2.7.7.6) catalyses the transcription of DNA into RNA. It consists of at least eight subunits, this is the 19 kDa subunit.

\ \N \N \N 26412 IPR007985

This family consists of haemolysin expression modulating protein (HHA) homologues. YmoAand Hha are highly similar bacterial proteins down regulating gene expression in Yersinia enterocolitica and Escherichia coli,\ respectively.

\ \ \N \N \N 26413 IPR007986

This family consists of NINE proteins from several bacteriophage and from Escherichia coli.

\ \N \N \N 26414 IPR007987

This family consists of several poxvirus A21 proteins.

\ \N \N \N 26415 IPR007988

This family consists of several variants of the human and chimpanzee(Pan troglodytes) sperm antigen proteins (HE2 and EP2\ respectively). The EP2 gene codes for a family of androgen-dependent, epididymis-specific\ secretory proteins.The EP2 gene uses alternative promoters and differential splicing to produce a\ family of variant messages. The translated putative protein variants differ significantly from each\ other. Some of these putative proteins have similarity to -defensins, a family of antimicrobial\ peptides [MEDLINE:20277601].

\ \ \N \N \N 26410 IPR007983

This family contains several baculovirus late expression factor 1 or LEF-1 proteins. LEF-1 isnow known to be a DNA primase enzyme [MEDLINE:21826692].

\ \ \N \N \N 26408 IPR007981

This family consists of several thermopsin proteins from archaebacteria. Thermopsin is athermostable acid protease which is capable of hydrolysing the following bonds: Leu-Val, Leu-Tyr,\ Phe-Phe, Phe-Tyr, and Tyr-Thr. The specificity of thermopsin is therefore similar to that of pepsin,\ that is, it prefers large hydrophobic residues at both sides of the scissile bond\ [MEDLINE:90110210].

\ \ \N \N \N 26409 IPR007982

This family consists of several Tombusvirus movementproteins. These proteins allow the virus to move from cell-to-cell and allow host-specific systemic\ spread [MEDLINE:21376428].

\ \ \N \N viral transmission ; GO:0019089 26406 IPR007979

This family consists of several ICEA proteins from Helicobacterpylori. H. pylori infection causes gastritis and\ peptic ulcer disease, and the bacteria is classified as a definite carcinogen of gastric cancer. ICEA1 is speculated\ to be associated with peptic ulcer disease and may have endonuclease activity [MEDLINE:21833331].

\ \ \N \N \N 26407 IPR007980

This family consists of the Saccharomyces cerevisiaemitochondrial ribosomal proteins VAR1. Mitochondria possess their own ribosomes responsible for\ the synthesis of a small number of proteins encoded by the mitochondrial genome. In S. cerevisiae the two ribosomal RNAs and a single ribosomal\ protein, VAR1, are products of mitochondrial genes, and the remaining approximately 80 ribosomal\ proteins are encoded in the nucleus [MEDLINE:97142008]. VAR1 along with 15S rRNA are necessary\ for the formation of mature 37S subunits [MEDLINE:95287858].

\ \ \N \N \N 26405 IPR007978

This family consists of several baculovirus occlusion-derived virus envelope proteins (EC27 orE27) which appear to act as a multifuntional cyclins during the host cell cycle. The ODV-E27 protein has distinct functional characteristics compared to cellular and viral\ cyclins. When associated with cdc2, it\ exhibits cyclin B-like activity; when associated with cdk6, the complex possesses cyclin D-like activity and binds PCNA (proliferating cell nuclear antigen). [MEDLINE:98409635].

\ \ \N viral envelope ; GO:0019031 \N 26401 IPR007974

This family consists of tenuivirus NS-3 (PV3 or GV3) proteins. The function of this protein isunknown although it is thought to be a replication protein.

\ \ \N \N \N 26402 IPR007975

Autographa californica nucleopolyhedrovirus p31 is anuclear phosphoprotein that accumulates in the virogenic stroma, which is the viral replication centre\ in the infected-cell nucleus. The protein binds to DNA, and serves as a late expression factor\ [MEDLINE:96386564].

\ \ \N \N \N 26403 IPR007976

This family consists of several bacterial coenzyme PQQ synthesis protein C or PQQC proteins.Pyrroloquinoline quinone (PQQ) is the prosthetic group of several bacterial enzymes, including\ methanol dehydrogenase of methylotrophs and the glucose dehydrogenase of a number of bacteria\ [MEDLINE:22325478]. PQQC has been found to be required in the synthesis of PQQ but its function is\ unclear.

\ \ \N \N \N 26404 IPR007977

The p21 membrane protein of vaccinia virus, encoded by the A17L (or A18L) gene, has beenreported to localise on the inner of the two membranes of the intracellular mature virus (IMV). It has\ also been shown that p21 acts as a membrane anchor for the externally located fusion protein P14\ (A27L gene) [MEDLINE:21880844].

\ \ \N \N \N 26384 IPR007957

L11L is an integral membrane protein of the African swine fevervirus, which is expressed late in the virus replication cycle. The protein is thought to be\ non-essential for growth in vitro and for virus virulence in domestic pigs [MEDLINE:98264496].

\ \ \N \N \N 26385 IPR007958

This family contains various secreted scorpion short toxins which seem to be unrelated to those described inIPR001947.

\ \ \N \N \N 26386 IPR007959

This family consists of dinoflagellate luciferase and luciferin binding proteins. Luciferase isinvolved in catalysing the light emitting reaction in bioluminescence and luciferin binding protein\ (LBP) is known to bind to luciferin (the substrate for luciferase) to stop it reacting with the enzyme\ and therefore switching off the bioluminescence function. The expression of these two proteins is\ controlled by a circadian clock at the translational level, with synthesis and degradation occurring on\ a daily basis [MEDLINE:21614420].

\ \ \N \N \N 26387 IPR007960

This family consists of several forms of mammalian taste receptor proteins (TAS2Rs). TAS2Rsare G protein-coupled receptors expressed in subsets of taste receptor cells of the tongue and palate\ epithelia and are organised in the genome in clusters. The proteins are genetically linked to loci that\ influence bitter perception in mice and humans\ [MEDLINE:20222571].

\ \ \N \N \N 26388 IPR007961

This family consists of several latent membrane protein 1 or LMP1s mostly from Human herpesvirus 4. LMP1 of EBV isa 62-65 kDa plasma membrane protein possessing six membrane spanning regions, a short\ cytoplasmic N terminus and a long cytoplasmic carboxy tail of 200 amino acids. EBV latent\ membrane protein 1 (LMP1) is essential for EBV-mediated transformation and has been associated\ with several cases of malignancies. EBV-like viruses in Cynomolgus monkeys (Macaca fascicularis) have been associated with high lymphoma rates in\ immunosuppressed monkeys [MEDLINE:22346339]

\ \ \N \N \N 26389 IPR007962

This family consists of Bombinin and Maximin proteins from Bombinamaxima. Two groups of antimicrobial peptides have been isolated from skin secretions of\ B. maxima. Peptides in the first group, named maximins 1,\ 2, 3, 4 and 5, are structurally related to bombinin-like peptides (BLPs). Unlike BLPs, sequence\ variations in maximins occurred all through the molecules. In addition to the potent antimicrobial\ activity, cytotoxicity against tumour cells and spermicidal action of maximins, maximin 3 possessed a\ significant anti-Simian-Human immunodeficiency virus activity.\ Maximins 1 and 3 have been found to be toxic to mice.\ Peptides in the second group, termed maximins H1, H2, H3 and H4, are homologous with bombinin\ H peptides [MEDLINE:21826911].

\ \ antimicrobial peptide activity ; GO:0003795 extracellular ; GO:0005576 defense response ; GO:0006952 26390 IPR007963

M61 family peptidase are glycyl aminopeptidases. The predicted active site residues for members of this familyoccur in the motif HEXXH.

\ \ \N \N \N 26391 IPR007964

This family consists of several uncharacterised mammalian proteins of unknown function.

\ \N \N \N 26392 IPR007965

This family consists of several uncharacterised eukaryotic proteins of unknown function.

\ \N \N \N 26393 IPR007966

This family consists of several uncharacterised Chlamydia proteins of unknown function.

\ \N \N \N 26394 IPR007967

This family consists of several uncharacterised eukaryotic proteins of unknown function.

\ \N \N \N 26395 IPR007968

This family consists of several uncharacterised tobravirus proteins of unknown function.

\ \N \N \N 26396 IPR007969

This family consists of several uncharacterised Mycobacterium tuberculosis proteins of unknown function.

\ \N \N \N 26397 IPR007970

This family consists of several uncharacterised Drosophila melanogaster proteins of unknown function.

\ \N \N \N 26398 IPR007971

This family consists of several bundlin proteins from Escherichiacoli. Bundlin is a type IV pilin protein that is the only known structural component of\ enteropathogenic E. coli bundle-forming pili (BFP). BFP\ play a role in virulence, antigenicity, autoaggregation, and localised adherence to epithelial cells\ [MEDLINE:20536453].

\ \ \N \N \N 26399 IPR007972

This family consists of several uncharacterised eukaryotic proteins of unknown function.

\ \N \N \N 26400 IPR007973

This family consists of several bacterial sex pilus assembly and synthesis proteins (TraE).Conjugal transfer of plasmids from donor to recipient cells is a complex process in which a\ cell-to-cell contact plays a key role. Many genes encoded by self-transmissible plasmids are\ required for various processes of conjugation, including pilus formation, stabilisation of mating pairs,\ conjugative DNA metabolism, surface exclusion and regulation of transfer gene expression\ [MEDLINE:20223621]. The exact function of the TraE protein is unknown.

\ \ \N \N \N 26378 IPR007951

This family consists of several mouse anagen-specificprotein mKAP13 (PMG1 and PMG2). PMG1 and 2 contain characteristic repeats reminiscent of\ the keratin-associated proteins (KAPs). Both genes are expressed in growing hair follicles in skin as\ well as in sebaceous and eccrine sweat glands. Interestingly, expression is also detected in the\ mammary epithelium where it is limited to the onset of the pubertal growth phase and is independent\ of ovarian hormones. Their broad, developmentally controlled expression pattern, together with their\ unique amino acid composition, demonstrate that pmg-1 and pmg-2 constitute a novel KAP gene\ family participating in the differentiation of all epithelial cells forming the epidermal appendages\ [MEDLINE:99376690].

\ \ \N \N \N 26379 IPR007952

This family consists of several poxvirus A3L or A2_5L proteins. The entry of vaccinia virus (VV) into the host cell results in the delivery of the double-stranded DNA genome-containing core into thecytoplasm. The core is disassembled, releasing the viral DNA in order to initiate VV cytoplasmic transcription and DNA replication.\ A3L protein is a part of that core [MEDLINE:20193790]. The A2.5L gene product is an\ all--helical protein with a conserved Cxx(x)C motif in the N-terminal -helix. It appears to be an integral component of intracellular virions [MEDLINE:22240491].

\ \ \N \N \N 26380 IPR007953

This family consists of several borrelial hemolysin accessory proteins (BLYB). BLYB wasthought to be an accessory protein, which was proposed to comprise a hemolysis system but it is\ now thought that BlyA and BlyB function instead as a prophage-encoded holin or holin-like system\ [MEDLINE:20528331].

\ \ \N \N \N 26381 IPR007954

This entry contains the Baculovirus immediate-early protein IE-0.

\ \N \N \N 26382 IPR007955

Trophinin and tastin form a cell adhesion molecule complex that potentially mediates an initialattachment of the blastocyst to uterine epithelial cells at the time of implantation. Trophinin and tastin\ bind to an intermediary cytoplasmic protein called bystin. Bystin may be involved in implantation and\ trophoblast invasion because bystin is found with trophinin and tastin in the cells at human implantation sites and also in the intermediate trophoblasts at\ invasion front in the placenta from early pregnancy [MEDLINE:98226761]. This family also includes the\ Saccharomyces cerevisiae protein ENP1. ENP1 is an essential\ protein in S. cerevisiae and is localised in the nucleus\ [MEDLINE:97186709]. It is thought that ENP1 plays a direct role in the early steps of rRNA processing\ as enp1 defective S. cerevisiae cannot synthesise 20S\ pre-rRNA and hence 18S rRNA, which leads to reduced formation of 40S ribosomal subunits\ [MEDLINE:22415706].

\ \ \N \N \N 26383 IPR007956

This family consists of several eukaryotic malonyl-CoA decarboxylase (MLYCD) proteins.Malonyl-CoA, in addition to being an intermediate in the de novo synthesis of fatty acids, is\ an inhibitor of carnitine palmitoyltransferase I, the enzyme that regulates the transfer of long-chain\ fatty acyl-CoA into mitochondria, where they are oxidised. After exercise, malonyl-CoA\ decarboxylase participates with acetyl-CoA carboxylase in regulating the concentration of\ malonyl-CoA in liver and adipose tissue, as well as in muscle. Malonyl-CoA decarboxylase is\ regulated by AMP-activated protein kinase (AMPK) [MEDLINE:22194281].

\ \ \N \N \N 26376 IPR007949

This family consists of several SDA1 protein homologues. SDA1 is a Saccharomyces cerevisiae protein which is involved in the control of theactin cytoskeleton. The protein is essential for cell viability and is localised in the nucleus\ [MEDLINE:20171451].

\ \ \N \N \N 26377 IPR007950

This family consists of several bacterial fertility inhibition (FINO) proteins. The conjugativetransfer of F-like plasmids is repressed by FinO, an RNA binding protein. FinO blocks the\ translation of TraJ, a positive activator of transcription of genes required for conjugation. FinO binds a TraJ antisense RNA, FinP,\ thereby protecting it from degradation, and catalyzes FinP-TraJ mRNA hybridization. Interactions between these two RNAs are\ predicted to block the TraJ ribosomal binding site. FinO is largely helical, binds to its highest affinity binding site within FinP as a monomer, and contains two distinct RNA binding\ regions \ [MEDLINE:20336896].

\ \ \N \N \N 26375 IPR007948

This family consists of several uncharacterised bacterial proteins of unknown function.

\ \N \N \N 26367 IPR007940

The SH3 domain-binding protein inhibits the auto and transphophorylation of BTK and acts as a negative regulator of BTK-related signalling in B cells.

\ \N \N \N 26368 IPR007941

This family consists of several uncharacterised eukaryotic proteins.

\ \N \N \N 26369 IPR007942

This family contains several phospholipase-like proteins from Arabidopsis thaliana which are homologous to PEARLI 4.

\ \N \N \N 26370 IPR007943

This domain is found in members of the junctin, junctate and aspartyl -hydroxylaseprotein families. Junctate is an integral ER/SR membrane calcium binding protein, which comes from an\ alternatively spliced form of the same gene that generates aspartyl -hydroxylase and junctin\ [MEDLINE:21599411]. Aspartyl -hydroxylase catalyses the post-translational hydroxylation of\ aspartic acid or asparagine residues contained within epidermal growth factor (EGF) domains of\ proteins [MEDLINE:21935316].

\ \ \N \N \N 26371 IPR007944

This family consists of several bacterial flagellar transcriptional activator (FlhC) proteins. FlhCcombines with FlhD to form a regulatory complex in Escherichia coli,\ this complex has been shown to be a global regulator involved in many cellular processes as well as\ a flagellar transcriptional activator [MEDLINE:21184412].

\ \ \N \N \N 26372 IPR007945

The neuroendocrine protein 7B2 (secretory granule endocrine protein I) is a secretory protein of neuroendocrine cells and may play a role in regulation of secretion in the endocrine. The precursor undergoes cleavage and maturation in secretory granules to produce the active peptides.

\ \N \N \N 26373 IPR007946

This family consists of several eukaryotic AAR2-like proteins. The Saccharomyces cerevisiae protein AAR2 is involved in splicing pre-mRNAof the a1 cistron and other genes that are important for cell growth [MEDLINE:92017850].

\ \ \N \N \N 26374 IPR007947

CD164 is a mucin-like receptor, or sialomucin, with specificity inreceptor/\ ligand interactions that depends on the structural characteristics of the\ mucin-like receptor. Its functions include mediating, or regulating,\ haematopoietic progenitor cell adhesion and the negative regulation of their\ growth and/or-differentiation. It exists in the native state as a\ disulphide-\ linked homodimer of two 80-85kDa subunits. It is usually expressed by CD34+\ and CD341o/- haematopoietic stem cells and associated microenvironmental\ cells. It contains, in its extracellular region, two mucin domains (I and\ II)\ linked by a non-mucin domain, which has been predicted to contain intra-\ disulphide bridges. This receptor may play a key role in haematopoiesis\ by facilitating the adhesion of human CD34+ cells to bone marrow stroma and\ by negatively regulating CD34+ CD341o/- haematopoietic progenitor cell\ proliferation. These effects involve the CD164 class I and/or II epitopes\ recognised by the monoclonal antibodies (mAbs) 105A5 and 103B2/9E10. These\ epitopes are carbohydrate-dependent and are located on the N-terminal\ mucin domain I [MEDLINE:99421764], [MEDLINE:21125778].

It has been found that murine MGC-24v and rat endolyn share significant\ sequence similarities with human CD164. However, CD164 lacks the consensus\ glycosaminoglycan (GAG)-attachment site found in MGC-24; it is possible\ that GAG-association is responsible for the high molecular weight of the\ epithelial-derived MGC-24 glycoprotein [MEDLINE:98438314].\

Genomic structure studies have placed CD164 within the mucin-subgroup\ that\ comprises multiple exons, and demonstrate the diverse chromosomal\ distribution of this family of molecules. Molecules with such multiple\ exons may have sophisticated regulatory mechanisms that involve not only\ post-translational modifications of the oligosaccharide side chains, but\ also differential exon usage. Although differences in the intron and exon\ sizes are seen between the mouse and human genes, the predicted proteins\ are similar in size and structure, maintaining functionally important\ motifs that regulate cell proliferation or subcellular distribution \ [MEDLINE:21125778].\

CD164 is a gene whose expression depends on differential usage of poly-\ adenylation sites within the 3'-UTR. The conserved distribution of the\ 3.2- and 1.2-kb CD164 transcripts between mouse and human suggests that\ (i) a mechanism may exist to regulate tissue-specific polyadenylation, and\ (ii) differences in polyadenylation are important for the expression and\ function of CD164 in different tissues. Two other aspects of the structure\ of CD164 are of particular interest. First, it shares one of several\ conserved features of a cytokine-binding pocket - in this respect, it is\ notable that evidence exists for a class of cell-surface sialomucin\ modulators that directly interact with growth factor receptors to regulate\ their response to physiological ligands. Second, its cytoplasmic tail\ contains a C-terminal YHTL motif found in many endocytic membrane proteins\ or receptors. These Tyr-based motifs bind to adaptor proteins, which mediate\ the sorting of membrane proteins into transport vesicles from the plasma\ membrane to the endosomes, and between intracellular compartments.\

\ \ \ \N \N \N 26365 IPR007938

This family consists of several nucleopolyhedrovirus occlusion-derived virus envelope E25proteins. The N terminus of this protein is extremely hydrophobic, studies suggest that this defined hydrophobic domain is sufficient to direct the protein to\ induced membrane microvesicles within a baculovirus-infected cell nucleus and the viral envelope. In addition,\ movement of the protein into the nuclear envelope may initiate through cytoplasmic membranes, such as endoplasmic reticulum, and\ that transport into the nucleus may be mediated through the outer and inner nuclear membrane [MEDLINE:97268695].

\ \ \N host cell nucleus ; GO:0042025 \N 26366 IPR007939

This family consists of several bacterial copper resistance proteins. Copper is essential andserves as a cofactor for more than 30 enzymes yet a surplus of copper is toxic and leads to free radical\ formation and oxidation of biomolecules. Therefore, copper homeostasis is a key requisite for every\ organism. CopB serves to extrude copper when it approaches toxic levels [MEDLINE:21553175] and has been\ shown to act as an ATPase (EC: 3.6.1.3).

\ \ \N \N \N 26363 IPR007936

This family contains several bacterial virulence-associated protein E like proteins.

\ \N \N \N 26364 IPR007937

Vaccinia viral RNA synthesis is carried out by a virus coded, multi-subunit, eukaryotic-like RNA polymerase. RNA polymerase subunits are synthesizedthroughout infection and the assembled RNA polymerase is packaged into nascent virions late in infection. The RNA polymerase exists in two different forms, one\ specific for early genes and one specific for late genes. Both forms of the RNA polymerase have in common eight subunits, ranging in size from 147 to 7 kDa This family consists of several poxvirus DNA-dependent RNA polymerase 22 kDa\ subunits.

\ \ DNA-directed RNA polymerase activity ; GO:0003899 \N viral transcription ; GO:0019083 26361 IPR007934

This family consists of several fungal -L-arabinofuranosidase B proteins. L-Arabinose is aconstituent of plant cell wall polysaccharides. It is found in a polymeric form in L-arabinan, in which\ the backbone is formed by 1,5-a- linked l-arabinose residues that can be branched via 1,2-a- and\ 1,3-a-linked l-arabinofuranose side chains. AbfB hydrolyses 1,5-a, 1,3-a and 1,2-a linkages in both\ oligosaccharides and polysaccharides, which contain terminal non-reducing l-arabinofuranoses in\ side chains [MEDLINE:99231860].

\ \ \N \N \N 26362 IPR007935

This family consists of several tobravirus 2B proteins. It is known that the 2B protein is requiredfor transmission by both Paratrichodorus pachydermus and Paratrichodorus\ anemones nematodes [MEDLINE:21109107]. Transmission of the tobraviruses Tobacco rattle virus by trichodorid vector nematodes\ requires the viral coat protein (CP) and the 2B protein, a nonstructural protein encoded by RNA2, the smaller of the two viral genomic\ RNAs. It is hypothesized that the 2B protein functions by interacting with a small, flexible domain located at the C-terminus of the CP,\ forming a bridge between the virus particle and the internal surface of the vector nematode feeding apparatus [MEDLINE:22192476].

\ \ \N \N viral transmission ; GO:0019089 26353 IPR007926

This family consists of several Borrelia P83/P100 antigen proteins.

\ \N \N \N 26354 IPR007927

This family contains several bacteriophage proteins ofunknown function.

\ \ \N \N \N 26355 IPR007928

This family consists of several antifreeze proteins from the insect Choristoneura fumiferana (Spruce budworm). Antifreeze proteins (AFPs)and antifreeze glycoproteins (AFGPs) are present in many organisms that must survive sub-zero\ temperatures. These proteins bind to seed ice crystals and inhibit their growth through an\ adsorption-inhibition mechanism [MEDLINE:22194403].

\ \ \N \N \N 26356 IPR007929

This family contains several uncharacterised proteins from Neisseriameningitidis. These proteins may have a role in DNA binding.

\ \ \N \N \N 26357 IPR007930

This family contains several uncharacterised proteins found exclusively in Arabidopsis thaliana.

\ \N \N \N 26358 IPR007931

This family contains several Drosophila proteins of unknown function.

\ \N \N \N 26359 IPR007932

This family contains several Gp38 proteins from T-even-like phages. Gp38, together with asecond phage protein, gp57, catalyses the organisation of gp37 but is absent from the phage\ particle. Gp37 is responsible for receptor recognition [MEDLINE:98343789].

\ \ \N \N \N 26360 IPR007933

This family consists of several phage CII regulatory proteins. CII plays a key role in thelysis-lysogeny decision in\ bacteriophage lambda and related phages [MEDLINE:22317399].

\ \ \N \N \N 26348 IPR007921

This domain corresponds to an amidase function. Many of the proteins containing this domain are involved in bacterial cellwall metabolism. This domain is found at the N terminus of P43675.

\ \ \N \N \N 26349 IPR007922

This family contains several actinomycete proteins of unknown function.

\ \N \N \N 26350 IPR007923

This family consists of several herpesvirus glycoprotein L or UL1 proteins. Glycoprotein L isknown to form a complex with glycoprotein H but the function of this complex is poorly understood\ [MEDLINE:97410287].

\ \ \N \N \N 26339 IPR007912

Adenoviruses have evolved multiple mechanisms to evade the host immune response. Several of the immunomodulatory adenoviralproteins are encoded in early transcription unit 3 (E3). The E3A/19K protein interferes with antigen presentation and T cell recognition [MEDLINE:98374307].

\ \ \N \N \N 26352 IPR007925

The TraM protein is an essential part of the DNA transfer machinery of the conjugativeresistance plasmid R1 (IncFII). On the basis of mutational analyses, it was shown that the essential\ transfer protein TraM has at least two functions. First, a functional TraM protein was found to be\ required for normal levels of transfer gene expression. Second, experimental evidence was obtained\ that TraM stimulates efficient site-specific single-stranded DNA cleavage at the oriT, in vivo.\ Furthermore, a specific interaction of the cytoplasmic TraM protein with the membrane protein TraD\ was demonstrated, suggesting that the TraM protein creates a physical link between the relaxosomal\ nucleoprotein complex and the membrane-bound DNA transfer apparatus [MEDLINE:21159140].

\ \ \N \N \N 26351 IPR007924

In Escherichia coli, Salmonellaenterica, and Pseudomonas aeruginosa, the waaP (rfaP)\ gene product is required for the addition of phosphate to O-4 of the first heptose residue of the\ lipopolysaccharide (LPS) inner core region. This phosphate substitution is particularly important to\ the biology of these bacteria; it has previously been shown that WaaP is necessary for resistance to\ hydrophobic and polycationic antimicrobials in E. coli and\ that it is required for virulence in invasive strains of S. enterica\ \ \ \ [MEDLINE:21101922].

WaaP shares homology with eukaryotic protein kinases in the conserved functional motifs (I-IX), indicating that it is also a protein kinase. WaaP is capable\ of catalyzing tyrosine auto-phosphorylation as well as phosphorylating an exogenous synthetic co-polymer poly(Glu, Tyr). WaaP was\ localized to the cytoplasm, suggesting that phosphorylation of the LPS core occurred prior to translocation to the periplasm and\ attachment of O-antigen [MEDLINE:21826485].

\ \ \N \N \N 26340 IPR007913

This family of proteins is functionally uncharacterised.

\ \N \N \N 26341 IPR007914

This family of proteins is functionally uncharacterised.

\ \N \N \N 26342 IPR007915

This family of proteins is functionally uncharacterised.

\ \N \N \N 26343 IPR007916

This family of proteins is functionally uncharacterised.

\ \N \N \N 26344 IPR007917

This family of proteins is functionally uncharacterised.

\ \N \N \N 26345 IPR007918

This family of proteins is functionally uncharacterised.

\ \N \N \N 26346 IPR007919

This family of proteins is functionally uncharacterised.

\ \N \N \N 26347 IPR007920

This family of proteins is functionally uncharacterised.

\ \N \N \N 26333 IPR007906

This family consists of the lactophorin precursors proteose peptone component 3 (PP3) andglycosylation-dependent cell adhesion molecule 1 (GlyCAM-1). GlyCAM-1 functions as a ligand\ for L-selectin, a saccharide-binding protein on the surface of circulating leukocytes, and mediates\ the trafficking of blood-born lymphocytes into secondary lymph nodes. In this context, sulphatation\ of the carbohydrates of GlyCAM-1 has been shown to be a critical structural requirement to be\ recognised by L-selectin. GlyCAM-1 is also expressed in pregnant and lactating mammary glands\ of mouse and in an unknown site in the lung, in the bovine uterus and rat\ cochlea [MEDLINE:22053172].

\ \ \N \N \N 26334 IPR007907

This family consists of several uncharacterised baculovirus proteins of unknown function.

\ \N \N \N 26335 IPR007908

This family consists of several outer membrane proteins (2a and 2b) from Brucella abortus.Brucellae abortus is Gram-negative, facultative intracellular bacteria that can infect many species of animals\ and humans [MEDLINE:99098687].

\ \ \N \N \N 26336 IPR007909

This family consists of several bacterial conjugal transfer proteins, TrbD. TrbD contains anucleotide binding motif and may provide energy for the export of DNA or the export of other Trb\ proteins [MEDLINE:96312368].

\ \ \N \N \N 26337 IPR007910

This family consists of several uncharacterised Borreliaburgdorferi proteins of unknown function.

\ \ \N \N \N 26338 IPR007911

This family consists of several bacterial flagellar transcriptional activator (FlhD) proteins. FlhDcombines with FlhC to form a regulatory complex in Escherichia coli.\ This complex has been shown to be a global regulator involved in many cellular processes as well as\ a flagellar transcriptional activator [MEDLINE:21184412].

\ \ \N \N \N 26329 IPR007902

This family includes CHL4 that is involved in chromosome segregation [MEDLINE:94063474]. Itis required for chromosome stability but is non-essential for growth.

\ \ \N \N \N 26330 IPR007903

The PRC-barrel is an all barrel domain found in photosystem reaction centre subunit H ofthe purple bacteria. PRC-barrels are\ approximately 80 residues long, and found widely represented in bacteria, archaea and plants. This\ domain is also present at the C terminus of the pan-bacterial protein RimM, which is involved in\ ribosomal maturation and processing of 16S rRNA. A family of small proteins conserved in all\ known euryarchaea are composed entirely of a single stand-alone copy of the domain\ [MEDLINE:22316862].

\ \ \N \N \N 26331 IPR007904

This domain is found at the C terminus of the Apolipoprotein B mRNA editing enzyme. Apobec-1 catalyzes C to U editing of apolipoprotein B (apoB) mRNA in the mammalian intestine. C to U RNA editing of mammalian apolipoprotein B (apoB) RNA is a site-specific posttranscriptional modification in which a single cytidine is enzymaticallydeaminated to uridine, thereby generating a UAA stop codon in the edited mRNA. The function\ of this domain is currently unknown.

\ \ \N \N \N 26332 IPR007905

Emopamil binding protein (EBP) is a nonglycosylated type I integralmembrane protein of endoplasmic reticulum and shows high level expression in epithelial tissues. The\ EBP protein has emopamil binding domains, including the sterol acceptor site and the catalytic\ centre, which show Delta8-Delta7 sterol isomerase activity. Human sterol isomerase, a homologue\ of mouse EBP, is suggested not only to play a role in\ cholesterol biosynthesis, but also to affect lipoprotein internalisation. In humans, mutations of EBP\ are known to cause the genetic disorder of X-linked dominant chondrodysplasia punctata (CDPX2).\ This syndrome of humans is lethal in most males, and affected females display asymmetric\ hyperkeratotic skin and skeletal abnormalities [MEDLINE:21363801].

\ \ \N \N \N 26319 IPR007892

CHASE4 is an extracellular sensory domain, which is present in various classes oftransmembrane receptors that are upstream of signal transduction pathways in prokaryotes. Specifically,\ CHASE4 domains are found in histidine kinases in archaea and in predicted diguanylate\ cyclases/phosphodiesterases in bacteria. Environmental factors that are recognized by CHASE4\ domains are not known at this time [MEDLINE:22373692].

\ \ \N \N \N 26320 IPR007893

Protein U is a spore coat protein produced at the late stage of development of Myxococcus xanthus. Protein U is produced as a secretory precursor, pro-protein U, which is then secreted across the membrane toassemble on the spore surface. This domain of unknown function is found in the bacterial family of spore coat proteins [MEDLINE:91258348].

\ \ \N \N \N 26321 IPR007894

This domain of unknown function is often found adjacent to the GGDEF domain in bacteria (IPR000160).

\ \N \N \N 26322 IPR007895

This is a domain of unknown function found in proteins of unknown function.

\ \ \N \N \N 26328 IPR007901

This putative domain is found in the MoeZ protein and the MoeB protein. The domain has twoCXXC motifs that are only partly conserved. MoeZ is necessary for the synthesis of pyridine-2,6-bis(thiocarboxylic acid), a small secreted metabolite that has a high affinity for transition\ metals, increases iron uptake efficiency by 20% in Pseudomonas stutzeri, has the ability to reduce both soluble and mineral forms of\ iron, and has antimicrobial activity towards several species of bacteria. MoeB is the molybdopterin synthase activating enzyme in the molybdopterin cofactor biosynthesis pathway.\ Both these enzymes are members of a superfamily consisting of related but structurally distinct proteins that are members of pathways involved in the\ transfer of sulfur-containing moieties to metabolites PUB00010435 and both also contain the UBA/THIF-type NAD/FAD binding fold (IPR000594).

\ \ \N \N \N 26323 IPR007896

This domain represents a conserved pair of transmembrane helices. It appears to be found as twotandem repeats in a family of hypothetical proteins.

\ \ \N \N \N 26324 IPR007897

The proteins this domain is found in are typically involved in regulating polymer accumulation inbacteria, for example the production of poly--hydroxybutyrate (PHB) which is formed via the polymerization of D(-)-3-hydroxybutyryl-CoA [MEDLINE:99121024]. The function of\ this domain is unknown.

\ \ \N \N \N 26325 IPR007898

The protein Rrn10 has been identified as a component of the Upstream Activating Factor(UAF), an RNA polymerase I (pol I) specific transcription stimulatory factor that recognizes the upstream ribosomal RNA\ (rRNA) gene promoter in a sequence specific manner and which stimulates rRNA synthesis [MEDLINE:22379127].

\ \ \N \N \N 26326 IPR007899

The CHAD domain is an -helical domain functionally associated with some members of the adenylate cyclase family IPR008172. It has conserved histidines that may chelate metalsPUB00010433.

\ \ \N \N \N 26327 IPR007900

Accurate transcription initiation at protein-coding genes by RNA polymerase II requires the assembly of a multiproteincomplex around the mRNA start site. Transcription factor TFIID is one of the general factors involved in this process. Yeast TFIID comprises the TATA binding protein and 14 TBP-associated factors (TAFIIs), nine of which contain\ histone-fold domains (IPR007124). The C-terminal region of the TFIID-specific yeast TAF4 (yTAF4) containing the HFD shares\ strong sequence similarity with Drosophila (d)TAF4 and human TAF4. A structure/function\ analysis of yTAF4 demonstrates that the HFD, a short conserved C-terminal domain (CCTD), and the region separating them\ are all required for yTAF4 function. This region of similarity is found in Transcription initiation factor TFIID component TAF4\ [MEDLINE:22323266].

\ \ \N \N \N 26315 IPR007888

This family of proteins includes the DNA-binding meisosis-specific protein NDT80 [MEDLINE:22340337]. It also describes PhoGand its homologues, proteins that have been found to increase acid phosphatase activity within certain fungi [MEDLINE:93366181]. It\ is not clear that these proteins are actually the acid phosphatase themselves.

\ \ \N \N \N 26316 IPR007889

This DNA-binding motif is found in four copies in the pipsqueak protein of Drosophila melanogaster\ \ \ [MEDLINE:98447711]. In pipsqueak this domain\ binds to GAGA sequence [MEDLINE:98447711]. The pipsqueak family, which includes proteins from fungi, sea urchins,\ nematodes, insects, and vertebrates appear to be proteins essential for sequence-specific targeting of a polycomb group protein\ complex [MEDLINE:22157910].

\ \ \N \N \N 26317 IPR007890

CHASE2 is an extracellular sensory domain, which is present in various classes oftransmembrane receptors that are upstream of signal transduction pathways in bacteria. Specifically,\ CHASE2 domains are found in histidine kinases, adenylate cyclases, serine/threonine kinases and\ predicted diguanylate cyclases/phosphodiesterases. Environmental factors that are recognized by\ CHASE2 domains are not known at this time [MEDLINE:22373692].

\ \ \N \N \N 26318 IPR007891

CHASE3 is an extracellular sensory domain, which is present in various classes oftransmembrane receptors that are upstream of signal transduction pathways in bacteria. Specifically,\ CHASE3 domains are found in histidine kinases, adenylate cyclases, methyl-accepting chemotaxis\ proteins and predicted diguanylate cyclases/phosphodiesterases. Environmental factors that are\ recognized by CHASE3 domains are not known at this time [MEDLINE:22373692].

\ \ \N \N \N 26314 IPR007887

The multiple antibiotic resistance of methicillin-resistantstrains of Staphylococcus aureus (MRSA) has become a\ major clinical problem worldwide. Methicillin resistance in MRSA strains is\ due to the acquisition of the mecA gene via horizontal transfer\ from an unidentified species which encodes penicillin-binding protein 2a (PBP2a).

The structure of the N-terminal domain from MecA is known [MEDLINE:22289680]\ \ \ \ Q53707. The length of the PBP2A N-terminal domain\ (which positions the transpeptidase active site more than 100 � from the\ expected C terminus of the transmembrane anchor) suggests a\ possible structural role and potentially gives the transpeptidase\ domain substantial reach from the cell membrane. This domain seems unlikely to have an enzymatic function.

\ \ \N \N \N 26310 IPR007883 This family contains proteins of unknown function from Caenorhabditis elegans.\ \N \N \N 26311 IPR007884 This family contains DREV protein homologues from several eukaryotes. The function of this protein is unknown [MEDLINE:21015028]. However, these proteins appear to be related to other methyltransferases.\ \N \N \N 26312 IPR007885 This family contains several Mycoplasma MgpC like-proteins.\ \N \N \N 26313 IPR007886

Alanine dehydrogenases (EC: 1.4.1.1) and pyridine nucleotide transhydrogenase (EC: 1.6.1.1) have beenshown to share regions of similarity [MEDLINE:93176150]. Alanine dehydrogenase catalyzes the NAD-dependent\ reversible reductive amination of pyruvate into alanine. Pyridine nucleotide transhydrogenase catalyzes\ the reduction of NADP⁺ to NADPH with the concomitant oxidation of NADH to NAD⁺. This enzyme is located\ in the plasma membrane of prokaryotes and in the inner membrane of the mitochondria of eukaryotes. The\ transhydrogenation between NADH and NADP is coupled with the translocation of a proton across the\ membrane. In prokaryotes the enzyme is composed of two different subunits, an chain (gene pntA)\ and a chain (gene pntB), while in eukaryotes it is a single chain protein. The sequence of alanine\ dehydrogenase from several bacterial species are related with those of the subunit of bacterial\ pyridine nucleotide transhydrogenase and of the N-terminal half of the eukaryotic enzyme. The two most\ conserved regions correspond respectively to the N-terminal extremity of these proteins, represented in this entry, and to a central\ glycine-rich region which is part of the NAD(H)-binding site.

\ \ \N \N \N 26304 IPR007877 This family consists of uncharacterised proteins from Arabidopsis thaliana.\ \N \N \N 26305 IPR007878 This family contains a number of corona virus non-structural proteins of unknown function. The family also includes a polymerase protein fragment from Berne virus and does not seem to be related to the IPR006841\ \ \ Coronavirus NS2 family.\ \ \N \N \N 26306 IPR007879 This family consists of a series of unidentified baculoviral P33 protein homologues of unknown function.\ \N \N \N 26307 IPR007880 This family consists of Spiralin proteins found in spiroplasma bacteria. Spiroplasmas are helically shaped pathogenic bacteria related to the mycoplasmas. The surface of spiroplasma bacteria is crowded with the membrane-anchored lipoprotein spiralin whose structure and function are unknown although its cellular function is thought to be a structural and mechanical one rather than catalytical [MEDLINE:21984021].\ \N \N \N 26308 IPR007881 This family contains several eukaryotic transmembrane proteins which are related to the Caenorhabditis elegans protein UNC-50 Q10045. A mammalian homologue, UNCL is a novel inner nuclear membrane protein that associates with RNA and is involved in the cell-surface expression of neuronal nicotinic receptors. UNCL plays a broader role because UNCL homologues are present in two yeast and a plant species, none of which express nicotinic receptors and it is also found in tissues that lack nicotinic receptors.\ \N \N \N 26309 IPR007882 Neurons contain abundant subsets of highly stable microtubules that resist de-polymerising conditions such as exposure to the cold. Stable microtubules are thought to be essential for neuronal development, maintenance, and function. STOP is a major factor responsible for the intriguing stability properties of neuronal microtubules and is important for synaptic plasticity. Additionally knowledge of STOPs function and properties may help in the treatment of neuroleptics in illnesses such as schizophrenia, currently thought to result from synaptic defects [MEDLINE:22217798].\ \N \N \N 26301 IPR007874 In Escherichia coli P06138. The C-terminal half of MinC is the most conserved and interacts with MinD. The N-terminal half is thought to interact with FtsZ.\ \N \N \N 26302 IPR007875 This family consists of eukaryotic Sprouty protein homologues. Sprouty proteins have been revealed as inhibitors of the Ras/mitogen-activated protein kinase (MAPK) cascade, a pathway crucial for developmental processes initiated by activation of various receptor tyrosine kinases [MEDLINE:21588664]. The sprouty gene has found to be expressed in the the brain, cochlea, nasal organs, teeth, salivary gland, lungs, digestive tract, kidneys and limb buds in mouse [MEDLINE:22278858].\ \N \N \N 26303 IPR007876 This family is comprised of several flagellar sheath adhesin proteins also called neuraminyllactose-binding hemagglutinin precursor (NLBH) or N-acetylneuraminyllactose-binding fibrillar hemagglutinin receptor-binding subunits. NLBH is found exclusively in Helicobacter which are gut colonising bacteria and bind to sialic acid rich macromolecules present on the gastric epithelium [MEDLINE:21844528].\ \N \N \N 26299 IPR007872 This probable zinc binding motif contains four cysteines that may chelate zinc. This domain is often found associated with N-terminal domain of heat shock protein DnaJ IPR001623 domain. The molecular function of these proteins is uncertain. This domain is named after the conserved motif of the final cysteine.\ \N \N \N 26300 IPR007873 The formation of N-glycosidic linkages of glycoproteins involves the ordered assembly of the common Glc3Man9GlcNAc2 core-oligosaccharide on the lipid carrier dolichyl pyrophosphate. Whereas early mannosylation steps occur on the cytoplasmic side of the endoplasmic reticulum with GDP-Man as donor, the final reactions from Man5GlcNAc2-PP-Dol to Man9GlcNAc2-PP-Dol on the lumenal side use Dol-P-Man [MEDLINE:21202230]. The ALG3 gene encodes the Dol-P-Man:Man5GlcNAc2-PP-Dol mannosyltransferase.\ \N \N \N 26296 IPR007869 Homing endonucleases are encoded by mobile DNA elements that are found inserted within host genes in all domains of life. The crystal structure of the homing nuclease PI-Sce [MEDLINE:22239878] revealed two domains: an endonucleolytic centre resembling the C-terminal domain of Drosophila melanogaster Hedgehog protein, and a second domain containing the protein-splicing active site. This domain corresponds to the C-terminal domain, which has structural similarity to IPR001767.\ \N \N \N 26297 IPR007870 DNA transcription, replication, repair and/or recombination require DNA accessibility to factors involved in the initiation of such processes. In addition, protein complexes, whose size is large compared to a nucleosome, should be able to scan the DNA packaged in chromatin. This requires sequential changes into chromatin structure. To achieve such chromatin structural changes two major mechanisms have been proposed:

the post-translational modification of histones; and
the action of ATP-dependent chromatin remodelling complexes.

The function of this particular chromatin remodelling protein is currently unknown.\ \ \N \N \N 26298 IPR007871 This family of eukaryotic proteins has no characterised function. The alignment contains some conserved cysteines and histidines that might form a zinc binding site.\ \N \N \N 26294 IPR007867 The glucose-methanol-choline (GMC) oxidoreductase oxidoreductases are FAD flavoproteins oxidoreductases. The function of this domain is currently unknown.\ \N \N \N 26295 IPR007868 Homing endonucleases are encoded by mobile DNA elements that are found inserted within host genes in all domains of life. The crystal structure of the homing nuclease PI-Sce [MEDLINE:22239878] revealed two domains: an endonucleolytic center resembling the C-terminal domain of Drosophila melanogaster Hedgehog protein, and a second domain containing the protein-splicing active site. This domain corresponds to the protein-splicing domain.\ \N \N \N 26291 IPR007864

UreE is a urease accessory protein. Urease IPR005848.

\ \N \N \N 26292 IPR007865 The aminopeptidase P, N-terminal domain is structurally very similar [MEDLINE:98188227] to the creatinase N-terminal domain (IPR000587). However, little or no sequence similarity exists between the two families.\ \N \N \N 26293 IPR007866 This family of proteins has no known function. This region may contain transmembrane

helices. The domain is found in a variety of metazoan species.\ \N \N \N 26284 IPR007857 The human homologue of Saccharomyces cerevisiae Skb1 (Shk1 kinase-binding protein 1) is a protein methyltransferase [MEDLINE:20002682]. These proteins seem to play a role in Jak signalling.\ \N \N \N 26285 IPR007858 This domain is about 40 residues long and is probably formed of two

-helices. It is found in the Dpy-30 proteins hence the motifs name. It may be a dimerisation motif analogous that found in the cAMP-dependent protein kinase regulator, type II PKA R subunit IPR003117.\ \N \N \N 26286 IPR007859 Electron-transfer flavoprotein-ubiquinone oxidoreductase (ETF-QO) in the inner mitochondrial membrane accepts electrons from electron-transfer flavoprotein which is located in the mitochondrial matrix and reduces ubiquinone in the mitochondrial membrane. The two redox centers in the protein, FAD and a [4Fe4S] cluster, are present in a 64 kDa monomer [MEDLINE:94139702].\ \N \N \N 26287 IPR007860 This domain is found in proteins of the MutS family (DNA mismatch repair proteins) and is found associated with several other domains, IPR000432).\ \N \N \N 26288 IPR007861 This domain is found in proteins of the MutS family (DNA mismatch repair proteins) and is found associated with several other domains (see IPR000432.\ \N \N \N 26289 IPR007862 Comparisons of adenylate kinases have revealed a particular divergence in the active site lid. In some organisms, particularly the Gram-positive bacteria, residues in the lid domain have been mutated to cysteines and these cysteine residues are responsible for the binding of a zinc ion. The bound zinc ion in the lid domain is clearly structurally homologous to Zinc-finger domains. However, it is unclear whether the adenylate kinase lid is a novel zinc-finger DNA/RNA binding domain, or that the lid bound zinc serves a purely structural function [MEDLINE:98379761].\ \N \N \N 26290 IPR007863 Peptidase M16 consists of two structurally related domains. One is the active peptidase, whereas the other is inactive. The two domains hold the substrate like a clamp [MEDLINE:21364070].\ \N \N \N 26283 IPR007856

Synonym(s):cerebroside sulfate activator, CSAct

Saposin B is a small non-enzymatic glycoprotein required for the breakdownof cerebroside sulfates (sulfatides) in lysosomes. Saposin B contains three intramolecular disulfide bridges, exists as a dimer and is remarkably heat, protease, and pH stable. The crystal structure of human saposin B reveals an unusual shell-like dimer consisting of a monolayer of -helices enclosing a large hydrophobic cavity. Although the secondary structure of saposin B is similar to that of the known monomeric members of the saposin-like superfamily, the helices are repacked into a different tertiary arrangement to form the homodimer. A comparison of the two forms of the saposin B dimer suggests that extraction of target lipids from membranes involves a conformational change that facilitates access to the inner cavity [MEDLINE:22406333].

\ \ \ \N \N \N 26275 IPR007848 This domain is found in ribosomal RNA small subunit methyltransferase C (eg P44453).\ \N \N \N 26276 IPR007849 ATP10 is an inner membrane protein essential for the assembly of a functional mitochondrial ATPase complex, possibly by acting as a chaperone molecule [MEDLINE:90277691].\ \N \N \N 26277 IPR007850 Proteins containing this region include Caenorhabditis elegans, UNC-89. This region is found repeated in UNC-89 and shows conservation in prolines, lysines and glutamic acids. Proteins with RCSD are involved in muscle M-line assembly, but the function of this region RCSD is\ not clear. \ \ \N \N \N 26278 IPR007851 The Saccharomyces cerevisiae member of this family is found to be required for the assembly of preribosomal 40S subunits in the nucleolus [MEDLINE:20481756]. KRR1 is highly expressed in dividing cells and its expression ceases almost completely when cells enter the stationary phase.\ \N \N \N 26279 IPR007852

Paf1 is an RNA polymerase II-associated protein in yeast, which defines a complex that is distinct from the Srb/Mediator holoenzyme.The Paf1 complex, which also contains Cdc73, Ctr9, Hpr1, Ccr4, Rtf1 and Leo1, is required for full expression of a subset of yeast genes, particularly those responsive to signals from the Pkc1/MAP kinase cascade. The complex appears to play an essential role in RNA elongation [MEDLINE:22227258].

\ \ \N \N \N 26280 IPR007853 This short presumed domain probably binds to zinc. It is found in a number of eukaryotic proteins of unknown function. The domain is named after a short C-terminal motif of D(N/H)L.\ \N \N \N 26281 IPR007854 This short motif is about 40 amino acids in length. In the Fip1 protein that is a component of a Saccharomyces cerevisiae pre-mRNA polyadenylation factor that directly interacts with poly(A) polymerase [MEDLINE:95254648]. This region of Fip1 is needed for the interaction with the Yth1 subunit of the complex and for specific polyadenylation of the cleaved mRNA precursor [MEDLINE:21137223].\ \N \N \N 26282 IPR007855 This family of proteins are eukaryotic RNA dependent RNA polymerases. These proteins are involved in post transcriptional gene silencing where they are thought to amplify dsRNA templates.\ \N \N \N 26274 IPR007847 This domain is found individually and at the N terminus of a number of multi-domain proteins, including several found in the bacterium Deinococcus radiodurans which is capable of surviving ionizing irradiation and other DNA-damaging assaults at doses that are lethal to all other organisms.\ \N \N \N 26271 IPR007844 The AsmA protein is involved in the assembly of outer membrane proteins in Escherichia coli\ \ \ [MEDLINE:97020028]. AsmA mutations were isolated as extragenic suppressors of an OmpF assembly mutant [MEDLINE:96065706]. AsmA may have a role in LPS biogenesis [MEDLINE:96065706].\ \ \N \N \N 26272 IPR007845 The Yersinia enterocolitica O:8 periplasmic binding protein-dependent transport system consisted of four proteins: the periplasmic haemin-binding protein HemT, the haemin permease protein HemU, the ATP-binding hydrophilic protein HemV and the haemin-degrading protein HemS (this family).\ \N \N \N 26273 IPR007846 The MPPN (Mitotic PhosphoProtein N end) family is uncharacterised however it probably plays a role in the cell cycle because the family includes mitotic phosphoproteins O13026\ \ \ [MEDLINE:97277270]. This family also includes O13026/> a suppressor of thermosensitive mutations in the DNA polymerase delta gene, Pol III [MEDLINE:95166178]. The conserved central region appears to be distantly related to the RNA-binding region RNP-1 (RNA recognition motif, IPR000504), suggesting an RNA binding function for this protein.\ \ \N \N \N 26265 IPR007838 This is a family of eubacterial hypothetical proteins.\ \N \N \N 26266 IPR007839 This protein family of unknown function is named GGDN after the most conserved motif. The proteins are 200-270 amino acids in length.\ \N \N \N 26267 IPR007840 This is a family of eubacterial hypothetical proteins.\ \N \N \N 26268 IPR007841 The proteins in this family are functionally uncharacterised. The proteins are around 450 amino acids long.\ \N \N \N 26269 IPR007842 This family of proteins are functionally uncharacterised.\ \N \N \N 26270 IPR007843 Selenoprotein W contains selenium as selenocysteine in the primary protein structure and levels of this selenoprotein are affected by selenium [MEDLINE:22292687]. The precise role of this family is unclear.\ \N \N \N 26263 IPR007836 L41 associates with the ribonucleoprotein particles of the 60S subunit late in the ribosomal maturation process. L41 is encoded by the smallest known open reading frame and in yeast is composed of only 24 amino acids, 17 of which are arginine or lysine.\ \N \N \N 26264 IPR007837 DNA damage-inducible (din) genes in Bacillus subtilis are coordinately regulated and together compose a global regulatory network that has been termed the SOS-like or SOB regulon. This family includes DinB from Bacillus subtilis\ \ \ [MEDLINE:91154125].\ \ \N \N \N 26262 IPR007835 The MOFRL(multi-organism fragment with rich Leucine) domain is found in bacteria and eukaryotes. The function of this domain is not clear, although it exists in some putative enzymes such as reductases and kinases.\ \N \N \N 26252 IPR007825 This family consists of major outer membrane protein precursors from Legionella pneumophila.\ \N \N \N 26253 IPR007826 This family consists of Photosystem II reaction centre M proteins (PsbM) from plants and cyanobacteria. During the photosynthetic light reactions in the thylakoid membranes of cyanobacteria, algae, and plants, photosystem II (PSII), a multi-subunit membrane protein complex, catalyses the oxidation of water to molecular oxygen and the reduction of plastoquinon [MEDLINE:22064965].\ \N \N \N 26254 IPR007827 This family contains uncharacterised baculoviral proteins.\ \N \N \N 26255 IPR007828 This is a family of uncharacterised eukaryotic proteins. Some members have a described putative function, but a common theme is not evident.\ \N \N \N 26256 IPR007829 This domain is composed of a pair of transmembrane

helices connected by a short linker. The function of this domain is unknown, however it occurs in a wide range or protein contexts.\ \N \N \N 26257 IPR007830 RNA polymerase I is comprised of 14 different subunits. The Rpa43 sbunit is one of the subunits contacted by the transcription factor TIF-IA [MEDLINE:22316717].\ \N \N \N 26258 IPR007831 This domain is found at the N terminus of members of the general secretory system II protein E. Proteins in this subfamily are typically involved in Type IV pilus biogenesis (eg Q9X4G8).\ \N \N \N 26259 IPR007832 The family comprises a subunit specific to RNA Pol III, the tRNA specific polymerase. The C34 subunit of Saccharomyces cerevisiae RNA Pol III is part of a subcomplex of three subunits which have no counterpart in the other two nuclear RNA polymerases. This subunit interacts with TFIIIB70 and therefore participates in Pol III recruitment [MEDLINE:97459958].\ \N \N \N 26260 IPR007833 This family includes export proteins involved in capsule polysaccharide biosynthesis, such as KpsS P42218.\ \N \N \N 26261 IPR007834 This family contains SEM1 and DSS1 which are short acidic proteins. In Saccharomyces cerevisiae, SEM1 is a regulator of both exocyst function and pseudohyphal differentiation [MEDLINE:99128336]. Loss of DSS1 in humans has been associated with split hand/split foot malformations [MEDLINE:96375764]\ \N \N \N 26245 IPR007818 This is a family of plant proteins of unknown function.\ \N \N \N 26246 IPR007819 The proteins in this family have no known function. They contain many conserved aspartate residues that might suggest that members of this family are metalloproteins.\ \N \N \N 26247 IPR007820

This family is annotated as putative ammonia monooxygenase enzymes by the COGS database (http://www.ncbi.nlm.nih.gov), which presents a compilation of orthologous groups of proteins from completely sequenced organisms.Ammonia monooxygenase catalyzes the oxidation of NH(3) to NH(2)OH.

\ \ \N \N \N 26248 IPR007821 The function of this presumed domain is unknown. It is found in a range of bacterial as well as eukaryotic proteins.\ \N \N \N 26249 IPR007822 This family contains the lanthionine synthetase C-like proteins 1 and 2 which are related to the bacterial lanthionine synthetase components C (LanC). LANCL1(P40 seven-transmembrane-domain protein) and LANCL2 (testes-specific adriamycin sensitivity protein) are thought to be peptide-modifying enzyme components in eukaryotic cells. Both proteins are produced in large quantities in the brain and testes and may have role in the immune surveillance of these organs [MEDLINE:21272518].\ \N \N \N 26250 IPR007823 This family consists of uncharacterised eukaryotic proteins which are related to methyltransferases (IPR004033).\ \N \N \N 26251 IPR007824 This family consists of several eukaryotic paraflagellar rod component proteins. The eukaryotic flagellum represents one of the most complex macromolecular structures found in any organism and contains more than 250 proteins [MEDLINE:21062926]. In addition to its locomotive role, the flagellum is probably involved in nutrient uptake since receptors for host low-density lipoproteins are localised on the flagellar membrane as well as on the flagellar pocket membrane [MEDLINE:21036595].\ \N \N \N 26244 IPR007817 This family includes DIT1 that is involved in synthesizing dityrosine [MEDLINE:94240168]. Dityrosine is a sporulation-specific component of the Saccharomyces cerevisiae ascospore wall that is essential for the resistance of the spores to adverse environmental conditions. Q9I1L5.\ \N \N \N 26241 IPR007814 This family includes proteins such as PaaA and PaaC that are part of a catabolic pathway of phenylacetic acid [MEDLINE:98421522]. These proteins may form part of a dioxygenase complex.\ \N \N \N 26242 IPR007815 This family includes erythromycin esterase enzymes [MEDLINE:86006276], [MEDLINE:86259072] that confer resistance to the erythromycin antibiotic.\ \N \N \N 26243 IPR007816 This family includes both ResB and cytochrome c biogenesis proteins. Mutations in ResB indicate that they are essential for growth [MEDLINE:20305553]. ResB is predicted to be a transmembrane protein [MEDLINE:20305553].\ \N \N \N 26240 IPR007813

PilN is a plasmid-encoded, lipoprotein which locates to the outer membrane of bacteria and are part of a thin pilus required only for liquid mating [MEDLINE:20153815].

\ \N \N \N 26236 IPR007809 This family includes the FlgN protein, an export chaperone involved in flagellar synthesis [MEDLINE:21106007].\ \N \N \N 26237 IPR007810 This region is found in a number of proteins identified as being involved in Golgi function and vacuolar sorting. The molecular function of this region is unknown. Proteins containing this domain also contain a C-terminal ring finger domain.\ \N \N \N 26238 IPR007811 This family comprises a specific subunit for Pol III, the tRNA specific polymerase.\ \N \N \N 26239 IPR007812 This family consists of general secretion pathway protein L sequences from several gram-negative bacteria. The general secretion pathway of gram-negative bacteria is responsible for extracellular secretion of a number of different proteins, including proteases and toxins. This pathway supports secretion of proteins across the cell envelope in two distinct steps, in which the second step, involving translocation through the outer membrane, is assisted by at least 13 different gene products. GspL is predicted to contain a large cytoplasmic domain and has been shown to interact with the autophosphorylating cytoplasmic membrane protein GspE. It is thought that the tri-molecular complex of GspL, GspE and GspM might be involved in regulating the opening and closing of the secretion pore and/or transducing energy to the site of outer membrane translocation [MEDLINE:99255537].\ \N \N \N 26233 IPR007806 This domain is found in proteins involved in transferring a group of integrating conjugative DNA elements, such as pSAM2 from Streptomyces ambofaciens during mating [MEDLINE:93374848]. Their precise role is not known.\ \N \N \N 26234 IPR007807 This putative domain is about 350 amino acid residues long and appears to have a P-loop motif, suggesting this is an ATPase. This domain is often associated with IPR000182.\ \N \N \N 26235 IPR007808 This domain, largely found in short proteins, consists of a putative zinc binding domain with four conserved cysteines.\ \N \N \N 26225 IPR007798 This family consists of mammalian Ameloblastin precursor (Amelin) proteins. Matrix proteins of tooth enamel consist mainly of amelogenin but also of non-amelogenin proteins, which, although their volumetric percentage is low, have an important role in enamel mineralization. One of the non-amelogenin proteins is ameloblastin, also known as amelin and sheathlin. Ameloblastin (AMBN) is one of the enamel sheath proteins which is thought to have a role in determining the prismatic structure of growing enamel crystals [MEDLINE:21856501].\ \N \N \N 26226 IPR007799

This family consists of unidentified baculoviral p47 proteins which is one of the primary components of Autographa californicamultinucleocapsid polyhedrovirus encoded RNA polymerase, which initiates transcription from late and very late promoters [MEDLINE:98406201].\

\ \ \N \N \N 26227 IPR007800 This family consists of uncharacterised proteins from Borrelia burgdorferi.\ \N \N \N 26228 IPR007801 This family consists of uncharacterised bacterial proteins.\ \N \N \N 26229 IPR007802 This family consists of several Cytochrome B6-F complex subunit VI (PetL) proteins found in a number of plant species. PetL is one of the small subunits which make up the cytochrome b(6)f complex. PetL is not absolutely required for either the accumulation or for the function of cytochrome b6f; in its absence, however, the complex becomes unstable in vivo in aging cells and labile in vitro. It has been suggested that the N terminus of the protein is likely to lie in the thylakoid lumen [MEDLINE:21922793].\ \N \N \N 26230 IPR007803 The aspartyl/asparaginyl

-hydroxylase (EC: 1.14.11.16) specifically hydroxylates one aspartic or asparagine residue in certain epidermal growth factor-like domains of a number of proteins [MEDLINE:94316668].\ \N \N \N 26231 IPR007804

Gas vesicles are intracellular, protein-coated, and hollow organelles found in cyanobacteria and halophilic archaea. They are permeable to ambient gases by diffusion and provide buoyancy, enabling cells to move upwards in liquid to access oxygen and/or light. Proteins containing this domain are involved in the formation of gas vesicles ([MEDLINE:98233742]).\

\ \ \N \N \N 26232 IPR007805

\ \N \N \N 26224 IPR007797 This family consists of AF4 (Proto-oncogene AF4) and FMR2 (Fragile X E mental retardation syndrome) nuclear proteins. These proteins have been linked to Homo sapiens diseases such as acute lymphoblastic leukemia and mental retardation [MEDLINE:21098965]. The family also contains a Drosophila AF4 protein homologue Lilliputian which contains an AT-hook domain. Lilliputian represents a novel pair-rule gene that acts in cytoskeleton regulation, segmentation and morphogenesis in Drosophila [MEDLINE:21098966].\ \N \N \N 26222 IPR007795 This family contains uncharacterised bacterial membrane proteins of unknown function.\ \N \N \N 26223 IPR007796

This family consists of the BLLF1 viral late glycoprotein, also termed gp350/220. It is the most abundantly expressed glycoprotein in the viral envelope of the Herpesviruses and is the major antigen responsible for stimulating the production of neutralising antibodies in vivo. The binding of the viral major glycoprotein BLLF1 to the CD21 cellular receptor is thought to play an essential role during infection of B lymphocytes by the Epstein-Barr virus [MEDLINE:20481654].

\ \N viral envelope ; GO:0019031 viral infectious cycle ; GO:0019058 26221 IPR007794 The ribosome receptor is an integral endoplasmic reticulum protein that has been suggested to be involved in secretion. This highly conserved region is found towards the C terminus of the transmembrane domain [MEDLINE:21826698]. The function is unclear.\ \N \N \N 26220 IPR007793 The Bacillus subtilis divIVA1 mutation causes misplacement of the septum during cell division, resulting in the formation of small, circular, anucleate minicells [MEDLINE:97197532]. Inactivation of divIVA produces a minicell phenotype, whereas overproduction of DivIVA results in a filamentation phenotype [MEDLINE:97197532]. These proteins appear to contain coiled-coils.\ \N \N \N 26219 IPR007792 This family includes the Type IV secretory pathway VirB3 protein, that is found associated with bacterial inner and outer membranes and assists T pilus formation as an assembly factor [MEDLINE:94010218].\ \N \N \N 26217 IPR007790

The baculovirus Autographa californica nuclear polyhedrosis virus encodes a DNA-dependent RNA polymerase that is required for transcription of viral late genes. This polymerase is composed of four equimolar subunits, LEF-8, LEF-4, LEF-9, and p47. LEF-4 carries out all the enzymatic functions related to mRNA capping [MEDLINE:22120165].

\ \ \N \N \N 26218 IPR007791 This family contains the TerB tellurite resistance proteins from a number of bacteria.\ \N \N \N 26209 IPR007782 Using reduced vitamin K, oxygen, and carbon dioxide, gamma-glutamyl carboxylase post-translationally modifies certain glutamates by adding carbon dioxide to the gamma position of those amino acids. In vertebrates, the modification of glutamate residues of target proteins is facilitated by an interaction between a propeptide present on target proteins and the gamma-glutamyl carboxylase [MEDLINE:20309781].\ \N \N \N 26210 IPR007783 This family is made up of eukaryotic translation initiation factor 3 subunit 7 (eIF-3 zeta/eIF3 p66/eIF3d). Eukaryotic initiation factor 3 is a multi-subunit complex that is required for binding of mRNA to 40S ribosomal subunits, stabilisation of ternary complex binding to 40 S subunits, and dissociation of 40 and 60 S subunits. These functions and the complex nature of eIF3 suggest multiple interactions with many components of the translational machinery [MEDLINE:21125776]. The gene coding for the protein has been implicated in cancer in mammals [MEDLINE:21590031].\ \N \N \N 26216 IPR007789 This family contains uncharacterised proteins found in Arabidopsis thaliana.\ \N \N \N 26215 IPR007788 This family of enzymes EC: 2.3.2.5 catalyse the cyclization of free L-glutamine and N-terminal glutaminyl residues in proteins to pyroglutamate (5-oxoproline) and pyroglutamyl residues respectively [MEDLINE:20493505]. This family includes plant and bacterial enzymes and seems unrelated to the mammalian enzymes.\ \N \N \N 26211 IPR007784 This family consists of uncharacterised baculovirus proteins.\ \N \N \N 26212 IPR007785 This family contains several uncharacterised eukaryotic proteins of unknown function.\ \N \N \N 26213 IPR007786 The baculovirus Autographa californica nuclear polyhedrosis virus encodes a DNA-dependent RNA polymerase that is required for transcription of viral late genes. This polymerase is composed of four equimolar subunits, LEF-8, LEF-4, LEF-9, and p47. LEF-9 is homologous to the largest

-subunit of prokaryotic DNA-directed RNA polymerase [MEDLINE:22120165].\ transcriptional activator activity ; GO:0016563 \N viral transcription ; GO:0019083 26214 IPR007787 This family contains uncharacterised Chlamydia proteins.\ \N \N \N 26201 IPR007773 This family consists of uncharacterised baculovirus proteins.\ \N \N \N 26202 IPR007774 This family contains several uncharacterised bacterial proteins. These proteins are found in nitrogen fixation operons, so are likely to play a role in this process.\ \N \N \N 26203 IPR007775 B144/LST1 is a gene encoded in the human major histocompatibility complex that produces multiple forms of alternatively spliced mRNA and encodes peptides fewer than 100 amino acids in length. B144/LST1 is strongly expressed in dendritic cells. Transfection of B144/LST1 into a variety of cells induces morphologic changes including the production of long, thin filopodia [MEDLINE:21372017].\ \N \N \N 26204 IPR007777 This family consists of uncharacterised proteins from Borrelia burgdorferi. There is some evidence to suggest that the proteins may be outer surface proteins.\ \N \N \N 26205 IPR007778 This family consists of REP proteins from a number of Dictyostelium species (Slime molds). REP protein is probably involved in transcription regulation and control of DNA replication, specifically the amplification of plasmid at low copy numbers. The formation of homomultimers may be required for their regulatory activity [MEDLINE:99296681].\ \N \N \N 26206 IPR007779 Rotavirus particles consist of three concentric proteinaceous capsid layers. The innermost capsid (core) is made of VP2. The genomic RNA and the two minor proteins VP1 and VP3 are encapsidated within this layer [MEDLINE:94233776]. The N terminus of rotavirus VP2 is necessary for the encapsidation of VP1 and VP3 [MEDLINE:98080405].\ \N \N \N 26207 IPR007780 This family consists of several bacterial proteins which are closely related to NAD-glutamate dehydrogenase found in Streptomyces clavuligerus. Glutamate dehydrogenases (GDHs) are a broadly distributed group of enzymes that catalyse the reversible oxidative deamination of glutamate to ketoglutarate and ammonia [MEDLINE:20564327].\ \N \N \N 26208 IPR007781 Alpha-N-acetylglucosaminidase is a lysosomal enzyme required for the stepwise degradation of heparan sulfate [MEDLINE:20056274]. Mutations on the

-N-acetylglucosaminidase (NAGLU) gene can lead to Mucopolysaccharidosis type IIIB (MPS IIIB; or Sanfilippo syndrome type B) characterised by neurological dysfunction but relatively mild somatic manifestations [MEDLINE:22045044].\ \N \N \N 26197 IPR007769 This family contains poxvirus proteins belonging to the A19 family. The proteins are of unknown function.\ \N \N \N 26198 IPR007770 This family contains uncharacterised plant proteins of unknown function.\ \N \N \N 26199 IPR007771 This family contains uncharacterised proteins which seem to be found exclusively in Mesorhizobium loti.\ \N \N \N 26200 IPR007772 This family contains uncharacterised beak and feather disease virus proteins.\ \N \N \N 26191 IPR007763 This family contains the 17.2 kDa subunit of complex I of NADH:ubiquinone oxidoreductase and its homologues. The family also contains a second related eukaryotic protein of unknown function, e.g. Q9BV02.\ \N \N \N 26192 IPR007764 UL43 genes are expressed with true-late (gamma2) kinetics and have been identified as a virion tegument component [MEDLINE:22024834]. Studies suggest that the N-terminal sequences target UL43 to protein aggregates and that C-terminal sequences are important for incorporation into particles.\ \N \N \N 26193 IPR007765 The unidentified baculovirus protein p24 is associated with nucleocapsids of budded and polyhedra-derived virions [MEDLINE:21488685], [MEDLINE:93139770].\ \N \N \N 26194 IPR007766 Beta-tubulin cofactor D is essential for the folding of tubulin molecules. It also plays a role (along with co-factors C and E) in the assembly of the

- tubulin heterodimer and can interact with native tubulin, stimulating it to hydrolyse GTP and thus acting together as a

-tubulin GTPase activating protein (GAP) [MEDLINE:20293205].\ \N \N \N 26195 IPR007767 This family contains uncharacterised proteins from Caenorhabditis elegans.\ \N \N \N 26196 IPR007768 SUFU, encoding the human ortholog of Drosophila suppressor of fused, appears to have a conserved role in the repression of Hedgehog signalling. SUFU exerts its repressor role by physically interacting with GLI proteins in both the cytoplasm and the nucleus [MEDLINE:22145865]. SUFU has been found to be a tumour-suppressor gene that predisposes individuals to medulloblastoma by modulating the SHH signalling pathway [MEDLINE:22084371].\ \N \N \N 26187 IPR007759 The delta protein is a dispensable subunit of Bacillus subtilis RNA polymerase (RNAP) that has major effects on the biochemical properties of the purified enzyme. In the presence of delta, RNAP displays an increased specificity of transcription, a decreased affinity for nucleic acids, and an increased efficiency of RNA synthesis because of enhanced recycling [MEDLINE:99269144]. The delta protein, contains two distinct regions, an N-terminal domain and a glutamate and aspartate residue-rich C-terminal region [MEDLINE:95404613].\ \N \N \N 26188 IPR007760 Catalases are important antioxidant metalloenzymes that catalyse disproportionation of hydrogen peroxide, forming dioxygen and water. Two families of catalases are known, one having a haem cofactor, and this family that is a structurally distinct family containing non-haem manganese [MEDLINE:21472747].\ \N \N \N 26189 IPR007761 The mannitol operon of Escherichia coli, encoding the mannitol-specific enzyme II of the phosphotransferase system (MtlA) and mannitol phosphate dehydrogenase (MtlD) contains an additional downstream open reading frame which encodes the mannitol repressor (MtlR).\ \N \N \N 26190 IPR007762 Mrp10 belongs to the class of Saccharomyces cerevisiae mitochondrial ribosomal proteins that are essential for translation [MEDLINE:97218168] and is a component of the 37 S subunit of the mitochondrial ribosomes.\ \N \N \N 26183 IPR007755 This is a family of conserved Chordopoxvirinae A11 family proteins. A conserved region spans the entire protein in the majority of family members.\ \N \N \N 26184 IPR007756 This domain is about 85 residues in length and very rich in charged residues, hence the name RICH (Rich In CHarged residues). It is found in secreted proteins such as PspC Q9KK19. This domain could be involved in bacterial adherence or cell wall binding.\ \N \N \N 26185 IPR007757 MT-A70 is the S-adenosylmethionine-binding subunit of human mRNA:m6A methyl-transferase (MTase), an enzyme that sequence-specifically methylates adenines in pre-mRNAs.\ \N \N \N 26186 IPR007758 The rotavirus nonstructural protein NSP1 is the least conserved protein in the rotavirus genome, and its function in the replication process is not fully understood although preribosome nuclear export requires the Nup82p-Nup159p-Nsp1p complex. This important region of Nsp1 is involved in binding Nup82 [MEDLINE:21548392] and probably forms a coiled-coil [MEDLINE:21548392].\ \N \N \N 26174 IPR007746 The prokaryotic MerE (or URF-1) protein is part of the mercury resistance operon. The protein is thought not to have any direct role in conferring mercury resistance to the organism but may be a mercury resistance transposon [MEDLINE:98148002], [MEDLINE:21604134].\ \N \N \N 26175 IPR007747 MEN1, the gene responsible for multiple endocrine neoplasia type 1, is a tumour suppressor gene that encodes a protein called Menin which may be an atypical GTPase stimulated by nm23 [MEDLINE:22254829].\ \N \N \N 26176 IPR007748 This is a family of uncharacterised viral proteins of unknown function.\ \N \N \N 26177 IPR007749 This family consists of AT14A like proteins from Arabidopsis thaliana. At14a contains a small domain that has sequence similarities to integrins from fungi, insects and humans. Transcripts of At14a are found in all Arabidopsis tissues and the protein localises partly to the plasma membrane [MEDLINE:99214065].\ \N \N \N 26178 IPR007750 This family is found in Arabidopsis thaliana and contains uncharacterised proteins.\ \N \N \N 26179 IPR007751 This region is associated with a group of uncharacterised eukaryotic proteins.\ \N \N \N 26180 IPR007752 The ActA family is found in Listeria and is associated with motility. ActA protein acts as a scaffold to assemble and activate host cell actin cytoskeletal factors at the bacterial surface, resulting in directional actin polymerization and propulsion of the bacterium through the cytoplasm of the host cell [MEDLINE:21884388], [MEDLINE:21843092].\ \N \N \N 26181 IPR007753 Orbivirus are double stranded RNA retroviruses of which the bluetongue virus is a member. The core of bluetongue virus (BTV) is a multienzyme complex composed of two major proteins (VP7 and VP3) and three minor proteins (VP1, VP4 and VP6) in addition to the viral genome. VP4 has been shown to perform all RNA capping activities and has both methyltransferase type 1 and type 2 activities associated with it [MEDLINE:99030604].\ \N viral capsid ; GO:0019028 \N 26182 IPR007754

N-acetylglucosaminyltransferase II (EC: 2.4.1.143) is a Golgi resident enzyme that catalyzes an essential step in the biosynthetic pathway leading from high mannose to complex N-linked oligosaccharides [MEDLINE:95318086]. Mutations in the MGAT2 gene lead to a congenital disorder of glycosylation (CDG IIa). CDG IIa patients have an increased bleeding tendency, unrelated to coagulation factors [MEDLINE:21480189].

Synonym(s): UDP-N-acetyl-D-glucosamine:-6-D-mannoside -1,2-N- acetylglucosaminyltransferase II, GnT II/MGAT2.

\ \ \N \N \N 26170 IPR007742

Bacterial nitrous oxide (N(2)O) reductase is the terminal oxidoreductase of a respiratory process that generates dinitrogen fromN(2)O. To attain its functional state, the enzyme is subjected to a maturation process which involves the protein-driven synthesis of a\ unique copper-sulfur cluster and metallation of the binuclear Cu(A) site in the periplasm. NosD is a periplasmic protein which is thought to insert copper into the exported reductase apoenzyme [MEDLINE:96198150].

\ \ \N \N \N 26171 IPR007743 Interferon-inducible GTPase (IIGP) is thought to play a role in in intracellular defense. IIGP is predominantly associated with the Golgi apparatus and also localizes to the endoplasmic reticulum and exerts a distinct role in IFN-induced intracellular membrane trafficking or processing [MEDLINE:21904525].\ \N \N \N 26172 IPR007744 This family includes several proteins of unknown function and seems to be specific to Caenorhabditis elegans.\ \N \N \N 26173 IPR007745 Cox17p is essential for the assembly of functional cytochrome c oxidase (CCO) and for delivery of copper ions to the mitochondrion for insertion into the enzyme in Saccharomyces cerevisiae\ \ \ [MEDLINE:22257961].\ \ \N \N \N 26168 IPR007740 This family of proteins has been identified as part of the mitochondrial large ribosomal subunit in Saccharomyces cerevisiae\ \ \ [MEDLINE:22280971].\ \ \N \N \N 26169 IPR007741 Proteins containing this domain are located in the mitochondrion and include ribosomal protein L51, and S25. This domain is also found in mitochondrial NADH-ubiquinone oxidoreductase B8 subunit (CI-B8) EC: 1.6.5.3. It is not known whether all members of this family form part of the NADH-ubiquinone oxidoreductase and whether they are also all ribosomal proteins.\ \N \N \N 26165 IPR007737 Mga is a DNA-binding protein that activates the expression of several important virulence genes in group A streptococcus in response to changing environmental conditions [MEDLINE:21950954]. The family also contains VirR like proteins which match only at the C terminus of the alignment.\ \N \N \N 26166 IPR007738 The homeobox gene Prox1 is expressed in a subpopulation of endothelial cells that, after budding from veins, gives rise to the mammalian lymphatic system [MEDLINE:21924682]. Prox1 has been found to be an early specific marker for the developing liver and pancreas in the mammalian foregut endoderm [MEDLINE:22239702]. This family contains an atypical homeobox domain.\ \N \N \N 26167 IPR007739 This family consists of a group of proteins which are related to the Streptococcal rhamnose-glucose polysaccharide assembly protein (RgpF). Rhamnan backbones are found in several O-polysaccharides found in phytopathogenic bacteria and are regarded as pathogenic factors [MEDLINE:22006890].\ \N \N \N 26164 IPR007736 This family contains plant proteins related to caleosin. Caleosins contain calcium-binding domains and have an oleosin-like association with lipid bodies. Caleosins are present at relatively low levels and are mainly bound to microsomal membrane fractions at the early stages of seed development. As the seeds mature, overall levels of caleosins increased dramatically and they were associated almost exclusively with storage lipid bodies [MEDLINE:21116828]. The calcium binding domain is probably related to the calcium-binding EF-hands motif IPR002048.\ \N \N \N 26162 IPR007734

Heparan sulfate (HS) is a long unbranched polysaccharide found covalently attached to various proteins at the cell surface and in theextracellular matrix, where it acts as a co-receptor for a number of growth factors, morphogens, and adhesion proteins. HS-O-sulfotransferase (Hs2st) occupies a critical position in the succession of enzymes responsible for the biosynthesis of HS, catalysing the transfer of sulfate to the C2-position of selected hexuronic acid residues within the nascent HS chain. Mice that lack HS2ST undergo developmental failure after midgestation, the most dramatic effect being the complete failure of kidney development [MEDLINE:21953193]. This family is related to IPR005331.

\ \ \N \N \N 26163 IPR007735 This family consists of the C-terminal region of the pecanex protein homologues. The pecanex protein is a maternal-effect neurogenic gene found in Drosophila [MEDLINE:93094953].\ \N \N \N 26146 IPR007718 This presumed domain is found at the C terminus of the Saccharomyces cerevisiae SRP40 protein P32583 and its homologues. SRP40/nopp40 is a chaperone involved in nucleocytoplasmic transport. SRP40 is also a suppressor of mutant AC40 subunit of RNA polymerase I and III.\ \N \N \N 26147 IPR007719 Phytochelatin synthase is the enzyme responsible for the synthesis of heavy-metal-binding peptides (phytochelatins) from glutathione and related thiols [MEDLINE:21674957].\ \N \N \N 26148 IPR007720 Glycosylphosphatidylinositol (GPI) represents an important anchoring molecule for cell surface proteins. The first step in its synthesis is the transfer of N-acetylglucosamine (GlcNAc) from UDP-N-acetylglucosamine to phosphatidylinositol (PI). This chemically simple step is genetically complex because three or four genes are required in both Saccharomyces cerevisiae (GPI1, GPI2 and GPI3) and mammals (GPI1, PIG A, PIG H and PIG C), respectively [MEDLINE:21839611].\ \N \N \N 26149 IPR007721 The Escherichia coli high-affinity ribose-transport system consists of six proteins encoded by the rbs operon (rbsD, rbsA, rbsC, rbsB, rbsK and rbsR). Of the six components, RbsD is the only one whose function is unknown although it is thought that it somehow plays a critical role in PtsG-mediated ribose transport [MEDLINE:21263937]. This family also includes FucU a protein from the fucose biosynthesis operon that is presumably also involved in fucose transport by similarity to RbsD.\ \N \N \N 26150 IPR007722 This presumed domain is always found to the N-terminal side of the NUDIX hydrolase domain IPR000086.\ \N \N \N 26151 IPR007723 TIP120A is thought to be a unique global transcription factor that can interact with TBP and can stimulate all classes of eukaryotic transcription [MEDLINE:21160565]. TIP120B is specifically expressed in the skeletal muscle and heart, it is speculated that this protein is required for muscle cell development [MEDLINE:22197095].\ \N \N \N 26152 IPR007724 Poly(ADP-ribose) glycohydrolase (PARG) is a ubiquitously expressed exo- and endoglycohydrolase which mediates oxidative and excitotoxic neuronal death [MEDLINE:21477454].\ \N \N \N 26153 IPR007725 The timeless (tim) gene is essential for circadian function in Drosophila. Putative homologues of Drosophila tim have been identified in both mice and humans (mTim and hTIM, respectively). Mammalian TIM is not the true orthologue of Drosophila TIM, but is the likely orthologue of a fly gene, timeout (also called tim-2) [MEDLINE:21131728]. mTim has been shown to be essential for embryonic development, but does not have substantiated circadian function [MEDLINE:20364017]. Some family members contain a SANT domain in this region.\ \N \N \N 26154 IPR007726 The SSXT or SS18 protein is involved in synovial sarcoma in humans. A SYT-SSX fusion gene resulting from the chromosomal translocation t(X;18) (p11;q11) is characteristic of synovial sarcomas. This translocation fuses the SSXT (SYT) gene from chromosome 18 to either of two homologous genes at Xp11, SSX1 or SSX2 [MEDLINE:22162922].\ \N \N \N 26155 IPR007727 This family of proteins includes Spo12 from Saccharomyces cerevisiae\ \ \ P17123.\ \ \N \N \N 26156 IPR007728 This protein motif is a zinc binding motif [MEDLINE:22289681]. It contains 9 conserved cysteines that coordinate three zinc ions. It is thought that this region plays a structural role in stabilising SET domains.\ \N \N \N 26157 IPR007729 2-keto-3-deoxy-galactonokinase EC: 2.7.1.58 catalyses the second step in D-galactonate degradation.\ \N \N \N 26158 IPR007730 This 35 residue repeat is found in proteins involved in sporulation and cell division such as FtsN, DedD, and CwlM. This repeat might be involved in binding peptidoglycan. FtsN is an essential cell division protein with a simple bitopic topology: a short N-terminal cytoplasmic segment fused to a large carboxy periplasmic domain through a single transmembrane domain. These repeats lay at the periplasmic C terminus. FtsN localises to the septum ring complex. The CwlM gene is a cell wall hydrolase so this repeat may help localise the protein to the cell wall.\ \N \N \N 26145 IPR007717 The HRD4 gene is identical to NPL4, a gene previously implicated in nuclear transport. Using a diverse set of substrates and direct ubiquitination assays, analysis revealed that HRD4/NPL4 is required for a poorly characterized step in ER-associated degradation following ubiquitination of target proteins but preceeding their recognition by the 26S proteasome [MEDLINE:21602844]. Npl4p physically associates with Cdc48p via Ufd1p to form a Cdc48p-Ufd1p-Npl4p complex. The Cdc48-Ufd1-Npl4 complex functions in the recognition of several polyubiquitin-tagged proteins and facilitates their presentation to the 26S proteasome for processive degradation or even more specific processing.\ \N \N \N 26161 IPR007733 The agouti protein regulates pigmentation in the mouse hair follicle producing a black hair with a subapical yellow band. A highly homologous protein agouti signal protein (ASIP) is present in humans and is expressed at highest levels in adipose tissue where it may play a role in energy homeostasis and possibly human pigmentation [MEDLINE:21824813], [MEDLINE:21832512].\ \N \N \N 26159 IPR007731 This is a family of phage proteins of unknown function.\ \N \N \N 26160 IPR007732

Flavocytochrome b558 is the catalytic core of the respiratory-burst oxidase, an enzyme complex that catalyzes theNADPH-dependent reduction of O2 into the superoxide anion O2 in phagocytic cells. Flavocytochrome b558 is anchored in the plasma membrane. It is a heterodimer that consists of a large glycoprotein gp91phox (phox forphagocyte oxidase) ( subunit) and a\ small protein p22phox ( subunit). The other components of the respiratory-burst oxidase are water-soluble proteins of cytosolic\ origin, namely p67phox, p47phox, p40phox and Rac. Upon cell stimulation, they assemble with the membrane-bound\ flavocytochrome b558 which becomes activated and generates O2-. [MEDLINE:96394426].\

\ \ \N \N \N 26142 IPR007714 This family of proteins are highly conserved in eukaryotes. Some proteins in the family are annotated as transcription factors. However, there is currently no support for this in the literature.\ \N \N \N 26143 IPR007715 Coq4p was shown to peripherally associate with the matrix face of the mitochondrial inner membrane. The putative mitochondrial- targeting sequence present at the N terminus of the polypeptide efficiently imports it to mitochondria. The function of Coq4p is unknown, although its presence is required to maintain a steady-state level of Coq7p, another component of the Q biosynthetic pathway [MEDLINE:21362964].\ \N \N \N 26144 IPR007716 The HRD4 gene is identical to NPL4, a gene previously implicated in nuclear transport. Using a diverse set of substrates and direct ubiquitination assays, analysis revealed that HRD4/NPL4 is required for a poorly characterized step in ER-associated degradation after ubiquitination of target proteins but before their recognition by the 26S proteasome [MEDLINE:21602844]. This region of the protein contains possibly two zinc binding motifs. Npl4p physically associates with Cdc48p via Ufd1p to form a Cdc48p-Ufd1p-Npl4p complex. The Cdc48-Ufd1-Npl4 complex functions in the recognition of several polyubiquitin-tagged proteins and facilitates their presentation to the 26S proteasome for processive degradation or even more specific processing.\ \N \N \N 26140 IPR007712 Members of this family are involved in plasmid stabilization. The exact molecular function of this protein is not known.\ \N \N \N 26141 IPR007713 This short repeat consists of the motif WXXh where X can be any residue and h is a hydrophobic residue. The repeat is named TMP after its occurrence in the tape measure protein (TMP). Tape measure protein is a component of phage tail and probably forms a

-helix. Truncated forms of TMP lead to shortened tail fibres [MEDLINE:20497003]. This repeat is also found in non-phage proteins where it may play a structural role.\ \N \N \N 26139 IPR007711 Several plasmids with proteic killer gene systems have been reported. All of them encode a stable toxin and an unstable antidote. Upon loss of the plasmid, the less stable inhibitor is inactivated more rapidly than the toxin, allowing the toxin to be activated. The activation of those systems result in cell filamentation and cessation of viable cell production. It has been verified that both the stable killer and the unstable inhibitor of the systems are short polypeptides. This family corresponds to the toxin.\ \N \N \N 26133 IPR007705

This family includes the Golgi SNAP receptor (SNARE) complex protein, which is involved in transport from the endoplasmic reticulum to the golgi apparatus and intra-golgi transport, and the vesicle transport v-SNARE protein, that mediates vesicle transport pathways through interaction with T-SNAREs on the target membrane.

\ \N \N \N 26134 IPR007706

This family contains EBNA-3A, -3B, and -3C which are latent infection nuclear proteins important for Epstein-Barr virus (EBV)-induced B-cell immortalisation and the immune response to EBV infection.

\ \N host cell nucleus ; GO:0042025 viral life cycle ; GO:0016032 26135 IPR007707 This family contains the proteins TACC 1, 2 and 3, found concentrated in the centrosomes of eukaryotes which may play a conserved role in organising centrosomal microtubules. The human TACC proteins have been linked to cancer and TACC2 has been identified as a possible tumour suppressor (AZU-1) [MEDLINE:20570483].\ \N \N \N 26136 IPR007708

This presumed domain is found at the C terminus of lariat debranching enzyme. This domain is always found in association with a metallo-phosphoesterase domain IPR004843. RNA lariat debranching enzyme is capable of digesting a variety of branched nucleic acid substrates and multicopy single-stranded DNAs. The enzyme degrades intron lariat structures during splicing.

\ \N \N \N 26137 IPR007709 Formylglutamate amidohydrolase (FGase) catalyzes the terminal reaction in the five-step pathway for histidine utilization in Pseudomonas putida. By this action, N-formyl-L-glutamate (FG) is hydrolyzed to produce L-glutamate plus formate [MEDLINE:88007416].\ \N \N \N 26138 IPR007710

Nucleoside 2-deoxyribosyltransferase (EC: 2.4.2.6) catalyzes the cleavage of the glycosidic bonds of 2'-deoxyribonucleosides [MEDLINE:95318137].

\ \N \N \N 26130 IPR007702 This family is comprised of the Ocnus, Janus-A and Janus-B proteins. These proteins have been found to be testes specific in Drosophila melanogaster\ \ \ [MEDLINE:21219192].\ \ \N \N \N 26131 IPR007703 This family contains several uncharacterised viral proteins of unknown function.\ \N \N \N 26132 IPR007704 PIG-M has a DXD motif. The DXD motif is found in many glycosyltransferases that utilise nucleotide sugars. It is thought that the motif is involved in the binding of a manganese ion that is required for association of the enzymes with nucleotide sugar substrates [MEDLINE:21145445].\ \N \N \N 26127 IPR007699 This domain was thought to be unique to the SGT1-like proteins, but is also found in calcyclin binding proteins. Sgt1p is a highly conserved eucaryotic protein that is required for both SCF (Skp1p/Cdc53p-Cullin-F-box)-mediated ubiquitination and kinetochore function in yeast and also plays a role in the cAMP pathway. Calcyclin (S100A6) is a member of the S100A family of calcium binding proteins and appears to play a role in cell proliferation [MEDLINE:22464564].\ \N \N \N 26128 IPR007700 This is a family of uncharacterised plant proteins of unknown function.\ \N \N \N 26129 IPR007701 Interferon-related developmental regulator (IFRD1) is the human homologue of the Rattus norvegicus early response protein PC4 and its murine homolog TIS7 [MEDLINE:97203201]. The exact function of IFRD1 is unknown but it has been shown that PC4 is necessary for muscle differentiation and that it might have a role in signal transduction. This family also contains IFRD2 and its murine equivalent SKMc15, which are highly expressed soon after gastrulation and in the hepatic primordium, suggesting an involvement in early hematopoiesis [MEDLINE:98390186].\ \N \N \N 26126 IPR007698

This is a C-terminal domain of alanine dehydrogenases (EC: 1.4.1.1). This domain is also found in the lysine 2-oxoglutarate reductases.

\ \ oxidoreductase activity ; GO:0016491 \N electron transport ; GO:0006118 26125 IPR007696

This domain is found in proteins of the MutS family (DNA mismatch repair proteins) and is found associated with MutS_V, MutS_II, MutS_I and MutS_IV. The MutS family of proteins is named after the Salmonella typhimurium MutS protein involved in mismatch repair; other members of the family included the eukaryotic MSH 1, 2, 3, 4, 5 and 6 proteins. These have various roles in DNA repair and recombination. Human MSH has been implicated in non-polyposis colorectal carcinoma (HNPCC) and is a mismatch binding protein. The aligned region corresponds with domain III, which is central to the structure of Thermus aquaticus MutS.

\ \N \N \N 26123 IPR007694

The hexameric helicase DnaB unwinds the DNA duplex at the Escherichia coli chromosome replication fork. Although the mechanism by which DnaB both couples ATP hydrolysis to translocation along DNA and denatures the duplex is unknown, a change in the quaternary structure of the protein involving dimerization of the N-terminal domain has been observed and may occur during the enzymatic cycle. This C-terminal domain contains an ATP-binding site and is therefore probably the site of ATP hydrolysis.

\ ATP binding activity ; GO:0005524 \N DNA replication ; GO:0006260 26124 IPR007695 This signature is of the N-terminal domain of proteins in the mutS family of DNA mismatch repair proteins and is found associated with IPR000432 located in the C-terminal region. Yeast MSH3, bacterial proteins involved in DNA mismatch repair and the predicted protein product of the Rep-3 gene of mouse share extensive sequence similarity. \ This family of proteins is named after the Salmonella typhimurium MutS protein that is involved in replication repair and plays a role in preventing recombination between non-identical sequences [MEDLINE:93288013]. \ Human MSH has been implicated in non-polyposis colorectal carcinoma (HNPCC) and is a mismatch binding protein.\ \

Mismatch repair contributes to the overall fidelity of DNA replication [MEDLINE:87297443]. It\ involves the correction of mismatched base pairs that have been missed by the\ proofreading element of the DNA polymerase complex. The sequence of some\ proteins involved in mismatch repair in different organisms have been found to\ be evolutionary related [MEDLINE:91330898], [MEDLINE:93288013].

\ \ ATP binding activity ; GO:0005524 \N mismatch repair ; GO:0006298 26121 IPR007692

This family includes the replicative DNA helicases (EC: 3.6.1.-), helicase DnaB, which exhibitDNA-dependent ATPase activity. Helicase DnaB is a homohexameric protein required for DNA replication. The homohexamer can form a ring around a single strand of DNA near a replication fork. An intein of more than 400 residues is found at a conserved location in DnaB of Synechocystis PCC6803, Rhodothermus marinus (both experimentally confirmed), and Mycobacterium tuberculosis. The intein removes itself by a self-splicing reaction. Replication protein, GP12 from Enterobacteria phage P22\ also belongs to this family.

\ \ ATP binding activity ; GO:0005524 \N DNA replication ; GO:0006260 26122 IPR007693

The hexameric helicase DnaB unwinds the DNA duplex at the Escherichia coli chromosome replication fork. Although the mechanism by which DnaB both couples ATP hydrolysis to translocation along DNA and denatures the duplex is unknown, a change in the quaternary structure of the protein involving dimerization of the N-terminal domain has been observed and may occur during the enzymatic cycle. This N-terminal domain is required both for interaction with other proteins in the primosome and for DnaB helicase activity.

\ ATP binding activity ; GO:0005524 \N DNA replication ; GO:0006260 26117 IPR007688

VirB proteins are suggested to act at the bacterial surface and there play an important role in directing t-DNA transfer to plant cells. VirB6 from Agrobacterium tumefaciens is an essential component of the type IV secretion machinery for T pilus formation and genetic transformation of plants. Absence of VirB6 leads to\ reduced cellular levels of VirB5 and VirB3, which were proposed to assist T pilus formation as minor component(s) or assembly\ factor(s), respectively.\

\ \ \N \N conjugation with cellular fusion ; GO:0000747 26118 IPR007689 Mating-type protein A-

specifies the A-

-Y mating type. The A-

-Y protein binds to the AalphaZ protein of another mating type in Schizophyllum commune [MEDLINE:97432792] and may also regulate gene expression of the homokaryotic cell.\ protein binding activity ; GO:0005515 \N regulation of transcription ; GO:0045449 26119 IPR007690 This is a family of membrane proteins involved in the secretion of a number of molecules in Gram-negative bacteria. The precise function of these proteins is unknown, though in Vibrio cholerae, the EpsM protein interacts with the EpsL protein, and also forms homodimers [MEDLINE:99255537].\ \N \N extracellular transport ; GO:0006858 26120 IPR007691 UDP-3-O-[3-hydroxymyristoyl] glucosamine N-acyltransferase (EC: 2.3.1.-) catalyses an early step in lipid A biosynthesis [MEDLINE:93374989]:

UDP-3-O-(3-hydroxytetradecanoyl)glucosamine + (R)-3-hydroxytetradecanoyl- [acyl carrier protein] = UDP-2,3-bis(3-hydroxytetradecanoyl)glucosamine + [acyl carrier protein]

Members of this family also contain a hexapeptide repeat (IPR001451). This entry represents the non-repeating region of LPXD proteins.\ transferase activity, transferring groups other than amino-acyl groups ; GO:0016747 \N lipid A biosynthesis ; GO:0009245 26116 IPR007687 Methyl coenzyme M reductase (MCR) catalyses the final step in methanogenesis. MCR is composed of three subunits,

(IPR003183) and gamma (IPR003183/>) [MEDLINE:97016827]. Genes encoding the

(mcrB) and gamma (mcrG) subunits are separated by two open reading frames coding for two proteins C and D [MEDLINE:89008091]. The function of proteins C and D is unknown.\ enzyme activity ; GO:0003824 \N methanogenesis ; GO:0015948 26115 IPR007686 This family represents a family of bacterial phosphatidylglycerophosphatases (EC: 3.1.3.27), known as PgpA. It appears that bacteria possess several phosphatidylglycerophosphatases, and thus, PgpA is not essential in Escherichia coli [MEDLINE:92104964].\ phosphatidylglycerophosphatase activity ; GO:0008962 \N lipid metabolism ; GO:0006629 26111 IPR007682 Lantibiotics are antibiotic peptides distinguished by the presence of the rare thioether amino acids lanthionine and/or methyllanthionine. They are produced by Gram-positive bacteria as gene-encoded precursor peptides and undergo post-translational modification to generate the mature peptide. Based on their structural and functional features lantibiotics are currently divided into two major groups: the flexible amphiphilic type-A and the rather rigid and globular type-B. Type-A lantibiotics act primarily by pore formation in the bacterial membrane by a mechanism involving the interaction with specific docking molecules such as the membrane precursor lipid II [MEDLINE:95324573].\ \N extracellular ; GO:0005576 secondary metabolism ; GO:0019748 26112 IPR007683 This domain is found in bacterial proteins associated with virulence. It consists of a conserved region found at the N terminus of the VapD protein [MEDLINE:93014173].\ \N \N viral transmission ; GO:0019089 26113 IPR007684 This is a viral family of phage zinc-binding transcriptional activators, which also contains cryptic members in some bacterial genomes [MEDLINE:92283767]. The P4 phage delta protein contains two such domains attached covalently, while the P2 phage Ogr proteins possess one domain but function as dimers. All the members of this family have the following consensus sequence: C-X(2)-C-X(3)-A-(X)2-R-X(15)-C-X(4)-C-X(3)-F [MEDLINE:97288307].\ transcription regulator activity ; GO:0030528 \N regulation of transcription ; GO:0045449 26114 IPR007685 The functions of Escherichia coli RelA and SpoT differ somewhat. RelA (EC: 2.7.6.5) produces pppGpp (or ppGpp) from ATP and GTP (or GDP). SpoT (EC: 3.1.7.2) degrades ppGpp,\ but may also act as a secondary ppGpp synthetase. The two proteins are strongly similar.\ In many species, a single homolog to SpoT and RelA appears reponsible for both ppGpp\ synthesis and ppGpp degradation. \

(p)ppGpp is a regulatory metabolite of the stringent response, but appears also to be\ involved in antibiotic biosynthesis in some species.

\ \ \N \N guanosine tetraphosphate (5'-ppGpp-3') metabolism ; GO:0015969 26103 IPR007674 Previously uncharacterised I6 protein binds tightly and with great specificity to the hairpin form of the viral telomeric sequence. This telomere binding protein is thought to play a role in the initiation of vaccinia virus genome replication and/or genome encapsidation [MEDLINE:21465032].\ \N \N viral life cycle ; GO:0016032 26104 IPR007675

Protein F15 is found in a number of Poxviruses.

\ \N \N \N 26105 IPR007676 Ribophorin I is an essential subunit of oligosaccharyltransferase (OST), which is also known as dolichyl-diphosphooligosaccharide--protein glycosyltransferase, (EC: 2.4.1.119). OST catalyses the transfer of an oligosaccharide from dolichol pyrophosphate to selected asparagine residues of nascent polypeptides as they are translocated into the lumen of the rough endoplasmic reticulum. Ribophorin I and OST48 are thought to be responsible for OST catalytic activity [MEDLINE:21336308]. Both yeast and mammalian proteins are glycosylated but the sites are not conserved. Glycosylation may contribute towards general solubility but is unlikely to be involved in a specific biochemical function [MEDLINE:95237386]. Most family members are predicted to have a transmembrane helix at the C terminus of this region.\ \N \N \N 26106 IPR007677 The precise function of this protein is unknown. A deletion/insertion mutation is associated with an autosomal dominant non-syndromic hearing impairment form [MEDLINE:98442658]. In addition, this protein has also been found to contribute to acquired etoposide resistance in melanoma cells [MEDLINE:21195330].\ \N \N \N 26107 IPR007678

Protein G5 is found in a number of Poxviruses.

\ \N \N \N 26108 IPR007679 This is a family of hypothetical proteins. Some family members contain two copies of the region.\ \N \N \N 26109 IPR007680 Arabinosyltransferase is involved in arabinogalactan (AG) biosynthesis pathway in mycobacteria. AG is a component of the macromolecular assembly of the mycolyl-AG-peptidoglycan complex of the cell wall. This enzyme has important clinical applications as it is believed to be the target of the antimycobacterial drug Ethambutol [MEDLINE:97030297].\ \N \N \N 26110 IPR007681 Segregation of nuclear and cytoplasmic processes facilitates regulation of many eukaryotic cellular functions such as gene expression and cell cycle progression. Trafficking through the nuclear pore requires a number of highly conserved soluble factors that escort macromolecular substrates into and out of the nucleus. The Mob1 protein has been shown to interact with RanGTP, which stimulates guanine nucleotide release, suggesting Mog1 regulates the nuclear transport functions of Ran. The human homologue of Mog1 is thought to be alternatively spliced.\ \N \N \N 26101 IPR007672 SelP is the only known eukaryotic selenoprotein that contains multiple selenocysteine (Sec) residues, and accounts for more than 50% of the selenium content of rat and human plasma [MEDLINE:20239644]. It is thought to be glycosylated [MEDLINE:21110713]. SelP may have antioxidant properties. It can attach to epithelial cells, and may protect vascular endothelial cells against peroxynitrite toxicity [MEDLINE:20239644]. The high selenium content of SelP suggests that it may be involved in selenium intercellular transport or storage [MEDLINE:21110713]. The promoter structure of bovine SelP suggests that it may be involved in countering heavy metal intoxication, and may also have a developmental function [MEDLINE:98019090]. The N-terminal region always contains one Sec residue, and this is separated from the C-terminal region (9-16 sec residues) by a histidine-rich sequence [MEDLINE:21110713]. The large number of Sec residues in the C-terminal portion of SelP suggests that it may be involved in selenium transport or storage. However, it is also possible that this region has a redox function [MEDLINE:21110713].\ \N \N \N 26102 IPR007673 Condensin is a multi-subunit protein complex that acts as an essential regulator of chromosome condensation. It contains both SMC (structural maintenance of chromosomes) and non-SMC subunits. This family represents one of the non-SMC subunits, known as Cnd1 in Schizosaccharomyces pombe, and XCAP-D2 in Xenopus laevis. This subunit is phosphorylated at several sites by Cdc2. This phosphorylation process increases the supercoiling activity of condensin [MEDLINE:98447791], [MEDLINE:99415811].\ \N \N \N 26093 IPR007664 This is a family of conserved Poxvirus A28 family proteins. Conserved region spans entire protein in the majority of family members.\ \N \N \N 26094 IPR007665 This is a family of proteins known to be involved in conjugal transfer. The TrbF protein is thought to compose part of the pilus required for transfer [MEDLINE:21835718].\ \N \N \N 26095 IPR007666 In archaea a novel type of glycolytic pathway exists that is deviant from the classical Embden-Meyerhof pathway. This pathway utilises two novel proteins: an ADP-dependent glucokinase and an ADP-dependent phosphofructokinase. This conserved region is present at the C-terminal of both these proteins. Interestingly this family contains sequences from higher eukaryotes.\ \N \N \N 26096 IPR007667 This is a family of proteins thought to be involved in the response to hypoxia. Family members mostly come from diverse eukaryotic organisms however eubacterial members have been identified. This region is found at the N terminus of the member proteins which are predicted to be transmembrane [MEDLINE:21117151].\ \N \N \N 26097 IPR007668 The RFX family is a family of winged-helix DNA-binding proteins. RFX1 is a regulatory factor essential for expression of MHC class II genes. This region is to found N-terminal to the RFX DNA-binding region (IPR003150.\ \N \N \N 26098 IPR007669 This family represents a conserved region, found in several Caenorhabditis elegans proteins.\ \N \N \N 26099 IPR007670 This family contains several uncharacterised proteins.\ \N \N \N 26100 IPR007671 SelP is the only known eukaryotic selenoprotein that contains multiple selenocysteine (Sec) residues, and accounts for more than 50% of the selenium content of rat and human plasma [MEDLINE:20239644]. It is thought to be glycosylated [MEDLINE:21110713]. SelP may have antioxidant properties. It can attach to epithelial cells, and may protect vascular endothelial cells against peroxynitrite toxicity [MEDLINE:20239644]. The high selenium content of SelP suggests that it may be involved in selenium intercellular transport or storage [MEDLINE:21110713]. The promoter structure of bovine SelP suggests that it may be involved in countering heavy metal intoxication, and may also have a developmental function [MEDLINE:98019090]. The N-terminal region of SelP can exist independently of the C-terminal region. Zebrafish selenoprotein Pb (Q98SV0.\ \N \N \N 26090 IPR007661 This is a family of uncharacterised proteins.\ \N \N \N 26091 IPR007662 Protein sigmaC in its native state was shown to be a homotrimer. It was demonstrated that the sigmaC subunits are not covalently bound via disulfide linkages and the formation of an intrachain disulfide bond between the two cysteine residues of the sigmaC polypeptide may have a negative effect on oligomer stability. The susceptibility of the trimer to pH, temperature, ionic strength, chemical denaturants and detergents indicates that hydrophobic interactions contribute much more to oligomer stability than do ionic interactions and hydrogen bonding [MEDLINE:21623843].\ \N \N \N 26092 IPR007663 Baculoviruses are distinct from other virus families in that there are two viral phenotypes: budded virus (BV) and occlusion-derived virus (ODV). BVs disseminate viral infection throughout the tissues of the host and ODVs transmit baculovirus between insect hosts. GFP tagging experiments implicate p74 as an ODV envelope protein [MEDLINE:90085829], [MEDLINE:21405833].\ \N \N viral infectious cycle ; GO:0019058 26081 IPR007652 The glycosphingolipids (GSL) form part of eukaryotic cell membranes. They consist of a hydrophilic carbohydrate moiety linked to a hydrophobic ceramide tail embedded within the lipid bilayer of the membrane. Lactosylceramide, Gal1,4Glc1Cer (LacCer), is the common synthetic precursor to the majority of GSL found in vertebrates. Alpha 1.4-glycosyltransferases utilise UDP donors and transfer the sugar to a

-linked acceptor. This region appears to be confined to higher eukaryotes. No function has been yet assigned to this region [MEDLINE:20400459].\ \N \N \N 26082 IPR007653 Translocation of polypeptide chains across the endoplasmic reticulum membrane is triggered by signal sequences. During translocation of the nascent chain through the membrane, the signal sequence of most secretory and membrane proteins is cleaved off. Cleavage occurs by the signal peptidase complex (SPC), which consists of four subunits in yeast and five in mammals. This family is common to yeast and mammals [MEDLINE:96216505], [MEDLINE:97294726].\ \N \N \N 26083 IPR007654 This region is found in some SIR2 proteins (IPR003000).\ \N \N \N 26084 IPR007655 This is a family of hypothetical bacterial proteins.\ \N \N \N 26085 IPR007656 This is a family of uncharacterised proteins.\ \N \N \N 26086 IPR007657 This is a family of uncharacterised proteins.\ \N \N \N 26087 IPR007658 This is a family of uncharacterised proteins.\ \N \N \N 26088 IPR007659 This is a family of keratins, high-sulphur matrix proteins. The keratin products of mammalian epidermal derivatives such as wool and hair consist of microfibrils embedded in a rigid matrix of other proteins. The matrix proteins include the high-sulphur and high-tyrosine keratins, having molecular weights of 6-20 kDa, whereas microfibrils contain the larger, low-sulphur keratins (40-56 kDa) [MEDLINE:73067712].\ \N \N \N 26089 IPR007660

This is a family of Chordopoxvirinae D3 protein. The conserved region occupies the entire length of D3 protein.

\ \N \N \N 26078 IPR007649 This entry represents a conserved region in a number of uncharacterised plant proteins.\ \N \N \N 26079 IPR007650 This is a family of uncharacterised proteins.\ \N \N \N 26080 IPR007651 Mutations in the lipin gene lead to fatty liver dystrophy in mice. The protein has been shown to be phosphorylated by the TOR Ser/Thr protein kinases in response to insulin stimulation. The conserved region is found at the N terminus of the member proteins [MEDLINE:20578762], [MEDLINE:21664391].\ \N \N \N 26073 IPR007644

RNA polymerases catalyse the DNA dependent polymerisation of RNA. Prokaryotes contain a single RNA polymerase compared to three in eukaryotes (not including mitochondrial and chloroplast polymerases). This domain forms one of the two distinctive lobes of the Rpb2 structure. This domain is also known as the protrusion domain [MEDLINE:88011299]. The other lobe, RNA polymerase Rpb2, domain 2, is nested within this domain.

\ \N \N \N 26074 IPR007645 RNA polymerases catalyse the DNA dependent polymerisation of RNA. Prokaryotes contain a single RNA polymerase compared to three in eukaryotes (not including mitochondrial and chloroplast polymerases). Domain 3, is also known as the fork domain and is proximal to catalytic site [MEDLINE:21291401].\ \N \N \N 26075 IPR007646 RNA polymerases catalyse the DNA dependent polymerisation of RNA. Prokaryotes contain a single RNA polymerase compared to three in eukaryotes (not including mitochondrial and chloroplast polymerases). Domain 4, is also known as the external 2 domain [MEDLINE:21291401].\ \N \N \N 26076 IPR007647 RNA polymerases catalyse the DNA dependent polymerisation of RNA. Prokaryotes contain a single RNA polymerase compared to three in eukaryotes (not including mitochondrial and chloroplast polymerases). Domain 5, is also known as the external 2 domain [MEDLINE:21291401].\ \N \N \N 26077 IPR007648 ATP synthase inhibitor prevents the enzyme from switching to ATP hydrolysis during collapse of the electrochemical gradient, for example during oxygen deprivation [MEDLINE:97121257] ATP synthase inhibitor forms a one-to-one complex with the F1 ATPase, possibly by binding at the

interface. It is thought to inhibit ATP synthesis by preventing the release of ATP. The minimum inhibitory region for bovine inhibitor (P01096.\ \N \N \N 26064 IPR007635 All proteins of this entry contain a tandem repeat of CCCH zinc fingers (IPR000571). Tis11B, Tis11D and their homologues are thought to be regulatory proteins involved in the response to growth factors. The function of the C terminus is unknown.\ \N \N \N 26065 IPR007636 This family consists of type II restriction enzymes (EC: 3.1.21.4) that recognise the double-stranded sequence CTCGAG and cleave after C-1.\ \N \N \N 26066 IPR007637 Members of this family are type II restriction enzymes (EC: 3.1.21.4). They recognise the double-stranded unmethylated sequence GATC and cleave before G-1 [MEDLINE:20576151].\ \N \N \N 26067 IPR007638 This is a region found N-terminal to the catalytic domain of glutaminyl-tRNA synthetase (EC: 6.1.1.18) in eukaryotes but not in Escherichia coli. This region is thought to bind RNA in a non-specific manner, enhancing interactions between the tRNA and enzyme, but is not essential for enzyme function [MEDLINE:99278425].\ \N \N \N 26068 IPR007639 This is a region found N-terminal to the catalytic domain of glutaminyl-tRNA synthetase (EC: 6.1.1.18) in eukaryotes but not in Escherichia coli. This region is thought to bind RNA in a non-specific manner, enhancing interactions between the tRNA and enzyme, but is not essential for enzyme function [MEDLINE:99278425].\ \N \N \N 26069 IPR007640 UL17 protein is required for DNA cleavage and packaging in herpes viruses. It has been shown to associate with immature B-type capsids [MEDLINE:20214228], and is required for the localisation of capsids and capsid proteins to the intranuclear sites where viral DNA is cleaved and packaged [MEDLINE:99092481]. In the virion, UL17 is a component of the tegument, which is a protein layer surrounding the viral capsid [MEDLINE:98216738].\ \N virion ; GO:0019012 DNA packaging ; GO:0006323 26070 IPR007641

RNA polymerases catalyse the DNA-dependent polymerisation of RNA. Prokaryotes contain a single RNA polymerase compared to three in eukaryotes (not including mitochondrial and chloroplast polymerases). Rpb2 is the second largest subunit of the RNA polymerase. This domain comprised of the structural domains anchor and clamp. The clamp region (C-terminal) contains a zinc-binding motif. The clamp region is named due to its interaction with the clamp domain found in Rpb1. The domain also contains a region termed switch 4. The switches within the polymerase are thought to signal different stages of transcription [MEDLINE:21291401].

\ \N \N \N 26071 IPR007642

RNA polymerases catalyse the DNA-dependent polymerisation of RNA. Prokaryotes contain a single RNA polymerase compared to three in eukaryotes (not including mitochondrial and chloroplast polymerases). Rpb2 is the second largest subunit of the RNA polymerase. This domain forms one of the two distinctive lobes of the Rpb2 structure. This domain is also known as the lobe domain [MEDLINE:21291401]. DNA has been demonstrated to bind to the concave surface of the lobe domain, and plays a role in maintaining the transcription bubble. Many of the bacterial members contain large insertions within this domain, a region known as dispensable region 1 (DRI).

\ \N \N \N 26072 IPR007643 The Dictyostelium discoideum spore coat is a polarised extracellular matrix composed of glycoproteins and cellulose. Four of the major coat glycoproteins exist as a multi-protein complex within the prespore vesicles before secretion. Of these, SP96 and SP70 are members of this family. The presence of SP96 and SP70 in the complex is necessary for the cellulose binding activity of the complex, which is in turn necessary for normal spore coat assembly [MEDLINE:20391829]. The function of this region is not known.\ \N \N \N 26060 IPR007631 The domain is found in the primary vegetative sigma factor. The function of this domain is unclear.\ \N \N \N 26061 IPR007632 This family contains several uncharacterised eukaryotic proteins.\ \N \N \N 26062 IPR007633 Holins are a diverse family of proteins that cause bacterial membrane lysis during late-protein synthesis. It is thought that the temporal precision of holin-mediated lysis may occur through the build-up of a holin oligomer which causes the lysis [MEDLINE:21374369].\ \N \N \N 26063 IPR007634 This DNA-binding domain is based on peptide fragmentation data. This domain is proximal to DNA in the promoter/holoenzyme complex. Furthermore, this region contains a putative helix-turn-helix motif. At the C terminus, there is a highly conserved region known as the RpoN box and is the signature of the sigma-54 proteins [MEDLINE:20353443].\ \N \N \N 26059 IPR007630 Region 4 of sigma-70 like sigma-factors is involved in binding to the -35 promoter element via a helix-turn-helix motif [MEDLINE:21930343]. Due to the way Pfam works, the threshold has been set artificially high to prevent overlaps with other helix-turn-helix families. Therefore there are many false negatives.\ \N \N \N 26054 IPR007625 UL51 protein is a virion protein. In pseudorabies virus, UL51 (Q85227.\ \N \N \N 26055 IPR007626 This protein is known as R50 in cytomegalovirus.\ \N \N \N 26056 IPR007627 Region 2 of sigma-70 is the most conserved region of the entire protein. All members of this class of sigma-factor contain region 2. The high conservation is due to region 2 containing both the -10 promoter recognition helix and the primary core RNA polymerase binding determinant. The core-binding helix, interacts with the clamp domain of the largest polymerase subunit,

prime [MEDLINE:21930343], [MEDLINE:97011145]. The aromatic residues of the recognition helix, found at the C terminus of this domain are thought to mediate strand separation, thereby allowing transcription initiation [MEDLINE:21930343], [MEDLINE:97011145].\ \N \N \N 26057 IPR007628 This is a family of uncharacterised proteins.\ \N \N \N 26058 IPR007629 UL20 is predicted to be a transmembrane protein with multiple membrane spans. It is involved in the trans-cellular transport of enveloped virions, and is therefore important for viral egress. However, UL20 operates in different cellular compartments and different stages of egress in pseudorabies virus and herpes simplex virus. This is thought to be due to differences in egress pathways between these two viruses [MEDLINE:97332407].\ \N \N viral assembly, maturation, egress, and release ; GO:0019067 26031 IPR007602 This family includes NS2 proteins from other members of the Orbivirus genus. NS2 is a non-specific single-stranded RNA-binding protein that forms large homomultimers and accumulates in viral inclusion bodies of infected cells. Three RNA-binding regions have been identified in Bluetongue virus serotype 17 (P33473.\ RNA binding activity ; GO:0003723 \N \N 26032 IPR007603 This is a family of uncharacterised proteins.\ \N \N \N 26033 IPR007604 This entry represents a conserved region in the CP2 transcription factor family.\ \N \N \N 26034 IPR007605 E protein causes host cell lysis by inhibiting MraY, a peptidoglycan biosynthesis enzyme. This leads to cell wall failure at septation [MEDLINE:22096008]. The N-terminal transmembrane region matches the signal peptide model and must be omitted from the family.\ \N \N \N 26035 IPR007606 This family contains several uncharacterised chlamydial proteins.\ \N \N \N 26036 IPR007607 This family contains several uncharacterised hypothetical proteins.\ \N \N \N 26037 IPR007608 This family contains several uncharacterised proteins.\ \N \N \N 26038 IPR007609

This family represents the 18kD cysteine-rich protein from ssRNA positive strand viruses.

\ \N \N \N 26039 IPR007610

This region represents the N-termini of bromovirus 2a protein, and is always found N-terminal to a predicted RNA dependent RNA polymerase region (IPR001788).

\ \N \N \N 26040 IPR007611 This family is named after the human herpesvirus protein, but has been characterised in cytomegalovirus as UL47. Cytomegalovirus UL47 is a component of the tegument, which is a protein layer surrounding the viral capsid. UL47 co-precipitates with UL48 and UL69 tegument proteins, and the major capsid protein UL86. A UL47-containing complex is thought to be involved in the release of viral DNA from the disassembling virus particle [MEDLINE:21635483].\ \N \N viral assembly ; GO:0019068 26041 IPR007612 This is a family of plant and bacterial uncharacterised proteins.\ \N \N \N 26042 IPR007613 This is a family of uncharacterised plant proteins.\ \N \N \N 26043 IPR007614 This is a domain of Drosophila proteins related to the C-terminal region of the fly Retinin protein. Conserved region is found towards the C terminus of the member proteins.\ \N \N \N 26044 IPR007615 This is a conserved region found in the Adenovirus E4 34 kDa protein.\ \N \N \N 26045 IPR007616 The proteins in this family have no known function. Cytomegalovirus UL88 is also a member of this family.\ \N \N \N 26046 IPR007617 This is a family of ssRNA positive-strand viral proteins. Conserved region is found in the Beta C and Beta D transcripts.\ \N \N \N 26047 IPR007618 This domain is found at the N-termini of some human herpesvirus U58 proteins, and some cytomegalovirus UL87 proteins. This region is always found N-terminal to the UL87 (IPR004285), which has no known function.\ \N \N \N 26048 IPR007619 In cytomegalovirus this protein is known as UL71. This family of proteins has no known function.\ \N \N \N 26049 IPR007620 In herpes simplex virus type 2, UL56 is thought to be a tail-anchored type II membrane protein involved in vesicular trafficking. The C-terminal hydrophobic region is required for association with the cytoplasmic membrane, and the N-terminal proline-rich region is important for the translocation of UL56 to the Golgi apparatus and cytoplasmic vesicles [MEDLINE:22045650].\ \N \N \N 26050 IPR007621 This is a family of uncharacterised proteins. They are found in both eukarya and eubacteria. In eubacteria the region is towards the N-terminal of the protein and is accompanied by an N-terminal signal sequence. The C-terminal of eubacterial proteins typically contains one or more putative transmembrane regions. In eukaryotes the region is not accompanied by a signal sequence.\ \N \N \N 26051 IPR007622 In infected cells, UL55 is associated with the nuclear matrix, and found adjacent to compartments containing the capsid protein ICP35. UL55 was not detected in assembled virions. It is thought that UL55 may play a role in virion assembly or maturation [MEDLINE:98378050].\ \N \N viral assembly, maturation, egress, and release ; GO:0019067 26052 IPR007623

This family includes the human p75NTR-associated cell death executor (Nerve growth factor receptor associated protein 1), which may be a signalling adaptor molecule involved in p75NTR-apoptosis induced by nerve growth factor. It may be important in neurogenetic diseases.

\ \N \N \N 26053 IPR007624 Region 3 forms a discrete compact three helical domain within the sigma-factor. Region is not normally involved in the recognition of promoter DNA, but in some specific bacterial promoters containing an extended -10 promoter element, residues within region 3 play an important role. Region 3 primarily is involved in binding the core RNA polymerase in the holoenzyme [MEDLINE:21930343].\ \N \N \N 26016 IPR007587

This family includes a conserved region from a group of yeast proteins that associate with the SIT4 phosphatase. This association is required for SIT4's role in G1 cyclin transcription and for bud formation. This family also includes homologous regions from other eukaryotes.

\ \N \N \N 26017 IPR007588

This domain is a potential FLYWCH Zn-finger found in a number of eukaryotic proteins.

\ \N \N \N 26018 IPR007589 This family constitutes the 39 kDa major capsid protein of the Baculoviridae [MEDLINE:89130948].\ structural molecule activity ; GO:0005198 viral capsid ; GO:0019028 \N 26019 IPR007590 This is a family of eukaryotic proteins with undetermined function.\ \N \N \N 26020 IPR007591 This is a family of eukaryotic single-stranded DNA binding-proteins with specificity to a pyrimidine-rich element found in the promoter region of the alpha2(I) collagen gene.\ \N \N \N 26021 IPR007592 This is a family of uncharacterised proteins.\ \N \N \N 26022 IPR007593 This family includes the human leukocyte antigen CD225, which is an interferon inducible transmembrane protein, and is associated with interferon induced cell growth suppression [MEDLINE:96007544].\ \N \N \N 26023 IPR007594

RFT is an integral membrane protein involved in nuclear division.

\ \N \N \N 26024 IPR007595 This family contains several uncharacterised staphylococcal proteins.\ \N \N \N 26025 IPR007596 The repeat is found in the A-type inclusion protein of the Poxvirus family [MEDLINE:88089536].\ \N \N viral life cycle ; GO:0016032 26026 IPR007597 The precise function of these proteins is unclear, but some of them are involved in flagella motor switch [MEDLINE:21580208]. The region represented in this entry is found in the CheC, CheX, CheA and FliY proteins. In some cases, this region is repeated in multiple copies.\ \N \N \N 26027 IPR007598 This is a family of Arabidopsis thaliana proteins. Many of these members contain a repeated region.\ \N \N \N 26028 IPR007599

The endoplasmic reticulum (ER) of the yeast Saccharomyces cerevisiae contains a proteolytic system able to selectively degrade misfolded lumenal secretory proteins. For examination of the components involved in this degradation process, mutants were isolated. They could be divided into four complementation groups. The mutations led to stabilization of two different substrates for this process, and the classes were called der for degradation in the ER. DER1 was cloned by complementation of the der1-2 mutation. The DER1 gene codes for a novel, hydrophobic protein that is localized to the ER. Deletion of DER1 abolished degradation of the substrate proteins, suggesting that the function of the Der1 protein may be specifically required for the degradation process associated with the ER [MEDLINE:96181354]. Interestingly this family seems distantly related to the Rhomboid family of membrane peptidases. This family may also mediate degradation of misfolded proteins.

\ \N \N \N 26029 IPR007600 Polyhedra are large crystalline occlusion bodies containing nucleopolyhedrovirus virions, and surrounded by an electron-dense structure called the polyhedron envelope or polyhedron calyx. The polyhedron envelope (associated) protein PEP is thought to be an integral part of the polyhedron envelope. PEP is concentrated at the surface of polyhedra, and is thought to be important for the proper formation of the periphery of polyhedra. It is thought that PEP may stabilise polyhedra and protect them from fusion or aggregation [MEDLINE:94231162].\ \N \N \N 26030 IPR007601 Polyhedra are large crystalline occlusion bodies containing nucleopolyhedrovirus virions, and surrounded by an electron-dense structure called the polyhedron envelope or polyhedron calyx. The polyhedron envelope (associated) protein PEP is thought to be an integral part of the polyhedron envelope. PEP is concentrated at the surface of polyhedra, and is thought to be important for the proper formation of the periphery of polyhedra. It is thought that PEP may stabilise polyhedra and protect them from fusion or aggregation [MEDLINE:94231162].\ \N \N \N 26007 IPR007578 This is a protein of unknown function, found in herpesvirus and cytomegalovirus.\ \N \N \N 26008 IPR007579

Poxvirus T4 protein is thought to be retained in the endoplasmic reticulum. M-T4 of myxoma virus (O55698.

\ \N \N \N 26009 IPR007580

Poxvirus T4 protein is thought to be secreted or retained in the endoplasmic reticulum if the protein also contains an additional C-terminal region (IPR007579.

\ \N \N \N 26010 IPR007581 Endonuclease V is specific for single-stranded DNA or for duplex DNA that contains uracil or that is damaged by a variety of agents [MEDLINE:97144513].\ \N \N \N 26011 IPR007582 This region, possibly a domain is found in subunits of transcription factor TFIID. The function of this region is unknown.\ \N \N \N 26012 IPR007583 GRASP55 (Golgi reassembly stacking protein of 55 kDa) and GRASP65 (a 65 kDa) protein are highly homologous. GRASP55 is a component of the Golgi stacking machinery. GRASP65, an N-ethylmaleimide-sensitive membrane protein required for the stacking of Golgi cisternae in a cell-free system [MEDLINE:99417576].\ \N \N \N 26013 IPR007584 UL35 represents a true late gene which encodes a 12 kDa capsid protein [MEDLINE:92219347].\ \N viral capsid ; GO:0019028 \N 26014 IPR007585 Protein E2 is a viral encoded protein that can complex with protein E1. Only when the Protein E1, a helicase, is bound by E2, can the origin of DNA replication be located. Protein E2 can also interact directly with host transcription factors in basal keratinocytes to promote viral transcription [MEDLINE:21964445].\ \N \N \N 26015 IPR007586 The 25 kDa product of Vaccinia virus gene L4R is also known as VP8. VP8 is found in the cores of Vaccinia virions and is essential for the formation of transcriptionally competent viral particles. It binds both single stranded and double stranded DNA and RNA with similar affinities. Binding is thought to involve cooperative interactions between protein subunits. The protein is proteolytically cleaved during viral assembly at an Ala-Gly-Ala site. Possible roles for VP8 include packaging and maintaining the DNA genome in a transcribable configuration; binding ssDNA during transcription initiation; and cooperation with I8R protein to unwind early promoter regions. VP8 may also function in either transcription elongation or release of mRNA molecules from viral particles [MEDLINE:97465939].\ structural molecule activity ; GO:0005198 viral capsid ; GO:0019028 \N 25986 IPR007555 This is a family of uncharacterised hypothetical prokaryotic proteins.\ \N \N \N 25987 IPR007556 This is a family of uncharacterised prokaryotic proteins.\ \N \N \N 25988 IPR007557 This region is present in both eukaryotes and eubacteria. The yeast PSP1 protein is involved in suppressing mutations in the DNA polymerase

subunit in yeast [MEDLINE:98190324].\ \N \N \N 25989 IPR007560 This is a prokaryotic family found in type II restriction enzymes containing the hallmark (D/E)-(D/E)XK active site. Presence of catalytic residues implicates this region in the enzymatic cleavage of DNA [MEDLINE:91317743], [MEDLINE:21213902].\ \N \N \N 25990 IPR007561 This is a family of uncharacterised proteins.\ \N \N \N 25991 IPR007562 This is a family of uncharacterised archaeal proteins.\ \N \N \N 25992 IPR007563

This is a family of uncharacterised prokaryotic proteins. Multiple predicted transmembrane regions suggest that the protein is membrane associated.

\ \N \N \N 25993 IPR007564 This is a family of uncharacterised, hypothetical archaeal proteins.\ \N \N \N 25994 IPR007565 This is a family of uncharacterised, hypothetical prokaryotic proteins.\ \N \N \N 25995 IPR007566 This is a family of uncharacterised, hypothetical archaeal proteins.\ \N \N \N 25996 IPR007567 This family represents a region near the C terminus of Mid2, which contains a transmembrane region. The remainder of the protein sequence is serine-rich and of low complexity, and is therefore impossible to align accurately. Mid2 is thought to act as a mechanosensor of cell wall stress. The C-terminal cytoplasmic region of Mid2 is known to interact with Rom2, a guanine nucleotide exchange factor (GEF) for Rho1, which is part of the cell wall integrity signalling pathway.\ \N \N \N 25997 IPR007568 This family is comprised of fungal proteins with multiple transmembrane regions. RTA1 (P53047.\ \N \N \N 25998 IPR007569 This is a family of uncharacterised proteins.\ \N \N \N 25999 IPR007570 This is a protein of unknown function found in a cyanobacterium, and the chloroplasts of algae.\ \N \N \N 26000 IPR007571 This is a protein of unknown function found in algal chloroplasts and in a cyanobacterium.\ \N \N \N 26001 IPR007572 This is a predicted transmembrane protein found in plants, chloroplasts and cyanobacteria. This family is also known as YCF20.\ \N \N \N 26002 IPR007573 This is a family of related proteins that is plant specific.\ \N \N \N 26003 IPR007574 In the cyanobacterium Synechococcus species PCC 7942 (P35087), nblA triggers degradation of light-harvesting phycobiliproteins in response to deprivation nutrients including nitrogen, phosphorus and sulphur. The mechanism of nblA function is not known, but it has been hypothesised that nblA may act by disrupting phycobilisome structure, activating a protease or tagging phycobiliproteins for proteolysis. Members of this family have also been identified in the chloroplasts of some red algae.\ \N \N \N 26004 IPR007575 Members of this family have only been identified in species of the Streptomyces genus. Two family members are known to be part of gene clusters involved in the synthesis of polyketide-based spore pigments, homologous to clusters involved in the synthesis of polyketide antibiotics. The function of this protein is unknown, but it has been speculated to contain a NAD(P) binding site [MEDLINE:93345807].\ \N \N \N 26005 IPR007576 CITED, CBP/p300-interacting transactivator with ED-rich tail, is characterised by a conserved 32-amino acid sequence at the C terminus. CITED protein does not bind DNA directly and is thought to function as a transcriptional co-activator [MEDLINE:21864169].\ \N \N \N 26006 IPR007577 The DXD motif is a short conserved motif found in many families of glycosyltransferases, which add a range of different sugars to other sugars, phosphates and proteins. DXD-containing glycosyltransferases all use nucleoside diphosphate sugars as donors and require divalent cations, usually manganese. The DXD motif is expected to play a carbohydrate binding role in sugar-nucleoside diphosphate and manganese dependent glycosyltransferases [MEDLINE:98318591].\ \N \N \N 25976 IPR007545 Lysine-oxoglutarate reductase/Saccharopine dehydrogenase (LOR/SDH) is a bifunctional enzyme. This conserved region is commonly found immediately N-terminal to saccharopine dehydrogenase conserved region (IPR005097.\ \N \N \N 25977 IPR007546 This is a family of hypothetical bacterial proteins.\ \N \N \N 25978 IPR007547 This is a family of uncharacterised proteins.\ \N \N \N 25979 IPR007548 This is a family of uncharacterised prokaryotic proteins.\ \N \N \N 25980 IPR007549

This is a family of uncharacterised prokaryotic proteins. It is often found C-terminal to the radical SAM domain (IPR007197).

\ \N \N \N 25981 IPR007550 This is a family of hypothetical bacterial proteins. It is a possible zinc finger at N terminus.\ \N \N \N 25982 IPR007551 This is a family of uncharacterised proteins.\ \N \N \N 25983 IPR007552 This is a family of hypothetical prokaryotic proteins.\ \N \N \N 25984 IPR007553 This is a family of uncharacterised bacterial proteins.\ \N \N \N 25985 IPR007554 Wall-associated teichoic acids are a heterogeneous class of phosphate-rich polymers that are covalently linked to the cell wall peptidoglycan of gram-positive bacteria. They consist of a main chain of phosphodiester-linked polyols and/or sugar moieties attached to peptidoglycan via a linkage unit. CDP-glycerol:poly(glycerophosphate) glycerophosphotransferase is responsible for the polymerisation of the main chain of the teichoic acid by sequential transfer of glycerol-phosphate units from CDP-glycerol to the linkage unit lipid [MEDLINE:20115549].\ \N \N \N 25974 IPR007543 This family is involved in organic solvent tolerance in bacteria. The region contains several highly conserved, potentially catalytic, residues [MEDLINE:95110156].\ \N \N \N 25975 IPR007544 Many Gram-positive bacteria produce antimicrobial peptides, generally termed bacteriocins. These peptides are usually cationic, less than 50 amino acid residues long, contain an amphiphilic or hydrophobic region, and often kill their target cells by permeabilizing the cell membrane. Antimicrobial peptides with these characteristics are also produced by plants and a wide variety of animals, including humans, and are thus widely distributed in nature. The Linocin_M18 region is found mostly in eubacteria, though homologous sequences have been identified in archaea [MEDLINE:97077222], [MEDLINE:95077379].\ \N \N \N 25966 IPR007535

This domain is the N-terminal region of catechol, chlorocatechol or hydroxyquinol 1,2-dioxygenase proteins. This region is always found adjacent to the dioxygenase domain (IPR000627).

\ \N \N \N 25967 IPR007536 This is a protein of unknown function found in proteobacteria. In Salmonella typhimurium, expression of this protein is regulated by heat shock [MEDLINE:20096699].\ \N \N \N 25973 IPR007542 This family includes the major capsid protein of iridoviruses, chlorella virus and Spodoptera ascovirus, which are all dsDNA viruses with no RNA stage. This is the most abundant structural protein and can account for up to 45% of virion protein [MEDLINE:99180426]. In Chlorella virus PBCV-1 the major capsid protein is a glycoprotein [MEDLINE:92230218].\ structural molecule activity ; GO:0005198 viral capsid ; GO:0019028 \N 25972 IPR007541 These basic secretory proteins (BSPs) are believed to be part of the plants defence mechanism against pathogens [MEDLINE:99219139].\ \N \N \N 25971 IPR007540 Fimbriae, also known as pili, form filaments radiating from the surface of the bacterium to a length of 0.5-1.5 micrometres. They enable the cell to colonise host epithelia. This family constitutes the major subunits of CS1 like pili, including CS2 and CFA1 from Escherichia coli, and also the Cable type II pilin major subunit from Burkholderia cepacia [MEDLINE:99140427]. The major subunit of CS1 pili is called CooA. Periplasmic CooA is mostly complexed with the assembly protein CooB. In addition, a small pool of CooA multimers, and CooA-CooD complexes exists, but the functional significance is unknown [MEDLINE:99140427]. A member of this family has also been identified in Salmonella typhi and Salmonella enterica [MEDLINE:99348391].\ \N \N \N 25969 IPR007538 This entry represents the N terminus of a protein of unknown function, found in dsDNA viruses with no RNA stage, including bacteriophages lambda and P22, and also in some Escherichia coli prophages.\ \N \N \N 25970 IPR007539 This entry represents the C terminus of a protein of unknown function, found in dsDNA viruses with no RNA stage, including bacteriophages lambda and P22, and also in some Escherichia coli prophages.\ \N \N \N 25968 IPR007537 This is a family of uncharacterised eukaryotic proteins.\ \N \N \N 25957 IPR007526 This SWIRM domain is a small

-helical domain of about 85 amino acid residues found in chromosomal proteins. This domain is predicted to be a protein-protein interaction unit.\ \N \N \N 25958 IPR007527

The SWIM Zn-chelating domain is found in a variety of prokaryotic and eukaryotic proteins, including mitogen-activated protein kinase kinase kinase 1 and several hypothetical proteins.

\ \N \N \N 25959 IPR007528 This family includes RINT-1, a Rad50 interacting protein which participates in radiation induced checkpoint control [MEDLINE:21125812], as well as the TIP-1 protein from yeast that seems to be involved in a complex with Sec20p that is required for golgi transport [MEDLINE:93327772].\ \N \N \N 25960 IPR007529

This presumed zinc finger contains up to 6 cysteine residues that could coordinate zinc. The domain is named after the HIT protein P46973, that specifically interacts with the ligand binding domain of the thyroid receptor.

\ \N \N \N 25961 IPR007530

Also known as aminoglycoside 6-adenylyltransferase (EC: 2.7.7.-), this protein confers resistance to aminoglycoside antibiotics.

\ \N \N \N 25962 IPR007531 This is a family of uncharacterised proteins from the hypothalamus.\ \N \N \N 25963 IPR007532 The poxvirus early transcription factor (VETF), in addition to the viral RNA polymerase, is required for efficient transcription of early genes in vitro. VETF is a heterodimeric protein that binds specifically to early gene promoters. The heterodimer is comprised of an 82 kDa (this family) subunit and a 70 kDa subunit.\ transcriptional activator activity ; GO:0016563 \N positive regulation of transcription ; GO:0045941 25964 IPR007533 Cytochrome c oxidase assembly protein is essential for the assembly of functional cytochrome oxidase protein. In eukaryotes it is an integral protein of the mitochondrial inner membrane. Cox11 is essential for the insertion of Cu(I) ions to form the CuB site. This is essential for the stability of other structures in subunit I, for example haems a and a3, and the magnesium/manganese centre. Cox11 is probably only required in sub-stoichiometric amounts relative to the structural units [MEDLINE:20085086]. The C-terminal region of the protein is known to form a dimer. Each monomer coordinates one Cu(I) ion via three conserved cysteine residues (111, 208 and 210) in Saccharomyces cerevisiae (P19516.\ \N \N \N 25965 IPR007534 LuxE is an acyl-protein synthetase found in bioluminescent bacteria. LuxE catalyses the formation of an acyl-protein thiolester from a fatty acid and a protein. This is the second step in the bioluminescent fatty acid reduction system, which converts tetradecanoic acid to the aldehyde substrate of the luciferase-catalysed bioluminescence reaction [MEDLINE:97096327]. A conserved cysteine found at position 364 in Photobacterium phosphoreum LuxE (Q52100), which is involved in the biosynthesis of the O-antigen component 3-deoxy-L-glycero-tetronic acid.\ \N \N \N 25955 IPR007524 This region is found N-terminal to the pectate lyase domain (IPR002022) in some plant pectate lyase enzymes.\ \N \N \N 25956 IPR007525

Coenzyme F420 hydrogenase (EC: 1.12.99.1) reduces the low-potential two-electron acceptor coenzyme F420. This family contains the C-termini of F420 hydrogenase and dehydrogenase subunits [MEDLINE:91002562], [MEDLINE:20309738]. The C terminus of Methanobacterium formicicum formate dehydrogenase chain (EC: 1.2.1.2, P06130.

\ \N \N \N 25949 IPR007518 This is a eukaryotic protein of unknown function.\ \N \N \N 25950 IPR007519

This domain is the N terminus of Saccharomyces cerevisiae Bul1. Bul1 binds the ubiquitin ligase Rsp5, via an N-terminal PPSY motif (157-160 in P48524.

\ \N \N \N 25951 IPR007520

This domain is the C terminus of Saccharomyces cerevisiae Bul1. Bul1 binds the ubiquitin ligase Rsp5, via an N-terminal PPSY motif (157-160 in P48524.

\ \N \N \N 25944 IPR007513 Members of this family are short proteins that are rich in aspartate, glutamate, lysine and arginine. Although the function of these proteins is unknown, they are found to be ubiquitously expressed [MEDLINE:98400264].\ \N \N \N 25945 IPR007514 Members of this family are probably coiled-coil proteins that are similar to the CHD5 (Congenital heart disease 5) protein. The exact molecular function of these eukaryotic proteins is unknown.\ \N \N \N 25946 IPR007515

Guanine nucleotide exchange factor MSS4 (Rab interacting factor) is a guanine-nucleotide releasing protein that acts on members of the SCE4/YPT1/RAB subfamily. It stimulates release of GDP and may play a role in vesicular transport.

\ \N \N \N 25947 IPR007516

Coenzyme F420 hydrogenase (EC: 1.12.99.1) reduces the low-potential two-electron acceptor coenzyme F420. This entry contains the N termini of F420 hydrogenase and dehydrogenase subunits [MEDLINE:91002562], [MEDLINE:20309738]. The N terminus of Methanobacterium formicicum formate dehydrogenase chain (EC: 1.2.1.2, P06130.

\ \N \N \N 25948 IPR007517 The Mre11 complex (Mre11 Rad50 Nbs1) is central to chromosomal maintenance and functions in homologous recombination, telomere maintenance and sister chromatid association. The Rad50 coiled-coil region contains a dimer interface at the apex of the coiled coils in which pairs of conserved Cys-X-X-Cys motifs form interlocking hooks that bind one Zn ion. This alignment includes the zinc hook motif and a short stretch of coiled-coil on either side.\ \N \N \N 25952 IPR007521

This domain is found N-terminal to choline/ethanolamine kinase regions (IPR002573). This region is only found in some members of the choline kinase family, and is therefore unlikely to contribute to catalysis.

\ \N \N \N 25953 IPR007522 This is a protein of unknown function.\ \N \N \N 25954 IPR007523

This is a family of uncharacterised proteins possibly involved in DNA repair.

\ \N \N \N 25929 IPR007498

Paraquat is a superoxide radical-generating agent. The promoter for the pqiA gene is also inducible by other known superoxide generators [MEDLINE:95270582]. This is predicted to be a family of integral membrane proteins, possibly located in the inner membrane. This family is related to NADH dehydrogenase subunit 2 (IPR001750).

\ \N \N \N 25930 IPR007499 The DNA single-strand annealing proteins (SSAPs), such as RecT, Red-

, ERF and Rad52, function in RecA-dependent and RecA-independent DNA recombination pathways. This family includes proteins related to ERF PUB00009986.\ \N \N \N 25931 IPR007500

This domain is always found in conjunction with the HHE domain (IPR005544) at the N terminus.

\ \N \N \N 25932 IPR007501 This is a family of hypothetical archaeal proteins.\ \N \N \N 25933 IPR007502 This presumed domain is about 90 amino acid residues in length. It is found as a diverse set of RNA helicases. Its function is unknown, however it seems likely to be involved in nucleic acid binding.\ \N \N \N 25934 IPR007503 This is a family of hypothetical archaeal proteins.\ \N \N \N 25935 IPR007504 Gar1 is a small nucleolar RNP that is required for pre-mRNA processing and pseudouridylation [MEDLINE:20155000]. It is co-immunoprecipitated with the H/ACA families of snoRNAs. This family represents the conserved central region of Gar1. This region is necessary and sufficient for normal cell growth, and specifically binds two snoRNAs snR10 and snR30. This region is also necessary for nucleolar targeting, and it is thought that the protein is co-transported to the nucleolus as part of a nucleoprotein complex [MEDLINE:98225155]. In humans, Gar1 is also component of telomerase in vivo [MEDLINE:20221550].\ \N \N \N 25926 IPR007495 This is a family of putative periplasmic proteins.\ \N \N \N 25927 IPR007496

This is an uncharacterised bacterial integral membrane protein, possibly involved in cysteine biosynthesis. It is speculated to be involved in sulphate transport.

\ \N \N \N 25928 IPR007497 Members of this family have so far been found in bacteria and mouse SwissProt or TrEMBL entries. However possible family members have also been identified in translated rat (GenBank:AW144450) and human (GenBank:AI478629) ESTs. A mouse family member has been named SIMPL (signalling molecule that associates with mouse pelle-like kinase). SIMPL appears to facilitate and/or regulate complex formation between IRAK/mPLK (IL-1 receptor-associated kinase) and IKK (inhibitor of kappa-B kinase) containing complexes, and thus regulate NF-kappa-B activity [MEDLINE:21269335]. Separate experiments demonstrate that a mouse family member (named LaXp180) binds the Listeria monocytogenes surface protein ActA, which is a virulence factor that induces actin polymerisation. It may also bind stathmin, a protein involved in signal transduction and in the regulation of microtubule dynamics [MEDLINE:21128561]. In bacteria its function is unknown, but it is thought to be located in the periplasm or outer membrane.\ \N \N \N 25942 IPR007511 This is a family of uncharacterised bacterial proteins.\ \N \N \N 25943 IPR007512 This family of short eukaryotic proteins has no known function. Most of the members of this family are only 80 amino acid residues long. However the Arabidopsis homologue is over 300 residues long. The presumed domain contains a conserved N-terminal cysteine and a conserved motif GXGXGXG in the carboxy terminal half that may be functionally important.\ \N \N \N 25940 IPR007509 This is a family of hypothetical archaeal proteins.\ \N \N \N 25941 IPR007510 This is a family of hypothetical archaeal proteins.\ \N \N \N 25939 IPR007508 This is a family of hypothetical proteins. It is present in prokaryotes and Arabidopsis.\ \N \N \N 25936 IPR007505 This is a family of hypothetical prokaryotic proteins.\ \N \N \N 25937 IPR007506 This is a family of hypothetical proteins.\ \N \N \N 25938 IPR007507

This is a domain found in proteins that transfer activated sugars to a variety of substrates, including glycogen, fructose-6-phosphate and lipopolysaccharides. Proteins bearing this domain transfer UDP, ADP, GDP or CMP linked sugars. This region is flanked at the N terminus by a signal peptide and at the C terminus by a glycosyl transferase group 1 domain (IPR001296.

\ \N \N \N 25917 IPR007486 Some family members may be secreted or integral membrane proteins.\ \N \N \N 25918 IPR007487 This is a family of putative secreted proteins of unknown function.\ \N \N \N 25919 IPR007488

Family member Shigella flexneri VirK (Q99QA5), which is thought to be membrane-associated.

\ \N \N \N 25920 IPR007489 This is a C-terminal region from several bacterial proteins of unknown function that may be involved in a theta-type replication mechanism.\ \N \N \N 25921 IPR007490

This family is the B22R protein from Poxviruses.

\ \N \N \N 25922 IPR007491 Some members of this plant protein family have one or more zinc-finger motifs towards the C terminus of the region represented in this family.\ \N \N \N 25923 IPR007492

This domain is found in a variety of bacterial transcriptional regulators. The domain binds to a specific DNA sequence pattern [MEDLINE:22030819]. The N-terminal of the protein contains a response regulator receiver domain (IPR001789).

\ \N \N \N 25924 IPR007493 This family consists of several plant proteins of unknown function.\ \N \N \N 25925 IPR007494

Glutaredoxins are a multifunctional family of glutathione-dependent disulphide oxidoreductases. Unlike other glutaredoxins, glutaredoxin 2 (Grx2) cannot reduce ribonucleotide reductase. Grx2 has significantly higher catalytic activity in the reduction of mixed disulphides with glutathione (GSH) compared with other glutaredoxins. The active site residues (Cys9-Pro10-Tyr11-Cys12, in Escherichia coli Grx2, P39811.

\ \N \N \N 25913 IPR007482 This family includes the mammalian protein tyrosine phosphatase-like protein, PTPLA. A significant variation of PTPLA from other protein tyrosine phosphatases is the presence of proline instead of catalytic arginine at the active site. It is thought that PTPLA proteins have a role in the development, differentiation, and maintenance of a number of tissue types [MEDLINE:20112754].\ \N \N \N 25914 IPR007483

This family includes the hamartin protein which is thought to function as a tumour suppressor. The hamartin protein interacts with the tuberin protein IPR003913.

\ \N \N \N 25915 IPR007484

This domain is found in the peptidase family M28 proteins, which also contain a transferrin receptor-like dimerisation domain (IPR007365)

\ \N \N \N 25916 IPR007485 The Escherichia coli family member has been named Rare lipoprotein B (RplB). Thioglyceride and N-fatty acyl residues may be attached to the N-terminal cysteine, which is conserved in this family. RplB is speculated to be involved in cell duplication [MEDLINE:88058785].\ \N \N \N 25910 IPR007479 This is a small bacterial protein of unknown function.\ \N \N \N 25911 IPR007480 This entry represents a repeated region found in several Theileria parva proteins.\ \N \N \N 25912 IPR007481

Escherichia coli stringent starvation protein B (SspB), is thought to enhance the specificity of degradation of tmRNA-tagged proteins by the ClpXP protease. The tmRNA tag, also known as ssrA, is an 11-aa peptide added to the C terminus of proteins stalled during translation, targets proteins for degradation by ClpXP and ClpAP. SspB is a cytoplasmic protein that specifically binds to residues 1-4 and 7 of the tag. Binding of SspB enhances degradation of tagged proteins by ClpX, and masks sequence elements important for ClpA interactions, inhibiting degradation by ClpA [MEDLINE:21438018]. However, more recent work has cast doubt on the importance of SspB in wild-type cells [MEDLINE:21669034]. SspB is encoded in an operon whose synthesis is stimulated by carbon, amino acid, and phosphate starvation. SspB may play a special role during nutrient stress, for example by ensuring rapid degradation of the products of stalled translation, without causing a global increase in degradation of all ClpXP substrates [MEDLINE:20465307].

\ \N \N \N 25904 IPR007473 This is a bacterial protein of unknown function, possibly secreted.\ \N \N \N 25905 IPR007474

Members of this family include the bacterial protein ApaG and the C termini of some F-box proteins (IPR001810.

\ \N \N \N 25906 IPR007475 This is a family of uncharacterised proteins.\ \N \N \N 25907 IPR007476 Members of the RdgC family may have exonuclease activity. RdgC is required for efficient pilin variation in Neisseria gonorrhoeae, suggesting that it may be involved in recombination reactions [MEDLINE:20157034]. In Escherichia coli, RdgC is required for growth in recombination-deficient exonuclease-depleted strains. Under these conditions, RdgC may act as an exonuclease to remove collapsed replication forks, in the absence of the normal repair mechanisms [MEDLINE:96400909].\ \N \N \N 25908 IPR007477

This presumed domain is found in proteins containing FERM domains IPR000299. This domain is found to bind to both spectrin and actin, hence the name SAB (Spectrin and Actin Binding) domain.

\ \N \N \N 25909 IPR007478 The N-terminal module of the D6R/N1R proteins defines a novel, conserved DNA-binding domain (the KilA-N domain) that is found in a wide range of proteins of large bacterial and eukaryotic DNA viruses. The KilA-N domain is suggested to be homologous to the fungal DNA-binding APSES domain. The KilA-N and APSES domains may also share a common fold with the nucleic acid-binding modules of the LAGLIDADG nucleases and the N-terminal domains of the tRNA endonuclease [MEDLINE:21895514].\ \N \N \N 25903 IPR007472

This entry represents the C-terminal region of the enzyme arginine-tRNA-protein transferase (EC: 2.3.2.8), which catalyses the post-translational conjugation of arginine to the N terminus of a protein. In eukaryotes, this functions as part of the N terminu rule pathway of protein degradation by conjugating a destabilising amino acid to the N-terminal aspartate or glutamate of a protein, targeting the protein for ubiquitin-dependent proteolysis. N-terminal cysteine is sometimes modified [MEDLINE:99077957]. The N-terminal is represented by IPR007471.

\ \N \N \N 25890 IPR007458 Members of this family are uncharacterised proteins.\ \N \N \N 25891 IPR007459 The DNA polymerase III holoenzyme (EC: 2.7.7.7) is the polymerase responsible for the replication of the Escherichia coli chromosome. The holoenzyme is composed of the DNA polymerase III core, the sliding clamp, and the DnaX clamp loading complex. The DnaX complex contains either the tau or gamma product of gene dnax, complexed to delta.delta and to chi psi. Chi forms a 1:1 heterodimer with psi. The chi psi complex functions by increasing the affinity of tau and gamma for delta.delta allowing a functional clamp-loading complex to form at physiological subunit concentrations. Psi is responsible for the interaction with DnaX (gamma/tau), but psi is insoluble unless it is in a complex with chi [MEDLINE:96094361].\ \N \N \N 25892 IPR007460 Members of this family are uncharacterised proteins.\ \N \N \N 25893 IPR007461

Proteins in this family often also contain an SH3 domain (IPR001452).

\ \N \N \N 25894 IPR007462 This protein is predicted to be an integral membrane protein.\ \N \N \N 25895 IPR007463 This is a bacterial protein of unknown function.\ \N \N \N 25896 IPR007464 This is a family of bacteriocins from lactic acid bacteria.\ \N \N \N 25897 IPR007465 This is a family of uncharacterised proteins from Caenorhabditis elegans.\ \N \N \N 25898 IPR007466

Peptidyl-arginine deiminase (PAD) enzymes catalyse the deimination of the guanidino group from carboxy-terminal arginine residues of various peptides to produce ammonia. PAD from Porphyromonas gingivalis (PPAD) appears to be evolutionarily unrelated to mammalian PAD (IPR004303.

\ \N \N \N 25899 IPR007468 This is a bacterial protein of unknown function.\ \N \N \N 25900 IPR007469

This may be the N-terminal region of an uroporphyrin-III C-methyltransferase (EC: 2.1.1.107) [MEDLINE:89098348]. It often occurs together with the C-terminal domain IPR007470.

\ \N \N \N 25901 IPR007470

This may be the C-terminal region of an uroporphyrin-III C-methyltransferase (EC: 2.1.1.107) [MEDLINE:89098348]. It often occurs together with the N-terminal domain IPR007469.

\ \N \N \N 25902 IPR007471

This entry represents the N-terminal region of the enzyme arginine-tRNA-protein transferase (EC: 2.3.2.8), which catalyses the post-translational conjugation of arginine to the N terminus of a protein. In eukaryotes, this functions as part of the N terminus rule pathway of protein degradation by conjugating a destabilising amino acid to the N-terminal aspartate or glutamate of a protein, targeting the protein for ubiquitin-dependent proteolysis. N-terminal cysteine is sometimes modified [MEDLINE:99077957]. In Saccharomyces cerevisiae, Cys20, 23, 94 and/or 95 are thought to be important for activity [MEDLINE:96097009]. Of these, only Cys 94 appears to be completely conserved in this family. The C-terminal is represented by IPR007472.

\ \N \N \N 25888 IPR007456 Members of this family of uncharacterised proteins are often named Smg.\ \N \N \N 25889 IPR007457 Methionine start codon is known to be cleaved from Escherichia coli protein YggX (P52065.\ \N \N \N 25882 IPR007450

This is a bacterial outer membrane lipoprotein, possibly involved in maintaining the structural integrity of the cell envelope [MEDLINE:99138728]. The lipid attachment site is a conserved N-terminal cysteine residue sometimes found adjacent to the OmpA domain (IPR006665).

\ \N \N \N 25883 IPR007451 Protein of unknown function, cotranscribed with purB in Escherichia coli, but with function unrelated to purine biosynthesis [MEDLINE:97124206].\ \N \N \N 25884 IPR007452 This family contains several proteins of uncharacterised function.\ \N \N \N 25885 IPR007453

Family member P45573.

\ \N \N \N 25886 IPR007454 This family includes several proteins of uncharacterised function.\ \N \N \N 25887 IPR007455 Serglycin is the most prevalent proteoglycan produced in haemopoietic cells. Serglycin is a proteinase resistant secretory granule proteoglycan [MEDLINE:91084531].\ \N \N \N 25860 IPR007428 VacJ is required for the intercellular spreading of Shigella flexneri. It is attached to the outer membrane by a lipid anchor [MEDLINE:94195110].\ \N \N \N 25861 IPR007429 This family contains uncharacterised protein encoded on Trypanosomal kinetoplast minicircles.\ \N \N \N 25862 IPR007430 VirB8 is a bacterial virulence protein with cytoplasmic, transmembrane, and periplasmic regions. It is thought that it is a primary constituent of a DNA transporter. The periplasmic region interacts with VirB9, VirB10, and itself [MEDLINE:21264376].\ \N \N \N 25863 IPR007431 This family includes several bacterial proteins of uncharacterised function.\ \N \N \N 25864 IPR007432 This family consists of several proteins of uncharacterised function.\ \N \N \N 25865 IPR007433 This family includes several proteins of uncharacterised function.\ \N \N \N 25866 IPR007434 This family contains several proteins of uncharacterised function.\ \N \N \N 25867 IPR007435 This family consists of several proteins of uncharacterised function.\ \N \N \N 25868 IPR007436 This family includes several putative integral membrane proteins.\ \N \N \N 25869 IPR007437 This family contains several proteins of uncharacterised function.\ \N \N \N 25870 IPR007438 This family includes several proteins of uncharacterised function.\ \N \N \N 25871 IPR007439

This family represents the bacterial chemotaxis phosphatase, CheZ. This protein forms a dimer characterised by a long four-helix bundle, composed of two helices from each monomer. CheZ dephosphorylates CheY in a reaction that is essential to maintain a continuous chemotactic response to environmental changes. It is thought that CheZ's conserved residue Gln 147 orientates a water molecule for nucleophilic attack at the CheY active site.

\ \N \N \N 25872 IPR007440 Chorismate lyase catalyses the first step in ubiquinone synthesis, i.e. the removal of pyruvate from chorismate, to yield 4-hydroxybenzoate.\ \N \N \N 25873 IPR007441 EutH is a bacterial membrane protein whose molecular function is unknown. It has been suggested that it may act as an ethanolamine transporter, responsible for carrying ethanolamine from the periplasm to the cytoplasm [MEDLINE:99395039].\ \N \N \N 25874 IPR007442 FliO is an essential component of the flagellum-specific protein export apparatus [MEDLINE:99175434]. It is an integral membrane protein. Its precise molecular function is unknown.\ \N \N \N 25875 IPR007443 This family includes several bacterial outer membrane antigens, whose molecular function is unknown.\ \N \N \N 25876 IPR007444 This family represents MdoG, a protein that is necessary for the synthesis of periplasmic glucans. The function of MdoG remains unknown. It has been suggested that it may catalyse the addition of branches to a linear glucan backbone.\ \N \N \N 25877 IPR007445 PilO proteins are involved in the assembly of pilin. However, the precise function of this family of proteins is not known.\ \N \N \N 25878 IPR007446 PilQ is essential for the biogenesis of type IV pili. Its precise function is unknown, but it has been suggested that it may act as a pilus channel in the final stages of pilus assembly.\ \N \N \N 25879 IPR007447 This family includes ProQ, which is required for full activation of the osmoprotectant transporter, ProQ, in Escherichia coli.\ \N \N \N 25880 IPR007448 This family includes bacterial transcriptional regulators that are thought to act through an interaction with the conserved region 4 of the sigma(70) subunit of RNA polymerase. The Pseudomonas aeruginosa homologue, AlgQ, positively regulates virulence gene expression and is associated with the mucoid phenotype observed in Pseudomonas aeruginosa isolates from cystic fibrosis patients.\ \N \N \N 25881 IPR007449 This entry represents the ZipA C-terminal domain. ZipA is involved in septum formation in bacterial cell division. Its C-terminal domain binds FtsZ, a major component of the bacterial septal ring. The structure of this domain is an

fold with three

helices and a

sheet of six antiparallel

strands. The major loops protruding from the

sheet surface are thought to form a binding site for FtsZ [MEDLINE:20384201].\ \N \N \N 25845 IPR007413 Some members of this family are thought to possess an ATP-binding domain towards their N terminus.\ \N \N \N 25846 IPR007414 This is a family of uncharacterised yeast proteins.\ \N \N \N 25847 IPR007415 This short protein is found in the nif (nitrogen fixation) operon. Its function is unknown but it is probably involved in nitrogen fixation or regulating some component of this process. This 75 residue region is presumed to be a domain. It is found in isolation in some members and in the N-terminal half of the longer NifZ proteins.\ \N \N \N 25848 IPR007416

This is a family of bacterial proteins with no known function.

\ \N \N \N 25849 IPR007417 This is a family of uncharacterised archaeal proteins.\ \N \N \N 25850 IPR007418 This is a family of uncharacterised archaeal/bacterial proteins.\ \N \N \N 25851 IPR007419

The two Fe ions are each coordinated by two conserved cysteine residues. This domain occurs alone in small proteins such as bacterioferritin-associated ferredoxin (BFD, P13655).

\ \N \N \N 25852 IPR007420 Family members are found in small bacterial proteins, and also in the heavy chains of eukaryotic myosin and kinesin, C-terminal of the motor domain. Members of this family may form coiled coil structures.\ \N \N \N 25853 IPR007421 This is a family of uncharacterised archaeal proteins.\ \N \N \N 25854 IPR007422 This is a family of uncharacterised archaeal proteins.\ \N \N \N 25855 IPR007423 This is a small bacterial protein of unknown function.\ \N \N \N 25856 IPR007424

This sequence is usually found in association with IPR007425) in lysyl-tRNA synthases.

\ \N \N \N 25857 IPR007425

This sequence is usually found in association with IPR007424) in lysyl-tRNA synthases.

\ \N \N \N 25858 IPR007426

This sequence is usually found in association with IPR007424) in lysyl-tRNA synthases.

\ \N \N \N 25859 IPR007427 This protein is predicted to be an integral membrane protein with multiple membrane spans.\ \N \N \N 25839 IPR007407 This is a putative periplasmic protein.\ \N \N \N 25840 IPR007408 This is an archaeal protein of unknown function.\ \N \N \N 25841 IPR007409

This domain is often found adjacent to a methylase domain (IPR002052) in a putative restriction endonuclease.

\ \N \N \N 25842 IPR007410 This is a putative membrane or periplasmic protein.\ \N \N \N 25843 IPR007411 This family consists of bacterial proteins of uncharacterised function.\ \N \N \N 25844 IPR007412 FlgM binds and inhibits the activity of the transcription factor sigma 28. Inhibition of sigma 28 prevents the expression of genes from flagellar transcriptional class 3, which include genes for the filament and chemotaxis. Correctly assembled basal body-hook structures export FlgM, relieving inhibition of sigma 28 and allowing expression of class 3 genes. NMR studies show that free FlgM is mostly unfolded, which may facilitate its export. The C-terminal half of FlgM adopts a tertiary structure when it binds to sigma 28. All mutations in FlgM that prevent sigma 28 inhibition affect the C-terminal domain and is the region thought to constitute the binding domain. A minimal binding domain has been identified between Glu 64 and Arg 88 in Salmonella typhimurium (P26477.\ \N \N \N 25830 IPR007398 This is a family of uncharacterised proteins.\ \N \N \N 25831 IPR007399 This is a putative lipoprotein.\ \N \N \N 25832 IPR007400 FldA (Q9L3A0.\ \N \N \N 25833 IPR007401 This is a predicted membrane protein.\ \N \N \N 25834 IPR007402 This is a family of uncharacterised proteins.\ \N \N \N 25835 IPR007403 This is a family of putative membrane proteins.\ \N \N \N 25836 IPR007404 This is a family of predicted membrane-bound metal-dependent hydrolases, based on Q97LP7.\ \N \N \N 25837 IPR007405 This is a family of uncharacterised eubacterial proteins.\ \N \N \N 25838 IPR007406 This is the N-terminal region of MukB, which is one of a group of bacterial proteins essential for the movement of nucleoids from mid-cell towards the cell quarters (i.e. chromosome partitioning). The structure of the N-terminal domain consists of an antiparallel six-stranded

sheet surrounded by one helix on one side and by five helices on the other side [MEDLINE:20015369]. It contains an exposed Walker A loop in an unexpected helix-loop-helix motif. In other proteins, Walker A motifs generally adopt a P loop conformation as part of a strand-loop-helix motif embedded in a conserved topology of alternating helices and (parallel)

strands [MEDLINE:20015369].\ \N \N \N 25827 IPR007395

Zinc metallopeptidase zinc-binding regions have been predicted in all family members by a match to IPR006025.

\ \N \N \N 25828 IPR007396 In Bacillus subtilis, family member P21341.\ \N \N \N 25829 IPR007397

Proteins containing this domain are associated with F-box domains (IPR001810 is involved in binding to N-glycosylated proteins.

\ \N \N \N 25825 IPR007393 This is a family of uncharacterised proteins.\ \N \N \N 25826 IPR007394 Members of this family are predicted to contain a helix-turn-helix motif, for example residues 37-55 in Mycoplasma mycoides p13 (O05290.\ \N \N \N 25824 IPR007392

This domain is found at the C-terminus of D-galactarate dehydratase (EC: 4.2.1.42) which is thought to catalyse the reaction

D-galactarate = 5-keto-4-deoxy-D-glucarate + H2O,

\ \ \ [MEDLINE:98447507] and altronate hydrolase (altronic acid hydratase, EC: 4.2.1.7), which catalyses

D-altronate = 2-keto-2-deoxygluconate + H₂O

\ \ \ \ [MEDLINE:98240225]. As purified, both enzymes are catalytically inactive in the absence of added Fe²⁺, Mn²⁺, and

-mercaptoethanol. Synergistic activation of altronate hydrolase activity is seen in the presence of both iron and manganese ions, suggesting that the enzyme may have two ion binding sites. Mn²⁺ appears to be part of the enzyme active centre, but the function of the single bound Fe²⁺ ion is unknown. The hydratase has no Fe-S core [MEDLINE:87275954]. The N-terminal is represented by IPR007389.

\ \ \N \N \N 25823 IPR007391 Members of this family include vancomycin resistance protein W (VanW). Genes encoding members of this family have been found in vancomycin resistance gene clusters vanB [MEDLINE:21270249] and vanG [MEDLINE:20493149]. The function of VanW is unknown.\ \N \N \N 25822 IPR007390 One of the family members P37875.\ \N \N \N 25810 IPR007378 The preprotein translocation at the inner envelope membrane of chloroplasts so far involves five proteins: Tic110, Tic55, Tic40, Tic22 (this family) and Tic20. The molecular function of these proteins has not yet been established [MEDLINE:22027696].\ \N \N \N 25811 IPR007379

Tim44 is an essential component of the machinery that mediates the translocation of nuclear-encoded proteins across the mitochondrial inner membrane [MEDLINE:99362681]. Tim44 is thought to bind phospholipids of the mitochondrial inner membrane both by electrostatic interactions and by penetrating the polar head group region [MEDLINE:99362681].

\ \N \N \N 25812 IPR007380 This is a family of uncharacterised proteins.\ \N \N \N 25813 IPR007381 This is an archaeal protein of unknown function.\ \N \N \N 25814 IPR007382 This protein is predicted to be an integral membrane protein.\ \N \N \N 25815 IPR007383 This protein is predicted to be a membrane protein.\ \N \N \N 25816 IPR007384

This family includes an N-terminal region of unknown function from the Erwinia cartovora exoenzyme regulation regulon orf1 protein, which also contains a domain found in RNA pseudouridylate synthase IPR006145.

\ \N \N \N 25817 IPR007385 This is a bacterial protein MukE involved in chromosome partitioning.\ \N \N \N 25818 IPR007386 This is an archaeal protein of unknown function.\ \N \N \N 25819 IPR007387 The function of the members of this family is unknown, but DctQ homologues are invariably found in the tripartite ATP-independent periplasmic transporters [MEDLINE:20090467].\ \N \N \N 25820 IPR007388 Spore maturation protein A (SpmA) is involved in spore core dehydration in Bacillus subtilis. Spore dehydration is important for heat resistance and for processing of the spore germination protease GPR into an active form. SpmA might be involved in import or export from the forespore, or in modification of the cortex peptidoglycan structure. SpmA is predicted to be an integral membrane protein [MEDLINE:95370151].\ \N \N \N 25821 IPR007389

This domain is found at the N terminus of D-galactarate dehydratase (EC: 4.2.1.42) which is thought to catalyse the reaction

D-galactarate = 5-keto-4-deoxy-D-glucarate + H2O,

\ \ \ [MEDLINE:98447507] and altronate hydrolase (altronic acid hydratase, EC: 4.2.1.7), which catalyses

D-altronate = 2-keto-2-deoxygluconate + H₂O

\ \ \ \ [MEDLINE:98240225]. As purified, both enzymes are catalytically inactive in the absence of added Fe²⁺, Mn²⁺, and

\ \ \N \N \N 25804 IPR007372 Escherichia coli YceI is a base-induced periplasmic protein. Its function has not yet been characterised [MEDLINE:22103114].\ \N \N \N 25805 IPR007373 Thiamin pyrophosphokinase (TPK, EC: 2.7.6.2) catalyzes the transfer of a pyrophosphate group from ATP to vitamin B1 (thiamin) to form the coenzyme thiamin pyrophosphate (TPP). Thus, TPK is important for the formation of a coenzyme required for central metabolic functions. The structure of thiamin pyrophosphokinase suggest that the enzyme may operate by a mechanism of pyrophosphoryl transfer similar to those described for pyrophosphokinases functioning in nucleotide biosynthesis [MEDLINE:21345421].\ \N \N \N 25806 IPR007374 This is an archaeal protein of unknown function.\ \N \N \N 25807 IPR007375 Sarcosine oxidase is a hetero-tetrameric enzyme that contains both covalently bound FMN and non-covalently bound FAD and NAD⁺. This enzyme catalyzes the oxidative demethylation of sarcosine to yield glycine, H₂O₂, and 5,10-CH2-tetrahydrofolate (H4folate) in a reaction requiring H4folate and O₂ [MEDLINE:21229520], [MEDLINE:95355441].\ sarcosine oxidase activity ; GO:0008115 \N tetrahydrofolate metabolism ; GO:0046653 25808 IPR007376 This family consists of uncharacterised bacterial proteins.\ \N \N \N 25809 IPR007377 Tagatose 1,6-diphosphate aldolase (EC: 4.1.2.40) is part of the tagatose-6-phosphate pathway of galactose-6-phosphate degradation [MEDLINE:92011355].\ \N \N \N 25793 IPR007361 This is a family of uncharacterised proteins.\ \N \N \N 25794 IPR007362 This is a family of uncharacterised proteins.\ \N \N \N 25795 IPR007363 This is a family of uncharacterised proteins.\ \N \N \N 25796 IPR007364 This is a family of uncharacterised proteins.\ \N \N \N 25797 IPR007365

This domain is involved in dimerisation of the transferrin receptor as shown in its crystal structure. It is also found in a number of other proteins including glutamate carboxypeptidase II and N-acetylated--linked acidic dipeptidase like protein.

\ \N \N \N 25798 IPR007366 This is an archaeal protein of unknown function.\ \N \N \N 25799 IPR007367 This is a family of uncharacterised proteins.\ \N \N \N 25800 IPR007368 This is a family of uncharacterised proteins.\ \N \N \N 25801 IPR007369

The members of this family are membrane proteins of unknown function. In some proteins this region is found associated with PA domain IPR003137.

\ \N \N \N 25802 IPR007370 This is a family of bacterial glutamate-cysteine ligases (EC: 6.3.2.2) that carry out the first step of the glutathione biosynthesis pathway.\ \N \N \N 25803 IPR007371 Thiamin pyrophosphokinase (TPK, EC: 2.7.6.2) catalyzes the transfer of a pyrophosphate group from ATP to vitamin B1 (thiamin) to form the coenzyme thiamin pyrophosphate (TPP). Thus, TPK is important for the formation of a coenzyme required for central metabolic functions. The structure of thiamin pyrophosphokinase suggests that the enzyme may operate by a mechanism of pyrophosphoryl transfer similar to those described for pyrophosphokinases functioning in nucleotide biosynthesis [MEDLINE:21345421].\ \N \N \N 25780 IPR007348 CopC is a bacterial blue copper protein that binds 1 atom of copper per protein molecule. Along with CopA, CopC mediates copper resistance by sequestration of copper in the periplasm [MEDLINE:92020961].\ \N \N \N 25781 IPR007349

Tihs is a probable integral membrane protein. It is usually found associated with the domain of unknown function DUF405 (IPR007299).

\ \N \N \N 25782 IPR007350

This domain corresponds to a C-terminal cysteine rich region that probably binds to a metal ion and could be DNA-binding. It is found in association with the DDE superfamily (IPR004875).

\ \N \N \N 25783 IPR007351 This is a family of uncharacterised proteins.\ \N \N \N 25784 IPR007352 This is a predicted membrane protein with four transmembrane helices.\ \N \N \N 25785 IPR007353 This family of uncharacterised proteins is known as YDFR family\ \N \N \N 25786 IPR007354 This protein is predicted to be an integral membrane protein.\ \N \N \N 25787 IPR007355 This is an archaeal protein of unknown function.\ \N \N \N 25788 IPR007356 Family member HYNA is the product of a novel gene expressed in human liver cancer tissue.\ \N \N \N 25789 IPR007357 This family appears to be related to DNA photolyases.\ \N \N \N 25790 IPR007358

The Escherichia coli nucleoid contains DNA in a condensed but functional form. Analysis of proteins released from isolated spermidine nucleoids after treatment with DNase I reveals significant amounts of two proteins not previously detected in wild-type Escherichia coli. Partial amino-terminal sequencing has identified them as the products of rdgC and yejK. These proteins are strongly conserved in Gram-negative bacteria, suggesting that they have important cellular roles [MEDLINE:99296598].

\ \N \N \N 25791 IPR007359 This bacterial family of integral membrane proteins represents a positive regulator of the sigma(E) transcription factor, namely RseC/MucC. The sigma(E) transcription factor is up-regulated by cell envelope protein misfolding, and regulates the expression of genes that are collectively termed ECF (devoted to Extra-Cellular Functions) [MEDLINE:97303091]. In Pseudomonas aeruginosa, derepression of sigma(E) is associated with the alginate-overproducing phenotype characteristic of chronic respiratory tract colonization in cystic fibrosis patients. The mechanism by which RseC/MucC positively regulates the sigma(E) transcription factor is unknown. RseC is also thought to have a role in thiamine biosynthesis in Salmonella typhimurium [MEDLINE:97474279]. In addition, this family also includes an N-terminal part of RnfF, a Rhodobacter capsulatus protein, of unknown function, that is essential for nitrogen fixation. This protein also contains a domain found in ApbE protein IPR003374, which is itself involved in thiamine biosynthesis.\ \N \N \N 25792 IPR007360 SirB up-regulates Salmonella typhimurium invasion gene transcription. It is, however, not essential for the expression of these genes. Its function is unknown [MEDLINE:99255533].\ \N \N \N 25778 IPR007346 Bacterial periplasmic or secreted (EC: 3.1.21.1) Escherichia coli endonuclease I (EndoI) is a sequence independent endonuclease located in the periplasm. It is inhibited by different RNA species. It is thought to normally generate double strand breaks in DNA, except in the presence of high salt concentrations and RNA, when it generates single strand breaks in DNA. Its biological role is unknown [MEDLINE:95172402]. Other family members are known to be extracellular [MEDLINE:87248107]. This family also includes a non-specific, Mg²⁺-activated ribonuclease precursor (Q03091.\ nuclease activity ; GO:0004518 \N \N 25779 IPR007347 In Bacillus subtilis this protein interferes with sporulation at an early stage and this inhibitory effect is overcome by SpoIIB and SpoVG. SpoVS seems to play a positive role in allowing progression beyond stage V of sporulation. Null mutations in the spoVS gene block sporulation at stage V, impairing the development of heat resistance and coat assembly [MEDLINE:96032401].\ \N \N \N 25775 IPR007343 Members of this family have a predicted zinc-binding motif characteristic of neutral zinc metallopeptidases.\ \N \N \N 25776 IPR007344 This family of uncharacterised proteins is also known as GrpB.\ \N \N \N 25777 IPR007345 Pyruvyl-transferases are involved in peptidoglycan-associated polymer biosynthesis. CsaB in Bacillus anthracis is necessary for the non-covalent anchoring of proteins containing an SLH (S-layer homology) domain to peptidoglycan-associated pyruvylated polysaccharides. WcaK and AmsJ are involved in the biosynthesis of colanic acid in Escherichia coli and of amylovoran in Erwinia amylovora [MEDLINE:20428417].\ \N \N \N 25762 IPR007330

The MIT domain is found in vacuolar sorting proteins, spastin (probable ATPase involved in the assembly or function of nuclear protein complexes), and a sorting nexin, which may play a role in intracellular trafficking.

\ \N \N \N 25763 IPR007331 This domain is found in HtaA, a secreted protein implicated in iron acquisition and transport [MEDLINE:20223649].\ \N \N \N 25764 IPR007332 The function of the members of this bacterial protein family is unknown. Some members may be involved in conferring cation resistance.\ \N \N \N 25765 IPR007333 This family consists of bacterial transmembrane proteins with a putative sugar-specific permease function, analogous to the IIC component of the PTS system (IPR003352.\ \N \N \N 25766 IPR007334 This family consists of bacterial uncharacterised proteins.\ \N \N \N 25767 IPR007335 This is a family of uncharacterised proteins.\ \N \N \N 25768 IPR007336 This family includes several bacterial proteins of unknown function, although at least one member (P95508) is a putative coproporphyrinogen III oxidase.\ \N \N \N 25769 IPR007337 RelE and RelB form a toxin-antitoxin system. RelE represses translation, probably through binding ribosomes [MEDLINE:21172892], [MEDLINE:22120292]. RelB stably binds RelE, presumably deactivating it.\ \N \N \N 25770 IPR007338 This is a bacterial family of uncharacterised proteins.\ \N \N \N 25771 IPR007339 This family of uncharacterised proteins appears to be restricted to proteobacteria.\ \N \N \N 25772 IPR007340 This family includes the Haemophilus influenzae opacity-associated protein. This protein is required for efficient nasopharyngeal mucosal colonization, and its expression is associated with a distinctive transparent colony phenotype. OapA is thought to be a secreted protein, and its expression exhibits high-frequency phase variation [MEDLINE:96100454].\ \N \N \N 25773 IPR007341 This bacterial protein is predicted to be an integral membrane protein. Some family members have been annotated as transglycosylase-associated proteins, but no experimental evidence is provided. This family was annotated based on the information in P76011.\ \N \N \N 25774 IPR007342 Indigoidine is a blue pigment synthesised by Erwinia chrysanthemi implicated in pathogenicity and protection from oxidative stress. IdgA is involved in indigoidine biosynthesis, but its specific function is unknown [MEDLINE:21650660].\ \N \N \N 25753 IPR007321

This domain is found in a family of plant gene products and is thought to be related to gypsy type transposons. There is a domain of unknown function, DUF390 (IPR007228), at the C terminus of the proteins.

\ \N \N \N 25754 IPR007322 The bunyaviruses are enveloped viruses with a genome consisting of 3 ssRNA segments (called L, M and S). The nucleocapsid protein is encoded by the small (S) genomic RNA. The L segment codes for an RNA polymerase. This family contains the RNA dependent RNA polymerase on the L segment.\ RNA-directed RNA polymerase activity ; GO:0003968 \N viral genome replication ; GO:0019079 25755 IPR007323 Birnaviruses are dsRNA viruses. This family corresponds to the RNA dependent RNA polymerase. This protein is also known as VP1. All of the birnavirus VP1 proteins contain conserved RdRp motifs that reside in the catalytic palm domain of all classes of polymerases. However, the birnavirus RdRps lack the highly conserved Gly-Asp-Asp (GDD) sequence, a component of the proposed catalytic site of this enzyme family that exists in the conserved motif VI of the palm domain of other RdRps [MEDLINE:22066034].\ RNA-directed RNA polymerase activity ; GO:0003968 \N viral genome replication ; GO:0019079 25756 IPR007324

This probable domain is found in bacterial transcriptional regulators such as DeoR and SorC. One of these proteins, Q8U7I7 that binds to DNA. This domain is probably the ligand regulator binding region. SorC is regulated by sorbose and other members of this family are likely to be regulated by other sugar substrates.

\ transcription regulator activity ; GO:0030528 \N \N 25757 IPR007325 Proteins in this family are thought to be cyclase enzymes. They are found in proteins involved in antibiotic synthesis. However they are also found in organisms that do not make antibiotics pointing to a wider role for these proteins. The proteins contain a conserved motif HXGTHXDXPXH that is likely to form a part of the active site.\ \N \N \N 25758 IPR007326 This presumed domain is about 100 amino acids in length. It is found in lipoprotein of unknown function and is greatly expanded in Mycoplasma pulmonis. The domain is found in up to five copies in some proteins.\ \N \N \N 25759 IPR007327 The hD52 gene was originally identified through its elevated expression level in human breast carcinoma. Cloning of D52 homologues from other species has indicated that D52 may play roles in calcium-mediated signal transduction and cell proliferation. Two human homologues of hD52, hD53 and hD54, have also been identified, demonstrating the existence of a novel gene/protein family [MEDLINE:98143307]. These proteins have an N-terminal coiled-coil that allows members to form homo- and heterodimers with each other [MEDLINE:98143307].\ \N \N \N 25760 IPR007328 Mytilus foot protein-3 (Mfp-3) is a highly polymorphic protein family located in the byssal adhesive plaques of blue mussels.\ \N \N \N 25761 IPR007329 This conserved region includes the FMN-binding site of the NqrC protein [MEDLINE:21145502] as well as the NosR and NirI regulatory proteins.\ \N \N \N 25743 IPR007311 The ST7 (for suppression of tumorigenicity 7) protein is thought to be a tumour suppressor gene. The molecular function of this protein is uncertain.\ \N \N \N 25744 IPR007312 This family includes both bacterial phospholipase C enzymes (EC: 3.1.4.3) and eukaryotic acid phosphatases EC: 3.1.3.2.\ hydrolase activity, acting on ester bonds ; GO:0016788 \N \N 25745 IPR007313 This is a bacterial family of cytoplasmic membrane proteins. It includes two transmembrane regions. The molecular function of FxsA is unknown, but in Escherichia coli its overexpression has been shown to alleviate the exclusion of phage T7 in those cells with an F plasmid.\ \N membrane ; GO:0016020 \N 25746 IPR007314 No function is known for any member of this family.\ \N \N \N 25747 IPR007315 This is a family of eukaryotic membrane proteins with unknown function.\ \N \N \N 25748 IPR007316 eIF-3 is a multisubunit complex that stimulates translation initiation in vitro at several different steps. This family corresponds to the gamma subunit of eIF3 [MEDLINE:95347586], [MEDLINE:99069213].\ translation initiation factor activity ; GO:0003743 \N regulation of translational initiation ; GO:0006446 25749 IPR007317 This is a family of conserved eukaryotic proteins with undetermined function.\ \N \N \N 25750 IPR007318 The Saccharomyces cerevisiae phospholipid methyltransferase (EC: 2.1.1.16) has a broad substrate specificity of unsaturated phospholipids [MEDLINE:88058872].\ N-methyltransferase activity ; GO:0008170 \N phospholipid metabolism ; GO:0006644 25751 IPR007319 Utp21 is a subunit of U3 snoRNP, which is essential for synthesis of 18S rRNA.\ \N \N \N 25752 IPR007320

PDCD2 is localized predominantly in the cytosol of cells situated at the opposite pole of the germinal center from the centroblasts as well as in cells in the mantle zone. It has been shown to interact with BCL6, an evolutionarily conserved Kruppel-type zinc finger protein that functions as a strong transcriptional repressor and is required for germinal center development. The rat homologue, Rp8, is associated with programmed cell death in thymocytes.

\ apoptosis regulator activity ; GO:0016329 cytoplasm ; GO:0005737 apoptosis ; GO:0006915 25731 IPR007299

This protein is predicted to be an integral membrane protein. Several family members are annotated as potential transport proteins, but there is no experimental evidence to suggest the function of any family member. It is usually found associated with the domain of unknown function DUF418 (IPR007349).

\ \N \N \N 25732 IPR007300 The two products of the lrgAB operon are potential membrane proteins, and LrgA and LrgB are both thought to control murein hydrolase activity and penicillin tolerance [MEDLINE:20179791].\ \N membrane ; GO:0016020 \N 25733 IPR007301 DoxD is a subunit of the terminal quinol oxidase present in the plasma membrane of Acidianus ambivalens. The protein has a calculated molecular mass of 20.4 kDa [MEDLINE:97175566].\ \N membrane ; GO:0016020 \N 25734 IPR007302

This is a protein of unknown function. It sometimes occurs in combination with two domains of unknown function DUF403 (IPR007296).

\ \N \N \N 25735 IPR007303 The TOR signalling pathway activates a cell-growth program in response to nutrients [MEDLINE:20067967]. TIP41 interacts with TAP42 and negatively regulates the TOR signaling pathway [MEDLINE:21617588].\ \N \N \N 25736 IPR007304 The TOR signalling pathway activates a cell-growth program in response to nutrients [MEDLINE:20067967]. TIP41 interacts with TAP42 and negatively regulates the TOR signaling pathway [MEDLINE:21617588].\ \N \N regulation of signal transduction ; GO:0009966 25737 IPR007305 Traffic through the yeast Golgi complex depends on a member of the syntaxin family of SNARE proteins, Sed5, present in early Golgi cisternae. Got1 is thought to facilitate Sed5-dependent fusion events [MEDLINE:99335465].\ \N \N vesicle-mediated transport ; GO:0016192 25738 IPR007306

This enzyme (EC: 2.4.2.-) modifies exclusively the initiator tRNA in position 64 using 5'-phosphoribosyl-1'-pyrophosphate as the modification donor. As the initiator tRNA participates both in the initiation and elongation of translation, the 2'-O-ribosyl phosphate modification discriminates the initiator tRNAs from the elongator tRNAs.

\ \ transferase activity, transferring pentosyl groups ; GO:0016763 \N regulation of translation ; GO:0006445 25739 IPR007307

The low-temperature viability protein LTV1 was identified in Saccharomyces cerevisiae, the exact function of this protein is unknown.

\ \N \N \N 25740 IPR007308 This is a protein of unknown function.\ \N \N \N 25741 IPR007309 Yeast transcription factor IIIC (TFIIIC) is a multisubunit protein complex that interacts with two control elements of class III promoters called the A and B blocks. This family represents the subunit within TFIIIC involved in B-block binding [MEDLINE:93066269].\ transcription factor activity ; GO:0003700 \N regulation of transcription ; GO:0045449 25742 IPR007310 Bacteria solve the iron supply problem caused by the insolubility of Fe(3+) by synthesizing iron-complexing compounds, called siderophores, and by using iron sources of their hosts, such as heme and iron bound to transferrin and lactoferrin. Escherichia coli, as an example of Gram-negative bacteria, forms sophisticated Fe(3+)-siderophore and heme transport systems across the outer membrane. LucA and IucC catalyse discrete steps in biosynthesis of the siderophore aerobactin from N epsilon-acetyl-N epsilon-hydroxylysine and citrate [MEDLINE:86250617].\ siderochrome-iron transporter activity ; GO:0015343 \N siderochrome biosynthesis ; GO:0019290 25730 IPR007298 This family represents a bacterial outer membrane lipoprotein that is necessary for signalling by the Cpx pathway [MEDLINE:21843835]. This pathway responds to cell envelope disturbances and increases the expression of periplasmic protein folding and degradation factors. While the molecular function of the NlpE protein is unknown, it may be involved in detecting bacterial adhesion to abiotic surfaces. NlpE from Escherichia coli and Salmonella typhi is also known to confer copper tolerance in copper-sensitive strains of E. coli, and may be involved in copper efflux and delivery of copper to copper-dependent enzymes [MEDLINE:95362641].\ \N \N \N 25724 IPR007292

Nuclear fusion protein tht1 is an integral membrane protein that was shown [MEDLINE:98106170] by mutation studies to be required for the fusion of nuclear envelopes during karyogamy.

\ \N \N \N 25725 IPR007293 This domain is found in functionally uncharacterised proteins from such pathogenic bacteria as Helicobacter pylori, Campylobacter jejuni, and Vibrio cholerae. The H. pylori protein Q9ZL07 consists of two copies of this domain.\ \N \N \N 25726 IPR007294 Members of this family are predicted to have 10 transmembrane regions.\ \N \N \N 25727 IPR007295 Family member FomD is a predicted protein from a fosfomycin biosynthesis gene cluster in Streptomyces wedmorensis [MEDLINE:96091152]. Its function is unknown.\ \N \N \N 25728 IPR007296

This is a protein of unknown function. It sometimes occurs in combination with two domains of unknown function DUF404 (IPR007297).

\ \N \N \N 25729 IPR007297

This is a protein of unknown function. It sometimes occurs in combination with two domains of unknown function DUF403 (IPR007296).

\ \N \N \N 25716 IPR007284 This domain is found in Caenorhabditis elegans. It is probably extracellular and contains 2 or 4 cysteines that could form 1 or 2 disulphide bridges. The function of these proteins is uncertain.\ \N \N \N 25717 IPR007285 Chlamydia trachomatis is an obligate intracellular bacterium that develops within a parasitophorous vacuole termed an inclusion. The inclusion is nonfusogenic with lysosomes but intercepts lipids from a host cell exocytic pathway. Initiation of chlamydial development is concurrent with modification of the inclusion membrane by a set of C. trachomatis-encoded proteins collectively designated Incs. One of these Incs, IncA, is functionally associated with the homotypic fusion of inclusions [MEDLINE:22060701].\ \N \N \N 25718 IPR007286

EAP30 is a subunit of the ELL complex. The ELL is an 80-kDa RNA polymerase II transcription factor. ELL interacts with three other proteins to form the complex known as ELL complex. The ELL complex is capable of increasing that catalytic rate of transcription elongation, but is unable to repress initiation of transcription by RNA polymerase II as is the case of ELL. EAP30 is thought to lead to the derepression of ELL's transcriptional inhibitory activity.

\ \N \N \N 25719 IPR007287 Sof1 is essential for cell growth and is a component of the nucleolar rRNA processing machinery [MEDLINE:93285126].\ \N \N \N 25720 IPR007288 The NB glycoprotein is found in Influenza type B virus. Its function is unknown.\ \N \N \N 25721 IPR007289 This short protein has no known function and is found in Jaagsiekte sheep retrovirus. Jaagsiekte sheep retrovirus (JSRV) is the etiological agent of a contagious lung tumour of sheep known as sheep pulmonary adenomatosis. JSRV exhibits a simple genetic organization, characteristic of the type D and type B retroviruses, with the canonical retroviral sequences gag, pro, pol and env encoding the structural proteins of the virion and an additional open reading frame (orf-x), of approximately 500 bp overlapping pol [MEDLINE:20120940].\ \N \N \N 25722 IPR007290 Arv1 is a transmembrane protein with potential zinc-binding motifs. ARV1 is a novel mediator of eukaryotic sterol homeostasis [MEDLINE:20576215].\ \N \N \N 25723 IPR007291 Circoviruses are small circular single stranded viruses. This family includes the VP1 protein from the chicken anemia virus which is the viral coat protein.\ \N viral capsid ; GO:0019028 \N 25710 IPR007278 The function of this family is unknown. It has been suggested that some members of this family are regulators of transcription.\ \N \N \N 25711 IPR007279 Exportin-t is a specific mediator of tRNA export. It shuttles rapidly between nucleus and between nucleus and cytoplasm and interacts with nuclear pore complexes. Exportin-t binds tRNA directly and with high affinity [MEDLINE:98325350].\ \N \N \N 25712 IPR007280 This domain is normally found at the C terminus of secreted bacterial peptidases. They are not present in the active peptidase. It is possible that they fulfil a role similar to the PKD (IPR000601) domain, which also is found in this context. Visual analysis suggests that PKD and PPC are distantly related.\ \N \N \N 25713 IPR007281 The Mre11 complex is a multi-subunit nuclease that is composed of Mre11, Rad50 and Nbs1/Xrs2, and is involved in checkpoint signalling and DNA replication [MEDLINE:21984524]. Mre11 has an intrinsic DNA-binding activity that is stimulated by Rad50 on its own or in combination with Nbs1 [MEDLINE:20300914].\ \N \N \N 25714 IPR007282 NOT1, NOT2, NOT3, NOT4 and NOT5 form a nuclear complex that negatively regulates the basal and activated transcription of many genes. This family includes NOT2, NOT3 and NOT5.\ \N \N \N 25715 IPR007283 Cnd3 is a member of the five subunit condensin complex. Each subunit is essential for mitotic condensation. This C-terminal region was determined by Q9BVY1.\ \N \N \N 25700 IPR007268 Rad9 is required for transient cell-cycle arrests and transcriptional induction of DNA repair in response to DNA damage.\ \N \N \N 25701 IPR007269 The isoprenylcysteine o-methyltransferase (EC: 2.1.1.100) carries out carboyxl methylation of cleaved eukaryotic proteins that terminate in a CaaX motif. In Saccharomyces cerevisiae this methylation is carried out by Ste14p, an integral endoplasmic reticulum membrane protein. Ste14p is the founding member of the isoprenylcysteine carboxyl methyltransferase (ICMT) family, whose members share significant sequence homology [MEDLINE:21345160].\ \N \N \N 25702 IPR007270 This family includes functionally uncharacterised proteins from such pathogenic bacteria as Helicobacter pylori, Campylobacter jejuni, and Vibrio cholerae.\ \N \N \N 25703 IPR007271

This family of membrane proteins transport nucleotide sugars from the cytoplasm into golgi vesicles. P78382.

\ \N \N \N 25704 IPR007272 This entry includes YeeE and YedE from Escherichia coli. These proteins are integral membrane proteins of unknown function. Many of these proteins contain two homologous regions that are represented by this entry. This region contains several conserved glycines and an invariant cysteine that is probably an important functional residue.\ \N \N \N 25705 IPR007273 In vertebrates, secretory carrier membrane proteins (SCAMPs) 1-3 constitute a family of putative membrane-trafficking proteins composed of cytoplasmic N-terminal sequences with NPF repeats, four central transmembrane regions (TMRs), and a cytoplasmic tail. SCAMPs probably function in endocytosis by recruiting EH-domain proteins to the N-terminal NPF repeats but may have additional functions mediated by their other sequences [MEDLINE:20504667].\ \N \N \N 25706 IPR007274

The redox active metal copper is an essential cofactor in critical biological processes such as respiration, iron transport, oxidative stress protection, hormone production, and pigmentation. A widely conserved family of high-affinity copper transport proteins (Ctr proteins) mediates copper uptake at the plasma membrane. A series of clustered methionine residues in the hydrophilic extracellular domain, and an MXXXM motif in the second transmembrane domain, are important for copper uptake. These methionines probably coordinate copper during the process of metal transport.

\ \N \N \N 25707 IPR007275 This family of poorly characterised proteins contains Q9QY02.\ \N \N \N 25708 IPR007276 Emg1 and Nop14 are novel proteins whose interaction is required for the maturation of the 18S rRNA and for 40S ribosome production [MEDLINE:21551532].\ \N \N \N 25709 IPR007277 This is a family of conserved eukaryotic transmembrane proteins.\ \N \N \N 25694 IPR007262 Vps55 is involved in the secretion of the Golgi form of the soluble vacuolar carboxypeptidase Y, but not the trafficking of the membrane-bound vacuolar alkaline phosphatase. Both Vps55 and obesity receptor gene-related protein are important for functioning membrane trafficking to the vacuole/lysosome of eukaryotic cells [MEDLINE:22001557].\ \N \N \N 25695 IPR007263 Members of this family have two highly conserved cysteine residues near their N terminus. The function of these proteins is unknown.\ \N \N \N 25696 IPR007264 Nop10p is a nucleolar protein that is specifically associated with H/ACA snoRNAs. It is essential for normal 18S rRNA production and rRNA pseudouridylation by the ribonucleoprotein particles containing H/ACA snoRNAs (H/ACA snoRNPs). Nop10p is probably necessary for the stability of these RNPs [MEDLINE:99059744].\ \N \N \N 25697 IPR007265

Sec34 and Sec35 form a sub-complex in a seven-protein complex that includes Dor1. This complex is thought to be important for tethering vesicles to the Golgi [MEDLINE:21563418].

\ \N \N \N 25698 IPR007266 Members of this family are required for the formation of disulphide bonds in the endoplasmic reticulum [MEDLINE:20219760], [MEDLINE:20437746].\ \N \N \N 25699 IPR007267

Members of this family are predicted to be integral membrane proteins with three or four transmembrane spans. They are involved in the synthesis of cell surface polysaccharides. The GtrA family is a subset of this family. GtrA is predicted to be an integral membrane protein with 4 transmembrane spans. It is involved in O antigen modification by Shigella flexneri bacteriophage X (SfX), but does not determine the specificity of glucosylation. Its function remains unknown, but it may play a role in translocation of undecaprenyl phosphate linked glucose (UndP-Glc) across the cytoplasmic membrane [MEDLINE:99303336]. Another member of this family is a DTDP-glucose-4-keto-6-deoxy-D-glucose reductase, which catalyses the conversion of dTDP-4-keto-6-deoxy-D-glucose to dTDP-D-fucose, which is involved in the biosynthesis of the serotype-specific polysaccharide antigen of Actinobacillus actinomycetemcomitans Y4 (serotype b) [MEDLINE:99287888]. This family also includes the teichoic acid glycosylation protein, GtcA, which is a serotype-specific protein in some Listeria innocua and Listeria monocytogenes strains. Its exact function is not known, but it is essential for decoration of cell wall teichoic acids with glucose and galactose [MEDLINE:20485569].

\ \N \N \N 25680 IPR007248 The 22 kDa peroxisomal membrane protein (PMP22) is a major component of peroxisomal membranes. PMP22 seems to be involved in pore-forming activity and may contribute to the unspecific permeability of the organelle membrane. PMP22 is synthesized on free cytosolic ribosomes and then directed to the peroxisome membrane by specific targeting information [MEDLINE:21634822]. Mpv17 is a closely related peroxisomal protein involved in the development of early-onset glomerulosclerosis [MEDLINE:21226134].\ \N \N \N 25681 IPR007249 DopA is the founding member of the Dopey family and is required for correct cell morphology and spatiotemporal organisation of multicellular structures in the filamentous fungus Aspergillus nidulans. DopA homologues are found in mammals. Saccharomyces cerevisiae DOP1 is essential for viability and, affects cellular morphogenesis [MEDLINE:20402105].\ \N \N \N 25682 IPR007250 These heat shock proteins (Hsp9 and Hsp12) are strongly expressed and undergo an increase of 100 fold, upon entry into stationary phase in yeast [MEDLINE:91080870], [MEDLINE:96283803].\ \N \N \N 25683 IPR007251

The low affinity iron permease is an integral membrane protein required for ferrous iron low affinity uptake, and induced by iron deprivation.

\ \N \N \N 25684 IPR007252

Nup84p forms a complex with five proteins, including Nup120p, Nup85p, Sec13p, and a Sec13p homolog. This Nup84p complex in conjunction with Sec13-type proteins is required for correct nuclear pore biogenesis [MEDLINE:96152656].

\ \N \N \N 25685 IPR007253 This repeat is found in multiple tandem copies in proteins including amidase enhancers [MEDLINE:92407479] and adhesins [MEDLINE:21153574].\ \N \N \N 25686 IPR007254 This archaeal domain of unknown function is predicted to be an integral membrane protein with six transmembrane regions.\ \N \N \N 25687 IPR007255 Dor1 is involved in vesicle targeting to the yeast Golgi apparatus and complexes with a number of other trafficking proteins, which include Sec34 and Sec35 [MEDLINE:21563418].\ \N \N \N 25688 IPR007256 Proteins of this family have no known function.\ \N \N \N 25689 IPR007257

This is a eukaryotic specific domain of undetermined function.

\ \N \N \N 25690 IPR007258 Vps52 complexes with Vps53 and Vps54 to form a multi-subunit complex involved in regulating membrane trafficking events [MEDLINE:20105219].\ \N \N \N 25691 IPR007259 The spindle pole body (SPB) functions as the microtubule-organising centre in yeast. Members of this family are spindle pole body (SBP) components such as Spc97 and Spc98 that form a complex with gamma-tubulin.\ \N \N \N 25692 IPR007260 This family represents a putative ManNAc-6-P-to-GlcNAc-6P epimerase in the N-acetylmannosamine (ManNAc) utilization pathway found mainly in pathogenic bacteria.\ \N \N \N 25693 IPR007261 Vps36 is involved in Golgi to endosome trafficking.\ \N \N \N 25671 IPR007239 Apg5p is directly required for the import of aminopeptidase I via the cytoplasm-to-vacuole targeting pathway [MEDLINE:20177546].\ \N \N \N 25672 IPR007240 Apg17 is required for activating Apg1 protein kinases.\ \N \N \N 25673 IPR007241 In yeast, 15 Apg proteins coordinate the formation of autophagosomes. Autophagy is a bulk degradation process induced by starvation in eukaryotic cells [MEDLINE:21547934]. Apg9 plays a direct role in the formation of the cytoplasm to vacuole targeting and autophagic vesicles, possibly serving as a marker for a specialized compartment essential for these vesicle-mediated alternative targeting pathways [MEDLINE:20130271].\ \N \N \N 25674 IPR007242 In yeast, 15 Apg proteins coordinate the formation of autophagosomes. Autophagy is a bulk degradation process induced by starvation in eukaryotic cells [MEDLINE:21547934]. Apg12 is covalently bound to Apg5 [MEDLINE:99069367].\ \N \N \N 25675 IPR007243 In yeast, 15 Apg proteins coordinate the formation of autophagosomes. Autophagy is a bulk degradation process induced by starvation in eukaryotic cells [MEDLINE:21547934]. Apg6/Vps30p has two distinct functions in the autophagic process, either associated with the membrane or in a retrieval step of the carboxypeptidase Y sorting pathway [MEDLINE:98380442].\ \N \N \N 25676 IPR007244

NatC N()-terminal acetyltransferases contain Mak10p, Mak31p and Mak3p subunits. All three subunits are associated with each other to form the active complex [MEDLINE:21282931].

\ \N \N \N 25677 IPR007245 GPI (glycosyl phosphatidyl inositol) transamidase is a multiprotein complex. Gpi16, Gpi8 and Gaa1 for a sub-complex of the GPI transamidase. GPI transamidase adds glycosylphosphatidylinositols (GPIs) to newly synthesized proteins. Gpi16 is an essential N-glycosylated transmembrane glycoprotein. Gpi16 is largely found on the lumenal side of the ER. It has a single C-terminal transmembrane domain and a small C-terminal, cytosolic extension with an ER retrieval motif [MEDLINE:21482554].\ \N \N \N 25678 IPR007246

GPI (glycosyl phosphatidyl inositol) transamidase is a multiprotein complex required for a terminal step of adding the glycosylphosphatidylinositol (GPI) anchor attachment onto proteins. Gpi16, Gpi8 and Gaa1 form a sub-complex of the GPI transamidase.

\ \N \N \N 25679 IPR007247 Ureidoglycolate hydrolase (EC: 3.5.3.19) carries out the third step in the degradation of allantoin.\ \N \N \N 25666 IPR007234 Vps53 complexes with Vps52 and Vps54 to form a multi-subunit complex involved in regulating membrane trafficking events [MEDLINE:20105219].\ \N \N \N 25667 IPR007235

The biosynthesis of disaccharides, oligosaccharides and polysaccharides involves the action of hundreds of different glycosyltransferases. These are enzymes that catalyse the transfer of sugar moieties from activated donor molecules to specific acceptor molecules, forming glycosidic bonds. A classification of glycosyltransferases using nucleotide diphospho-sugar, nucleotide monophospho-sugar and sugar phosphates (EC: 2.4.1.-) and related proteins into distinct sequence based families has been described [MEDLINE:97474170]. This classification is available on the CAZy (CArbohydrate-Active EnZymes) web site PUB00007032. The same three-dimensional fold is expected to occur within each of the families. Because 3-D structures are better conserved than sequences, several of the families defined on the basis of sequence similarities may have similar 3-D strucures and therefore form 'clans'.

Glycosyltransferase family 28 CAZY:GT_28); -N-acetylglucosamine transferase (EC: 2.4.1.-).\ Structural analysis suggests the C-terminal domain contains the UDP-GlcNAc binding site.

\ \ \N \N \N 25668 IPR007236 The SlyX protein has no known function. It is short, less than 80 amino acids, and its gene is found close to the slyD gene. The SlyX protein has a conserved PPH(Y/W) motif at its C terminus. The protein may be a coiled-coil structure.\ \N \N \N 25669 IPR007237

This family includes the CD20 protein and the subunit of the high affinity receptor for IgE Fc. The high affinity receptor for IgE is a tetrameric structure consisting of a single IgE-binding subunit, a single subunit, and two disulfide-linked gamma subunits. The subunit of Fc epsilon RI and most Fc receptors are homologous members of the Ig superfamily. By contrast, the and gamma subunits from Fc epsilon RI are not homologous to the Ig superfamily. Both molecules have four putative transmembrane segments and a probable topology where both N- and C termini protrude into the cytoplasm [MEDLINE:90063076].

\ \N \N \N 25670 IPR007238 DNA primase is the polymerase that synthesises small RNA primers for the Okazaki fragments made during discontinuous DNA replication. DNA primase is a heterodimer of two subunits, the small subunit Pri1 (48 kDa in yeast), and the large subunit Pri2 (58 kDa in the yeast Saccharomyces cerevisiae) [MEDLINE:89384569]. Both subunits participate in the formation of the active site, but the ATP binding site is located on the small subunit [MEDLINE:91219475]. Primase function has also been demonstrated for human and mouse primase subunits [MEDLINE:94298818].\ \N \N \N 25658 IPR007226 Toxoplasma gondii is a persistent protozoan parasite capable of infecting almost any warm-blooded vertebrate. The surface of T. gondii is coated with a family of developmentally regulated glycosylphosphatidylinositol (GPI)-linked proteins (SRSs), of which SAG1 is the prototypic member. SRS proteins mediate attachment to host cells and interface with the host immune response to regulate the virulence of the parasite. The structure of the immunodominant SAG1 antigen reveals a homodimeric configuration [MEDLINE:98078707]. This family of surface antigens is found in other apicomplexans.\ \N \N \N 25659 IPR007227 MreD (murein formation D) protein is involved in the rod shape determination in Escherichia coli, and more generally in cell shape determination of bacteria whether or not they are rod-shaped.\ \N \N \N 25660 IPR007228

This domain is found in a family of long proteins that are currently found only in rice. They have no known function. However they may be some kind of transposable element. There is a putative gypsy type transposon domain (IPR007321) towards the N terminus of the proteins.

\ \N \N \N 25661 IPR007229 Nicotinate phosphoribosyltransferase (EC: 2.4.2.11) is the rate-limiting enzyme that catalyses the first reaction in the NAD salvage synthesis. This family also contains a number of closely related proteins for which a catalytic activity has not been experimentally demonstrated.\ \N \N \N 25662 IPR007230

The nuclear pore complex protein plays a role in bidirectional transport across the nucleoporin complex in nucleocytoplasmic transport.

\ \N \N \N 25663 IPR007231

The Nucleoporin interacting component is part of the nuclear pore complex required for protein transport in the nucleus.

\ \N \N \N 25664 IPR007232 The DNA single-strand annealing proteins (SSAPs), such as RecT, Red-

, ERF and Rad52, function in RecA-dependent and RecA-independent DNA recombination pathways. This family includes proteins related to Rad52. These proteins contain two helix-hairpin-helix motifs PUB00009986.\ \N \N \N 25665 IPR007233 Sybindin is a physiological syndecan-2 ligand on dendritic spines, the small protrusions on the surface of dendrites that receive the vast majority of excitatory synapses [MEDLINE:21435678].\ \N \N \N 25647 IPR007215 DsrH is involved in oxidation of intracellular sulphur in the phototrophic sulphur bacterium Chromatium vinosum D [MEDLINE:98361034].\ \N \N \N 25648 IPR007216 Two of the members in this family have been characterised as being involved in regulation of Ste11 regulated sex genes [MEDLINE:98336254], [MEDLINE:98107674].\ \N \N \N 25649 IPR007217 A member of this family has been implemented in protein processing in the endoplasmic reticulum [MEDLINE:20293053].\ \N \N \N 25650 IPR007218

DNA polymerase is responsible for effective DNA replication. The function of the delta subunit 4 of DNA polymerase is not yet known.

\ \N \N \N 25651 IPR007219

This domain is found in a number of fungal transcription factors including transcriptional activator xlnR, yeast regulatory protein GAL4, and other transcription proteins regulating a variety of cellular and metabolic processes.

\ \N \N \N 25652 IPR007220

All DNA replication initiation is driven by a single conserved eukaryotic initiator complex termed the origin recognition complex (ORC). The ORC is a six protein complex. The function of ORC is reviewed in [MEDLINE:95172409]. This entry is subunit 2, which binds the origin of replication. It plays a role in chromosome replication and mating type transcriptional silencing.

\ \N \N \N 25653 IPR007221 MreC (murein formation C) is involved in the rod shape determination in Escherichia coli, and more generally in cell shape determination of bacteria whether or not they are rod-shaped.\ \N \N \N 25654 IPR007222

SRP is a complex of six distinct polypeptides and a 7S RNA that is essential for transferring nascent polypeptide chains that are destined for export from the cell to the translocation apparatus of the endoplasmic reticulum membrane [MEDLINE:20200474]. SRP binds hydrophobic signal sequences as they emerge from the ribosome, and arrests translation. This is the N-terminal of SRP, the C-terminal is IPR000897.

\ \N \N \N 25655 IPR007223

Peroxin-13 is a component of the peroxisomal translocation machinery with Peroxin-14 and Peroxin-17. Both termini of Peroxin-13 are oriented to the cytosol. It is required for peroxisomal association of peroxin-14 [MEDLINE:20341060]. The proteins also contain an SH3 domain (IPR001452).

\ \N \N \N 25656 IPR007224

The RNA polymerase I specific transcription initiation factor is a member of a multiprotein complex essential for the initiation of transcription by RNA polymerase I. Binding to the DNA template is dependent on the initial binding of other factors.

\ \N \N \N 25657 IPR007225

Sec15 is a component of the exocyst complex involved in the docking of exocystic vesicles with a fusion site on the plasma membrane. The exocyst complex is composed of Sec3, Sec5, Sec6, Sec8, Sec10, Sec15, Exo70 and Exo84.

\ \N \N \N 25642 IPR007210 This domain is a part of a high affinity multicomponent binding-protein-dependent transport system involved in bacterial osmoregulation. This domain is often fused to the permease component of the transporter complex. It is often found in integral membrane proteins or proteins predicted to be attached to the membrane by a lipid anchor. Glycine betaine is involved in protection from high osmolarity environments for example in Bacillus subtilis [MEDLINE:95348093]. OpuBC is closely related and involved in choline transport. Choline is necessary for the biosynthesis of glycine betaine [MEDLINE:99232519]. L-carnitine is important for osmoregulation in Listeria monocytogenes. This domain is found also in proteins binding l-proline (ProX), histidine (HisX) and taurine (TauA).\ \N \N \N 25643 IPR007211 This is a predicted transmembrane domain of unknown function. The majority of the proteins have two predicted transmembrane regions.\ \N \N \N 25644 IPR007212

This is a probable metal-binding domain. It is found in a probable precorrin-3B C17-methyltransferase from Methanobacterium thermoautotrophicum, that catalyses the methylation of C-17 in precorrin-3B to form precorrin-4.

\ \N \N \N 25645 IPR007213 This is a family of leucine carboxyl methyltransferases (EC: 2.1.1.-). This family may need to be subdivided as the full alignment contains a significantly shorter mouse sequence.\ \N \N \N 25646 IPR007214 This domain of unknown function is found in numerous prokaryote organisms. The structure of YbaK shows a novel fold. This domain also occurs in a number of prolyl-tRNA synthetases (proRS) from prokaryotes. Thus, the domain is thought to be involved in oligonucleotide binding, with possible roles in recognition/discrimination or editing of prolyl-tRNA [MEDLINE:20274096].\ \N \N \N 25636 IPR007204 This component of ARP2/3 actin-organizing complex is involved in actin assembly and function.\ \N \N \N 25637 IPR007205

This is a protein of unknown function. It is found N-terminal to another domain of unknown function, DUF384 (IPR007206).

\ \N \N \N 25638 IPR007206

This is a protein of unknown function. It is found C-terminal to another domain of unknown function, DUF383 (IPR007205).

\ \N \N \N 25639 IPR007207

The Ccr4-Not complex (Not1, Not2, Not3, Not4 and Not5) is a global regulator of transcription that affects genes positively and negatively and is thought to regulate transcription factor TFIID [MEDLINE:95011559]. This domain is the N-terminal region of the Not proteins.

\ \N \N \N 25640 IPR007208 Members of the PhaF/MrpF family are predicted to be integral membrane proteins with three transmembrane regions, involved in regulation of pH. PhaF is part of a potassium efflux system involved in pH regulation. It is also involved in symbiosis in Rhizobium meliloti [MEDLINE:21255662]. MrpF is a part of a Na⁺/H⁺ antiporter complex, also involved in pH homeostasis. MrpF is thought to be an efflux system for Na⁺ and cholate [MEDLINE:99214087]. The Mrp system in Gram-positive species may also have primary energisation capacities [MEDLINE:98343795].\ \N \N \N 25641 IPR007209 This is a possible metal-binding domain in endoribonuclease RNase L inhibitor. It is found at the N-terminal end of RNase L inhibitor proteins, adjacent to the 4Fe-4S binding domain, fer4, IPR001450.\ \N \N \N 25632 IPR007200 The B subunit of the DNA polymerase

plays an essential role at the initial stage of DNA replication in Saccharomyces cerevisiae and is phosphorylated in a cell cycle-dependent manner.\ \N \N \N 25633 IPR007201

This RNA recognition motif 2 is found in Meiosis protein mei2. It is found C-terminal to the RNA-binding region RNP-1 (IPR000504).

\ \N \N \N 25634 IPR007202 These proteins contain a domain with four conserved cysteines that probably form an Fe-S redox cluster.\ \N \N \N 25635 IPR007203

ORMDL1 belongs to a novel gene family comprising three genes in humans (ORMDL1, ORMDL2 and ORMDL3), and homologs in yeast, microsporidia, plants, Drosophila, urochordates and vertebrates. ORMDLs are involved in protein folding in the endoplasmic reticulum.

\ \N \N \N 25622 IPR007190 This domain is found in PWP2, a member of the WD-repeat family of proteins, which is an essential Saccharomyces cerevisiae protein involved in cell separation.\ \N \N \N 25623 IPR007191

Sec8 is a component of the exocyst complex involved in the docking of exocystic vesicles with a fusion site on the plasma membrane. The exocyst complex is composed of Sec3, Sec5, Sec6, Sec8, Sec10, Sec15, Exo70 and Exo84.

\ \N \N \N 25624 IPR007192

The anaphase-promoting complex is composed of eight protein subunits, including BimE (APC1), CDC27 (APC3), CDC16 (APC6), and CDC23 (APC8). This entry is for CDC23.

\ \N \N \N 25625 IPR007193 Transcripts harbouring premature signals for translation termination are recognized and rapidly degraded by eukaryotic cells through a pathway known as nonsense-mediated mRNA decay. In Saccharomyces cerevisiae, three trans-acting factors (Upf1 to Upf3) are required for nonsense-mediated mRNA decay [MEDLINE:20528636].\ \N \N \N 25626 IPR007194 TRAPP plays a key role in the targeting and/or fusion of ER-to-Golgi transport vesicles with their acceptor compartment. TRAPP is an 800 kDa protein that contains at least 10 subunits.\ \N \N \N 25627 IPR007195 TolB is an essential periplasmic component of the tol-dependent translocation system. The function of this N-terminal domain is uncertain.\ \N \N \N 25628 IPR007196 The Ccr4-Not complex is a global regulator of transcription that affects genes positively and negatively and is thought to regulate transcription factor TFIID PUB00010586.\ \N \N \N 25629 IPR007197

Radical SAM proteins catalyze diverse reactions, including unusual methylations, isomerization, sulfur insertion, ring formation, anaerobic oxidation and protein radical formation. Evidence exists that these proteins generate a radical species by reductive cleavage of S:-adenosylmethionine (SAM) through an unusual Fe-S center PUB00010539.

\ \N \N \N 25630 IPR007198

Ssl1-like proteins are 40 kDa subunits of the transcription factor II H complex. This domain is often found associated with the C2H2 type Zn-finger (IPR007087).

\ \N \N \N 25631 IPR007199

Replication factor-a protein 1 (RPA1) forms a multiprotein complex with RPA2 and RPA3 that binds single-stranded DNA and functions in the recognition of DNA damage for nucleotide excision repair. The complex binds to single-stranded DNA sequences participating in DNA replication in addition to those mediating transcriptional repression and activation, and stimulates the activity of cognate strand exchange protein Sep1. It cooperates with T-AG and DNA topoisomerase I to unwind template DNA containing the Simian Virus 40 origin of replication.

\ \N \N \N 25620 IPR007187 RNA undergoing nuclear export first encounters the basket of the nuclear pore. Nup133 is a nucleoporin accessible on the basket side of the pore.\ \N \N \N 25621 IPR007188 Arp2/3 protein complex has been implicated in the control of actin polymerisation in cells. The human complex consists of seven subunits, which include the actin related Arp2 and Arp3, and five others referred to as p41-Arc, p34-Arc, p21-Arc, p20-Arc, and p16-Arc [MEDLINE:97375667]. This family represents the p34-Arc subunit.\ \N \N \N 25594 IPR007161 This is an archaeal domain of unknown function.\ \N \N \N 25595 IPR007162 This is an archaeal domain of unknown function.\ \N \N \N 25596 IPR007163 This is a predicted transmembrane domain of unknown function. Proteins usually have between 6 and 9 predicted transmembrane segments.\ \N \N \N 25597 IPR007164 This is family of archaebacterial proteins, which are about 170 amino acids in length. They have no known function. The most conserved portion of the protein contains the sequence GEEDL that may be important for its function.\ \N \N \N 25598 IPR007165 These proteins are predicted transmembrane proteins with probably four transmembrane spans. The function of these bacterial proteins is unknown. The sequences do not appear to contain any conserved polar residues that could form an active site.\ \N \N \N 25599 IPR007166 This family of archaeal proteins has no known function. They contain an N-terminal motif QXSXEXXXL that is likely to be functionally important.\ \N \N \N 25600 IPR007167 This family includes FeoA a small protein, probably involved in Fe²⁺ transport [MEDLINE:94012482].\ \N \N \N 25601 IPR007168 This domain is found in Phage shock protein C (PspC) that is thought to be a transcriptional regulator. The presumed domain is 60 amino acid residues in length.\ \N \N \N 25602 IPR007169 This is a bacterial domain of unknown function.\ \N \N \N 25603 IPR007170 This is a stage V sporulation protein G. It is essential for sporulation and specific to stage V sporulation in Bacillus megaterium and Bacillus subtilis [MEDLINE:92223102]. In B. subtilis, expression decreases after 30-60 minutes of cold shock [MEDLINE:96345629].\ \N \N \N 25604 IPR007171 This is an archaeal domain of unknown function.\ \N \N \N 25605 IPR007172 This is a bacterial domain of unknown function.\ \N \N \N 25606 IPR007173 This domain is specific to D-arabinono-1,4-lactone oxidase EC: 1.1.3.37, which is involved in the final step of the D-erythroascorbic acid biosynthesis pathway [MEDLINE:99140446].\ \N \N \N 25607 IPR007174 Las1 is an essential nuclear protein involved in cell morphogenesis and cell surface growth [MEDLINE:96129264].\ \N \N \N 25608 IPR007175 This family contains a ribonuclease P subunit of human and yeast. Other members of the family include the probable archaeal homologues. This subunit possibly binds the precursor tRNA [MEDLINE:21388393].\ \N \N \N 25609 IPR007176 This is an archaeal domain of unknown function.\ \N \N \N 25610 IPR007177

This domain is found in a family of proteins of unknown function. It appears to be found in eukaryotes and archaebacteria, and occurs associated with a potential metal-binding region in RNase L inhibitor, RLI (IPR007209).

\ \N \N \N 25611 IPR007178

DNA-directed RNA polymerase catalyses the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. In Sulfolobus acidocaldarius, RpoE2 is one of 13 subunits in the RNA polymerase. RpoE2 in Methanococcus jannaschii contains a predicted C4-type zinc finger at positions 4 to 19 and this sequence has been noted as a potential metal binding motif in Sulfolobus acidocaldarius [MEDLINE:94173739]. It is possible that family members contain a C4 zinc finger.

\ \N \N \N 25612 IPR007179

This is a family of proteins of unknown function. It is found N-terminal to another domain of unknown function, DUF381 (IPR007181).

\ \N \N \N 25613 IPR007180 This domain is specific to the human splicing factor 3b subunit 2 and its orthologs.\ \N \N \N 25614 IPR007181

This is a strongly conserved YPLM motif. It is found C-terminal to another domain of unknown function, DUF372 (IPR007179).

\ \ \N \N \N 25615 IPR007182

This domain is found in a possible subunit of the Na⁺/H⁺ antiporter [MEDLINE:99069340], [MEDLINE:21255662] as well as in the bacterial NADH dehydrogenase subunit. Usually four transmembrane regions are found in this domain.

\ \N \N \N 25616 IPR007183 This is a protein of unknown function.\ \N \N \N 25617 IPR007184 This is a protein of unknown function.\ \N \N \N 25618 IPR007185 DNA polymerase epsilon is essential for cell viability and chromosomal DNA replication in budding yeast. In addition, DNA polymerase epsilon may be involved in DNA repair and cell-cycle checkpoint control. The enzyme consists of at least four subunits in mammalian cells as well as in yeast. The largest subunit of DNA polymerase epsilon is responsible for polymerase activity. In mouse, the DNA polymerase epsilon subunit B is the second largest subunit of the DNA polymerase. A part of the N-terminal was found to be responsible for the interaction with SAP18. Experimental evidence suggests that this subunit may recruit histone deacetylase to the replication fork to modify the chromatin structure [MEDLINE:21861935].\ \N \N \N 25619 IPR007186

This domain inhibits pectin methylesterases (PMEs) and invertases through formation of a non-covalent 1:1 complex [MEDLINE:96085159]. It has been implicated in the regulation of fruit development, carbohydrate metabolism and cell wall extension. It may also be involved in inhibiting microbial pathogen PMEs. It has been observed that it is often expressed as a large inactive preprotein [MEDLINE:96085159]. It is also found at the N-termini of PMEs predicted from DNA sequences, suggesting that both PMEs and their inhibitors are expressed as a single polyprotein and subsequently processed. It has two disulphide bridges and is mainly -helical [MEDLINE:20341134].

\ \N \N \N 25593 IPR007160 This domain is found in some iron-sulphur proteins.\ \N \N \N 25591 IPR007158 The proteins in this family are around 200 amino acids long with the exception of O29206 that has an additional 100 amino acids at its N terminus. The function of these bacterial protein is unknown, however, they do contain several conserved histidines and aspartates that might form a metal-binding site.\ \N \N \N 25592 IPR007159 This domain is found in AbrB from Bacillus subtilis. The product of the abrB gene is an ambiactive repressor and activator of the transcription of genes expressed during the transition state between vegetative growth and the onset of stationary phase and sporulation [MEDLINE:89356632]. AbrB is thought to interact directly with the transcription initiation regions of genes under its control [MEDLINE:96345614]. AbrB contains a helix-turn-helix structure, but this domain ends before the helix-turn-helix begins [MEDLINE:91348201]. The product of the Bacillus subtilis gene spoVT is another member of this family and is also a transcriptional regulator [MEDLINE:96345614]. DNA-binding activity in this AbrB homologue requires hexamerisation [MEDLINE:20435284]. Another family member has been isolated from the Sulfolobus solfataricus and has been identified as a homologue of bacterial repressor-like proteins. The Escherichia coli family member SohA or Prl1F appears to be bifunctional and is able to regulate its own expression as well as relieve the export block imposed by high-level synthesis of

-galactosidase hybrid proteins [MEDLINE:90094216].\ \N \N \N 25575 IPR007142

Hemagglutinin esterases are membrane glycoproteins present on the surface of the virus and are involved with the cell infection process. Hemagglutinin esterase contains Hemagglutinin chain 1 (HE1) and Hemagglutinin chain 2 (HE2), and forms a homotrimer with each monomer being formed by two chains linked by a disulphide bond.

\ \ hydrolase activity, acting on ester bonds ; GO:0016788 \N initiation of viral infection ; GO:0019059 25576 IPR007143

Vacuolar protein sorting-associated protein VPS28 is required for normal endocytic and biosynthetic traffic to the yeast vacuole. It may facilitate the formation of transport intermediates required for efficient transport out of the prevacuolar endosome.

\ \N \N \N 25577 IPR007144 This protein is found to be part of a large ribonucleoprotein complex containing the U3 snoRNA [MEDLINE:22082292]. Depletion of the Utp proteins impedes production of the 18S rRNA, indicating that they are part of the active pre-rRNA processing complex. This large RNP complex has been termed the small subunit (SSU) processome [MEDLINE:22082292].\ \N \N \N 25578 IPR007145 This is a family of microtubule associated proteins. One of its members is the yeast anaphase spindle elongation protein.\ \N \N \N 25579 IPR007146 This family contains Sas10 which has been identified as a regulator of chromatin silencing [MEDLINE:98278808]. The family also contains Utp3 a component of the U3 ribonucleoprotein complex [MEDLINE:22082292]. The exact molecular function of this family is unknown.\ \N \N \N 25580 IPR007147 This is a family of proteins of unknown function found in yeast.\ \N \N \N 25581 IPR007148 This domain is found at the C terminus of proteins containing WD40 repeats. These proteins are part of the U3 ribonucleoprotein and the yeast protein is called Utp12 or DIP2 Q12220\ \ \ [MEDLINE:22082292].\ \ \N \N \N 25582 IPR007149 Members of this family are part of the Paf1/RNA polymerase II complex [MEDLINE:21924707], [MEDLINE:21881932]. The Paf1 complex probably functions during the elongation phase of transcription [MEDLINE:21924707].\ \N \N \N 25583 IPR007150 Hus1, Rad1, and Rad9 are three evolutionarily conserved proteins required for checkpoint control in fission yeast. These proteins are known to form a stable complex in vivo [MEDLINE:21602816]. Hus1-Rad1-Rad9 complex may form a PCNA-like ring structure, and could function as a sliding clamp during checkpoint control.\ \N \N \N 25584 IPR007151 This family includes proteins related to Mpp10 (M phase phosphoprotein 10). The U3 small nucleolar ribonucleoprotein (snoRNP) is required for three cleavage events that generate the mature 18S rRNA from the pre-rRNA. In Saccharomyces cerevisiae, depletion of Mpp10, a U3 snoRNP-specific protein, halts 18S rRNA production and impairs cleavage at the three U3 snoRNP-dependent sites [MEDLINE:98054269].\ \N \N \N 25585 IPR007152 Members of this family are around 350 amino acids in length. They are found in archaea and have no known function.\ \N \N \N 25586 IPR007153 Members of this family are around 160 amino acids in length and are mainly found in archaebacteria, with a small number of eubacterial examples. The high level of conservation in this family suggests some as yet unknown important biological function.\ \N \N \N 25587 IPR007154 Members of this family are around 120 amino acids in length and are found in some archaebacteria. The function of this family is unknown. However it contains a conserved motif IHPPAH that may be involved in its function.\ \N \N \N 25588 IPR007155 Members of this family are short (less than 100 amino acids) proteins found in archaebacteria. The function of these proteins is unknown.\ \N \N \N 25589 IPR007156 The members of this family are related to the LemA protein P71452. The exact molecular function of this protein is uncertain.\ \N \N \N 25590 IPR007157 This family includes PspA a protein that suppresses sigma54-dependent transcription. The PspA protein, a negative regulator of the Escherichia coli phage shock psp operon, is produced when virulence factors are exported through secretins in many Gram-negative pathogenic bacteria and its homologue in plants, VIPP1, plays a critical role in thylakoid biogenesis, essential for photosynthesis. Activation of transcription by the enhancer-dependent bacterial sigma54-containing RNA polymerase occurs through ATP hydrolysis-driven protein conformational changes enabled by activator proteins that belong to the large AAA(+) mechanochemical protein family. It has been shown that PspA directly and specifically acts upon and binds to the AAA(+) domain of the PspF transcription activator [MEDLINE:22075348].\ \N \N \N 25574 IPR007141 This domain is currently only found in a small set of Streptomyces coelicolor secreted proteins. There are four conserved cysteines that probably form two disulphide bonds. Proteins 2SCK31.15C (Q9ADK5) also have probable

-propellers at their C termini.\ \N \N \N 25569 IPR007136 This repeat is found as four tandem repeats in a family of bacterial membrane proteins. Each repeat contains two transmembrane regions and a conserved tryptophan.\ \N \N \N 25570 IPR007137 This domain normally occurs as tandem repeats; however it is found as a single copy in the Saccharomyces cerevisiae DNA-binding nuclear protein YCR593 (P25357).\ \N \N \N 25571 IPR007138 This domain is found in monooxygenases involved in the biosynthesis of several antibiotics by Streptomyces species. Its occurrence as a repeat in Streptomyces coelicolor SCO1909 (Q9X9W3) is suggestive that the other proteins function as multimers. There is also a conserved histidine which is likely to be an active site residue.\ \N \N \N 25572 IPR007139 This motif is found singly or as up to five tandem repeats in a small set of bacterial proteins. There are two or three

-helices, and possibly a

-strand.\ \N \N \N 25573 IPR007140 This motif occurs in a small set of bacterial proteins. It has two transmembrane regions, and often occurs as tandem repeats. The are no conserved catalytic residues.\ \N \N \N 25561 IPR007128 NNF1 is an essential yeast gene required for proper spindle orientation, nucleolar and nuclear envelope structure and mRNA export [MEDLINE:97388361].\ \N \N \N 25562 IPR007129

Yeast biquinol-cytochrome C chaperone is required for assembly of coenzyme QF-2-cytochrome C reductase. It appears to be found in a number of different organisms including human, Caenorhabditis elegans and Rhizobium meliloti.

\ \N \N \N 25563 IPR007130 The terminal step of triacylglycerol (TAG) formation is catalysed by the enzyme diacylglycerol acyltransferase (DAGAT) [MEDLINE:21623571], PUB00010588.\ \N \N \N 25564 IPR007131

The SLA1 homology domain is found in the cytoskeleton assembly control protein SLA1, which is responsible for the correct formation of the actin cytoskeleton.

\ \N \N \N 25565 IPR007132 This repeat was found as seven tandem copies in one protein. It is predicted to be composed of

-strands. Thus it is likely that it forms a

-propeller structure. It is found in association with BNR repeats, which also form a

-propeller.\ \N \N \N 25566 IPR007133 Members of this family are components of the RNA polymerase II associated Paf1 complex. The Paf1 complex functions during the elongation phase of transcription in conjunction with Spt4-Spt5 and Spt16-Pob3i [MEDLINE:21924707], [MEDLINE:21881932].\ \N \N \N 25567 IPR007134

Autophagocytosis is a starvation-induced process responsible for transport of cytoplasmic proteins to the vacuole. This domain is the N-terminal while the C-terminal is represented by IPR007135.

\ \N \N \N 25568 IPR007135

Autophagocytosis is a starvation-induced process responsible for transport of cytoplasmic proteins to the vacuole. This domain is the C-terminal while the N-terminal is represented by IPR007134.

\ \N \N \N 25555 IPR007122

Gelsolin is a cytoplasmic, calcium-regulated, actin-modulating protein that binds to the barbed ends of actin filaments, preventing monomer exchange (end-blocking or capping) [MEDLINE:87054019]. It can promote nucleation (the assembly of monomers into filaments), as well as sever existing filaments. In addition, this protein binds with high affinity to fibronectin. Plasma gelsolin and cytoplasmic gelsolin are derived from a single gene by alternate initiation sites and differential splicing.

Sequence comparisons indicate an evolutionary relationship between gelsolin, villin, fragmin and severin [MEDLINE:89094858]. Six large repeating segments occur in gelsolin and villin, and 3 similar segments in severin and fragmin. While the multiple repeats have yet to be related to any known function of the actin-severing proteins, the superfamily appears to have evolved from an ancestral sequence of 120 to 130 amino acid residues [MEDLINE:89094858].

\ \ actin binding activity ; GO:0003779 \N \N 25556 IPR007123

Gelsolin is a cytoplasmic, calcium-regulated, actin-modulating protein that bindsto the barbed ends of actin filaments, preventing monomer exchange (end-blocking or\ capping) [MEDLINE:87054019]. It can promote nucleation (the assembly of\ monomers into filaments), as well as sever existing filaments. In addition, this protein\ binds with high affinity to fibronectin. Plasma gelsolin and cytoplasmic gelsolin are\ derived from a single gene by alternate initiation sites and differential splicing.

Sequence comparisons indicate an evolutionary relationship between gelsolin,\ villin, fragmin and severin [MEDLINE:89094858]. Six large repeating segments\ occur in gelsolin and villin, and 3 similar segments in severin and fragmin. While the\ multiple repeats have yet to be related to any known function of the actin-severing\ proteins, the superfamily appears to have evolved from an ancestral sequence of 120\ to 130 amino acid residues [MEDLINE:89094858].

\ \ \N \N \N 25557 IPR007124 The core histones together with some other DNA binding proteins appear to form a superfamily defined by a common fold and distant sequence\ similarities [MEDLINE:95380285], [MEDLINE:97169409]. Some proteins contain\ local homology domains related to the histone fold [MEDLINE:97449368].\ \ DNA binding activity ; GO:0003677 \N \N 25558 IPR007125

The core histones together with some other DNA binding proteins appear to forma superfamily defined by a common fold and distant sequence similarities [MEDLINE:95380285],\ [MEDLINE:97169409]. Some proteins contain local\ homology domains related to the histone fold [MEDLINE:97449368].

\ \ DNA binding activity ; GO:0003677 \N \N 25559 IPR007126 This is a family of proteins encoded by plasmids found in Borrelia burgdorferi.\ \N \N \N 25554 IPR007121 DNA-dependent RNA polymerases (EC: 2.7.7.6) are ubiquitous enzymes necessary for the transcription of genomic DNA into RNA. Prokaryotes contain a single RNA polymerase compared to three in eukaryotes (not including mitochondrial and chloroplast polymerases). Most RNA polymerases are multimeric enzymes and are composed of a variable number of subunits. However the two largest subunits (generally known as

and

chains) are present in all known multimeric RNA polymerases. The

chains are proteins of from 900 to 1400 amino acid residues. A well conserved region of 13 residues that contains two conserved lysines and which is thought to be part of the active site is located in the C-terminal part of all

chains [MEDLINE:94267933].\ DNA-directed RNA polymerase activity ; GO:0003899 \N transcription ; GO:0006350 25560 IPR007127

The bacterial core RNA polymerase complex, which consists of five subunits, is sufficient for transcription elongation and termination but is unable to initiate transcription. Transcription initiation from promoter elements requires a sixth,\ dissociable subunit called a sigma factor, which reversibly associates with the core RNA polymerase complex to form a\ holoenzyme PUB00000061. RNA polymerase recruits alternative sigma factors\ as a means of switching on specific regulons. Most bacteria express a multiplicity of sigma factors. Two of these factors, \ sigma-70 (gene rpoD), generally known as the major or primary sigma factor, and sigma-54 (gene rpoN or ntrA) \ direct the transcription of a wide variety of genes. The other sigma factors, known as alternative sigma \ factors, are required for the transcription of specific subsets of genes.

With regard to sequence similarity, \ sigma factors can be grouped into two classes, the sigma-54 and sigma-70 families. Sequence alignments of the sigma70 family members reveal four conserved regions that can be further divided into subregions eg. sub-region 2.2, which\ may be involved in the binding of the sigma factor to the core RNA polymerase; and sub-region 4.2, which \ seems to harbor a DNA-binding 'helix-turn-helix' motif involved in binding the conserved -35 region of \ promoters recognized by the major sigma factors PUB00000061, PUB00002181. \

Region 1.1 modulates DNA binding by region 2 and 4 when sigma is unbound by the core RNA polymerase PUB00002181, [MEDLINE:20082865]. Region 1.1 is also involved in promoter binding.

\ \ \N \N \N 25552 IPR007119

This group of phage proteins is characterised by a conserved N-terminal region, typically about 325 residues in length. The proteins have not been characterized functionally.

\ \N \N \N 25553 IPR007120

RNA polymerases (EC: 2.7.7.6) catalyse the DNA dependent polymerisation of RNA.Prokaryotes contain a single RNA polymerase compared to three in eukaryotes (not\ including mitochondrial. and chloroplast polymerases). This domain represents the\ hybrid binding domain and the wall domain [MEDLINE:21291401]. The\ hybrid-binding domain binds the nascent RNA strand / template DNA strand in the\ Pol II transcription elongation complex. This domain contains the important structural\ motifs, switch 3 and the flap loop and binds an active site metal ion [MEDLINE:21291401]. This domain is also involved in binding to Rpb1 and Rpb3\ [MEDLINE:21291401]. Many of the bacterial members contain large insertions\ within this domain, which is known as dispensable region 2 (DRII).

\ \ DNA-directed RNA polymerase activity ; GO:0003899 \N transcription ; GO:0006350 25547 IPR007114

Among the different families of transporter only two occur ubiquitously in all classifications of organisms. These are the ATP-Binding Cassette (ABC) superfamily and the Major Facilitator Superfamily (MFS). The MFS transporters are single-polypeptide secondary carriers capable only of transporting small solutes in response to chemiosmotic ion gradients [MEDLINE:98190790], [MEDLINE:99085261].

\ The MFS family contains members that function as uniporters, symporters or antiporters. In addition their solute specificity are also diverse. MFS proteins contain 12 transmembrane regions (with some variations).\

\ \ \N \N \N 25548 IPR007115

6-pyruvoyl tetrahydropterin synthase (EC: 4.2.3.12) (PTPS) [MEDLINE:94185630] catalyzes the second step in the biosynthesis of tetrahydrobiopterin (BH4); a complex rearrangement of 7,8-dihydroneopterin triphosphate into 6-pyruvoyl tetrahydropterin.

PTPS is a small protein of about 145 residues and forms a homooligomeric complex of two trimers assembled in a head-to-head fashion [MEDLINE:94185630]. It binds a magnesium atom which is ligated by three histidine residues. Three residues are implicated in the catalytic mechanism: a cysteine, a histidine and a glutamate. This family also includes several hypothetical proteins.

\ \ \N \N \N 25549 IPR007116

\ \ \ 6-pyruvoyltetrahydropterin synthase activity ; GO:0003874\ \N \N tetrahydrobiopterin biosynthesis ; GO:0006729 25551 IPR007118

Expansins are unusual proteins that mediate cell wall extension in plants [MEDLINE:96016146]. They are believed to act as a sort of chemical grease, allowing polymers to slide past one another by disrupting non-covalent hydrogen bonds that hold many wall polymers to one another. This process is notdegradative and hence does not weaken the wall, which could otherwise rupture under internal pressure during growth.

Sequence comparisons indicate at least four distinct expansin cDNAs in rice and at least six in Arabidopsis. The proteins are highly conserved in\ size and sequence (75-95% amino acid sequence similarity between any pairwise comparison), and phylogenetic trees indicate that this multigene\ family formed before the evolutionary divergence of monocotyledons and dicotyledons [MEDLINE:96016146]. Sequence and motif analyses show no similarities to known functional domains that might account for expansin action on wall extension. It is thought that several highly-conserved tryptophans may function in expansin binding to cellulose, or other glycans. The high conservation of the family indicates that the mechanism by which expansins promote wall extensin tolerates little variation in protein structure.

Grass pollens, such as pollen from timothy grass, represent a major cause of type I allergy [MEDLINE:95015525]. Interestingly, expansins share a high degree of\ sequence similarity with the Lol p I family of allergens.

\ \ \N extracellular ; GO:0005576 \N 25550 IPR007117

Grass pollens, such as pollen from timothy grass, represent a major cause of type I allergy [MEDLINE:95015525] ]. Interestingly, expansins share a high degree of\ sequence similarity with the Lol p I family of allergens. This entry represents the C-terminal domain.

\ \ \N \N \N 25546 IPR007113

The term cupin (from the Latin term 'cupa', for a small barrel or cask) has been given to a -barrel structural domain identified in a superfamily of prokaryotic and eukaryotic proteins. The cupin domain is found in one or two copies in proteins whose functions vary from isomerase and epimerase activities involved in the modification of cell wall carbohydrates in bacteria, to non-enzymatic storage proteins in plant seeds, and transcription factors linked to congenital baldness in mammals. The characteristic cupin domain comprises two conserved motifs, each corresponding to two strands. For the first conserved motif, the characteristic conserved sequence is G-x(5)-H-x-H-x(3,4)-E-x(6)-G, and for second conserved motif this is G-x(5)-P-x-G-x(2)-H-x(3)-N. Between these two motifs (usually His containing) is a less conserved region composed of two strands with an intervening loop of variable length. It has been proposed that the compact -barrel structure that makes up the cupin core has been coopted for a variety of purposes, many or all of which require a thermostable, pepsin-resistant framework, usually containing metal-binding ligands [MEDLINE:21605898], [MEDLINE:21165333], [MEDLINE:20171904].

\ \N \N \N 25544 IPR007111

The NACHT domain is a 300 to 400 residue predicted nucleoside triphosphatase (NTPase) domain, which is found in animal, fungal and bacterial proteins. The NACHT domain has been named after NAIP, CIITA, HET-E and TP1. It is found inassociation with other domains, such as the CARD domain (IPR001315), the\ DAPIN domain (IPR001315/>), the HEAT repeat (IPR004155), the WD\ repeat (IPR004155/>), the leucine-rich repeat (LRR) or the BIR repeat (IPR001370.

\ The NACHT domain consists of seven distinct conserved motifs, including the ATP/GTPase specific P-loop, the Mg(2+)-binding site (Walker\ A and B motifs, respectively) and five more specific motifs. The unique features of the NACHT domain include the prevalence of 'tiny' residues\ (glycine, alanine or serine) directly C-terminal of the Mg(2+)-coordinating aspartate in the Walker B motif, in place of a second acidic residue prevalent\ in other NTPases. A second acidic residue is typically found in the NACHT-containing proteins two positions downstream. Furthermore, the distal motif VII contains a conserved pattern of polar, aromatic and hydrophobic residues that is not seen in any other NTPase family [MEDLINE:20245680].

\ \ \N \N \N 25545 IPR007112

Expansins are secreted proteins of 25 to 27 Kd that were isolated first from young cucumber seedling and subsequently from other plant tissues. Expression of expansin genes correlates with growth of cells. Increase in expansin content also occurs during fruit ripening. Expansins act on the cell wall to promote its extensibility. The model for its mechanism of action postulates that expansins break non-covalent bonds between cell-wall polysaccharides, thereby permitting pressure dependant expansion of the cell [MEDLINE:76033922], [MEDLINE:21521099].

\ Group-I pollen allergens of grasses have limited but significant sequence homology to expansin. These proteins are the main causative agent of hay fever and seasonal asthma induced by grass pollen. Extracts containing group-I allergens are also active in loosening cell-walls. Group-I pollen allergens and related proteins in vegetative tissues have been classified as -expansins, whereas the earlier discovered expansins are now referred to as -expansins [MEDLINE:97322412].

\ Expansin-like proteins are also found in some fungi. In Trichoderma reesei an expansin-like protein (Cel12A) acts as a glycoside hydrolase on xyloglucan and 1-4 -glucan. These hydrolytic actions differ from the action by expansins, which induce wall extension by a non-hydrolytic mechanism [MEDLINE:21437957]. According to sequence analysis expansins can be divided in two domains, a cysteine-rich region that displays some homology to family-45 endoglucanases (EG45-like domain) and the carboxy-terminal part that may function as a cellulose-binding domain (CBD). Two entries are available for this family, the first one is for the EG45-like domain, this entry, while the second profile detects the cellulose-binding\ domain.\ \

\ \ \N \N \N 25541 IPR007108

Homeobox transcription factors form one of the largest families of specifically eukariotic transcription factors. They are characterized by the presence of a homeodomain, which is a conserved DNA-binding domain. The wide family of homeodomains can be divided into several subfamilies, one of which is the cut-homeodomain subfamily.

\ The word 'cut' originates from the Drosophila cut gene encoding a cut-homeodomain transcription factor. Mammalian counterparts of the Drosophila cut homeoprotein are human CCAAT displacement protein (CDP) and murine Cux proteins [MEDLINE:21297175]. Cut-homeodomain proteins contain one, two or three cut domains (IPR003350) and one homeodomain downstream of the cut domains. Cut domains as well as homeodomains are DNA-binding domains and are not yet found in proteins that do not contain a homeodomain. CDP/Cux/Cut proteins form an evolutionarily conserved family. \ In Drosophila melanogaster cut gene functions as a determinant of cell-type specification in several tissues, notably in the peripheral nervous system, \ the wing margin and the Malpighian tubule. In vertebrates, the same functions appear to be fulfilled by two cut-related genes with distinct patterns of expression. The human CCAAT-displacement protein (CDP) was later found to be the DNA binding protein of the previously characterized histone nuclear \ factor D (HiNF-D).

\ Various combinations of Cut repeats and the Cut homeodomains can generate distinct DNA binding activities. These activities are elevated in \ proliferating cells and decrease during terminal differentiation. The role of CDP/Cux/Cut proteins reviewed in [MEDLINE:21297175].\ \

\ \ \N \N \N 25543 IPR007110

The basic structure of immunoglobulin (Ig) PUB00005317 molecules is a tetramer of two light chains and two heavy chains linked by disulfide bonds. There are two\ types of light chains: kappa and lambda, each composed of a constant domain\ (CL) and a variable domain (VL). There are five types of heavy chains: ,\ delta, epsilon, gamma and mu, all consisting of a variable domain (VH) and\ three (in , delta and gamma) or four (in epsilon and mu) constant\ domains (CH1 to CH4). The major histocompatibility complex (MHC) molecules are made of two chains.\ In class I PUB00005317 the chain is composed of three extracellular domains, a\ transmembrane region and a cytoplasmic tail. The chain (-2-microglobulin) is composed of a single extracellular domain. In class II PUB00002017,\ both the and the chains are composed of two extracellular domains,\ a transmembrane region and a cytoplasmic tail.

\ It is known PUB00002017, PUB00002014 that the Ig constant chain domains and a single\ extracellular domain in each type of MHC chains are related. These\ homologous domains are approximately one hundred amino acids long and\ include a conserved intradomain disulfide bond. Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include\ antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in\ protein-protein and protein-ligand interactions.

This entry is for immunoglobulin-like domains. Studies indicate that the interactions essential for\ defining the structure of these sandwich proteins are also important in nucleation of folding, and that proteins containing this fold may share similar folding pathways even though the proteins may have low sequence homology. The fold consists of a -sandwich formed of 7 strands in 2 sheets with a Greek-key topology. Some members of the fold have additional strands. The Pfam alignments do not include the first and last strand of the\ immunoglobulin-like domain.\

\ \ \ \N \N \N 25542 IPR007109

The Brix domain is found in a number of eukaryotic proteins including SSF proteins from yeast and humans, Arabidopsis thaliana Peter Pan-like protein and several hypothetical proteins.

\ \N \N \N 25540 IPR007107

Homeobox transcription factors form one of the largest families of specifically eukaryotic transcription factors.They are characterized by the presence of a homeodomain, which is a conserved DNA-binding domain.\ The wide family of homeodomains can be divided into several subfamilies, one of which is LIM-homeodomain subfamily.

\ LIM-homeodomain proteins contain two tandem LIM domains N-terminal to a homeodomain. Tandem LIM domains (IPR001781.

\ Whereas homeodomains are DNA-binding domains, LIM domains are essential for regulating the activity of LIM-homeodomain\ proteins by interacting with other proteins. LIM domains are also found in proteins that do not contain homeodomains, but are well conserved [MEDLINE:98257020].\

\ \ \N \N \N 25538 IPR007105

The Six (Drosophila sine oculis homeobox homologue) protein family [MEDLINE:20340561]consists of eukaryotic transcription factors that include a Six domain adjacent to a homeodomain (IPR001356).\ A number of studies suggest important roles for the Six genes in the development of the anterior part of the vertebrate CNS and eye, \ in myogenesis and perhaps also in the development of the auditory system, kidneys, digits and connective tissue [MEDLINE:20340561].

\ In each of the C. elegans, Drosophila, mouse and human genomes several members of the Six family of genes (named Six1, Six2, Six3, Six4,\ Six5, Six6 in vertebrates) were determined. Six family proteins possess extensive sequence similarity between one another in the Sine oculis-homologous region (Six domain and homeodomain) but they differ greatly in structure in some other regions. The Six domain is an approximately 120 amino acids motif adjacent to the N-terminal of a homeodomain. Both domains are essential for specific DNA binding [MEDLINE:20340561].\ The 3D structure of the Six domain has not yet been determined.

\ \ \N \N \N 25537 IPR007104

The homeobox domain was first identified in a number of Drosophila homeotic and segmentation proteins, but is now known to be well-conserved in many other animals, \ including vertebrates [MEDLINE:89323170], [MEDLINE:93032126], PUB00005540. Proteins containing \ homeobox domains are likely to play an important role in development and most are known \ to be sequence-specific DNA-binding transcription factors. The domain binds DNA through a \ helix-turn-helix (HTH) structure. The HTH motif is characterised by two -helices, \ which make intimate contacts with the DNA and are joined by a short turn. The second \ helix binds to DNA via a number of hydrogen bonds and hydrophobic interactions, which \ occur between specific side chains and the exposed bases and thymine methyl groups within \ the major groove of the DNA PUB00005540. The first helix helps to stabilise the \ structure.

The motif is very similar in sequence and structure in a wide range of \ DNA-binding proteins (e.g., cro and repressor proteins, homeotic proteins, etc.). One of \ the principal differences between HTH motifs in these different proteins arises from the \ stereo-chemical requirement for glycine in the turn which is needed to avoid steric \ interference of the -carbon with the main chain: for cro and repressor proteins the \ glycine appears to be mandatory, while for many of the homeotic and other DNA-binding \ proteins the requirement is relaxed.

This entry is a subfamily of homeobox domains known as the paired-like homeobox domain.

\ \ \N \N \N 25539 IPR007106

The Six (Drosophila sine oculis homeobox homologue) protein family [MEDLINE:20340561]consists of eukaryotic transcription factors that include a Six domain adjacent to a homeodomain.\ A number of studies suggest important roles for the Six genes in the development of the anterior part of the vertebrate CNS and eye, \ in myogenesis and perhaps also in the development of the auditory system, kidneys, digits and connective tissue [MEDLINE:20340561].

\ In each of the Caenorhabditis elegans, Drosophila melanogaster, mouse and human genomes several members of the Six family of genes (named Six1, Six2, Six3, Six4,\ Six5, Six6 in vertebrates) were determined. Six family proteins possess extensive sequence similarity between one another in the Sine oculis-homologous region (Six domain and homeodomain) but they differ greatly in structure in some other regions. The Six domain is an approximately 120 amino acids motif adjacent to the N-terminal of a homeodomain. Both domains are essential for specific DNA binding [MEDLINE:20340561].\ The 3D structure of the Six domain has not yet been determined. This entry describes the Six/sine subfamily of homeodomains.

\ \ \N \N \N 25534 IPR007101

Autonomous mobile genetic elements such as transposon or insertion sequences (IS) encode an enzyme, called transposase, required for excising and inserting the mobile element. On the basis of sequence similarities, transposases can be grouped into various families. One of these families is called IS21 family or IS21/IS408/IS1162 family [MEDLINE:21210161]. These proteins consist of 315 to 582 amino acids and contain putative DNA-binding domains (HTH domains, domains with helix-turn-helix structural motif) of 60 to 84 amino acids long. At the base of similarity of putative HTH-domain, the family can be divided onto two subfamilies.

\ The first subfamily, whose HTH domain is described by this entry, contains transposases from the following elements:

IS21 from Pseudomonas aeruginosa.
IS1326 from Pseudomonas aerigunosa
IS640 from Shigella sonnei
IS5376 from Bacillus stearotermophilus
IS232 from Bacillus thuringiensis
IS21-like from Bacteroides fragilis
A potentional insertion element from Chelatobacter heintzii

\ \ \N \N \N 25535 IPR007102

\ The HTH domain of first subfamily is described by IPR007101, the HTH-domain of the second subfamily is described by this entry. This subfamily contains:

a putative transposase Y4UI from Rhizobium sp. (strain NGR234)
a putative transposase Y4BL/Y4KJ/Y4TB from Rhizobium sp. (strain NGR234)
a transposase from IS408 from Burkholderia cepacia (syn. Pseudomonas cepacia)
a transposase from IS1162 from Pseudomonas fluorescens

\ \ \N \N \N 25536 IPR007103

POU proteins are eukaryotic transcription factors containing a bipartite DNA binding domain referred to as the POU domain. The acronym POU (pronounced 'pow') is derived from the names of three mammalian transcription factors, the pituitary-specific Pit-1, the octamer-binding proteins Oct-1 and Oct-2, and the neural Unc-86 from Caenorhabditis elegans. POU domain genes have been described in organisms as divergent as Caenorhabditis elegans, Drosophila, Xenopus, zebrafish and human but have not been yet identified in plants and fungi. The various members of the POU family have a wide variety of functions, all of which are related to the development of an organism [MEDLINE:21087503].

\ The POU domain is a bipartite domain composed of two subunits separated by a non-conserved region of 15-55 aa. The N-terminal subunit is known as POU-specific (POUs) domain (IPR000327.

\ In the wide family of well conserved homeodomains, those that occur in POU-proteins form the POU homeodomain subfamily. Members of the POU-homeodomain subfamily of the homeodomain family are highly conserved and represented by this entry.

\ \ \N \N \N 25532 IPR007099

RNA-directed RNA polymerase (RdRp) (EC: 2.7.7.48) is an essential protein encoded in the genomes of all RNA containing viruses with no DNA stage. It catalyses synthesis of the RNA strand complementary to a given RNA template. RdRp's of many viruses are products of processing of polyproteins. Some RdRp's consist of one polypeptide chain, others are complexes of several subunits.The domain organization [MEDLINE:99097433] and the 3D structure of the catalytic center of a wide range of RdPp's, even those with a low overall sequence homology, are conserved. The catalytic center is formed by several motifs containing a number of conserved amino acid residues.

\ \

There are 4 superfamilies of viruses that cover all RNA containing viruses with no DNA stage:

Viruses containing positive-strand RNA or double-strand RNA, except retroviruses and Birnaviridae: viral RNA-directed RNA polymerases including all positive-strand RNA viruses with no DNA stage, double-strand RNA viruses, and the Cystoviridae, Reoviridae, Hypoviridae, Partitiviridae, Totiviridae families.
Mononegavirales (negative-strand RNA viruses with non-segmented genomes).
Negative-strand RNA viruses with segmented genomes, i.e. Orthomyxoviruses (including influenza A, B, and C viruses, Thogotoviruses, and the infectious salmon anemia virus), Arenaviruses, Bunyaviruses, Hantaviruses, Nairoviruses, Phleboviruses, Tenuiviruses and Tospoviruses.
Birnaviridae family of dsRNA viruses.

\ The RNA-directed RNA polymerases may also be divided into the following three subgroups of the above superfamily:

All positive-strand RNA eukaryotic viruses with no DNA stage.
All RNA-containing bacteriophages -there are two families of RNA-containing bacteriophages: Leviviridae (positive ssRNA phages) and Cystoviridae (dsRNA phages).
Reoviridae family of dsRNA viruses.

\ \

This entry corresponds to a relatively conserved segment of 147 - 180 aa of RdRp or its catalytic subunit. \ The proteins in this family are: RNA polymerase PB1 subunits of Orthomyxoviruses and RNA polymerases (L proteins) of Arenaviruses, Bunyaviruses, Hantaviruses, Nairoviruses, Phleboviruses, Tenuiviruses and Tospoviruses.

\ \ RNA-directed RNA polymerase activity ; GO:0003968 \N viral genome replication ; GO:0019079 25533 IPR007100

\ \

There are 4 superfamilies of viruses that cover all RNA containing viruses with no DNA stage:

Viruses containing positive-strand RNA or double-strand RNA, except retroviruses and Birnaviridae: viral RNA-directed RNA polymerases including all positive-strand RNA viruses with no DNA stage, double-strand RNA viruses, and the Cystoviridae, Reoviridae, Hypoviridae, Partitiviridae, Totiviridae families.
Mononegavirales (negative-strand RNA viruses with non-segmented genomes).
Negative-strand RNA viruses with segmented genomes, i.e. Orthomyxoviruses (including influenza A, B, and C viruses, Thogotoviruses, and the infectious salmon anemia virus), Arenaviruses, Bunyaviruses, Hantaviruses, Nairoviruses, Phleboviruses, Tenuiviruses and Tospoviruses.
Birnaviridae family of dsRNA viruses.

\ The RNA-directed RNA polymerases may also be divided into the following three subgroups of the above superfamily:

All positive-strand RNA eukaryotic viruses with no DNA stage.
All RNA-containing bacteriophages -there are two families of RNA-containing bacteriophages: Leviviridae (positive ssRNA phages) and Cystoviridae (dsRNA phages).
Reoviridae family of dsRNA viruses.

\ \

This domain is found in the Birnaviridae family of dsRNA viruses. The domain corresponds \ to a conservative segment of 105 aa nearly in the middle of \ the polypepdide chain of RdRp.

\ \ RNA-directed RNA polymerase activity ; GO:0003968 \N viral genome replication ; GO:0019079 25530 IPR007097

\ \

There are 4 superfamilies of viruses that cover all RNA containing viruses with no DNA stage:

Viruses containing positive-strand RNA or double-strand RNA, except retroviruses and Birnaviridae: viral RNA-directed RNA polymerases including all positive-strand RNA viruses with no DNA stage, double-strand RNA viruses, and the Cystoviridae, Reoviridae, Hypoviridae, Partitiviridae, Totiviridae families.
Mononegavirales (negative-strand RNA viruses with non-segmented genomes).
Negative-strand RNA viruses with segmented genomes, i.e. Orthomyxoviruses (including influenza A, B, and C viruses, Thogotoviruses, and the infectious salmon anemia virus), Arenaviruses, Bunyaviruses, Hantaviruses, Nairoviruses, Phleboviruses, Tenuiviruses and Tospoviruses.
Birnaviridae family of dsRNA viruses.

\ The RNA-directed RNA polymerases may also be divided into the following three subgroups of the above superfamily:

All positive-strand RNA eukaryotic viruses with no DNA stage.
All RNA-containing bacteriophages -there are two families of RNA-containing bacteriophages: Leviviridae (positive ssRNA phages) and Cystoviridae (dsRNA phages).
Reoviridae family of dsRNA viruses.

\ \

This entry represents the Reoviridae family of dsRNA viruses.

\ \ RNA-directed RNA polymerase activity ; GO:0003968 \N viral genome replication ; GO:0019079 25531 IPR007098

\ \

There are 4 superfamilies of viruses that cover all RNA containing viruses with no DNA stage:

Viruses containing positive-strand RNA or double-strand RNA, except retroviruses and Birnaviridae: viral RNA-directed RNA polymerases including all positive-strand RNA viruses with no DNA stage, double-strand RNA viruses, and the Cystoviridae, Reoviridae, Hypoviridae, Partitiviridae, Totiviridae families.
Mononegavirales (negative-strand RNA viruses with non-segmented genomes).
Negative-strand RNA viruses with segmented genomes, i.e. Orthomyxoviruses (including influenza A, B, and C viruses, Thogotoviruses, and the infectious salmon anemia virus), Arenaviruses, Bunyaviruses, Hantaviruses, Nairoviruses, Phleboviruses, Tenuiviruses and Tospoviruses.
Birnaviridae family of dsRNA viruses.

\ The RNA-directed RNA polymerases may also be divided into the following three subgroups of the above superfamily:

All positive-strand RNA eukaryotic viruses with no DNA stage.
All RNA-containing bacteriophages -there are two families of RNA-containing bacteriophages: Leviviridae (positive ssRNA phages) and Cystoviridae (dsRNA phages).
Reoviridae family of dsRNA viruses.

\ \

This entry corresponds to the segment of 128 - 141 aa of RdRp, which contains three motifs putatively \ forming the catalytic center. RdRp's of these viruses can have descriptions: \ "Large protein", "L protein", "RNA polymerase subunit", \ "Polymerase subunit L".

\ \ RNA-directed RNA polymerase activity ; GO:0003968 \N viral genome replication ; GO:0019079 25529 IPR007096

\ \

There are 4 superfamilies of viruses that cover all RNA containing viruses with no DNA stage:

Viruses containing positive-strand RNA or double-strand RNA, except retroviruses and Birnaviridae: viral RNA-directed RNA polymerases including all positive-strand RNA viruses with no DNA stage, double-strand RNA viruses, and the Cystoviridae, Reoviridae, Hypoviridae, Partitiviridae, Totiviridae families.
Mononegavirales (negative-strand RNA viruses with non-segmented genomes).
Negative-strand RNA viruses with segmented genomes, i.e. Orthomyxoviruses (including influenza A, B, and C viruses, Thogotoviruses, and the infectious salmon anemia virus), Arenaviruses, Bunyaviruses, Hantaviruses, Nairoviruses, Phleboviruses, Tenuiviruses and Tospoviruses.
Birnaviridae family of dsRNA viruses.

\ The RNA-directed RNA polymerases may also be divided into the following three subgroups of the above superfamily:

All positive-strand RNA eukaryotic viruses with no DNA stage.
All RNA-containing bacteriophages -there are two families of RNA-containing bacteriophages: Leviviridae (positive ssRNA phages) and Cystoviridae (dsRNA phages).
Reoviridae family of dsRNA viruses.

\ \

This entry is for all RNA-containing bacteriophages. There are two families of \ RNA-containing bacteriophages: Leviviridae (positive ssRNA phages)\ and Cystoviridae (dsRNA phages).

\ \ RNA-directed RNA polymerase activity ; GO:0003968 \N viral genome replication ; GO:0019079 25528 IPR007095

\ \

There are 4 superfamilies of viruses that cover all RNA containing viruses with no DNA stage:

Viruses containing positive-strand RNA or double-strand RNA, except retroviruses and Birnaviridae: viral RNA-directed RNA polymerases including all positive-strand RNA viruses with no DNA stage, double-strand RNA viruses, and the Cystoviridae, Reoviridae, Hypoviridae, Partitiviridae, Totiviridae families.
Mononegavirales (negative-strand RNA viruses with non-segmented genomes).
Negative-strand RNA viruses with segmented genomes, i.e. Orthomyxoviruses (including influenza A, B, and C viruses, Thogotoviruses, and the infectious salmon anemia virus), Arenaviruses, Bunyaviruses, Hantaviruses, Nairoviruses, Phleboviruses, Tenuiviruses and Tospoviruses.
Birnaviridae family of dsRNA viruses.

\ The RNA-directed RNA polymerases may also be divided into the following three subgroups of the above superfamily:

All positive-strand RNA eukaryotic viruses with no DNA stage.
All RNA-containing bacteriophages -there are two families of RNA-containing bacteriophages: Leviviridae (positive ssRNA phages) and Cystoviridae (dsRNA phages).
Reoviridae family of dsRNA viruses.

\ \

This entry represents RNA-directed RNA polymerase from double-strand and positive-strand RNA viruses with no DNA stage including Arteriviridae, Bromoviridae, Caliciviridae, Comoviridae, \ Coronaviridae, Flaviviridae, Leviviridae, Luteoviridae, \ Picornaviridae, Potyviridae, Togaviridae, Tombusviridae,\ Capilloviruses, Carlaviruses, Potexviruses, Tobamoviruses,\ Tobraviruses, Trichoviruses, Tymoviruses, Hepatitis E-like viruses,\ Allexivirus and Sobemovirus.

\ \ RNA-directed RNA polymerase activity ; GO:0003968 \N viral genome replication ; GO:0019079 25526 IPR007093

Leucine-rich repeats (LRR) are tandemly repeated modules of about 24 amino acids. They occur in a large number of functionally diverse proteins [MEDLINE:95117131] , [MEDLINE:21622566]. Many LRR regions are known to function as protein-protein interaction domains. The fold of the LRR repeat units is known from several crystal structures, e.g. from:

ribonuclease inhibitor [MEDLINE:94088748]
U2a small nuclear protein [MEDLINE:98379985]
internalin B [MEDLINE:20101247]
Rab geranylgeranyltransferase [MEDLINE:20211860]

\ One LRR corresponds to a

-strand followed by either

-helix, 3(10)-helix \ or a polyproline II helix [MEDLINE:21622566]. The LRR proteins have been described as \ horseshoe-shaped molecules with a curved parallel

-sheet lining the inner \ circumference of the horeseshoe and the helices flanking its outer circumference. \ At least seven subfamilies of LRR proteins, characterized by different lengths \ and consensus sequences of the repeats, have been identified [MEDLINE:96097394], [MEDLINE:98202568].

This entry is for the Treponema pallidum type leucine-rich repeats.

\ \ \N \N \N 25527 IPR007094

\ \

There are 4 superfamilies of viruses that cover all RNA containing viruses with no DNA stage:

Viruses containing positive-strand RNA or double-strand RNA, except retroviruses and Birnaviridae: viral RNA-directed RNA polymerases including all positive-strand RNA viruses with no DNA stage, double-strand RNA viruses, and the Cystoviridae, Reoviridae, Hypoviridae, Partitiviridae, Totiviridae families.
Mononegavirales (negative-strand RNA viruses with non-segmented genomes).
Negative-strand RNA viruses with segmented genomes, i.e. Orthomyxoviruses (including influenza A, B, and C viruses, Thogotoviruses, and the infectious salmon anemia virus), Arenaviruses, Bunyaviruses, Hantaviruses, Nairoviruses, Phleboviruses, Tenuiviruses and Tospoviruses.
Birnaviridae family of dsRNA viruses.

\ The RNA-directed RNA polymerases may also be divided into the following three subgroups of the above superfamily:

All positive-strand RNA eukaryotic viruses with no DNA stage.
All RNA-containing bacteriophages -there are two families of RNA-containing bacteriophages: Leviviridae (positive ssRNA phages) and Cystoviridae (dsRNA phages).
Reoviridae family of dsRNA viruses.

\ \

This entry represents RNA-directed RNA polymerase from all positive-strand RNA eukaryotic viruses with no DNA stage.

\ \ RNA-directed RNA polymerase activity ; GO:0003968 \N viral genome replication ; GO:0019079 25522 IPR007089

ribonuclease inhibitor [MEDLINE:94088748]
U2a small nuclear protein [MEDLINE:98379985]
internalin B [MEDLINE:20101247]
Rab geranylgeranyltransferase [MEDLINE:20211860]

\ One LRR corresponds to a

-strand followed by either

-helix, 3(10)-helix \ or a polyproline II helix [MEDLINE:21622566]. The LRR proteins have been described as \ horseshoe-shaped molecules with a curved parallel

This entry is for the cysteine-containing leucine-rich repeat.

\ \ \N \N \N 25523 IPR007090

ribonuclease inhibitor [MEDLINE:94088748]
U2a small nuclear protein [MEDLINE:98379985]
internalin B [MEDLINE:20101247]
Rab geranylgeranyltransferase [MEDLINE:20211860]

\ One LRR corresponds to a

-strand followed by either

-helix, 3(10)-helix \ or a polyproline II helix [MEDLINE:21622566]. The LRR proteins have been described as \ horseshoe-shaped molecules with a curved parallel

This entry is for the plant specific leucine-rich repeat.

\ \ \N \N \N 25524 IPR007091

ribonuclease inhibitor [MEDLINE:94088748]
U2a small nuclear protein [MEDLINE:98379985]
internalin B [MEDLINE:20101247]
Rab geranylgeranyltransferase [MEDLINE:20211860]

\ One LRR corresponds to a

-strand followed by either

-helix, 3(10)-helix \ or a polyproline II helix [MEDLINE:21622566]. The LRR proteins have been described as \ horseshoe-shaped molecules with a curved parallel

This entry is for the ribonuclease inhibitor type leucine-rich repeat.

\ \ \N \N \N 25525 IPR007092

ribonuclease inhibitor [MEDLINE:94088748]
U2a small nuclear protein [MEDLINE:98379985]
internalin B [MEDLINE:20101247]
Rab geranylgeranyltransferase [MEDLINE:20211860]

\ One LRR corresponds to a

-strand followed by either

-helix, 3(10)-helix \ or a polyproline II helix [MEDLINE:21622566]. The LRR proteins have been described as \ horseshoe-shaped molecules with a curved parallel

This entry is for the SDS22+-like leucine-rich repeat.

\ \ \N \N \N 25520 IPR007087

Zinc finger domains [MEDLINE:88151019], PUB00005329 are nucleic acid-binding protein structures first identified in the Xenopus laevis transcription factor TFIIIA. These domains have since been found in \ numerous nucleic acid-binding proteins. A zinc finger domain is composed of 25 to 30 amino-acid \ residues including 2 conserved Cys and 2 conserved His residues in a C-2-C-12-H-3-H type motif. \ The 12 residues separating the second Cys and the first His are mainly polar and basic, implicating \ this region in particular in nucleic acid binding. The zinc finger motif is an unusually small, \ self-folding domain in which Zn is a crucial component of its tertiary structure. All bind 1 atom of \ Zn in a tetrahedral array to yield a finger-like projection, which interacts with nucleotides in the \ major groove of the nucleic acid. The Zn binds to the conserved Cys and His residues. Fingers have \ been found to bind to about 5 base pairs of nucleic acid containing short runs of guanine residues. \ They have the ability to bind to both RNA and DNA, a versatility not demonstrated by the helix-turn-helix motif. The zinc finger may thus represent the original nucleic acid binding protein. It has \ also been suggested that a Zn-centred domain could be used in a protein interaction, e.g. in protein \ kinase C. Many classes of zinc fingers are characterized according to the number and positions of the \ histidine and cysteine residues involved in the zinc atom coordination. In the first class to be \ characterized, called C2H2, the first pair of zinc coordinating residues are cysteines, while the \ second pair are histidines.

\ \ \ \N \N \N 25521 IPR007088

ribonuclease inhibitor [MEDLINE:94088748]
U2a small nuclear protein [MEDLINE:98379985]
internalin B [MEDLINE:20101247]
Rab geranylgeranyltransferase [MEDLINE:20211860]

\ One LRR corresponds to a

-strand followed by either

-helix, 3(10)-helix \ or a polyproline II helix [MEDLINE:21622566]. The LRR proteins have been described as \ horseshoe-shaped molecules with a curved parallel

This entry is for the bacterial-type leucine-rich repeat.

\ \ \N \N \N 25516 IPR007083 RNA polymerases catalyse the DNA dependent polymerisation of RNA. Prokaryotes contain a single RNA polymerase compared to three in eukaryotes (not including mitochondrial and chloroplast polymerases). This entry, domain 4, represents the funnel domain. The funnel domain contains the binding site for some elongation factors [MEDLINE:97066998], [MEDLINE:21291401].\ \N \N \N 25517 IPR007084

The BRICHOS domain is about 100 amino acids long. It is found in a variety of proteins implicated in dementia, respiratory distress and cancer.

\ \N \N \N 25518 IPR007085

The DNA/pantothenate metabolism flavoprotein (EC: 4.1.1.36) affects synthesis of DNA and pantothenate metabolism.

\ \N \N \N 25519 IPR007086

\ \ \N \N \N 25510 IPR007077

This domain is found in a number of bacterial proteins including the TfoX gene product of Haemophilus influenzae. TfoX may play a key role in the development of genetic competence by regulating the expression of late competence-specific genes [MEDLINE:95241551]. This family corresponds to the C-terminal presumed domain of TfoX. The domain is found in association with the N-terminal domain in some, but not all members of this group, suggesting this is an autonomous and functionally unrelated domain. For example it is found associated with Q9JZR1.

\ \N \N \N 25511 IPR007078 The CcmD protein is part of a C-type cytochrome biogenesis operon [MEDLINE:95362656]. The exact function of this protein is uncertain. It has been proposed that CcmC, CcmD and CcmE interact directly with each other, establishing a cytoplasm to periplasm haem delivery pathway for cytochrome c maturation [MEDLINE:20453456]. This protein is found fused to CcmE in P52224. These proteins contain a predicted transmembrane helix.\ \N \N \N 25512 IPR007079 This enzyme transforms N(2)-succinylglutamate into succinate and glutamate. This is the fifth and last step in arginine catabolism by the arginine succinyltransferase pathway.\ \N \N \N 25513 IPR007080

RNA polymerases catalyse the DNA-dependent polymerisation of RNA. Prokaryotes contain a single RNA polymerase compared to three in eukaryotes (not including mitochondrial and chloroplast polymerases). This domain, domain 1, represents the clamp domain, which is a mobile domain involved in positioning the DNA, maintenance of the transcription bubble and positioning of the nascent RNA strand [MEDLINE:97066998], [MEDLINE:21291401].

\ \N \N \N 25514 IPR007081 RNA polymerases catalyse the DNA dependent polymerisation of RNA. Prokaryotes contain a single RNA polymerase compared to three in eukaryotes (not including mitochondrial and chloroplast polymerases). This domain, domain 5, represents the discontinuous cleft domain that is required to form the central cleft or channel where the DNA is bound [MEDLINE:97066998], [MEDLINE:21291401].\ \N \N \N 25515 IPR007082 In Escherichia coli, nine gene products are known to be essential for assembly of the division septum. One of these, FtsL, is a bitopic membrane protein whose precise function is not understood. It has been proposed that FtsL interacts with the DivIC protein IPR007060\ \ \ [MEDLINE:20305030], however this interaction may be indirect [MEDLINE:21990420].\ \ \N \N \N 25509 IPR007076

This domain is found in a number of bacterial proteins including the TfoX gene product of Haemophilus influenzae. TfoX may play a key role in the development of genetic competence by regulating the expression of late competence-specific genes [MEDLINE:95241551]. This family corresponds to the N-terminal presumed domain of TfoX. The domain is found in association with the C-terminal domain in some, but not all members of this group, suggesting this is an autonomous and functionally unrelated domain.

\ \N \N \N 25505 IPR007072 Members of this family are about 220 amino acids long. The CmcI protein O85726. However this has not been experimentally verified.\ \N \N \N 25506 IPR007073 RNA polymerases catalyse the DNA dependent polymerisation of RNA. Prokaryotes contain a single RNA polymerase compared to three in eukaryotes (not including mitochondrial and chloroplast polymerases). This domain, domain 7, represents a mobile module of the RNA polymerase. Domain 7 interacts with the lobe domain of Rpb2 (IPR007642.\ \N \N \N 25507 IPR007074 The LICD family of proteins show high sequence similarity and are involved in phosphorylcholine metabolism. There is evidence to show that LicD2 mutants have a reduced ability to take up choline, have decreased ability to adhere to host cells and are less virulent [MEDLINE:99217023].\ \N \N \N 25508 IPR007075 RNA polymerases catalyse the DNA dependent polymerisation of RNA. Prokaryotes contain a single RNA polymerase compared to three in eukaryotes (not including mitochondrial and chloroplast polymerases). This domain, domain 6, represents a mobile module of the RNA polymerase. Domain 6 forms part of the shelf module [MEDLINE:97066998], [MEDLINE:21291401]. This family appears to be specific to the largest subunit of RNA polymerase II.\ \N \N \N 25501 IPR007067 This family represents the tail sheath protein Gp18 of bacteriophage T4 and its homologues.\ \N \N \N 25502 IPR007069 Transposases are needed for efficient transposition of the insertion sequence or transposon DNA. This family includes transposases IS1294 and IS801.\ \N \N \N 25503 IPR007070 This family of eukaryotic proteins include phosphatidylinositolglycan class N (PIG-N), which is the mammalian homologue of the yeast protein MCD4P expressed in the endoplasmic reticulum [MEDLINE:20044774]. PIG-N is essential for glycosylphosphatidylinositol anchor synthesis. Glycosylphosphatidylinositol (GPI)-anchored proteins are cell surface-localised proteins that serve many important cellular functions [MEDLINE:99169011].\ \N \N \N 25504 IPR007071 A-kinase (or PKA)-anchoring protein AKAP95 is implicated in mitotic chromosome condensation by acting as a targeting molecule for the condensin complex. The protein contains two zinc fingers which are thought to mediate the binding of AKAP95 to DNA [MEDLINE:21987933].\ \N \N \N 25488 IPR007052 The function of the CS domain is unknown. The CS domain is sometimes found C-terminal to the CHORD domain (IPR007051.\ \N \N \N 25489 IPR007053

This domain is found in proteins from viruses, bacteria and the eukayota. The domain contains a well-conserved NCEHF motif. The function of this domain is unknown.

\ \N \N \N 25490 IPR007054 The lysis S protein is a cytotoxic protein forming holes in membranes causing cell lysis. The action of Lysis S is independent of the proportion of acidic phospholipids in the membrane [MEDLINE:93223998].\ \N \N \N 25491 IPR007055 This domain is found in several secreted and transport-associated proteins.\ \N \N \N 25492 IPR007057

This family contains the archaeal flagellar protein F and related proteins, they appear to be distantly related to IPR007058.

\ \N \N \N 25493 IPR007058 This family appears to be distantly related to IPR002774 which are also components of the archaeal flagellar.\ \N \N \N 25494 IPR007059 The terminal electron transfer enzyme dimethyl sulphoxide reductase of Escherichia coli is a heterotrimeric enzyme composed of a membrane extrinsic catalytic dimer (DmsAB) and a membrane intrinsic polytopic anchor subunit (DmsC) [MEDLINE:93155163]. This family represents DmsC.\ \ \ \N \N \N 25495 IPR007060 DivIC from Bacillus subtilis is necessary for both vegetative and sporulation septum formation [MEDLINE:94156852]. These proteins are mainly composed of an N-terminal coiled-coil.\ \N \N \N 25496 IPR007061 This family is commonly found in Streptomyces coelicolor and is of unknown function. These proteins contain several conserved histidines at their N-terminus that may form a metal binding site.\ \N \N \N 25497 IPR007062 Protein phosphatase inhibitor 2 (IPP-2) is a phosphoprotein conserved among all eukaryotes, and it appears in both the nucleus and cytoplasm of tissue culture cells [MEDLINE:22220296].\ \N \N \N 25498 IPR007064 The NMD3 protein is involved in nonsense mediated mRNA decay. This N-terminal region contains four conserved CXXC motifs that could be metal binding. NMD3 is involved in export of the 60S ribosomal subunit is mediated by the adapter protein Nmd3p in a Crm1p-dependent pathway [MEDLINE:99147073].\ \N \N \N 25499 IPR007065 These proteins are integral membrane proteins with four transmembrane spanning helices. The most conserved region of an alignment of the proteins is a motif HPP. The function of these proteins is uncertain but they may be transporters.\ \N \N \N 25500 IPR007066 RNA polymerases catalyse the DNA dependent polymerisation of RNA. Prokaryotes contain a single RNA polymerase compared to three in eukaryotes (not including mitochondrial and chloroplast polymerases). This domain, domain 3, represents the pore domain. The 3' end of RNA is positioned close to this domain. The pore delimited by this domain is thought to act as a channel through which nucleotides enter the active site and/or where the 3' end of the RNA may be extruded during back-tracking [MEDLINE:97066998], [MEDLINE:21291401].\ \N \N \N 25479 IPR007043 This family of enzymes deaminates glutamine to glutamate EC: 3.5.1.2.\ \N \N \N 25480 IPR007044 This family is defined by the cyclodeaminase active site. In prokaryotes it is a single functional protein whereas in animals it occurs as a C-terminal domain in the the bifunctional enzyme formiminotransferase-cyclodeaminase (FTCD) EC: 4.3.1.4.\ \N \N \N 25481 IPR007045

This family of bacterial proteins have been characterized as, 4-deoxy-L-threo-5-hexosulose-uronate ketol-isomerase (EC: 5.3.1.17), an enzyme involved in pectin degradation.

\
 4-deoxy-L-threo-5-hexosulose uronate\
  =\
      3-deoxy-D-glycero-2,5-hexodiulosonate\

\ \ \N \N \N 25482 IPR007046 This domain makes a direct interaction with the core RNA polymerase, to form an enhancer dependent holoenzyme [MEDLINE:20353443]. The centre of this domain contains a very weak similarity to a helix-turn-helix motif, which may represent a DNA binding domain.\ \N \N \N 25483 IPR007047

This entry is for the fimbriae associated protein Flp/Fap pilin component.

\ \N \N \N 25484 IPR007048 These proteins from bacteriophage T4 and related phage may be a structural component of the outer wedge of the baseplate that has acidic lysozyme activity [MEDLINE:89041577].\ \N \N \N 25485 IPR007049

The carbohydrate-selective porin OprB family includes the Pseudomonas aeruginosa porin B, a substrate-selective channel for a variety of different sugars. This protein may facilitate diffusion of a variety of diverse compounds, but is probably restricted to carbohydrates, and does facilitate glucose fusion across the outer membrane.

\ \ \N \N \N 25486 IPR007050

Numerous bacterial transcription regulatory proteins bind DNA via a helix-turn-helix (HTH) motif. This entry represents the HTH DNA binding domain found in Halobacterium halobium and described as a putative bacterio-opsin activator.

\ \N \N \N 25487 IPR007051 CHORD represents a Zn binding domain. Silencing of the Caenorhabditis elegans CHORD-containing gene results in semisterility and embryo lethality, suggesting an essential function of the wild-type gene in nematode development. The CHORD domain is sometimes found N-terminal to the CS domain, IPR007052.\ \N \N \N 25472 IPR007036 This family includes succinylglutamate desuccinylase EC:3.1.-.- that catalyses the fifth and last step in arginine catabolism by the arginine succinyltransferase pathway. The family also includes aspartoacylase EC: 3.5.1.15 which cleaves acylaspartate into a fatty acid and aspartate. Mutations in P45381.\ \N \N \N 25473 IPR007037

This entry includes the vibriobactin utilization protein viuB, which is involved in the removal of iron from iron-vibriobactin complexes, as well as several hypothetical proteins.

\ \N \N \N 25474 IPR007038 This family of proteins are hydrogenase/urease accessory proteins. They contain many conserved histidines that are likely to be involved in nickel binding.\ \N \N \N 25475 IPR007039

Conjugal transfer protein, TrbC, has been identified as a subunit of the pilus precursor in bacteria. The protein undergoes three processing steps before gaining its mature cyclic structure [MEDLINE:22151900].

\ \N \N \N 25476 IPR007040 This protein associates with 70s ribosomes and converts them to a dimeric form (100S ribosomes) which appear during the transition from the exponential growth phase to the stationary phase of Escherichia coli cells.\ \N \N \N 25477 IPR007041 Arginine N-succinyltransferase EC: 2.3.1.109 catalyzes the transfer of succinyl-CoA to arginine to produce succinylarginine. This is the first step in arginine catabolism by the arginine succinyltransferase pathway.\ \N \N \N 25478 IPR007042 This conserved, predominantly, C-terminal region is found in a number of proteins including arsenite-resistance protein 2, which is thought to play a role in arsenite resistance [MEDLINE:99167000]. Arsenite is a carcinogenic compound which can act as a comutagen by inhibiting DNA repair.\ \N \N \N 25464 IPR007028 The function of this family of short bacterial proteins is unknown. \ \N \N \N 25465 IPR007029 This short presumed domain is about 50 amino acid residues long. It often contains two cysteines that may be functionally important. This domain is found in copper transporting ATPases, some phenol hydroxylases and in a set of uncharacterised membrane proteins including Q9CNI0. This domain is named after three of the most conserved amino acids it contains. The domain may be metal binding, possibly copper ions. This domain is duplicated in some copper transporting ATPases.\ \N \N \N 25466 IPR007030

This conserved region is about 120 residues long, encompassing nearly the total sequence length. It defines a family of Bacterial proteins whose functions have not been determined. This family is named after the most conserved motif found in the alignment of the family members. In a single instance it is found as an N-terminal domain fused to a putative RNA polymerase sigma factor containing a Myb-like DNA-binding domain Q9A8M4).

\ \N \N \N 25467 IPR007031 Members of this family are approximately 26 KDa, and are involved in trans-activation of late transcription [MEDLINE:96099447].\ transcriptional activator activity ; GO:0016563 \N regulation of viral transcription ; GO:0046782 25468 IPR007032

These proteins are homologues of vaccinia virus A51.

\ \N \N \N 25469 IPR007033 This is a family of hypothetical eukaryotic proteins.\ \N \N \N 25470 IPR007034 This conserved region is found in a number of uncharacterised eukaryotic proteins.\ \N \N \N 25471 IPR007035 The Bacillus subtilis DppA is a binuclear zinc-dependent, D-specific aminopeptidase. The structure reveals that DppA is a new example of a self-compartmentalising protease, a family of proteolytic complexes. Proteasomes are the most extensively studied representatives of this family. The DppA enzyme is composed of identical 30 kDa subunits organised in a decamer with 52 point-group symmetry. A 20 A wide channel runs through the complex, giving access to a central chamber holding the active sites. The structure shows DppA to be a prototype of a new family of metalloaminopeptidases characterised by the SXDXEG key sequence [MEDLINE:21366084]. The only known substrates are D-ala-D-ala and D-ala-gly-gly.\ \N \N \N 25455 IPR007019

The surfeit locus protein SURF-6 has been shown to be a component of the nucleolar matrix and has a strong binding capacity for nucleic acids [MEDLINE:98208152]. SURF-6 is always found in the nucleolus regardless of the phase of the cell cycle suggesting that it is a structural protein constitutively present in nucleolar substructures. A role in rRNA processing has been proposed for this protein.

\ \ \N \N \N 25456 IPR007020

These are proteins of unknown function found in Lactococcus lactis and in their associated bacteriophage.

\ \N \N \N 25457 IPR007021 These are transposase-like proteins with no known function.\ \N \N \N 25458 IPR007022 Survival motor neuron (SMN) interacting protein 1, SIP1, interacts with SMN protein and plays a crucial role in the biogenesis of spliceosomes. There is an evidence that the protein is linked to spinal muscular atrophy and amyotrophic lateral sclerosis in humans [MEDLINE:21940678].\ \N \N \N 25459 IPR007023

This is a family of eukaryotic ribosomal biogenesis regulatory proteins.

\ \N \N \N 25460 IPR007024 An FAD-binding domain, BLUF, exemplified by the N-terminus of the AppA protein, (Q53119.\ \N \N \N 25461 IPR007025 Late expression factor 8 (LEF-8) is one of the primary components of RNA polymerase produced by polyhedrosis viruses. LEF-8 shows homology to the second largest subunit of prokaryotic DNA-directed RNA polymerase[MEDLINE:22120165].\ \N \N \N 25462 IPR007026 This short domain contains four conserved cysteines that are probably required for the formation of two disulphide bonds. The domain is named after the characteristic CC motif.\ \N \N \N 25463 IPR007027 These proteins belong to the poxvirus F11 family. They are early virus proteins.\ \N \N \N 25449 IPR007013 Replicative DNA polymerases are capable of polymerizing tens of thousands of nucleotides without dissociating from their DNA templates. The high processivity of these polymerases is dependent upon accessory proteins that bind to the catalytic subunit of the polymerase or to the substrate. The Epstein-Barr virus (EBV) BMRF1 protein is an essential component of the viral DNA polymerase and is absolutely required for lytic virus replication [MEDLINE:99131385]. BMRF1 is also a transactivator [MEDLINE:99131385]. This family is predicted to have a UL42-like structure [MEDLINE:20337916].\ \N \N \N 25450 IPR007014 This is a family of short proteins found in eukaryotes and some archaea. Although the function of these proteins is not known they may contain transmembrane helices.\ \N \N \N 25451 IPR007015 Proteins of this family are predominantly nucleolar. The majority are described as transcription factor transactivators. The family also includes the fifth essential DNA polymerase (Pol5p) of Schizosaccharomyces pombe and Saccharomyces cerevisiae (EC: 2.7.7.7). Pol5p is localized exclusively to the nucleolus and binds near or at the enhancer region of rRNA-encoding DNA repeating units. \ \N \N \N 25452 IPR007016 This group of bacterial proteins is involved in the synthesis of O-antigen, a lipopolysaccharide found in the outer membrane in gram-negative bacteria. The enzyme is coded for by the gene wzy which is part of the O-antigen gene cluster [MEDLINE:22103117].\ \N \N \N 25453 IPR007017 The proteins in this family are about 150 amino acids in length. They are composed of three sections. The N-terminal region is of low complexity. The central region contains a GXXXGH motif and the C-terminal region contains four conserved cysteines that might be a metal binding site such as an iron-sulphur cluster.\ \N \N \N 25454 IPR007018 Regulation of mRNA synthesis requires intermediary proteins that transduce regulatory signals from upstream transcriptional activator proteins to basal transcription machinery at the core promoter. Three types of intermediary factors that enable the basal transcription machinery to respond to transcriptional activator proteins bound to regulatory DNA sequences have been identified: (i) TAFIIs, which associate with TATA-binding protein (TBP) to form TFIID; (ii) mediator, which associates with RNA polymerase II to form a holo-polymerase; and (iii) coactivators such as human upstream stimulatory activity (USA), mammalian CBP/P300, yeast ADA complex, and HMG proteins. The interaction of these multiprotein complexes with activators and general transcription factors is essential for transcriptional regulation. This family of proteins represent the transcriptional mediator protein that is required for activation of many RNA polymerase II promoters and which are conserved from yeast to humans [MEDLINE:97378038].\ \N \N \N 25447 IPR007011

Late embryogenesis abundant (LEA) proteins accumulate to high levels during the last stage of seed formation (when a natural desiccation of the seed tissues takes place) and during periods of water deficit in vegetative organs. LEA proteins have been grouped into at least six families on the basis of sequence similarity. Although significant similarity has not been detected between the members of the different classes, a unifying and outstanding feature of these proteins is their high hydrophilicity and high percentage of glycines. Amino acid sequence analysis allows one to predict that these proteins exist primarily as random coils. This property has been confirmed in few cases with purified proteins and is supported by the fact that proteins of this type do not coagulate upon heating. LEA protein families have been identified in a wide range of different plant species to the extent that they can be considered ubiquitous in plants. Moreover, it has been shown that members of at least one of the LEA protein families, the so-called dehydrins, are present in a range of photosynthetic organisms, including lower plants, algae, and cyanobacteria. In addition similar proteins, the hydrophilins are induced in a variety of different taxons, of non-photosynthetic organsims, in response to osmotic stress. All of these proteins have a high hydrophilicity index, generally greater than 1.0 [MEDLINE:20148771].

This conserved region identifies a set of plant seed maturation proteins described as LEA D34.

\ \ \N \N \N 25448 IPR007012

In eukaryotes, polyadenylation of pre-mRNA plays an essential role in the initiation step of protein synthesis, as well as in the export and stability of mRNAs. Poly(A) polymerase, the enzyme at the heart of the polyadenylation machinery, is a template-independent RNA polymerase which specifically incorporates ATP at the 3' end of mRNA. The crystal structure of bovine poly(A) polymerase bound to an ATP analog at 2.5 A resolutio has been determined [MEDLINE:20402325]. The structure revealed expected and unexpected similarities to other proteins. As expected, the catalytic domain of poly(A) polymerase shares substantial structural homology with other nucleotidyl transferases such as DNA polymerase and kanamycin transferase.

The central domain of Poly(A) polymerase shares structural similarity with the allosteric activity domain of ribonucleotide reductase R1, which comprises a four-helix bundle and a three-stranded mixed -sheet. Even though the two enzymes bind ATP, the ATP-recognition motifs are different.

\ \ \N \N \N 25436 IPR007000

Basement membranes separate dissimilar cell types and thus compartmentalize almost all tissues. They are thin sheets of extracellular matrix whose main components are type IV collagen, nidogen, sulfated proteoglycans, and laminins. Laminins are found in all basement membranes, but also in embryonic mesenchyme and loose connective tissue. Lamin is thought to mediate the attachment, migration and organisation of cells into tissues during embryonic development by interacting with other extracellular matrix components [MEDLINE:90368768].

All native laminins identified so far are composed of one , one , and one gamma chain and 12 different heterotrimers have been proposed based on five , three , and three gamma chains. In vitro studies have indicated that laminins mediate a variety of biological functions. First they form a self-assembling structural network to which other components of the basement membrane attach. Second, they attach cells to the extracellular matrix via -dystroglycan and integrin receptors. Third, they convey information to the cell interior via these receptors, as exemplified by mesenchymal to epithelial transitions in kidney, myogenesis in skeletal muscle, and outgrowth of neurites. Studies of mutated genes as well as gene targeting experiments have indicated different functional roles for the different laminins [MEDLINE:21966136].

\ \

This family of proteins represents the chain of laminin.

\ \ \N \N \N 25437 IPR007001 This domain represents the high-similarity N-terminal constant region shared by shufflon proteins. Shufflon proteins are created as a result of a clustered inversion region. The proteins retain a constant N-terminal domain, with different C-terminal domains.\ \N \N \N 25438 IPR007002

The dlt operon (dltA to dltD) of Lactobacillus rhamnosus 7469 encodes four proteins responsible for the esterification of lipoteichoic acid (LTA) by D-alanine. These esters play an important role in controlling the net anionic charge of the poly (GroP) moiety of LTA. DltA and DltC encode the D-alanine-D-alanyl carrier protein ligase (Dcl) and D-alanyl carrier protein (Dcp), respectively. Whereas the functions of DltA and DltC are defined, the functions of DltB and DltD are unknown. In vitro assays showed that DltD bound Dcp for ligation with D-alanine by Dcl in the presence of ATP. In contrast, the homologue of Dcp, the Escherichia coli acyl carrier protein (ACP), involved in fatty acid biosynthesis, was not bound to DltD and thus was not ligated with D-alanine. DltD also catalyzed the hydrolysis of the mischarged D-alanyl-ACP. The hydrophobic N-terminal sequence of DltD was required for anchoring the protein in the membrane. It is hypothesized that this membrane-associated DltD facilitates the binding of Dcp and Dcl for ligation of Dcp with D-alanine and that the resulting D-alanyl-Dcp is translocated to the primary site of D-alanylation [MEDLINE:20245544].

\ \

These sequences contain the central region of DltD.

\ \ \ \N \N \N 25439 IPR007003 This family includes several uncharacterised archaeal proteins.\ \N \N \N 25440 IPR007004 This is a family of hypothetical proteins, the majority is from Beet necrotic yellow vein virus.\ \N \N \N 25441 IPR007005 These proteins are found in a wide range of eukaryotes. Their function is uncertain though they are nuclear proteins, possibly with DNA-binding activity.\ \N \N \N 25442 IPR007006 The ALG10 protein from Saccharomyces cerevisiae encodes the

-1,2 glucosyltransferase of the endoplasmic reticulum. This protein has been characterised in rat as potassium channel regulator 1 [MEDLINE:98389735].\ \N \N \N 25443 IPR007007 Ninjurin (nerve injury-induced protein) is involved in nerve regeneration and in the formation of some tissues [MEDLINE:96374367].\ \N \N \N 25444 IPR007008

This is a family of poxvirus proteins of unknown function.

\ \N \N \N 25445 IPR007009 This conserved region identifies a set of hypothetical protein sequences from the Metazoa and Ascomycota which include SHQ1 from Saccharomyces cerevisiae.\ \N \N \N 25446 IPR007010

In eukaryotes, polyadenylation of pre-mRNA plays an essential role in the initiation step of protein synthesis, as well as in the export and stability of mRNAs. Poly(A) polymerase, the enzyme at the heart of the polyadenylation machinery, is a template-independent RNA polymerase which specifically incorporates ATP at the 3' end of mRNA. The crystal structure of bovine poly(A) polymerase bound to an ATP analog at 2.5 A resolution has been determined [MEDLINE:20402325]. The structure revealed expected and unexpected similarities to other proteins. As expected, the catalytic domain of poly(A) polymerase shares substantial structural homology with other nucleotidyl transferases such as DNA polymerase and kanamycin transferase.

The C-terminal domain unexpectedly folds into a compact domain reminiscent of the RNA-recognition motif fold. The three invariant aspartates of the catalytic triad ligate two of the three active site metals. One of these metals also contacts the adenine ring. Furthermore, conserved, catalytically important residues contact the nucleotide. These contacts, taken together with metal coordination of the adenine base, provide a structural basis for ATP selection by poly(A) polymerase.

\ \ \ \N \N \N 25430 IPR006994 This family includes a number of poorly characterised eukaryotic proteins.\ \N \N \N 25431 IPR006995 This is one of the chains of the nonenzymatic component (CF(0) subunit) of the mitochondrial ATPase complex.\ \N \N \N 25432 IPR006996 Dynamitin is a subunit of the microtubule-dependent motor complex, it is also implicated in cell adhesion by binding to macrophage-enriched myristoylated alanine-rice C kinase substrate (MacMARCKS) [MEDLINE:22194336].\ \N \N \N 25433 IPR006997

This is a family of Baculovirus proteins of unknown function.

\ \N \N \N 25434 IPR006998

\ \

These sequences contain the C-terminal region of DltD.

\ \ \N \N \N 25435 IPR006999

\ \

These sequences contain the N-terminal region of DltD.

\ \ \ \ \N \N \N 25427 IPR006990 None of the members of the tweety (tty) family have been functionally characterized. However, they are considered to be transmembrane proteins with five potential membrane-spanning regions. A number of potential functions have been suggested on the basis of homology to the yeast FTR1 and FTH1 iron transporter proteins and the mammalian neurotensin receptors 1 and 2 in that they have a similar hydrophobicity profiles\ although there is no detectable sequence homology to the tweety-related proteins. It has been proposed that the tweety-related\ proteins could be involved in transport of iron or other divalent cations or alternatively that they may be\ membrane-bound receptors [MEDLINE:20408891].\ \ \N \N \N 25428 IPR006992 These proteins are amidohydrolases that are related to the metal-dependent hydrolase superfamily [MEDLINE:97290007]. The family includes, the catalytic domain of urease

subunit, adenine deaminase (EC: 3.5.4.2) that hydrolyses adenine to form hypoxanthine and ammonia which is important for adenine utilization as a purine and also as a nitrogen source. The family also includes dihydroorotase and N-acetylglucosamine-6-phosphate deacetylases (EC: 3.5.1.25). These enzymes catalyse the reversible reaction:

\
 N-acetyl-D-glucosamine 6-phosphate + H2O  = D-glucosamine 6-phosphate + acetate. \

\ \ \N \N \N 25429 IPR006993

This family of proteins, which contains SH3BGRL3, is functionally uncharacterized. SH3BGRL3 is a highly conserved small protein, which is widely expressed and shows a significant similarity to glutaredoxin 1 (GRX1) of Escherichia coli which is predicted to belong to the thioredoxin superfamily. However, SH3BGRL3 lacks both conserved cysteine residues, which characterize\ the enzymatic active site of GRX. This structural feature raises the possibility that SH3BGRL3 and its homologues could function as\ endogenous modulators of GRX activity [MEDLINE:21338244].

\ \ \N \N \N 25425 IPR006988 Nab1 and Nab2 are co-repressors that specifically interact with and repress transcription mediated by the three members of the NGFI-A (Egr-1, Krox24, zif/268) family of eukaryotic (metazoa) transcription factors [MEDLINE:98078707]. This region consists of the N-terminal NAB conserved region 1, which interacts with the EGR1 inhibitory domain (R1) [MEDLINE:98078707]. It may also mediate multimerisation.\ \ \N \N \N 25426 IPR006989 Nab1 and Nab2 are co-repressors that specifically interact with and repress transcription mediated by the three members of the NGFI-A (Egr-1, Krox24, zif/268) family of eukaryotic (metazoa) transcription factors [MEDLINE:98078707]. This family consists of NAB conserved region 2, near the C terminus of the protein. It is necessary for transcriptional repression by the Nab proteins [MEDLINE:98078707]. It is also required for transcription activation by Nab proteins at Nab-activated promoters [MEDLINE:20200474].\ \N \N \N 25419 IPR006982

Glutamate synthase (GltS)1 is a key enzyme in the early stages of the assimilation of ammonia in bacteria, yeasts, and plants. In bacteria, L-glutamate is involved in osmoregulation, is the precursor for other amino acids, and can be the precursor for heme biosynthesis. In plants, GltS is especially essential in the reassimilation of ammonia released by photorespiration. On the basis of the amino acid sequence and the nature of the electron donor, three different classes of GltS can de defined as follows: 1) ferredoxin-dependent GltS (Fd-GltS), 2) NADPH-dependent GltS (NADPH-GltS), and 3) NADH-dependent GltS (properties of the three classes have been reviewed extensively [MEDLINE:99284123]). The enzyme is a complex iron-sulfur flavoprotein catalyzing the reductive transfer of the amido nitrogen from L-glutamine to 2-oxoglutarate to form two molecules of L-glutamate via intramolecular channeling of ammonia from the amidotransferase domain to the FMN-binding domain.

Reaction of amidotransferase domain:

 \
L-glutamine + H2O = L-glutamate + NH3\

\ \

Reactions of FMN-binding domain:

\ \

 \
2-oxoglutarate + NH3 = 2-iminoglutarate + H2O\

\ \ \ \

2e + FMNox = FMNred\

\ \ \ \

2-iminoglutarate + FMNred = L-glutamate + FMNox\

\ The central domain of glutamate synthase connects the N-terminal amidotransferase domain with the FMN-binding domain and has an

overall topology [MEDLINE:22086160].\ \ \N \N \N 25420 IPR006983 The MbeD and MobD proteins are plasmid encoded, and are involved in the plasmid mobilisation and transfer in the presence of conjugative plasmids [MEDLINE:89364735].\ \N \N \N 25421 IPR006984 This family is comprises of uncharacterized eukaryotic proteins.\ \N \N \N 25422 IPR006985 The calcitonin-receptor-like receptor can function as either a calcitonin-gene-related peptide or an adrenomedullin receptor. The receptors function is modified by receptor activity modifying protein or RAMP. RAMPs are single-transmembrane-domain proteins [MEDLINE:98282119].\ \N \N \N 25423 IPR006986 Nab1 and Nab2 are co-repressors that specifically interact with and repress transcription mediated by the three members of the NGFI-A (Egr-1, Krox24, zif/268) family of eukaryotic (metazoa) transcription factors [MEDLINE:98078707]. This C-terminal region is found only in the Nab1 subfamily.\ \N \N \N 25424 IPR006987 The vaccinia virus interferon (IFN)-gamma receptor (IFN-gammaR) is a 43 kDa soluble glycoprotein that is secreted from infected cells early during infection. IFN-gammaR from vaccinia virus, cowpox\ virus and camelpox virus exist naturally as homodimers, whereas the cellular IFN-gammaR dimerizes only upon\ binding the homodimeric IFN-gamma. The existence of the virus protein as a dimer in the absence of ligand may\ provide an advantage to the virus in efficient binding and inhibition of IFN-gamma in solution [MEDLINE:21830916].\ \ \N \N \N 25409 IPR006972 SseC is a secreted protein that forms a complex together with SecB and SecD on the surface of Salmonella typhimurium. All these proteins are secreted by the type III secretion system [MEDLINE:76000597]. Many mucosal pathogens use type III secretion systems for the injection of effector proteins into target cells. SecB, SseC and SecD are inserted into the target cell membrane. where they form a small pore or translocon [MEDLINE:76000597], [MEDLINE:21464504]. In addition to SseC, this family includes the bacterial secreted proteins PopB, PepB, YopB and EspD which are thought to be directly involved in pore formation, and type III secretion system translocon.\ \N \N \N 25410 IPR006973 This family represents Cwf15/Cwc15 (from Schizosaccharomyces pombe and Saccharomyces cerevisiae respectively) and their homologues. The function of these proteins is unknown, but they form part of the spliceosome and are thus thought to be involved in mRNA splicing [MEDLINE:21881936].\ \N \N \N 25411 IPR006974

This is a family of hypothetical proteins from Chlamydia pneumoniae.

\ \N \N \N 25412 IPR006975 NifQ is involved in early stages of the biosynthesis of the iron-molybdenum cofactor (FeMo-co) [MEDLINE:93302717], which is an integral part of the active site of dinitrogenase [MEDLINE:95042780]. The conserved C-terminal cysteine residues may be involved in metal binding [MEDLINE:93302717].\ \N \N \N 25413 IPR006976

This family contains several examples of the VanZ protein, but also contains examples of phosphotransbutyrylases. VanZ confers low-level resistance to the glycopeptide antibiotic teicoplanin (Te). Analysis of cytoplasmic peptidoglycan precursors, accumulated in the presence of ramoplanin, showed that VanZ-mediated Te resistance does not involve incorporation of a substituent of D-alanine into the peptidoglycan precursors [MEDLINE:95172409].

\ \N \N \N 25414 IPR006977 This domain defines a group of proteins of unknown function. \ \N \N \N 25415 IPR006978 This conserved region is found in the N-terminal region of a number of conserved archaeal proteins of unknown function.\ \N \N \N 25416 IPR006979

This conserved region is found in the C-terminal region of a number of conserved archaeal proteins of unknown function.

\ \N \N \N 25417 IPR006980 Ammonia monooxygenase plays a key role in the nitrogen cycle and degrades a wide range of hydrocarbons and halogenated hydrocarbons. This family represents the AmoC subunit. It also includes the particulate methane monooxygenase subunit PmoC from methanotrophic bacteria [MEDLINE:99001635], [MEDLINE:99303333].\ \N \N \N 25418 IPR006981

Reaction of amidotransferase domain:

 \
L-glutamine + H2O = L-glutamate + NH3\

\ \

Reactions of FMN-binding domain:

\ \

 \
2-oxoglutarate + NH3 = 2-iminoglutarate + H2O\

\ \ \ \

2e + FMNox = FMNred\

\ \ \ \

2-iminoglutarate + FMNred = L-glutamate + FMNox\

\ The amidotransferase domain from Fd-GltS contains the typical catalytic center of N-terminal nucleophile amidotransferases. \ The overall topology is characterized by a four layer

/beta/

architecture, which is similar to other N-terminal nucleophile amidotransferases [MEDLINE:22086160].\ \ \N \N \N 25402 IPR006965 This 19 kDa glycoprotein binds the major histocompatibility (MHC) class I antigens in the endoplasmic reticulum (ER). The ER retention signal at the C terminus of GP19K causes retention of the complex in the ER, preventing lysis of the cell by cytotoxic T-lymphocytes [MEDLINE:94069932].\ \N \N \N 25403 IPR006966 The Peroxin-3 family are peroxisomal proteins. They are thought to be involved in membrane vesicle biogenesis prior to the translocation of matrix proteins [MEDLINE:20307398].\ \N \N \N 25404 IPR006967 This family of proteins is found in the caudovirales. It may be a tail component.\ \N \N \N 25405 IPR006968

This is a family of proteins of unknown function, restricted to eukaryotes.

\ \N \N \N 25406 IPR006969 This family represents the Stig1 cysteine rich plant protein.The tobacco stigma-specific gene, STIG1 is developmentally regulated and expressed specifically in the stigmatic secretory zone. Pistils of transgenic STIG1-barnase tobacco plants undergo normal development, but lack the stigmatic secretory zone and are female sterile. Pollen grains are unable to penetrate the surface of the ablated pistils. Application of stigmatic exudate from wild-type pistils to the ablated surface increases the efficiency of pollen tube germination and growth and restores the capacity of pollen tubes to penetrate the style [MEDLINE:94313978]. The function of STIG1 is unknown.\ \N \N \N 25407 IPR006970

This short repeat is composed on the tetrapeptide XPTX. This repeat is found in a variety of proteins, however it is not clear if these repeats are homologous to each other.

\ \N \N \N 25408 IPR006971 This family includes M2 protein of unknown function from variola virus. \ \N \N \N 25393 IPR006956 This family includes variola (smallpox) and vaccinia virus L5 proteins. L5 is thought to contain a metal-binding region [MEDLINE:93190624].\ \N \N \N 25394 IPR006957 Ethylene insensitive 3 (EIN3) proteins are a family of plant DNA-binding proteins that regulate transcription in response to the gaseous plant hormone ethylene, and are essential for ethylene-mediated responses. \ In the presence of ethylene, dark-grown dicotyledonous\ seedlings undergo dramatic morphological changes collectively known as the 'triple response'. In Arabidopsis, these changes consist of a radial swelling of the hypocotyl, an exaggeration in the\ curvature of the apical hook, and the inhibition of cell elongation in the hypocotyl and root.\ \ \N \N \N 25395 IPR006958 The function of these proteins is unknown. The yeast orthologues have been implicated in cell cycle progression and biogenesis of 60S ribosomal subunits. The Schistosoma mansoni Mak16 has been shown to target protein transport to the nucleolus [MEDLINE:20299188].\ \N \N \N 25396 IPR006959 This family contains uncharacterised proteins from Vibrio cholerae.\ \N \N \N 25397 IPR006960 This protein family is uncharacterized. Proteins accumulate in large amounts in tenuivirus infected cells. They are found in the inclusion bodies that are formed after infection [MEDLINE:93303913].\ \N \N \N 25398 IPR006961 HrpZ (harpin elicitor) from the plant pathogen Pseudomonas syringae binds to lipid bilayers and forms a cation-conducting pore in vivo. This pore-forming activity may allow nutrient release or delivery of virulence factors during bacterial colonisation of host plants [MEDLINE:21065167].\ \N \N \N 25399 IPR006962

This family comprises the Baculovirus P48 proteins. They contain two possible membrane-spanning domains and a cysteine-rich domain that are conserved in all of the proteins. The Bombyx mori nuclear polyhedrosis\ virus protein, O92463, has been described as a putative DNA helicase.

\ \ \N \N \N 25400 IPR006963

The molybdopterin oxidoreductase Fe4S4 domain is found in a number of reductase/dehydrogenase families, which include the periplasmic nitrate reductase precursor and the formate dehydrogenase chain.

\ \N \N \N 25401 IPR006964

This domain represents the C-terminal conserved region of NUDE proteins. Aspergillus nidulans NUDE, acts in the cytoplasmic dynein/dynactin pathway and is required for distribution of nuclei [MEDLINE:21486518]. It is a homologue of the nuclear distribution protein RO11 of Neurospora crassa. NUDE interacts with the NUDF via an N-terminal coiled coil domain; this is the only domain which is absolutely required for NUDE function.

\ \ \ \ \N \N \N 25391 IPR006954 This family contains a conserved region found in a number of uncharacterised Caenorhabditis elegans proteins.\ \N \N \N 25392 IPR006955 This domain identifies a group of proteins, which are described as: General vesicular transport factor, Transcytosis associate protein (TAP) and Vesicle docking protein. This myosin-shaped molecule consists of an N-terminal globular head region, a coiled-coil tail which mediates dimerisation, and a short C-terminal acidic region [MEDLINE:21924819]. p115 tethers COP1 vesicles to the Golgi by binding the coiled coil proteins giantin (on the vesicles) and GM130 (on the Golgi), via its C-terminal acidic region. It is required for intercisternal transport in the Golgi stack. This domain is found in the acidic C-terminal region, which binds to the golgins giantin and GM130. p115 is thought to juxtapose two membranes by binding giantin with one acidic region, and GM130 with another [MEDLINE:22072092].\ \N \N \N 25386 IPR006949 The P2 bacteriophage J protein lies at the edge of the baseplate. This family also includes a number of bacterial homologues, which are thought to have been horizontally transferred.\ \N \N \N 25387 IPR006950 This family comprises the 11 kDa non-structural proteins found in segment S11 of the Rotavirus genome. They may form part of a complex that is involved in the replication of the genome.\ \N \N \N 25388 IPR006951 These are proteins of unknown function found in Borrelia burgdorferi, the Lyme disease spirochete.\ \N \N \N 25389 IPR006952 Retinal rod and cone cGMP phosphodiesterases function as the effector enzymes in the vertebrate visual transduction cascade. This family represents the inhibitory gamma subunit [MEDLINE:21897991], which is also expressed outside retinal tissues and has been shown to interact with the G-protein-coupled receptor kinase 2 signalling system to regulate the epidermal growth factor- and thrombin-dependent stimulation of p42/p44 mitogen-activated protein kinase in human embryonic kidney 293 cells [MEDLINE:21474361].\ \N \N \N 25390 IPR006953 This domain identifies a group of proteins, which are described as: General vesicular transport factor, Transcytosis associated protein (TAP) or Vesicle docking protein, this myosin-shaped molecule consists of an N-terminal globular head region, a coiled-coil tail which mediates dimerisation, and a short C-terminal acidic region [MEDLINE:21924819]. p115 tethers COP1 vesicles to the Golgi by binding the coiled coil proteins giantin (on the vesicles) and GM130 (on the Golgi), via its C-terminal acidic region. It is required for intercisternal transport in the Golgi stack. This domain is found in the head region. The head region is highly conserved, but its function is unknown. It does not seem to be essential for vesicle tethering [MEDLINE:21924819]. The N-terminal part of the head region contains context-detected Armadillo/

-catenin-like repeats.\ \N \N \N 25382 IPR006945 Circoviruses are small circular single stranded viruses. This family represents the VP2 protein.\ \N \N \N 25383 IPR006946 This family contains a conserved region found in a number of uncharacterised plant proteins.\ \N \N \N 25384 IPR006947 Allicin is a thiosulfinate that gives rise to dithiines, allyl sulfides and ajoenes, the three groups of active compounds in Allium species. Allicin is synthesised from sulfoxide cysteine derivatives by alliinase (EC: 4.4.1.4), whose C-S lyase activity cleaves C(

)-S(gamma) bonds. It is thought that this enzyme forms part of a primitive plant defence system PUB00008676.\ \N \N \N 25385 IPR006948 Allicin is a thiosulfinate that gives rise to dithiines, allyl sulfides and ajoenes, the three groups of active compounds in Allium species. Allicin is synthesised from sulfoxide cysteine derivatives by alliinase (EC: 4.4.1.4), whose C-S lyase activity cleaves C(

)-S(gamma) bonds. It is thought that this enzyme forms part of a primitive plant defence system PUB00008677.\ \N \N \N 25377 IPR006940 Securin is also known as pituitary tumour-transforming gene product. Over-expression of securin is associated with a number of tumours, and it has been proposed that this may be due to erroneous chromatid separation leading to chromosome gain or loss [MEDLINE:99340303].\ \N \N \N 25378 IPR006941 The major pathways of mRNA turnover in eukaryotes initiate with shortening of the poly(A) tail. CAF1 P39008).\ \N \N \N 25379 IPR006942 TH1 is a highly conserved but uncharacterised metazoan protein. No homologue has been identified in Caenorhabditis elegans [MEDLINE:20483332]. TH1 binds specifically to A-Raf kinase [MEDLINE:21948648].\ \N \N \N 25380 IPR006943 This conserved region is found in a number of plant proteins of unknown function.\ \N \N \N 25381 IPR006944 Positioned at one of the twelve icosahedral vertices, of the viral capsid, is a dodecameric complex of the virus encoded portal protein. This dodecameric complex, known as the portal or connector complex, forms the channel through which the viral DNA is packaged into the capsid, and through which it exits during infection. While the portal proteins from different phage show relatively little sequence homology and vary widely in molecular weight, portal complexes display significant morphological similarity as determined by electron microscopy. Morphologically, they present as disk-like structures approximately 150 Angstroms in diameter with radially arranged projections and a 30 Angstroms central channel. The packaging reaction is energy dependent and typically involves several components. ATP hydrolysis provides the driving force, and it is estimated that one ATP molecule is required for every base pair that is packaged. It appears that the portal motor may represent a new and extremely powerful class of motor which couples rotation to DNA translocation [MEDLINE:21828723].\ \N \N \N 25372 IPR006935 This family represents the res subunit of type III restriction enzymes (EC: 3.1.21.5) [MEDLINE:21103715], [MEDLINE:98290309].\ \N \N \N 25373 IPR006936 This conserved region is found in plant proteins including the resistance protein-like protein (O49468).\ \N \N \N 25374 IPR006937 This family represents a number of plant neutral invertases (EC: 3.2.1.26).\ \N \N \N 25375 IPR006938 This conserved region is found in uncharacterised or hypothetical bacterial proteins.\ \N \N \N 25376 IPR006939 SNF5 is a component of the yeast SWI/SNF complex, which is an ATP-dependent nucleosome-remodelling complex that regulates the transcription of a subset of yeast genes. SNF5 is a key component of all SWI/SNF-class complexes characterised so far [MEDLINE:99263045]. This family consists of the conserved region of SNF5, including a direct repeat motif. SNF5 is essential for the assembly promoter targeting and chromatin remodelling activity of the SWI-SNF complex [MEDLINE:21286923]. SNF5 is also known as SMARCB1, for SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily b, member 1, and also INI1 for integrase interactor 1. Loss-of function mutations in SNF5 are thought to contribute to oncogenesis in malignant rhabdoid tumours (MRTs) [MEDLINE:98334382].\ \N \N \N 25366 IPR006928

This entry represents the N-terminal domain of the Herpesvirus tegument protein.

\ \N \N \N 25367 IPR006930 Members of this family contain a conserved region found in most herpesvirus pp38 phosphoproteins.\ \N \N \N 25368 IPR006931 Calcipressin is also known as calcineurin-binding protein, since it inhibits calcineurin-mediated transcriptional modulation by binding to catalytic domain of calcineurin [MEDLINE:22035335].\ \N \N \N 25369 IPR006932 This is a family of Poxvirus A22 protein.\ \N \N \N 25370 IPR006933 This domain represents an N-terminal conserved region found in several huntingtin-associated protein 1 (HAP1) homologues. HAP1 binds to huntingtin in a polyglutamine repeat-length-dependent manner. However, its possible role in the pathogenesis of Huntingtons disease is unclear. This family also includes a similar N-terminal conserved region from hypothetical protein products of ALS2CR3 genes found in the human juvenile amyotrophic lateral sclerosis critical region 2q33-2q34 [MEDLINE:21100893].\ \N \N \N 25371 IPR006934 Baculovirus occlusion-derived virus (ODV) derives its envelope from an intranuclear membrane source. N-terminal amino acid sequences of the Autographa californica nuclear polyhedrosis virus (AcMNPV) envelope protein ODV-E66 is highly hydrophobic. This defined hydrophobic domain was shown to direct the protein, E66, to induce membrane microvesicles within a baculovirus-infected cell nucleus and the viral envelope. In addition, it was suggested that movement of this protein into the nuclear envelope may initiate through cytoplasmic membranes, such as endoplasmic reticulum, and that transport into the nucleus may be mediated through the outer and inner nuclear membrane [MEDLINE:97268695].\ \ \N viral envelope ; GO:0019031 \N 25364 IPR006926 This protein forms part of the Class C vacuolar protein sorting (Vps) complex. Vps16 is essential for vacuolar protein sorting, which is essential for viability in plants, but not yeast [MEDLINE:21559060]. The Class C Vps complex is required for SNARE-mediated membrane fusion at the lysosome-like yeast vacuole. It is thought to play essential roles in membrane docking and fusion at the Golgi-to-endosome and endosome-to-vacuole stages of transport [MEDLINE:21317488]. The role of VPS16 in this complex is not known.\ \N \N \N 25365 IPR006927

The sequences in this family are plant proteins of unknown function.

\ \N \N \N 25354 IPR006915

This group of sequences from Pseudomonas aeruginosa and Neisseria meningitidisa contain a conserved region which is often associated with a second conserved domain, IPR006914. These proteins may have hemagglutinin or hemolysin activity.

\ \N \N \N 25355 IPR006916

The Popeye (POP) family of proteins, is restricted to vertebrates and is preferentially expressed in developing and adult striated muscle. It is represented by a conserved region which includes three potential transmembrane domains [MEDLINE:20341060]. The strong conservation of POP genes during evolution and their preferential expression in heart and skeletal muscle suggest that these novel proteins may have an important function in these tissues in vertebrates.

\ \N \N \N 25356 IPR006917 This family represents a group of putative heme-binding proteins [MEDLINE:20109330]. It includes archaeal and bacterial homologues.\ \N \N \N 25357 IPR006918

This is a family of plant proteins believed to be phytochelatin synthetases. This enzyme is responsible for the production of phytochelatins, small glutamic acid, cysteine and glycine-rich peptides, produced in response to cadmium stress. In yeast it would appear that this activity is performed by glutathione synthetase (GSH2) (EC: 6.3.2.3), suggesting that the yeast GSH2 (P35669.

\ \ \ \N \N \N 25358 IPR006920 This is a family of Chordopoxvirus A9 proteins.\ \N \N \N 25359 IPR006921

This domain, primarily C-terminal, is found in a family of proteins thought to be involved in regulating gene activity in the proliferative and/or differentiative pathways induced by NGF [MEDLINE:98390186].

\ \N \N \N 25360 IPR006922 This domain represents an N-terminal conserved region of MbeB/MobB proteins. These proteins are essential for specific plasmid transfer.\ \N \N \N 25361 IPR006923

This is a family of Baculoviridae late expression factor 5, required for late and very late gene expression.

\ \N \N \N 25362 IPR006924 This small acidic protein is found in 30S ribosomal subunit of cyanobacteria and plant plastids. In plants it has been named plastid-specific ribosomal protein 3 (PSRP-3), and in cyanobacteria it is named Ycf65. Plastid-specific ribosomal proteins may mediate the effects of nuclear factors on plastid translation. The acidic PSRPs are thought to contribute to protein-protein interactions in the 30S subunit, and are not thought to bind RNA [MEDLINE:20435797].\ \N \N \N 25363 IPR006925 This protein forms part of the Class C vacuolar protein sorting (Vps) complex. Vps16 is essential for vacuolar protein sorting, which is essential for viability in plants, but not yeast [MEDLINE:21559060]. The Class C Vps complex is required for SNARE-mediated membrane fusion at the lysosome-like yeast vacuole. It is thought to play essential roles in membrane docking and fusion at the Golgi-to-endosome and endosome-to-vacuole stages of transport [MEDLINE:21317488]. The role of VPS16 in this complex is not known.\ \N \N \N 25348 IPR006909 This family represents a conserved C-terminal region found in eukaryotic cohesins of the Rad21, Rec8 and Scc1 families. Rad21/Rec8 like proteins mediate sister chromatid cohesion during mitosis and meiosis, as part of the cohesin complex [MEDLINE:21546456]. Cohesion is necessary for homologous recombination (including double-strand break repair) and correct chromatid segregation. These proteins may also be involved in chromosome condensation. Dissociation at the metaphase to anaphase transition causes loss of cohesion and chromatid segregation [MEDLINE:99223580].\ \N \N \N 25349 IPR006910 This domain represents a conserved N-terminal region found in eukaryotic cohesins of the Rad21, Rec8 and Scc1 families. Rad21/Rec8 like proteins mediate sister chromatid cohesion during mitosis and meiosis, as part of the cohesin complex [MEDLINE:21546456]. Cohesion is necessary for homologous recombination (including double-strand break repair) and correct chromatid segregation. These proteins may also be involved in chromosome condensation. Dissociation at the metaphase to anaphase transition causes loss of cohesion and chromatid segregation [MEDLINE:99223580].\ \N \N \N 25350 IPR006911 This domain is found in mammalian proteins of unknown function.\ \N \N \N 25351 IPR006912 This family of plant proteins have no known function.\ \N \N \N 25352 IPR006913

This is a family of uncharacterised proteins containing 5 strongly conserved cysteine residues.

\ \N \N \N 25353 IPR006914

This group of proteins, from Neisseria meningitidis, may have hemagglutinin or hemolysin activity. A number of them have a second conserved domain, IPR006915, which is found in possible Pseudomonas aeruginosa hemagglutinins.

\ \N \N \N 25337 IPR006898 This domain consists of an alternative C terminus of homeobox-containing transcription factor HNF-1, found in the HNF-1A isoform. Different isoforms of HNF-1 are generated by the differential use of polyadenylation sites and by alternative splicing. The C-terminal region of HNF-1 is responsible for the activation of transcription, and HNF-1A, which has this C-terminal extension, transactivates less well than the B and C isoforms [MEDLINE:94038905]. Mutations and polymorphisms in HNF-1 cause the type 3 form of maturity-onset diabetes of the young (MODY3) [MEDLINE:97278987].\ \N \N \N 25338 IPR006899 This domain consists of the N terminus of homeobox-containing transcription factor HNF-1. This region contains a dimerisation sequence [MEDLINE:91105074] and an acidic region that may be involved in transcription activation. Mutations and the common Ala/Val 98 polymorphism in HNF-1 cause the type 3 form of maturity-onset diabetes of the young (MODY3) [MEDLINE:97278987].\ \N \N \N 25339 IPR006900 COPII-coated vesicles carry proteins from the endoplasmic reticulum to the Golgi complex. This vesicular transport can be reconstituted by using three cytosolic components containing five proteins: the small GTPase Sar1p, the Sec23p/24p complex, and the Sec13p/Sec31p complex. This domain is composed of five

helices.\ \N \N \N 25340 IPR006901

This is a family of uncharacterised bacterial proteins.

\ \N \N \N 25341 IPR006902 The long distance movement protein of Umbraviruses mediates the movement of viral RNA through the phloem of infected plants [MEDLINE:21488924].\ \N \N \N 25342 IPR006903 This entry represents a conserved region found in a number of uncharacterised eukaryotic proteins.\ \N \N \N 25343 IPR006904

These sequences are a family of uncharacterised hypothetical proteins restricted to eukaryotes. Q9SLW7 represents a sequence from Nicotiana tabacum which is up regulated in response to TMV infection.

\ \N \N \N 25344 IPR006905 Tryptophan halogenase catalyses the chlorination of tryptophan to form 7-chlorotryptophan. This is the first step in the biosynthesis of pyrrolnitrin, an antibiotic with broad-spectrum anti-fungal activity. Tryptophan halogenase is NADH-dependent [MEDLINE:20016567].\ \N \N \N 25345 IPR006906

The timeless gene in Drosophila melanogaster and its homologues in a number of other insects and mammals (including human) are involved in circadian rhythm control [MEDLINE:21568585]. This family includes related proteins from a number of fungal species and from Arabidopsis thaliana.

\ \N \N \N 25346 IPR006907 This family includes several uncharacterised mouse proteins.\ \N \N \N 25347 IPR006908 This is a family of herpesvirus UL49 tegument proteins. It was shown that interactions between herpesvirus envelope and tegument proteins may play a role in secondary envelopment during herpesvirus virion maturation.\ \ \ \N \N \N 25334 IPR006895 COPII-coated vesicles carry proteins from the endoplasmic reticulum to the Golgi complex. This vesicular transport can be reconstituted by using three cytosolic components containing five proteins: the small GTPase Sar1p, the Sec23p/24p complex, and the Sec13p/Sec31p complex. This domain is found to be zinc binding domain.\ \N \N \N 25335 IPR006896 COPII-coated vesicles carry proteins from the endoplasmic reticulum to the Golgi complex. This vesicular transport can be reconstituted by using three cytosolic components containing five proteins: the small GTPase Sar1p, the Sec23p/24p complex, and the Sec13p/Sec31p complex. This domain is known as the trunk domain and has an

vWA fold and forms the dimer interface.\ \N \N \N 25336 IPR006897 This domain consists of a region found within the

isoform and at the C terminus of the

isoform of the homeobox-containing transcription factor of HNF-1. Different isoforms of HNF-1 are generated by the differential use of polyadenylation sites and by alternative splicing. The C-terminal region of HNF-1 is responsible for the activation of transcription [MEDLINE:94038905]. Mutations and polymorphisms in HNF-1 cause the type 3 form of maturity-onset diabetes of the young (MODY3) [MEDLINE:97278987].\ \N \N \N 25329 IPR006890 This is a family of poxvirus proteins.\ \N \N \N 25330 IPR006891 The enteropathogenic Escherichia coli EspF secreted protein induces host cell apoptosis. Its proline-rich structure suggests that it may act by binding to SH3 domains or EVH1 domains of host cell signalling proteins [MEDLINE:21196408].\ \N \N \N 25331 IPR006892 This is a conserved region from the Gemini virus AC4 and AC5 proteins.\ \N \N \N 25332 IPR006893

This family of proteins contains p23 from the citrus tristeza virus, which is a member of the Closteroviridae. CTV produces more positive than negative RNA strands, and p23 controls this asymmetrical RNA accumulation. Amino acids 42-180 are essential for function and are thought to contain RNA-binding and zinc finger domains [MEDLINE:21624246].

\ \N \N \N 25333 IPR006894 This domain represents a C-terminal conserved region found in these bacterial proteins necessary for hydrogenase synthesis. Their precise function is unknown [MEDLINE:94320794].\ \N \N \N 25326 IPR006887 This is a conserved region which characterizes a number of eukaryotic proteins of unknown function.\ \N \N \N 25327 IPR006888 Cor1 is a component of the chromosome core in the meiotic prophase chromosomes [MEDLINE:95181577]. Xlr is a lymphoid cell specific protein [MEDLINE:95121927]. Xmr is abundantly transcribed in testis in a tissue-specific and developmentally regulated manner. The protein is located in the nuclei of spermatocytes, early in the prophase of the first meiotic division, and later becomes concentrated in the XY nuclear subregion where it is in particular associated with the axes of sex chromosomes [MEDLINE:94139652].\ \N \N \N 25328 IPR006889

This is a family of plant infecting tospovirus NSM proteins a number of which contain the phospholipase A2 histidine active site, IPR001211.

\ \N \N \N 25311 IPR006871 This is a family of Baculovirus ssDNA-binding proteins.\ \N \N \N 25312 IPR006872 This is a family of poxvirus late H7 proteins.\ \N \N \N 25313 IPR006873 This is a family of uncharacterised proteins.\ \N \N \N 25314 IPR006874 This is a conserved region found in uncharacterised proteins from Caenorhabditis elegans.\ \N \N \N 25315 IPR006875 The dystrophin glycoprotein complex (DGC) is a membrane-spanning complex that links the interior cytoskeleton to the extracellular matrix in muscle. The sarcoglycan complex is a subcomplex within the DGC and is composed of several muscle-specific, transmembrane proteins (

-, gamma-, delta- and zeta-sarcoglycan). The sarcoglycans are asparagine-linked glycosylated proteins with single transmembrane domains. This family contains

, gamma and delta members [MEDLINE:22101953], [MEDLINE:22176631].\ \N \N \N 25316 IPR006876

This group of uncharacterised proteins have a conserved C-terminal region which is found in LMBR1 and in the lipocalin-1 receptor. LMBR1 was thought to play a role in preaxial polydactyly, but recent evidence now suggests this not to be the case [MEDLINE:22028981].

\ \N \N \N 25317 IPR006878 This is a family of herpesvirus proteins including Epstein-barr virus protein BBRF1.\ \N \N \N 25318 IPR006879 This is a family of YdjC-like proteins. It is possibly involved in the the cleavage of cellobiose-phosphate [MEDLINE:94012514].\ \N \N \N 25319 IPR006880 This is a group of proteins with a conserved C-terminal region which is found in PAPA-1, a PAP-1 binding protein, Q9C086. \ \N \N \N 25320 IPR006881 This is a family of plasmid encoded proteins involved in plasmid replication. The role of RepA in the replication process is not clearly understood [MEDLINE:21912308].\ \N \N \N 25321 IPR006882 This is a family of Herpesvirus proteins sharing a conserved region present in the ORF11 protein.\ \N \N \N 25322 IPR006883 This is a family of Baculovirus proteins of approximate mass 19 kDa.\ \N \N \N 25323 IPR006884 This is conserved C-terminal region is found in a number of putative transmembrane GTPase. The Fzo protein is a mediator of mitochondrial fusion [MEDLINE:97373825]. This conserved region is also found in the human mitofusin protein [MEDLINE:21102164].\ \N \N \N 25324 IPR006885 This is a family of pankaryotic NADH-ubiquinone oxidoreductase subunits (EC: 1.6.5.3, EC: 1.6.99.3) from complex I of the electron transport chain initially identified in Neurospora crassa as a 21 kDa protein [MEDLINE:95034970].\ \N \N \N 25325 IPR006886 This is a family of higher eukaryotic proteins. SIN was identified as a protein that interacts specifically with SXL (sex lethal) in a yeast two-hybrid assay. The interaction is mediated by one of the SXL RNA-binding domains [MEDLINE:99453303].\ \N \N \N 25303 IPR006863 Biogenesis of Fe/S clusters involves a number of essential mitochondrial proteins. Erv1p of Saccharomyces cerevisiae mitochondria is required for the maturation of Fe/S proteins in the cytosol. The ALR (augmenter of liver regeneration) represents a mammalian ortholog of yeast Erv1p. Both Erv1p and full-length ALR are located in the mitochondrial intermembrane and it is thought to operate downstream of the mitochondrial ABC transporter. [MEDLINE:21385004].\ \N \N \N 25304 IPR006864 This repeated sequence element is found in the LMP group of surface-located membrane proteins of Mycoplasma hominis. The the number of repeats in the protein affects the tendency of cells to spontaneously aggregate. Agglutination may be an important factor in colonization. Non-agglutinating microorganisms might easily be distributed whereas aggregation might provide a better chance to avoid an antibody response since some of the epitopes may be buried [MEDLINE:95369882].\ \N \N \N 25305 IPR006865 This domain represents a region of several plant proteins of unknown function. A C2H2 zinc finger is predicted in this region in some family members, but the spacing between the cysteine residues is not conserved throughout the family.\ \N \N \N 25306 IPR006866 This domain represents the N-terminal region of several plant proteins of unknown function.\ \N \N \N 25307 IPR006867 This conserved region contains a leucine zipper-like domain. The proteins are found only in plants and their functions are unknown.\ \N \N \N 25308 IPR006868 This region is sometimes found at the N terminus of putative plant bZIP proteins IPR006867. The function of this conserved region is not known.\ \N \N \N 25309 IPR006869 This is a conserved region found in uncharacterised proteins from Caenorhabditis elegans and Arabidopsis thaliana.\ \N \N \N 25310 IPR006870 M protein is involved in condensing and targeting the ribonucleoprotein (RNP) coil to the plasma membrane. M interacts specifically with the transmembrane spike protein (G) and it is important for the incorporation of G protein into budding virions [MEDLINE:99102580].\ \N viral envelope ; GO:0019031 viral life cycle ; GO:0016032 25288 IPR006847 This region is found in the N-terminal half of translation initiation factor IF-2. It is found in two copies in IF-2

isoforms, and in only one copy in the N-terminally truncated

and gamma isoforms [MEDLINE:92109780]. Its function is unknown.\ translation initiation factor activity ; GO:0003743 \N translational initiation ; GO:0006413 25289 IPR006848 This family represents a number of putative transcription repressor proteins found in several Lactococcus bacteriophages. Horizontal transfer may account for the presence of similar proteins in Lactococcus [MEDLINE:21235186].\ \N \N \N 25290 IPR006849 Members of this family are components of the elongator multi-subunit component of a novel RNA polymerase II holoenzyme for transcriptional elongation [MEDLINE:99149023].\ \N \N \N 25291 IPR006850 This represents a conserved region found in a number of Chlamydophila pneumoniae proteins.\ \N \N \N 25292 IPR006851 This is a family of chloroplast proteins of unknown function. Some members have two copies of the conserved region.\ \N \N \N 25293 IPR006852 This is a family of uncharacterised proteins.\ \N \N \N 25294 IPR006853 This is a family of Baculovirus p26 proteins.\ \N \N \N 25295 IPR006854 This is a family of poxvirus proteins required for virus morphogenesis. This protein is necessary for proteolytic processing of the major viral structural proteins, P4a and P4b [MEDLINE:92015507].\ DNA binding activity ; GO:0003677 \N viral protein processing ; GO:0019082 25296 IPR006855 This region of unknown function is found at the C terminus of Neurospora crassa acetylglutamate synthase (EC: 2.3.1.1). It is also found C-terminal to the amino acid kinase region in some fungal acetylglutamate kinase enzymes (IPR001048).\ \N \N \N 25297 IPR006856 This family includes Saccharomyces cerevisiae mating type protein

1 (P01365.\ \N \N \N 25298 IPR006858 This protein is found in the nucleus of infected cells and may act as a transcriptional regulator. It induces apoptosis, and is also known as apoptin (P54094).\ \N host cell nucleus ; GO:0042025 induction of apoptosis by virus ; GO:0019051 25299 IPR006859 BM2 is synthesised in the late phase of infection and incorporated into the virion. It may be phosphorylated in vivo. The function of BM2 is unknown [MEDLINE:20037820].\ \N \N \N 25300 IPR006860 FecR is involved in regulation of iron dicitrate transport. In the absence of citrate FecR inactivates FecI. FecR is probably a sensor that recognizes iron dicitrate in the periplasm.\ \N \N \N 25301 IPR006861 This family includes the HABP4 family of hyaluronan-binding proteins, and the PAI-1 mRNA-binding protein, PAI-RBP1. HABP4 has been observed to bind hyaluronan (a glucosaminoglycan), but it is not known whether this is its primary role in vivo. It has also been observed to bind RNA, but with a lower affinity than that for hyaluronan [MEDLINE:20449071]. PAI-1 mRNA-binding protein specifically binds the mRNA of type-1 plasminogen activator inhibitor (PAI-1), and is thought to be involved in regulation of mRNA stability [MEDLINE:21264806]. However, in both cases, the sequence motifs predicted to be important for ligand binding are not conserved throughout the family, so it is not known whether members of this family share a common function.\ \N \N \N 25302 IPR006862 This entry presents the N-termini of acyl-CoA thioester hydrolase and bile acid-CoA:amino acid N-acetyltransferase (BAAT) [MEDLINE:21638389]. This region is not thought to contain the active site of either enzyme. Thioesterase isoforms have been identified in peroxisomes, cytoplasm and mitochondria, where they are thought to have distinct functions in lipid metabolism [MEDLINE:20036578]. For example, in peroxisomes, the hydrolase acts on bile-CoA esters [MEDLINE:21638389].\ \N \N \N 25283 IPR006842 This is a family of putative transposases includes the YhgA sequence from Escherichia coli (P31667) and several prokaryotic homologues.\ \N \N \N 25284 IPR006843 This family identifies a conserved region found in a number of plastid lipid-associated proteins (PAPs), and in a number of putative fibrillin proteins.\ structural molecule activity ; GO:0005198 \N \N 25285 IPR006844 The proteins in this family are a part of a complex of eight ER proteins that transfers core oligosaccharide from dolichol carrier to Asn-X-Ser/Thr motifs [MEDLINE:95348180]. This family includes both OST3 and OST6, each of which contains four predicted transmembrane helices. Disruption of OST3 and OST6 leads to a defect in the assembly of the complex. Hence, the function of these genes seems to be essential for recruiting a fully active complex necessary for efficient N-glycosylation [MEDLINE:99287932].\ \N \N \N 25286 IPR006845

This region is the N-terminal part of the Pex2 and Pex12 peroxisomal biogenesis proteins, which contain two predicted transmembrane segments. The majority of these proteins have a C-terminal ring finger domain IPR001841.

\ \N \N \N 25287 IPR006846

\ \ \

This entry is for the ribosomal protein S30.

\ \ \N \N \N 25275 IPR006834 This is a family of Chordopoxvirus proteins composing one of the two subunits that make up VITF-3, a virally encoded complex necessary for intermediate stage transcription [MEDLINE:99178951].\ \N \N \N 25276 IPR006835 This represents a conserved region found in a number of Chlamydophila pneumoniae proteins.\ \N \N \N 25277 IPR006836 This family includes several uncharacterised proteins from Caenorhabditis elegans.\ \N \N \N 25278 IPR006837 This is a family of uncharacterised proteins.\ \N \N \N 25279 IPR006838 This family includes the hamster androgen-induced FAR-17a protein (Q60534. The function of these proteins is unknown. This family also includes homologous regions from a number of other metazoan proteins.\ \N \N \N 25280 IPR006839 This family of bacterial proteins has no known function.\ \N \N \N 25281 IPR006840 The ChaC protein is thought to be associated with the putative ChaA Ca²⁺/H⁺ cation transport protein in Escherichia coli. Its function is not known. This family also includes homologues regions from several other bacterial and eukaryotic proteins.\ \N \N \N 25282 IPR006841

This is a family of Coronavirus nonstructural protein NS2. Phosphoamino acid analysis confirmed the phosphorylated nature of NS2 and identified serine and threonine as its phosphorylated amino acid residues [MEDLINE:92024122]. It was also demonstrated that the ns2 gene product is not essential for murine hepatitis virus replication in transformed murine cells [MEDLINE:90376431].

\ \N \N \N 25271 IPR006830 This family represents the Salmonella outer membrane lipoprotein InvH. The molecular function of this protein is unknown, but it is required for the localisation to outer membrane of InvG, which is involved in a type III secretion apparatus mediating host cell invasion [MEDLINE:98343818], [MEDLINE:99000123].\ \N \N \N 25272 IPR006831 This family includes several uncharacterised Bacillus halodurans proteins.\ \N \N \N 25273 IPR006832

This is a family of herpes virus proteins of unknown function.

\ \N \N \N 25274 IPR006833 This is a family of membrane associated monooxygenases which utilise O₂ to oxidise their substrate. Family members include both ammonia and methane monooxygenases involved in the oxidation of their respective substrates. These enzymes are multi-subunit complexes. This family represents the B subunit of the enzyme; the A subunit is thought to contain the active site [MEDLINE:21665709], [MEDLINE:20163992].\ \N \N \N 25267 IPR006826 Lantibiotics are ribosomally synthesised antimicrobial agents derived from ribosomally synthesised peptides [MEDLINE:92171481]. They are produced by bacteria of the Firmicutes phylum, and include mutacin, subtilin, and nisin. Lantibiotic peptides contain thioether bridges termed lanthionines that are thought to be generated by dehydration of serine and threonine residues followed by addition of cysteine residues [MEDLINE:22122314]. This family constitutes the N terminus of the enzyme proposed to catalyse the dehydration step [MEDLINE:22122314], [MEDLINE:99234028].\ \N \N \N 25268 IPR006827 Lantibiotics are ribosomally synthesised antimicrobial agents derived from ribosomally synthesised peptides [MEDLINE:92171481]. They are produced by bacteria of the Firmicutes phylum, and include mutacin, subtilin, and nisin. Lantibiotic peptides contain thioether bridges termed lanthionines that are thought to be generated by dehydration of serine and threonine residues followed by addition of cysteine residues [MEDLINE:22122314]. This family constitutes the C-terminus of the enzyme proposed to catalyse the dehydration step [MEDLINE:22122314], [MEDLINE:99234028].\ \N \N \N 25269 IPR006828

This region is found in the subunit of the 5-AMP-activated protein kinase complex, and its yeast homologues Sip1, Sip2 and Gal83, which are found in the SNF1 kinase complex [MEDLINE:96224074]. This region is sufficient for interaction of this subunit with the kinase complex, but is not solely responsible for the interaction, and the interaction partner is not known [MEDLINE:95112798]. The isoamylase domain (IPR004193) is sometimes found associated with proteins that contain this C-terminal domain.

\ \N \N \N 25270 IPR006829 This family of putative transposases includes mostly Bacillus members. However, we have also found a Bacillus subtilis bacteriophage SPbetac2 homologue (O64023), possibly arising as a result of horizontal transfer.\ \N \N \N 25266 IPR006825 Eclosion hormone is an insect neuropeptide that triggers the performance of ecdysis behaviour, which causes shedding of the old cuticle at the end of a molt [MEDLINE:21947747], [MEDLINE:92340224].\ \N \N \N 25265 IPR006824 This is a family of Baculovirus DNA helicases, which are essential for the initiation of viral DNA replication and may contribute to other functions, such as controlling the switch to the late phase and leading to the inhibition of host protein synthesis.\ DNA helicase activity ; GO:0003678 \N viral genome replication ; GO:0019079 25256 IPR006815 This small protein is involved in DNA packaging, interacting with DNA via its hydrophobic C-terminus. In bacteriophage phi-X174, J is present in 60 copies, and forms an S-shaped polypeptide chain without any secondary structure. It is thought to interact with DNA through simple charge interactions [MEDLINE:78020823].\ \N \N \N 25257 IPR006816 This represents a conserved region found in a number of eukaryotic uncharacterised proteins.\ \N \N \N 25258 IPR006817

This repeating sequence, NAKVDQLSNDV, is found in the enterobacterial outer membrane lipoprotein LPP. The outer membrane lipoprotein is the most abundant protein in an Escherichia coli cell. The messenger RNA for the lipoprotein of the E. coli outer membrane codes for a putative precursor, prolipoprotein, which has 20 additional amino acid residues extending from the amino terminus of the lipoprotein.

\ \N \N \N 25259 IPR006818 This family includes the yeast ASF1 protein, which derepresses transcriptionally silenced genes. The human ASF1 homologue has been found to possess histone chaperone activity, which may explain the derepressing function of this family [MEDLINE:20223872].\ \N \N \N 25260 IPR006819 The virD operon in Agrobacterium encodes a site-specific endonuclease, and a number of other poorly characterised products. This family represents the VirD5 protein.\ \N \N \N 25261 IPR006820 This domain occurs at the N-terminal of proteins belonging to the caudal-related homeobox protein family. This region is thought to mediate transcription activation. The level of activation caused by mouse Cdx2 (P43241).\ \N \N \N 25262 IPR006821 This domain represents the N-terminal head region of intermediate filaments. Intermediate filament heads bind DNA [MEDLINE:21405006]. Vimentin heads are able to alter nuclear architecture and chromatin distribution, and the liberation of heads by HIV-1 protease liberates may play an important role in HIV-1 associated cytopathogenesis and carcinogenesis [MEDLINE:21095785]. Phosphorylation of the head region can affect filament stability [MEDLINE:22166807]. The head has been shown to interaction with the rod domain of the same protein [MEDLINE:22061058].\ \N \N \N 25263 IPR006822 This family represents the epsilon subunit of the coatomer complex, which is involved in the regulation of intracellular protein trafficking between the endoplasmic reticulum and the Golgi complex [MEDLINE:99401021].\ \N \N \N 25264 IPR006823 This family represents a group of neutral/alkaline ceramidases found in both bacteria and eukaryotes [MEDLINE:20219171], [MEDLINE:20347271], [MEDLINE:20062886].\ \N \N \N 25252 IPR006811 The yeast Ssu72 is an essential protein that may be involved in transcription start site specification [MEDLINE:96239511].\ \N \N \N 25253 IPR006812 Found in clostridia, this protein contains one active site selenocysteine and catalyses the reductive deamination of glycine, which is coupled to the esterification of orthophosphate resulting in the formation of ATP [MEDLINE:88124843]. A member of this family may also exist in Treponema denticola [MEDLINE:21654780].\ \N \N \N 25254 IPR006813 This family represents

-1,4-mannosyl-glycoprotein

-1,4-N-acetylglucosaminyltransferase (EC: 2.4.1.144). This enzyme transfers the bisecting GlcNAc to the core mannose of complex N-glycans. The addition of this residue is regulated during development and has functional consequences for receptor signalling, cell adhesion, and tumour progression [MEDLINE:22113010], [MEDLINE:21643992].\ \N \N \N 25255 IPR006814 This protein is associated with the oxygen-evolving complex of photosystem II. Its function in photosynthesis is not known. The C-terminal hydrophobic region functions as a thylakoid transfer signal but is not removed [MEDLINE:89121115].\ \N \N \N 25249 IPR006806 This is a family of eukaryotic NADH-ubiquinone oxidoreductase subunits (EC: 1.6.5.3) (EC: 1.6.99.3) from complex I of the electron transport chain initially identified in Neurospora crassa as a 29.9 kDa protein. The conserved region is found at the N-terminus of the member proteins [MEDLINE:91316140].\ \N \N \N 25250 IPR006808 The Fo sector of the ATP synthase is a membrane bound complex which mediates proton transport. It is composed of nine different polypeptide subunits (a, b, c, d, e, f, g F6, A6L). The function of subunit g is currently unknown. The conserved region covers all but the very N-terminus of the member sequences. No prokaryotic members have been identified thus far [MEDLINE:94281230].\ \N \N \N 25251 IPR006809 The general transcription factor, TFIID, consists of the TATA-binding protein (TBP) associated with a series of TBP-associated factors (TAFs) that together participate in the assembly of the transcription preinitiation complex. The conserved region is found at the C terminus of most member proteins. The crystal structure of hTAFII28 with hTAFII18 shows that this region is involved in the binding of these two subunits. The conserved region contains four

helices and three loops arranged as in histone H3 [MEDLINE:95246745], [MEDLINE:98359123]. \ \N \N \N 25244 IPR006801 Apolipoprotein A-II (ApoA-II) is the second major apolipoprotein of high density lipoprotein in human plasma. Mature ApoA-II is present as a dimer of two 77-amino acid chains joined by a disulphide bridge [MEDLINE:22114265]. ApoA-II regulates many steps in HDL metabolism, and its role in coronary heart disease is unclear [MEDLINE:22114265]. In bovine serum, the ApoA-II homologue is present in almost free form. Bovine ApoA-II shows antimicrobial activity against Escherichia coli and yeasts in phosphate buffered saline (PBS) [MEDLINE:98207057].\ \N \N \N 25245 IPR006802 This family includes the radial spoke head proteins RSP4 and RSP6 from Chlamydomonas reinhardtii, and several eukaryotic homologues, including mammalian RSHL1, the protein product of a familial ciliary dyskinesia candidate gene [MEDLINE:21134323].\ \N \N \N 25246 IPR006803

This entry represents the Poxvirus protein I5.

\ \N \N \N 25247 IPR006804

The members of this group of sequences contain a conserved N-terminal domain which is found in the BCL7 family. The function of BCL7 proteins is unknown, though they may be involved in early development. Notably, BCL7B is commonly hemizygously deleted in patients with Williams syndrome [MEDLINE:99132633].

\ \N \N \N 25248 IPR006805 Anthranilate synthase (EC: 4.1.3.27) catalyses the first step in the biosynthesis of tryptophan. Component I catalyses the formation of anthranilate using ammonia and chorismate. The catalytic site lies in the adjacent region, described in the chorismate binding enzyme family (IPR005801. This family also contains a region of Para-aminobenzoate synthase component I (EC 4.1.3.-).\ \N \N \N 25233 IPR006790 This is a family of viral structural glycoproteins [MEDLINE:92333656].\ structural molecule activity ; GO:0005198 virion ; GO:0019012 \N 25234 IPR006791

This entry represents the Pox virus D2 proteins.

\ \N \N \N 25235 IPR006792

This region is found in plant seed storage proteins, N-terminal to the Cupin domain (IPR006045.

\ \N \N \N 25236 IPR006793 This family represents a number of fimbrial protein transcription regulators found in Gram-negative bacteria. These proteins are thought to facilitate binding of the leucine-rich regulatory protein to regulatory elements, possibly by inhibiting deoxyadenosine methylation of these elements by deoxyadenosine methylase [MEDLINE:96059640], [MEDLINE:96112794].\ \N \N \N 25237 IPR006794 Zfx and Zfy are transcription factors implicated in mammalian sex determination. This region is found N-terminal to multiple copies of a C2H2 Zinc finger (IPR007087.\ \N \N \N 25238 IPR006795 This region is found in some members of the SpoU-type rRNA methylase family (IPR001537).\ \N \N \N 25239 IPR006796 Dickkopf proteins are a class of Wnt antagonists. They possess two conserved cysteine-rich regions. This family represents the N-terminal conserved region [MEDLINE:22157896]. The C-terminal region has been found to share significant sequence similarity to the colipase fold (IPR001981.\ \N \N \N 25240 IPR006797 This family includes a conserved region found in the yeast YLR168C gene MSF1 product. The function of this protein is unknown, though it is thought to be involved in intra-mitochondrial protein sorting. This region is also found in a number of other eukaryotic proteins.\ \N \N \N 25241 IPR006798

This entry represents the Poxvirus F16 proteins.

\ \N \N \N 25242 IPR006799 Anti-Mullerian hormone, AMH is a signalling molecule involved in male and female sexual differentiation [MEDLINE:92146272]. Defects in synthesis or action of AMH cause persistent Mullerian duct syndrome (PMDS), a rare form of male pseudohermaphroditism [MEDLINE:94214429]. This family represents the N-terminal part of the protein, which is not thought to be essential for activity [MEDLINE:94214429]. AMH contains a TGF-

domain (IPR001839), at the C-terminus.\ \N \N \N 25243 IPR006800 Pellino is involved in Toll-like signalling pathways, and associates with the kinase domain of the Pelle Ser/Thr kinase [MEDLINE:20317266], [MEDLINE:21015032], [MEDLINE:99264282] .\ \N \N \N 25225 IPR006782 This domain consists of the N-terminal regions of platelet-derived growth factor (PDGF, IPR000072) A and B chains.\ growth factor activity ; GO:0008083 membrane ; GO:0016020 cell growth and/or maintenance ; GO:0008151 25226 IPR006783 Autonomous mobile genetic elements such as transposon or insertion sequences (IS)encode an enzyme, transposase, that is required for excising and inserting\ the mobile element. Transposases have been grouped into various families [MEDLINE:94316508], [MEDLINE:92149305], [MEDLINE:92039004]. This family includes the putative transposase ISC1217 from archaebacteria.\ \ \N \N \N 25227 IPR006784 This family represents the Coronavirus ORF3 protein, also known as the X2A protein.\ \N \N \N 25228 IPR006785 This conserved region defines a group of peroxisomal membrane anchor proteins which bind the PTS1 (peroxisomal targeting signal) receptor and are required for the import of PTS1-containing proteins into peroxisomes. Loss of functional Pex14p results in defects in both the PTS1 and PTS2-dependent import pathways. Deletion analysis of this conserved region implicates it in selective peroxisome degradation. In the majority of members this region is situated at the N-terminus of the protein [MEDLINE:97248489], [MEDLINE:21576169].\ \N \N \N 25229 IPR006786

This conserved region is located adjacent and C-terminal to a N-terminal pinin/SKD domain IPR006787.

\ \N \N \N 25230 IPR006787

This conserved region is found at the N-terminal of the member proteins. It is located adjacent and N-terminal to the pinin/SKD/memA domain IPR006786.

\ \ \N \N \N 25231 IPR006788 MOBP is abundantly expressed in central nervous system myelin, and shares several characteristics with myelin basic protein (MBP), in terms of regional distribution and function. MOBP has been shown to be essential for normal arrangement of the radial component in central nervous system myelin [MEDLINE:99203311], [MEDLINE:21653182].\ \N \N \N 25232 IPR006789 The Arp2/3 protein complex has been implicated in the control of actin polymerization. The human complex consists of seven subunits which include the actin related proteins Arp2 and Arp3, and five others referred to as p41-Arc, p34-Arc, p21-Arc, p20-Arc, and p16-Arc. The precise function of p16-Arc is currently unknown. Its structure consists of a single domain containing a bundle of seven

helices [MEDLINE:97375667], [MEDLINE:21578272].\ \N \N \N 25220 IPR006776

The precise function of SsgA is unknown. It is an acidic, cytosolic protein which has been found to be essential for spore formation, and to stimulate cell division in Streptomyces coelicolor [MEDLINE:20461209].

\ \N \N \N 25221 IPR006777

Bacteriophage PhiX174 is one of the simplest viruses, having a single-stranded, closed circular DNA of 5386 nucleotide bases and four capsid proteins, J, F, G andH. A single molecule of H protein is found on each of the 12 spikes on the microvirus shell of the bacteriophage. H is involved in the ejection of the phage DNA, and at least one copy is injected into the hosts periplasmic space along with the ssDNA viral genome [MEDLINE:94210479]. Part of H is thought to lie outside the shell, where it recognises lipopolysaccharide from virus-sensitive bacterial strains [MEDLINE:99239784]. Part of H may lie within the capsid, since mutations in H can influence the DNA ejection mechanism by affecting the DNA-protein interactions [MEDLINE:93164249]. H may span the capsid through the hydrophilic channels formed by G proteins [MEDLINE:94210479].

\ \ \N viral capsid ; GO:0019028 viral life cycle ; GO:0016032 25222 IPR006779

S1FA is an unusual small plant peptide of only 70 amino acids with a basic domain which contains a nuclear localization signal and a putative DNA binding helix. S1FA is highly conserved\ between dicotyledonous and monocotyledonous plants and may be a DNA-binding protein that specifically recognises the negative promoter element S1F [MEDLINE:95258324].

\ \ DNA binding activity ; GO:0003677 nucleus ; GO:0005634 \N 25223 IPR006780

YABBY proteins are a group of plant-specific transcription factors involved in the specification of abaxial polarity in lateral organs such as leaves and floral organs [MEDLINE:20146193], [MEDLINE:21848574].

\ \N \N \N 25224 IPR006781

Exchangeableapolipoproteins are water-soluble protein components of lipoproteins that solubilize lipids and regulate their metabolism by binding to cell receptors or activating\ specific enzymes. Apolipoprotein C-I (ApoC-1) is the smallest exchangeable apolipoprotein and transfers among HDL (high density lipoprotein), VLDL (very low-density lipoprotein) and chlylomicrons. ApoC-1 activates lecithin:choline acetyltransferase (LCAT), inhibits cholesteryl ester transfer protein, can inhibit hepatic lipase and phospholipase 2 and can stimulate cell growth. ApoC-1 delays the clearance of -VLDL by inhibiting its uptake via the LDL receptor-related pathway [MEDLINE:21464449]. ApoC-1 has been implicated in hypertriglyceridemia [MEDLINE:21250893], and Alzheimer s disease [MEDLINE:21617711].

ApoC-1 is believed to\ comprise of two dynamic helices that are stabilized by interhelical interactions and are connected by a short linker region. The minimal folding unit in the lipid-free state of this and other exchangeable apolipoproteins comprises the\ helix-turn-helix motif formed of four 11-mer sequence repeats.

\ \ \N extracellular ; GO:0005576 lipoprotein metabolism ; GO:0042157 25215 IPR006771

The pathogenic dimorphic fungal organism Blastomyces dermatitidis exists as a budding yeast at 37 degrees C and as a mycelium at 25 degrees C. Bys1 is expressed specifically in the high temperature, unicellular yeast morphology and codes for a protein of 18.6 kDa that contains multiple\ putative phosphorylation sites, a hydrophobic N terminus, and two 34-amino-acid domains with similarly spaced nine-amino-acid\ degenerative repeating motifs [MEDLINE:21669961]. The molecular function of this protein is not known.

\ \ \N \N \N 25216 IPR006772

This is a family of Herpesvirus proteins of unknown function.

\ \N \N \N 25217 IPR006773

This is a family of eukaryotic proteins which are believed to be involved in cell adhesion. Members are involved in gastrulation and also in metastatis formation and the progression of cancer. Experimental evidence suggests that these proteins are transmembrane and possibly glycoproteins [MEDLINE:20076142], [MEDLINE:20374361].

\ \N \N \N 25218 IPR006774 ABF1 is a sequence-specific DNA binding protein involved in transcription activation, gene silencing and initiation of DNA replication. ABF1 is known to remodel chromatin, and it is proposed that it mediates its effects on transcription and gene expression by modifying local chromatin architecture [MEDLINE:21630032]. These functions require a conserved stretch of 20 amino acids in the C-terminal region of ABF1 (amino acids 639 to 662 Saccharomyces cerevisiae (P14164.\ DNA binding activity ; GO:0003677 nucleus ; GO:0005634 chromatin modeling ; GO:0006338 25219 IPR006775

This domain, usually associated with the C terminus, represents a conserved region in uncharacterised proteins with a pankaryotic distribution.

\ \N \N \N 25210 IPR006766 This is a family of conserved plant proteins. The conserved region was identified in a phosphate-induced protein of unknown function [MEDLINE:99205696].\ \N \N \N 25211 IPR006767

This group of sequences contain a conserved C-terminal domain which is found in the Schizosaccharomyces pombe protein CwfJ (Q09909, which is generally N-terminal and adjacent to this domain.

\ \N \N \N 25212 IPR006768

This group of sequences contain a conserved C-terminal domain which is found in the Schizosaccharomyces pombe protein CwfJ (Q09909, which is generally C-terminal and adjacent to this domain.

\ \ \ \N \N \N 25213 IPR006769 This family represents a conserved region found in several uncharacterised eukaryotic proteins.\ \N \N \N 25214 IPR006770

Opioid peptides act as growth factors in neural and non-neural cells and tissues, in addition to serving for neurotransmission/neuromodulation in the nervous system. The native opioid growth factor (OGF), [Met(5)]-enkephalin, is an\ inhibitory peptide that plays a role in cell proliferation and tissue organization during development, cancer, cellular renewal, wound\ healing, and angiogenesis. OGF action is mediated by a receptor mechanism, the receptor for OGF (OGFr) is an\ integral membrane protein associated with the nucleus.

\ \ \

OGFr is distinguished by containing a series of imperfect repeats. This entry describes a proline-rich repeat found in a human opioid growth factor receptor [MEDLINE:21888341].

\ \ receptor activity ; GO:0004872 membrane ; GO:0016020 cell growth and/or maintenance ; GO:0008151 25206 IPR006762

GTR1 was first identified in Saccharomyces cerevisiae as a suppressor of a mutation in RCC1. RCC1 catalyzes guanine nucleotide exchange on Ran, a well characterized nuclear Ras-like small G protein that plays an essential role in the import and export of proteins and RNAs across the nuclear membranethrough the nuclear pore complex. RCC1 is located inside the nucleus, bound to chromatin. The concentration of GTP within the cell is\ ~30 times higher than the concentration of GDP, thus resulting in the preferential production of the GTP form of Ran by RCC1 within the nucleus.

Gtr1p is located within both the cytoplasm and the nucleus and has been reported to play a role in cell growth. Biochemical analysis revealed that Gtr1 is in fact a G protein of the Ras family. The RagA/B proteins are the human homologues of Gtr1 and Rag A and Gtr1p belong to the sixth subfamily of the Ras-like small\ GTPase superfamily [MEDLINE:21269253].

\ \ small monomeric GTPase activity ; GO:0003925 cytoplasm ; GO:0005737 cell growth and/or maintenance ; GO:0008151 25207 IPR006763 To date many different Plasmodium antigens recognised by the hyperimmune system human sera have been cloned, sequenced and characterised. The majority contain tandemly repeated amino acid sequences which make up a considerable portion of the protein sequence. It has been suggested that these repeat-containing antigens may provide an immunological smokescreen to the parasite in order to evade the human immune system. This repeat is found exclusively in the Plasmodium falciparum Ag332 protein and occupies most of its length [MEDLINE:95354797].\ \N \N \N 25208 IPR006764 This is a family of uncharacterised proteins.\ \N \N \N 25209 IPR006765

Aromatic polyketides are assembled by a type II (iterative) polyketide synthase in bacteria. Iterative type II polyketide synthases produce polyketide chains of variable but defined length from a specific starter unit and a number of extender units. They also specify the initial regiospecific folding and cyclization pattern of nascent\ polyketides either through the action of a cyclase (CYC) subunit or through the combined action of site-specific ketoreductase \ and CYC subunits. Additional CYCs and other modifications may be necessary to produce linear aromatic polyketides.

This family represents a number of cyclases involved in polyketide synthesis in a number of actinobacterial species.

\ \ \N \N polyketide biosynthesis ; GO:0030639 25201 IPR006757 Opioid peptides act as growth factors in neural and non-neural cells and tissues, in addition to serving in neurotransmission/neuromodulation in the nervous system. The opioid growth factor receptor is an integral membrane protein associated with the nucleus. This conserved region is situated at the N-terminus of the member proteins with a series of imperfect repeats lying immediately to its C-terminal [MEDLINE:21888341].\ receptor activity ; GO:0004872 membrane ; GO:0016020 cell growth and/or maintenance ; GO:0008151 25202 IPR006758

The A32 protein is thought to be an ATPase involved in viral DNA packaging [MEDLINE:93227572].

\ \N \N \N 25203 IPR006759

The complex-type of oligosaccharides are synthesised through elongation by glycosyltransferases after trimming of the precursor oligosaccharides transferred to proteins in the endoplasmic reticulum. N-Acetylglucosaminyltransferases (GnTs) take part in the formation of branches in the biosynthesis of complex-type sugar chains.

In vertebrates, six GnTs, designated as GnT-I to -VI, which catalyse the transfer of GlcNAc to the core mannose residues of Asn-linked sugar chains, have been identified. GnT-IV (EC: 2.4.1.145) catalyzes the transfer of GlcNAc from UDP-GlcNAc to the GlcNAc1-2Man1-3 arm of core oligosaccharide [Gn2(22)core oligosaccharide] and forms a GlcNAc1-4(GlcNAc1-2)Man1-3 structure on the core oligosaccharide (Gn3(2,4,2)core oligosaccharide). In some members the conserved region occupies all but the very N-terminal, where there is a signal sequence on all members. For other members the conserved region does not occupy the entire protein but is still to the N-terminal end of the protein [MEDLINE:97426417].

\ transferase activity, transferring hexosyl groups ; GO:0016758 membrane ; GO:0016020 \N 25204 IPR006760

This is a conserved region found in both cAMP-regulated phosphoprotein 19 (ARPP-19) and / endosulfine. No function has yet been assigned to ARPP-19. Endosulfine is the endogenous ligand for the ATP-dependent potassium channels which occupy a key position in the control of insulin release from the pancreatic cell by coupling cell polarity to metabolism. In both cases the region occupies the majority of the protein [MEDLINE:21176103], [MEDLINE:21080885].

\ \N \N \N 25205 IPR006761

Tsg was identified in drosophila as being required to specify the dorsal-most structures in the embryo, for example the amnioserosa. Biochemical experiments have revealed three key properties of Tsg:

it can synergistically inhibit Dpp/BMP action in both Drosophila melanogaster and vertebrates by forming a tripartite complete between itself, SOG/chordin and a BMP ligand;

Tsg seems to enhance the Tld/BMP-1-mediated cleavage rate of SOG/chordin and may change the preference of site utilisation;

Tsg can promote the dissociation of chordin cysteine-rich-containing fragments from the ligand to inhibit BMP signalling [MEDLINE:95047309], [MEDLINE:21160350].

\ protein binding activity ; GO:0005515 \N embryonic development ; GO:0009790 25197 IPR006753

This is a family of conserved coat proteins from the single stranded DNA Nanoviruses [MEDLINE:20254542].

\ \N \N \N 25198 IPR006754

The 34-kDa protein encoded by the I3 gene of vaccinia virus is expressed at early and intermediate times postinfection and is phosphorylated on serine residues. I3 protein demonstrates a striking affinity for single-stranded, but not\ for double-stranded, DNA which suggests a role in DNA replication and/or repair. Electrophoretic mobility shift assays indicate that numerous I3 molecules can bind to a template,\ reflecting the stoichiometric interaction of I3 with DNA. Sequence analysis reveals that a pattern of aromatic and charged amino acids\ common to many replicative single-stranded DNA binding proteins (SSBs) is conserved in I3 [MEDLINE:98184524].

\ \ single-stranded DNA binding activity ; GO:0003697 \N \N 25199 IPR006755 This is a family of uncharacterised plant pathogen luteovirus proteins.\ \N \N \N 25200 IPR006756 Under aerobic conditions, phenol is usually hydroxylated to catechol and degraded via the meta or ortho pathways. Two types of phenol hydroxylase are known: one is a multi-component enzyme the other is a single-component monooxygenase. This region is found in both types of enzymes [MEDLINE:91072230], [MEDLINE:21455041].\ phenol 2-monooxygenase activity ; GO:0018662 \N \N 25194 IPR006750

This family contains uncharacterised bacterial proteins.

\ \N \N \N 25195 IPR006751 The general transcription factor, TFIID, consists of the TATA-binding protein (TBP) associated with a series of TBP-associated factors (TAFs) that together participate in the assembly of the transcription preinitiation complex. TAFII55 binds to TAFII250 and inhibits its acetyltransferase activity. The exact role of TAFII55 is currently unknown. The conserved region is situated towards the N-terminal of the protein [MEDLINE:21532905].\ \N \N \N 25196 IPR006752

Archaeal flagella are unique motility structures, and the absence of bacterial structural motility genes in the complete genome sequences of flagellated archaeal species has always suggested that archaeal flagellar biogenesis is likely mediated by novel components. FlaD and FlaE, are present in the cell as\ membrane-associated proteins but are not major components of isolated flagellar filaments. Interestingly, flaD was found to encode\ two proteins, each translated from a separate ribosome binding site.

\ \

This group of sequences contain the archaeal flaD and flaE proteins. The conserved region that defines these sequences is found in the N-teminal region of flaE but towards the C-terminal region of flaD [MEDLINE:21574152].

\ \ \N \N ciliary/flagellar motility ; GO:0001539 25187 IPR006743 This repeat is found in the extracellular (C-terminal) region of the variant surface antigen A (VlpA) of Mycoplasma hyorhinis. Mutations that change the number of repeats in the protein are involved in antigenic variation and immune evasion of this swine pathogen [MEDLINE:20138163].\ \N \N \N 25188 IPR006744

This family contains vaccinia virus protein A12 and its homologues. VVA12 is a virion protein though its function is unknown.

\ \N \N \N 25189 IPR006745

This family contains proteins from the Eukaryota; functionally they are uncharacterised.

\ \N \N \N 25190 IPR006746

The 26S proteasome is a self-compartmentalizing protease responsible for the degradation of intracellular proteins. This giant intracellular protease is formed by several subunits arranged into two 19S polar caps, where protein recognition and ATP-dependent\ unfolding occur, flanking a 20S central barrel-shaped structure with an inner proteolytic chamber. Proteins targeted to the 26S\ proteasome are conjugated with a polyubiquitin chain by an enzymatic cascade before delivery to the 26S proteasome for degradation\ into oligopeptides.

The 19S regulatory particle of the yeast 26S proteasome consists of six related ATPases (Rpt proteins) and at least 11 non-ATPase\ proteins (Rpn proteins). RPN12 (formerly Nin1) encodes an Rpn component of the 19S regulatory particle and is essential for\ growth. This conserved region occurs at the\ C-terminal of the Nin1-like regulatory subunit.

\ \ \ 19S proteasome regulatory particle ; GO:0005838\ \N \N proteolysis and peptidolysis ; GO:0006508 25191 IPR006747 This family includes several uncharacterised proteins.\ \N \N \N 25192 IPR006748

The aminoglycosides are a large group of biologically active bacterial secondary metabolites, best known for their antibiotic properties [MEDLINE:97355449] ]. Aminoglycoside phosphotransferases achieve inactivation of these enzymes by phosphorylation, utilising ATP. Likewise, hydroxyurea is inactivated by phosphorylation of the hydroxy group in the hydroxylamine moiety.

\ phosphotransferase activity, alcohol group as acceptor ; GO:0016773 \N secondary metabolism ; GO:0019748 25193 IPR006749 This family contains fowlpox virus protein E6 and its homologues. No equivalent protein exists in vaccinia virus. The members of this family are functionally uncharacterised [MEDLINE:20193820].\ \N \N \N 25183 IPR006739 This family includes several uncharacterised proteins from Borrelia species.\ \N \N \N 25184 IPR006740 This family includes a conserved region found in several uncharacterised plant proteins.\ \N \N \N 25185 IPR006741

The accessory gene regulator (agr) of Staphylococcus aureus is the central regulatory system that controls the gene expression for a large set of virulence factors. The arg locus consists of two transcripts: RNAII and RNAIII. RNAII encodes four genes (agrA, B, C, and D) whose gene products assemble a quorum sensing system. At low cell density, the agr genes are continuously expressed at basal levels. A signal molecule, autoinducing peptide\ (AIP), produced and secreted by the bacteria, accumulates outside of the cells. When the cell density increases and the AIP concentration reaches a\ threshold, it activates the agr response, i.e. activation of secreted protein gene expression and subsequent repression of cell wall-associated protein genes. AgrB and AgrD are essential for the production of the autoinducing peptide which functions as a signal for quorum sensing.

AgrB is a transmembrane protein [MEDLINE:21034797]. AgrB is\ involved in the proteolytic processing of AgrD and may have both proteolytic enzyme activity and a transporter facilitating the export of\ the processed AgrD peptide [MEDLINE:22218060].

\ \ \N membrane ; GO:0016020 \N 25186 IPR006742

This repeated sequence,WHWLQLKPGQPMY, characterizes the mating factor -1 or -1 mating pheromone [contains: Mating factor ].The hormone is excreted into the culture medium by haploid cells of the mating type and acts on cells of the opposite mating type (type A) by binding to a cognate G-protein coupled receptor which is coupled to a downstream signal transduction pathway. It inhibits DNA synthesis in type A cells synchronising them with type , and so mediates the conjugation process.

\ hormone activity ; GO:0005179 extracellular ; GO:0005576 sexual reproduction ; GO:0019953 25166 IPR006722

Sedlin is a 140 amino-acid protein with a putative role in endoplasmic reticulum-to-Golgi transport. Several missense mutations and deletion mutations in the SEDL gene, which result in protein truncation by frame shift, are responsible for\ spondyloepiphyseal dysplasia tarda, a progressive skeletal disorder (OMIM:313400). [MEDLINE:21313110].

This family represents an N-terminal conserved region.

\ \ intracellular transporter activity ; GO:0005478 intracellular ; GO:0005622 ER to Golgi transport ; GO:0006888 25167 IPR006723 This family includes a 69 kDa protein which has been identified as an islet cell autoantigen in type I diabetes mellitus [MEDLINE:97131517]. Its precise function is unknown.\ \N \N \N 25168 IPR006724

This family contains a major tail protein from phage.

\ \N \N \N 25169 IPR006725 This family includes several hypothetical baculoviral proteins, with predicted molecular weights of approximately 44 kDa.\ \N \N \N 25170 IPR006726 This domain includes a conserved region found in two proteins associated with fusaric acid resistance, P24128 from Klebsiella oxytoca. The function of this region is unknown.\ \N \N \N 25171 IPR006727

This is a family of unknown function found in the Herpes viruses.

\ \N \N \N 25172 IPR006728 This conserved region is found in several uncharacterised proteins from Gram-positive bacteria.\ \N \N \N 25173 IPR006729

This family of proteins is found in bacteria, eukaryotes and plants. None of the members have been functionally characterised.

\ \N \N \N 25174 IPR006730

Exposure of mammalian cells to hypoxia, radiation and certain chemotherapeutic agents promotes cell cycle arrest and/or apoptosis. Activation of p53 responsive genes is believed to play an important role in mediating such responses. PA26 is differentially induced\ by genotoxic stress (UV, gamma-irradiation and cytotoxic drugs) in a p53-dependent manner.\ \ PA26 gene is a novel p53 target gene with properties common to the GADD family of growth arrest and\ DNA damage-inducible stress-response genes, and, thus, a potential novel regulator of cellular growth [MEDLINE:99124117]. A homolgue found in Xenopus, XPA26, was initially detected in the anterior portion of developing notochord at neurula stages, and later in the entire\ notochord except its posterior region at tailbud stages [MEDLINE:21095182].

\ \ \N nucleus ; GO:0005634 cell cycle arrest ; GO:0007050 25175 IPR006731 This family includes UL25 proteins from HCMV, as well as U14 proteins from HHV 6 and HHV7. These 85 kDa phosphoproteins appear to act as structural antigens, but their precise function is otherwise unknown.\ \N \N \N 25176 IPR006732 The function of these viral proteins is not known.\ \N \N \N 25177 IPR006733

This family represents the E56 protein, which is localized to the occlusion derived virus (ODV) envelope, but not to the budded virus (BV) envelope [MEDLINE:96177127]. Signals necessary for transport and/or retention into this structure are believed to be found within the C-terminal portion of ODV-E56.

\ \N viral envelope ; GO:0019031 \N 25178 IPR006734 This family includes a conserved region in several uncharacterised plant proteins.\ \N \N \N 25179 IPR006735 This family represents several uncharacterised eukaryotic proteins.\ \N \N \N 25180 IPR006736

This family is described by a conserved region found in several uncharacterised plant proteins.

\ \N \N \N 25181 IPR006737

Motilin is a gastrointestinal regulatory polypeptide produced by motilin cells in the duodenal epithelium. It is released into the general circulation at about 100-min intervals during the inter-digestive state and is the most important factor in controlling the inter-digestive migrating contractions. Motilin also stimulates endogenous release of the endocrine pancreas [MEDLINE:97353940].

This domain is also found in ghrelin, a growth hormone secretagogue synthesised by endocrine cells in the stomach. Ghrelin stimulates growth hormone secretagogue receptors in the pituitary. These receptors are distinct from the growth hormone-releasing hormone receptors, and thus provide a means of controlling pituitary growth hormone release by the gastrointestinal system [MEDLINE:21203998].

This domain represents a peptide sequence that lies C-terminal to motilin/ghrelin (IPR006738) on the respective precursor peptide. Its function is unknown.

\ \N \N \N 25182 IPR006738

\ \N \N \N 25161 IPR006717 This domain constitutes the N-terminal of E1B 55 kDa (IPR002612. The role of the N-terminal in the function of E1B is not known.\ \N \N response to external stimulus ; GO:0009605 25162 IPR006718

The defective chorion-1 gene (dec-1) in Drosophila encodes follicle cell proteins necessary for proper eggshell assembly. Multiple products of the dec-1 gene are formed by alternative RNA splicing and proteolytic processing [MEDLINE:91032553]. Cleavage products include S80 (80 kDa) which is incorporated into the eggshell, and further proteolysis of S80 gives S60 (60 kDa).

This repeat is usually found in 12 copies in the central region of the protein. Its function is unknown. Length polymorphisms of Dec-1 have been observed in wild-type strains, and are caused by changes in the numbers of the first five repeats [MEDLINE:93353525].

\ \N \N \N 25163 IPR006719

This domain is present at the N-terminal of these proteins.

\ \ \N \N \N 25164 IPR006720

Alternative splicing generates different carboxy terminal ends in different protein isoforms. This domain is the most C-terminal region that is present in the main isoforms.

\ \N \N \N 25165 IPR006721

This family constitutes the mitochondrial ATP synthase epsilon subunit. This is not to be confused with the bacterial epsilon subunit, which is homologous to the mitochondrial delta subunit (IPR001469. ATP synthase produces ATP from ADP and Pi by using the transmembrane proton motive force generated by oxidative phosphorylation orphotosynthesis. It is composed of two major parts: a cytoplasmic F1 part that includes the three catalytic sites for ATP\ synthesis/hydrolysis and a membrane-embedded F0 part that constitutes a proton channel. These two parts are structurally\ connected by two stalks, a central stalk of the gamma and epsilon subunits and an outer stalk. A regulatory protein, IF1, is found also in isolated mitochondrial ATP synthases.

\ The epsilon subunit is located in the extrinsic membrane section F1, which is the catalytic site of ATP synthesis. The epsilon subunit was not well ordered in the crystal structure of bovine F1 [MEDLINE:94344236], but it is known to be located in the stalk region of F1 [MEDLINE:20193419]. The epsilon subunit acts as an inhibitor of the ATPase of the isolated F1 subunit, with all of the inhibitory effect caused by the C-terminal\ helix-turn-helix domain of the epsilon subunit. Recent studies have also demonstrated a role of the subunit in inhibition of the ATPase activity of EF1F0. The epsilon subunit can exist in two very different conformations of subunit within EF1F0 by which the subunit can function as a ratchet to differentially regulate\ ATP hydrolysis and ATP synthesis \ [MEDLINE:20193419].\ \ hydrogen-transporting two-sector ATPase activity ; GO:0003936 mitochondrion ; GO:0005739 ATP biosynthesis ; GO:0006754 25159 IPR006715 The N-terminal of the PEA3 transcription factors is implicated in transactivation and in inhibition of DNA binding [MEDLINE:97406554]. Transactivation is potentiated by activation of the Ras/MAP kinase and protein kinase A signalling cascades. The N-terminal region contains conserved MAP kinase phosphorylation sites [MEDLINE:97430051].\ \N \N \N 25160 IPR006716 This family consists of the fungal C-8 sterol isomerase and mammalian sigma1 receptor. C-8 sterol isomerase (delta-8--delta-7 sterol isomerase), catalyses a reaction in ergosterol biosynthesis, which results in unsaturation at C-7 in the B ring of sterols [MEDLINE:94363780]. Sigma 1 receptor is a low molecular mass mammalian protein located in the endoplasmic reticulum [MEDLINE:96353947], which interacts with endogenous steroid hormones, such as progesterone and testosterone [MEDLINE:98086386]. It also binds the sigma ligands, which are a set of chemically unrelated drugs including haloperidol, pentazocine, and ditolylguanidine [MEDLINE:96353947]. Sigma1 effectors are not well understood, but sigma1 agonists have been observed to affect NMDA receptor function, the

-adrenergic system and opioid analgesia.\ C-8 sterol isomerase activity ; GO:0000247 endoplasmic reticulum ; GO:0005783 ergosterol biosynthesis ; GO:0006696 25157 IPR006713 This family of adhesins bind to the Dr blood group antigen component of decay-accelerating factor. This mediates adherence of uropathogenic Escherichia coli to the urinary tract. This family contains both fimbriated and afimbriated adherence structures [MEDLINE:97313122]. This protein also confers the phenotype of mannose-resistant hemagglutination, which can be inhibited by chloramphenicol. The N-terminal portion of the protein is thought to be responsible for chloramphenicol sensitivity [MEDLINE:91099972].\ protein binding activity ; GO:0005515 \N \N 25158 IPR006714 Periplasmic flagella are the organelles of spirochete mobility, and are structurally different from the flagella of other motile bacteria. They reside inside the cell within the periplasmic space, and confer mobility in viscous gel-like media such as connective tissue [MEDLINE:90307197]. The flagella are composed of an outer sheath of FlaA proteins and a core filament of FlaB proteins. Each species usually has several FlaA protein species [MEDLINE:97144545].\ \N periplasmic space (sensu Gram-negative Bacteria) ; GO:0030288 ciliary/flagellar motility ; GO:0001539 25153 IPR006709 This protein is found to be part of a large ribonucleoprotein complex containing the U3 snoRNA [MEDLINE:22082292]. Depletion of the Utp proteins impedes production of the 18S rRNA, indicating that they are part of the active pre-rRNA processing complex. This large RNP complex has been termed the small subunit (SSU) processome [MEDLINE:22082292].\ \N \N \N 25154 IPR006710

O-Glycosyl hydrolases (EC 3.2.1.-) are a widespread group of enzymes that hydrolyse the glycosidic bond between two or more carbohydrates, or between a carbohydrate and a non-carbohydrate moiety. A classification system for glycosyl\ hydrolases, based on sequence similarity, has led to the definition of 85 different families [MEDLINE:92082464], [MEDLINE:93356744], [MEDLINE:96257770], [MEDLINE:92121114], [MEDLINE:96097392], PUB00005672. This classification\ is available on the CAZy (CArbohydrate-Active EnZymes) web site PUB00005672. Because the fold of proteins is better conserved than\ their sequences, some of the families can be grouped in 'clans'.

Glycoside hydrolase family 43 CAZY:GH_43).

\ \ hydrolase activity, hydrolyzing O-glycosyl compounds ; GO:0004553 \N \N 25155 IPR006711 This domain constitutes the N-terminal of the paralogous homeobox proteins HoxA9, HoxB9, HoxC9 and HoxD9. The N-terminal region is thought to act as a transcription activation region. Activation may be by interaction with proteins such as Btg proteins, which are thought to recruit a multi-protein Ccr4-like complex [MEDLINE:20085025].\ transcriptional activator activity ; GO:0016563 nucleus ; GO:0005634 transcription ; GO:0006350 25156 IPR006712

Homeodomain leucine zipper (HDZip) genes encode putative transcription factors that are unique to plants. This observation suggests that homeobox-leucine zipper genes evolved after the divergence of plants and animals, perhaps to mediate specific regulatory events [MEDLINE:94359937].

\ \ This domain is the N-terminal of plant homeobox-leucine zipper proteins. Its function is unknown.

\ \ transcriptional activator activity ; GO:0016563 nucleus ; GO:0005634 transcription ; GO:0006350 25149 IPR006705 In a variety of organisms, including plants and several eubacteria, isoprenoids are synthesized by the mevalonate-independent 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway. Although different enzymes of this pathway have been described, the terminal biosynthetic steps of the MEP pathway have not been fully elucidated. GcpE gene of Escherichia coli is involved in this pathway [MEDLINE:21172855].\ enzyme activity ; GO:0003824 \N terpenoid biosynthesis ; GO:0016114 25150 IPR006706

Extensins are homologous hydroxyproline-rich glycoproteins (HRGPs) found in the plant extracellular matrix. The key to the role of HRGPs in cell wall self-assembly and cell extension lies in their chemistry, which is dependent on extensive post-translational modifications (PTMs): hydroxylation, glycosylation,\ and cross-linking. Repetitive peptide motifs characterize HRGPs.

\ \

This is a family of extensin-like proteins.

\ \ \N \N \N 25151 IPR006707 This is a family of hypothetical bacterial proteins.\ \N \N \N 25152 IPR006708

Peroxisome(s) form an intracellular compartment, bounded by a typical lipid bilayer membrane. Peroxisome functions are often specialized by organism and cell type; two widely distributed and well-conserved functions are H2O2-based respiration and fatty acid �-oxidation. Other functions include ether lipid (plasmalogen) synthesis and cholesterol synthesis inanimals, the glyoxylate cycle in germinating seeds ("glyoxysomes"), photorespiration in leaves, glycolysis in trypanosomes ("glycosomes"), and methanol and/or amine\ oxidation and assimilation in some yeasts.

PEX genes encode the\ machinery ("peroxins") required to assemble the peroxisome. Membrane assembly and maintenance requires three of these (peroxins 3,\ 16, and 19) and may occur without the import of the matrix (lumen) enzymes. Matrix protein import follows a branched pathway of\ soluble recycling receptors, with one branch for each class of peroxisome targeting sequence (two are well characterized), and a\ common trunk for all. At least one of these receptors, Pex5p, enters and exits peroxisomes as it functions. Proliferation of the organelle\ is regulated by Pex11p. Peroxisome biogenesis is remarkably conserved among eukaryotes. A group of fatal, inherited\ neuropathologies are recognized as peroxisome biogenesis diseases.

\ \ \N peroxisome ; GO:0005777 \N 25147 IPR006703

This represents Arabidopsis protein AIG1 which appears to be involved in plant resistance to bacteria. The Arabidopsis disease resistance gene RPS2 is involved in recognition of bacterial pathogens carrying the avirulence gene avrRpt2. AIG1 (avrRpt2-induced gene) exhibits RPS2- and avrRpt2-dependent induction early after infection with Pseudomonas syringae carrying avrRpt2 [MEDLINE:96351417].

The pattern also recognises a number of mammalian proteins, for example the rat immune-associated nucleotide 4 protein, suggesting that the family may have a wider function.

\ \ \N \N \N 25148 IPR006704

CD47 (integrin-associated protein, IAP) is a widely expressed membrane protein with multiple functions in immunological and neuronal processes. For example, CD47-induces caspase-independent cell death which may be mediated by cytoskeleton reorganization [MEDLINE:22238327]. In red blood cells, CD47 acts like a marker of self by ligating the macrophage inhibitory receptor signal regulatory protein [MEDLINE:21981718]. The protein can also act as a thrombospondin receptor [MEDLINE:21977653].

\ \

This pattern also recognises a group of CD-47-like proteins found in Capripoxvirus.

\ \ \N \N \N 25145 IPR006701 Initiation of packaging of double-stranded viral DNA involves the specific interaction of the prohead with viral DNA in a process mediated by a phage-encoded terminase protein. The terminase enzymes are usually hetero-oligomers composed of a small and a large subunit. This region is found on the large subunit and possesses an endonuclease and ATPase activity that requires Mg²⁺ and a neutral or slightly basic reaction. This region is also found in bacterial sequences [MEDLINE:20519627], [MEDLINE:92194332].\ \N \N DNA packaging ; GO:0006323 25146 IPR006702 This family of plant proteins contains a domain that may have a catalytic activity. It has a conserved arginine and aspartate that could form an active site. These proteins are predicted to contain 3 or 4 transmembrane helices.\ \N \N \N 25144 IPR006700

This is a bacterial protein domain of unknown function.

\ \N \N \N 25140 IPR006696 This is a potential integral membrane protein with no known function.\ \N \N \N 25141 IPR006697

The exodeoxyribonuclease V enzyme is a multisubunit enzyme comprised of the proteins RecB (IPR004586. Its nuclease activity is controlled by Chi sites (5' G-C-T-G-G-T-G-G 3') in such a way that the enzyme produces a potent single-stranded DNA substrate for homologous pairing by RecA and single-stranded DNA binding proteins.

\ \N \N \N 25142 IPR006698

These are Bacterial and Archaeal proteins of unknown function.

\ \N \N \N 25143 IPR006699

Glycerol enters bacterial cells via facilitated diffusion, an energy-independent transport process catalysed by the glycerol transport\ facilitator GlpF, an integral membrane\ protein of the aquaporin family. Intracellular\ glycerol is usually converted to glycerol-3-P in an ATP-requiring\ phosphorylation reaction catalysed by glycerol kinase (GlpK).\ Glycerol-3-P, the inducer of the glpFK operon, is not a substrate for GlpF\ and hence remains entrapped in the cell where it is metabolized further. In\ some bacterial species, for example Bacillus subtilis, glycerol-3-P activates the antiterminator GlpP [MEDLINE:92236407]. In Bacillus subtilis, glpF and glpK are organized in an operon followed by the\ glycerol-3-P dehydrogenase-encoding glpD gene and preceded by glpP\ coding for an antiterminator regulating the expression of glpFK, glpD and\ glpTQ . Their induction\ requires the inducer glycerol-3-P, which activates the antiterminator GlpP\ by allowing it to bind to the leader region\ of glpD and presumably also of glpFK and glpTQ\ mRNAs.

\ \ transcription regulator activity ; GO:0030528 \N regulation of transcription ; GO:0045449 25137 IPR006693

The / hydrolase fold is common to several hydrolytic enzymes of widely differing phylogenetic origin andcatalytic function. The core of each enzyme is similar: an / sheet, not barrel, of eight -sheets connected by -helices [MEDLINE:93028317]. This entry describes a closely associated region, which is found in a number of lipases.

\ \ \N \N \N 25138 IPR006694

This is a group of related eukaryotic putative fatty acid hydrolases.

\ \N \N \N 25139 IPR006695 Centromere Protein B (CENP-B) is a DNA-binding protein localized to the centromere. Within the N-terminal 125 residues, there is a DNA-binding region, which binds to a corresponding 17bp CENP-B box sequence. CENP-B dimers either bind two separate DNA molecules or alternatively, they may bind two CENP-B boxes on one DNA molecule, with the intervening stretch of DNA forming a loop structure. The CENP-B DNA-binding domain consists of two repeating domains, RP1 and RP2. This family corresponds to RP1 has been shown to consist of four helices in a helix-turn-helix structure [MEDLINE:98119825].\ \N \N \N 25135 IPR006691 This repeat is found as 6 tandem copies at the C-termini of GyrA and ParC DNA gyrases. It is predicted to form 4

strands and to probably form a

-propeller structure [MEDLINE:21946018]. This region has been shown to bind DNA non-specifically and may stabilize the DNA-topoisomerase complex [MEDLINE:92036488].\ \N \N \N 25136 IPR006692

RET1P, the -subunit of the coatomer complex in Saccharomyces cerevisiae, participates in membrane transport between the endoplasmic reticulum and Golgi apparatus. The protein contains six WD-40 repeat motifs in its N-terminal region [MEDLINE:96194806].

\ \ \N \N \N 25134 IPR006690

Most of the bacterial outer membrane proteins in this group are porin-like integral membrane proteins (such as ompA) [MEDLINE:90361709], but some are small lipid-anchored proteins (such as pal) [MEDLINE:99445459]. It is also found in MotB and related proteins. They are present in the outer membrane of many Gram-negative organisms [MEDLINE:92167971]. This domain is found at the C-terminal half of these proteins and is well conserved. The N-terminal half is variable although some of the proteins in this group have the OmpA-like transmembrane domain IPR000498 at the N terminus.

\ \N \N \N 25132 IPR006688

The small ADP ribosylation factor (Arf) GTP-binding proteins are major regulators of vesicle biogenesis in intracellular traffic [MEDLINE:22316734]. They are the founding members of a growing family that includes Arl (Arf-like), Arp(Arf-related proteins) and the remotely related Sar (Secretion-associated and Ras-related) proteins. Arf proteins cycle between inactive GDP-bound and active GTP-bound forms that bind selectively to effectors. The classical structural GDP/GTP switch is characterized by conformational changes at the so-called switch 1 and switch 2 regions, which bind tightly to the gamma-phosphate of GTP but poorly or not at all to the GDP nucleotide. Structural studies of Arf1 and Arf6 have revealed that although these proteins feature the switch 1 and 2 conformational changes, they depart from other small GTP-binding proteins in that they use an additional, unique switch to propagate structural information from one side of the protein to the other.

The GDP/GTP structural cycles of human Arf1 and Arf6 feature a unique conformational change that affects the beta2beta3 strands connecting switch 1 and switch 2 (interswitch) and also the amphipathic helical N-terminus. In GDP-bound\ Arf1 and Arf6, the interswitch is retracted and forms a pocket to which the N-terminal helix binds, the latter serving as a molecular hasp to maintain the inactive conformation. In the GTP-bound form of these proteins, the interswitch undergoes a two-residue register shift that pulls switch 1 and switch 2 up, restoring an active conformation that can bind GTP. In this conformation, the interswitch projects out of the protein and extrudes the N-terminal hasp by occluding its binding pocket.

ADP-ribosylation factors (ARF) [MEDLINE:95288782], [MEDLINE:93342187], [MEDLINE:95082952] are 20 kDa GTP-binding proteins involved in protein trafficking. They may modulate vesicle budding and uncoating within the Golgi apparatus. ARF's also act as allosteric activators of cholera toxin ADP-ribosyltransferase activity. They are evolutionary conserved and present in all eukaryotes. At least six forms of ARF are present in mammals and three in budding yeast. The ARF family also includes proteins highly related to ARF's but which lack the cholera toxin cofactor activity, they are collectively known as ARL's (ARF-like). The ARFs are N-terminally myristoylated (the ARLs have not yet been shown to be modified in such a fashion).

\ \ \N \N \N 25133 IPR006689

\ \ \N \N \N 25129 IPR006685 Two proteins from M. jannaschii form mechanosensitive (MS) ion channels upon reconstitution into liposomes and functional examination by the patch-clamp technique. Therefore this family is likely to be MS channel proteins. \ \ \N membrane ; GO:0016020 \N 25130 IPR006686

Two proteins from M. jannaschii form mechanosensitive (MS) ion channels upon reconstitution into liposomes and functional examination by the patch-clamp technique. Therefore this family is likely to be MS channel proteins.

\ \ \N membrane ; GO:0016020 \N 25131 IPR006687

The SAR1 [MEDLINE:93011016], [MEDLINE:94186545] protein, first identified in budding yeast, is a 21 kDa GTP-\ binding protein involved in vesicular transport between the endoplasmic\ reticulum and the Golgi [MEDLINE:94085558]. It is a GTP-binding protein that takes part in the\ formation of secretory vesicles by binding to an ER type II membrane\ protein, Sec12p [MEDLINE:93011016]. It is evolutionary conserved and seems to be present\ in all eukaryotes.

\ SAR1 is generally included in the RAS 'superfamily' of small GTP-binding\ proteins, but it is only slightly related to other RAS proteins. It also\ differs from RAS proteins in that it lacks cysteine residues at the C terminus\ and is therefore not subject to prenylation. SAR1 is slightly related to ARFs.

\ \ \N \N \N 25126 IPR006682

This family of uncharacterized proteins shows a low level of similarity (possibly meaningful) to the predicted membrane protein YLR220W, which is involved in calcium homeostatis. It shows no similarity to any other characterized protein.This family is represented in three of the first four completed archaeal genomes, with two members in A. fulgidus.

\ \ \N \N \N 25127 IPR006683

This family contains a wide variety of enzymes, principally thioesterases. This family includes 4HBT (EC: 3.1.2.23) which catalyses the final step in the biosynthesis of 4-hydroxybenzoate from 4-chlorobenzoate in the soil dwelling microbe Pseudomonas CBS-3. This family includes various cytosolic long-chain acyl-CoA thioester hydrolases. Long-chain acyl-CoA hydrolases hydrolyse palmitoyl-CoA to CoA and palmitate, they also catalyse the hydrolysis of other long chain fatty acyl-CoA thioesters.

\ enzyme activity ; GO:0003824 \N \N 25128 IPR006684 4-hydroxybenzoyl-CoA thioesterase (EC: 3.1.2.23) is an enzyme from PseudomonasCBS-3, a soil-dwelling microbe that survives on 4-chlorobenzoate as its sole\ carbon source. This enzyme [MEDLINE:99057924] catalyzes the last of the three steps in the\ pathway from 4-chlorobenzoate to hydroxybenzoate, the cleavage of the\ thioester bond of 4-hydroxybenzoyl-CoA to form hydroxybenzoate.\

\
4-hydroxybenzoyl-CoA + H₂O = 4-hydroxybenzoate + CoA\

\ 4-hydroxybenzoyl-CoA thioesterase is a protein of 141 amino-acid residues that\ assemble as an homotetramer. An aspartate in the N-terminal domain is thought\ to participate in the catalytic mechanism.\ This enzyme is evolutionary related to a number of uncharacterized proteins.\ \ hydrolase activity ; GO:0016787 \N \N 25123 IPR006678

tRNA-intron endonucleases (EC: 3.1.27.9) cleave pre-tRNA producing 5'-hydroxyl and 2',3'-cyclic phosphate termini, and specifically removing the intron [MEDLINE:97344075]. This entry is for N-terminal domain of tRNA-intron endonuclease.

\ tRNA-intron endonuclease activity ; GO:0000213 tRNA-intron endonuclease complex ; GO:0000214 tRNA splicing ; GO:0006388 25124 IPR006679 Adenine deaminase (EC: 3.5.4.2) hydrolyses adenine to form hypoxanthineand ammonia. The enzyme is part of a large metal dependent hydrolase\ superfamily [MEDLINE:97290007].\ The adenine deaminase reaction is important for adenine utilization as\ a purine and also as a nitrogen source [MEDLINE:96146537].\ \ adenine deaminase activity ; GO:0000034 \N adenine catabolism ; GO:0006146 25125 IPR006680

This family of enzymes are a large metal dependent hydrolase superfamily [MEDLINE:96146537]. The family includes adenine deaminase (EC: 3.5.4.2) that hydrolyses adenine to form hypoxanthine and ammonia. The adenine deaminase reaction is important for adenine utilization as a purine and also as a nitrogen source [MEDLINE:97290007]. This family also includes dihydroorotase and N-acetylglucosamine-6-phosphate deacetylases (EC: 3.5.1.25). These enzymes catalyse the reaction:

 N-acetyl-D-glucosamine 6-phosphate + H2O = D-glucosamine 6-phosphate + acetate

This family includes the catalytic domain of urease

subunit [MEDLINE:95273988].

\ \N \N \N 25122 IPR006677

\ tRNA-intron endonuclease activity ; GO:0000213 tRNA-intron endonuclease complex ; GO:0000214 tRNA splicing ; GO:0006388 25119 IPR006674 This domain is found in a superfamily of enzymes with a predicted or known phosphohydrolase activity. These enzymes appear to be involved in the nucleic acid metabolism, signal transduction and possibly other functions in bacteria, archaea and eukaryotes.The fact that all the highly conserved residues in the HD superfamily are histidines or aspartates suggests that coordination of divalent cations is essential for the activity of these proteins [MEDLINE:99085258].\ \ \N \N \N 25120 IPR006675

This domain is found in a few known nucleotidyltransferes and in a large number of uncharacterized proteins. It contains four widely separated His residues, the second of which is part of an invariant dipeptide His-Asp in a region matched approximately by the motif HDIG.

\ \N \N \N 25121 IPR006676

tRNA-intron endonucleases (EC: 3.1.27.9) cleave pre-tRNA producing 5'-hydroxyl and 2',3'-cyclic phosphate termini, and specifically removing the intron [MEDLINE:97344075]. These enzymes catalyze the final stage in the maturation of tRNA molecules.

\ tRNA-intron endonuclease activity ; GO:0000213 tRNA-intron endonuclease complex ; GO:0000214 tRNA splicing ; GO:0006388 25111 IPR006665

\ \N \N \N 25112 IPR006667 This region is the integral membrane part of the eubacterial MgtE family of magnesium transporters. Related regions are found also in archaebacterial and eukaryotic proteins. All the archaebacterial and eukaryotic examples have two copies of the region. This suggests that the eubacterial examples may act as dimers. Members of this family probably transport Mg²⁺ or other divalent cations into the cell. The alignment contains two highly conserved aspartates that may be involved in cation binding (Bateman A unpubl.)\ cation transporter activity ; GO:0008324 \N cation transport ; GO:0006812 25113 IPR006668

This region is the integral membrane part of the eubacterial MgtE family of magnesium transporters. It is presumed to be an intracellular domain, that may be involved in magnesium binding.

\ cation transporter activity ; GO:0008324 \N cation transport ; GO:0006812 25114 IPR006669

This is the MgtE family of magnesium transporters. All the archaebacterial and eukaryotic examples have two copies of the integral membrane region. This suggests that the eubacterial examples may act as dimers. Members of this family probably transport Mg²⁺ or other divalent cations into the cell. The alignment contains two highly conserved aspartates that may be involved in cation binding.

\ cation transporter activity ; GO:0008324 \N cation transport ; GO:0006812 25115 IPR006670

Cyclins are eukaryotic proteins which play an active role in controlling nuclear cell division cycles PUB00001013, PUB00001013, PUB00005504 , and regulate cyclin dependent kinases (CDKs). Cyclins, together with the p34 (cdc2) or cdk2 kinases, form the Maturation Promoting Factor (MPF). There are two main groups of cyclins, G1/S cyclins, which are essential for the control of the cell cycle at the G1/S (start) transition, and G2/M cyclins, which are essential for the control of the cell cycle at the G2/M (mitosis) transition. G2/M cyclins accumulate steadily during G2 and are abruptly destroyed as cells exit from mitosis (at the end of the M-phase). In most species, there are multiple forms of G1 and G2 cyclins. For example, in vertebrates, there are two G2 cyclins, A and B, and at least three G1 cyclins, C, D, and E. A cyclin homolog has also been found in herpesvirus saimiri\ \ \ PUB00005504.

\ \

This domain is also found in TFIIB and retinoblastoma.

\ \ \N \N \N 25116 IPR006671

\ \ Cyclins contain two domains of similar all-

fold, of which this family corresponds with the N-terminal domain.\ \ \N \N \N 25117 IPR006672

This is a family of bacterial and archaebacterial proteins of unknown function. The group includes a multiple resistance and pH regulation related protein from Bacillus firmus. Members of this family are potential \ transmembrane proteins.

\ \ molecular_function unknown ; GO:0005554 integral to membrane ; GO:0016021 \N 25118 IPR006673

This is a family of cation transporters.

\ cation transporter activity ; GO:0008324 \N cation transport ; GO:0006812 25110 IPR006664 Most of the bacterial outer membrane proteins in this group are porin-like integral membrane proteins (such as ompA) [MEDLINE:90361709], but some are small lipid-anchored proteins (such as pal) [MEDLINE:99445459]. They are present in the outer membrane of many Gram-negative organisms [MEDLINE:92167971]. This domain is found at the C-terminal half of these proteins and is well conserved. The N-terminal half is variable although some of the proteins in this group have the OmpA-like transmembrane domain IPR000498 at the N terminus.\ \N \N \N 25109 IPR006663 Thioredoxins [MEDLINE:85277988], [MEDLINE:89340492], [MEDLINE:95308039], [MEDLINE:95308040] are small disulphide-containing redox proteins that have been found in all the kingdoms of living organisms. Thioredoxin serves as a general protein disulphide oxidoreductase. It interacts with a broad range of proteins by a redox mechanism based on reversible oxidation of 2 cysteine thiol groups to a disulphide, accompanied by the transfer of 2 electrons and 2 protons. The net result is the covalent interconversion of a disulphide and a dithiol.

TR-S₂ + NADPH + H⁺ -> TR-(SH)₂ + NADP⁺ (1)

\ \ \ \

trx-S₂ + TR-(SH)₂ -> trx-(SH)₂ + TR-S₂ (2)

\ \ \ \

Protein-S₂ + trx-(SH)₂ -> Protein-(SH)₂ + trx-S₂ (3)

\ In the NADPH-dependent protein disulphide reduction, thioredoxin reductase (TR) catalyses reduction of oxidised thioredoxin (trx) by NADPH using FAD and its redox-active disulphide (steps 1 and 2). Reduced thioredoxin then directly reduces the disulphide in the substrate protein (step 3) [MEDLINE:85277988]. Protein disulphide isomerase (PDI), a resident foldase of the endoplasmic recticulum, is a multi-functional protein that catalyses the formation and isomerisation of disulphide bonds during protein folding [MEDLINE:94308180], [MEDLINE:95074127]. PDI contains 2 redox active domains, near the N- and C-termini, that are similar to thioredoxin: both contribute to disulphide isomerase activity, but are functionally non-equivalent [MEDLINE:95074127]. Interestingly, a mutant PDI, with all 4 of the active cysteines replaced by serine, displays a low but detectable level of disulphide isomerase activity [MEDLINE:95074127]. Moreover, PDI exhibits chaperone-like activity towards proteins that contain no disulphide bonds, i.e. behaving independently of its disulphide isomerase activity [MEDLINE:95361853]. A number of endoplasmic reticulum proteins that differ from the PDI major isozyme contain 2 (ERp60, ERp5) or 3 (ERp72 [MEDLINE:90110091]) thioredoxin domains; all of them seem to be PDIs. 3D-structures have been determined for a number of thioredoxins [MEDLINE:96131880]. The molecule has a doubly-wound alternating

fold, consisting of a 5-stranded parallel

-sheet core, enclosed by 4

-helices. The active site disulphide is located at the N-terminus of helix 2 in a short segment that is separated from the rest of the helix by a kink caused by a conserved proline. The 4-membered disulphide ring is located on the surface of the protein. A flat hydrophobic surface lies adjacent to the disulphide, which presumably facilitates interaction with other proteins.

One invariant feature of all thioredoxins is a cis-proline located in a loop preceding -strand 4. This residue is positioned in van der Waals contact with the active site cysteines and is important both for stability and function [MEDLINE:96131880]. Thioredoxin belongs to a structural family that includes glutaredoxin, glutathione peroxidase, bacterial protein disulphide isomerase DsbA, and the N-terminal domain of glutathione transferase [MEDLINE:95308040]. Thioredoxins have a - unit preceding the motif common to all these proteins.

\ \ electron transporter activity ; GO:0005489 \N electron transport ; GO:0006118 25101 IPR006655 Members of this family include a number of molybdopterin-containing oxidoreductases, tungsten formylmethanofuran dehydrogenase subunit d (FwdD) and molybdenum formylmethanofuran dehydrogenase subunit (FmdD); where a single domain constitutes almost the entire subunit.\ The formylmethanofuran dehydrogenase catalyses the first step in\ methane formation from CO2 in methanogenic archaea and has a \ molybdopterin dinucleotide cofactor [MEDLINE:99035764]. \ \ \N \N electron transport ; GO:0006118 25102 IPR006656

This domain is found in a number of molybdopterin-containing oxidoreductases, tungsten formylmethanofuran dehydrogenase subunit d (FwdD) and molybdenum formylmethanofuran dehydrogenase subunit (FmdD); where a single domain constitutes almost the entire subunit.\ The formylmethanofuran dehydrogenase catalyses the first step in\ methane formation from CO2 in methanogenic archaea and has a \ molybdopterin dinucleotide cofactor [MEDLINE:99035764].

\ \ \N \N \N 25103 IPR006657

A domain in this entry corresponds to the C-terminal domain IV in dimethyl sulfoxide (DMSO)reductase\ which interacts with the 2-amino pyrimidone ring of both \ molybdopterin guanine dinucleotide molecules [MEDLINE:97045990].

\ \ \N \N \N 25104 IPR006658

This enzyme family shares sequence similarity and a requirement for a molydenum cofactor as the only prosthetic group. The form of the cofactor is a single molybdenum atom coordinated by two molybdopterin guanine dinucleotide molecules. Members of the family include biotin sulfoxide reductase, dimethylsulfoxide reductase, and trimethylamine-N-oxide reductase, although a single member may show all those activities and related activities; it may not be possible to resolve the primary function for members of this family by sequence comparison alone. A number of similar molybdoproteins in which the N-terminal region contains a CXXXC motif and may bind an iron-sulfur cluster are excluded from this set, including formate dehydrogenases and nitrate reductases. Also excluded is the A chain of a heteromeric, anaerobic DMSO reductase, which also contains the CXXXC motif [MEDLINE:97166177].

\ \ oxidoreductase activity ; GO:0016491 \N electron transport ; GO:0006118 25105 IPR006659

This entry describes a distinct clade, including ArsC itself, of the broader family of ArsC and related proteins. This clade is almost completely restricted to the proteobacteria. An anion-translocating ATPase has been identified as the product of the arsenical resistance operon of resistance plasmid R773 [MEDLINE:91126299]. When expressed in Escherichia coli this ATP-driven oxyanion pump catalyses extrusion of the oxyanions arsenite, antimonite and arsenate. The pump is \ composed of two polypeptides, the products of the arsA and arsB genes. The pump alone produces resistance to arsenite and antimonite. This protein, ArsC, catalyzes the reduction of arsenate to arsenite, and thus extends resistance to include arsenate.

\ \ arsenate reductase (glutaredoxin) activity ; GO:0008794 \N electron transport ; GO:0006118 25106 IPR006660

An anion-translocating ATPase has been identified as the product of the arsenical resistance operon of resistance plasmid R773\ \ \ [MEDLINE:91126299]. When expressed in Escherichia coli this ATP-driven oxyanion pump catalyses extrusion of the oxyanions arsenite, antimonite and arsenate. Maintenance of a low intracellular concentration of oxyanion produces resistance to the toxic agents. The pump is composed of two polypeptides, the products of the arsA and arsB genes. This two-subunit enzyme produces resistance to arsenite and antimonite. A third gene, arsC, expands the substrate specificity to allow for arsenate pumping and resistance. ArsC catalyzes the reduction of arsenate to arsenite.

\ \ oxidoreductase activity ; GO:0016491 \N electron transport ; GO:0006118 25107 IPR006661

Gram-negative bacteria produce a number of proteins that are secreted into the growth medium by a mechanism that does not require a cleaved N-terminal signal sequence. These \ proteins, while having different functions, seem to share two properties: they bind \ calcium and they contain a multiple tandem repeat of a nonapeptide [MEDLINE:90151607]. The \ nonapeptide is found in a group of bacterial exported proteins that includes haemolysin, \ cyclolysin, leukotoxin and two proteases.

It has been suggested that the internally \ repeated domain of haemolysin may be involved in Ca-mediated binding to erythrocytes. It \ has been shown that such a domain is involved in the binding of calcium ions in a \ parallel roll structure [MEDLINE:94074534].

\ \ \N \N \N 25108 IPR006662 Thioredoxins [MEDLINE:85277988], [MEDLINE:89340492], [MEDLINE:95308039], [MEDLINE:95308040] are small disulphide-containing redox proteins that have been found in all the kingdoms of living organisms. Thioredoxin serves as a general protein disulphide oxidoreductase. It interacts with a broad range of proteins by a redox mechanism based on reversible oxidation of 2 cysteine thiol groups to a disulphide, accompanied by the transfer of 2 electrons and 2 protons. The net result is the covalent interconversion of a disulphide and a dithiol.

TR-S₂ + NADPH + H⁺ -> TR-(SH)₂ + NADP⁺ (1)

\ \ \ \

trx-S₂ + TR-(SH)₂ -> trx-(SH)₂ + TR-S₂ (2)

\ \ \ \

Protein-S₂ + trx-(SH)₂ -> Protein-(SH)₂ + trx-S₂ (3)

fold, consisting of a 5-stranded parallel

-sheet core, enclosed by 4

\ \ electron transporter activity ; GO:0005489 \N electron transport ; GO:0006118 25100 IPR006654

Tryptophan synthase (EC: 4.2.1.20) catalyzes the last step in the biosynthesisof tryptophan [MEDLINE:90024964], [MEDLINE:90329239]:\

\
L-serine + 1-(indol-3-yl)glycerol 3-phosphate = L-tryptophan + glyceraldehyde 3-phosphate + H₂O\

\ It has two functional domains, each found in bacteria and plants on a\ separate subunit:

chain (IPR002028) is for the aldol cleavage of indoleglycerol phosphate to indole and\ glyceraldehyde 3-phosphate and

chain is for the synthesis of tryptophan from\ indole and serine. In fungi the two domains are fused together on a single multifunctional protein [MEDLINE:89282819].

\ \

The chain of the enzyme, represented here, requires pyridoxal-phosphate as a cofactor. The pyridoxal-phosphate group is attached to a lysine residue. The region around this lysine residue also contains two histidine residues which are part of the pyridoxal-phosphate binding site.

\ \ tryptophan synthase activity ; GO:0004834 \N tryptophan metabolism ; GO:0006568 25099 IPR006653

Tryptophan synthase (EC: 4.2.1.20) catalyzes the last step in the biosynthesisof tryptophan [MEDLINE:90024964], [MEDLINE:90329239]:\

\
L-serine + 1-(indol-3-yl)glycerol 3-phosphate = L-tryptophan + glyceraldehyde 3-phosphate + H₂O\

\ It has two functional domains, each found in bacteria and plants on a\ separate subunit:

chain (IPR002028) is for the aldol cleavage of indoleglycerol phosphate to indole and\ glyceraldehyde 3-phosphate and

chain is for the synthesis of tryptophan from\ indole and serine. In fungi the two domains are fused together on a single multifunctional protein [MEDLINE:89282819].

\ \

\ \ tryptophan synthase activity ; GO:0004834 \N tryptophan metabolism ; GO:0006568 25098 IPR006652

Kelch is a 50-residue motif, named after the Drosophila mutant in which it was first identified [MEDLINE:93201592]. The motif appears 6 times in Drosophila egg-chamber regulatory protein, and is also found in mouse protein MIPP [MEDLINE:93201592] and in a number of poxviruses. In addition, kelch repeats have been recognised in - and -scruin [MEDLINE:96019249], [MEDLINE:95122639], and in galactose oxidase from the fungus Dactylium dendroides\ \ \ [MEDLINE:94172626]. The structure of galactose oxidase reveals that the repeated sequence corresponds to a 4-stranded anti-parallel -sheet motif that forms the repeat unit in a super-barrel structural fold [MEDLINE:94238692].

The known functions of kelch-containing proteins are diverse: scruin is an actin cross-linking protein; galactose oxidase catalyses the oxidation of the hydroxyl group at the C6 position in D-galactose; neuraminidase hydrolyses sialic acid residues from glycoproteins; and kelch may have a cytoskeletal function, as it is localised to the actin-rich ring canals that connect the 15 nurse cells to the developing oocyte in Drosophila [MEDLINE:96019249]. Nevertheless, based on the location of the kelch pattern in the catalytic unit in galactose oxidase, functionally important residues have been predicted in glyoxal oxidase [MEDLINE:94172626].

\ \ \N \N \N 25095 IPR006649

This domain is found in small nuclear ribonucleoprotein. The Sm proteins are essential for pre-mRNA splicing and are implicated in the formation of stable, biologically active snRNP structures. The function of this domain is unknown.

\ \N \N \N 25096 IPR006650

Adenosine deaminase (EC: 3.5.4.4) catalyzes the hydrolytic deamination of adenosine into inosine and AMP deaminase (EC: 3.5.4.6) catalyzes the hydrolytic deamination of AMP into IMP.\ It has been shown [MEDLINE:91152042] that these two \ enzymes share three regions of sequence similarities; these regions are centered \ on residues which are proposed to play an important role in the catalytic mechanism of \ these two enzymes. This entry presents one of these\ regions, it contains two conserved aspartic acid residues that are potential\ active site residues.\

\ \ deaminase activity ; GO:0019239 \N purine ribonucleoside monophosphate biosynthesis ; GO:0009168 25097 IPR006651

\ \ \N \N \N 25092 IPR006645

The family of sequences identified by the NGN domain are represented by thebacterial antitermination protein nusG. In Arabidopsis and Caenorhabditis\ elegans the proteins have no known function. In Oryza sativa (Rice) the\ protein is described as a putative transcription factor.

\ \ \N \N \N 25093 IPR006646

The KOW (Kyrpides, Ouzounis, Woese) motif is found in a variety ofribosomal\ proteins and the Bacterial transcription antitermination proteins NusG. It is a nucleic acid interaction motif\ [MEDLINE:97141024].

\ \ \N \N \N 25094 IPR006647

This domain is found only in DNA primases. DNA primase (EC: 2.7.7.-) is a nucleotidyltransferase which synthesizes the oligoribonucleotide primers required for DNA replication on the lagging strand of the replication fork. It can also prime the leading strand and has been implicated in cell division [MEDLINE:94124015].

\ \N \N \N 25087 IPR006640

This family of proteins is predicted to have roles in transcription elongation [MEDLINE:22191968]. They contain a conserved HExxH motif, indicating a metalloprotease function. Three viral SprT homologues are known, in Mamestra configurata nucleopolyhedrovirus and\ Leucania separata nucleopolyhedrovirus. These are the only viral homologues of eukaryotic transcription elongation factors known.

\ \ \N \N \N 25088 IPR006641

YqgF proteins are likely to function as an alternative to RuvC in mostBacteria, and could be the\ principal holliday junction resolvases in low-GC Gram-positive Bacteria. In\ Spt6p orthologues, the\ catalytic residues are substituted indicating that they lack enzymatic\ functions [MEDLINE:20440383].

\ \ \N \N \N 25089 IPR006642

This domain has been found in proteins such as Saccharomyces cerevisiae RAD18. The domain is a potential zinc finger\ for nucleic acid binding and a putative nucleotide binding sequence PUB00005329.

\ \ \N \N \N 25090 IPR006643

The ZASP domain is a PDZ domain that binds to the COOH-terminal region of -actinin-2. It is a short motif (26 amino acids) and its function may be the direction of intracellular proteins to multiprotein complexes [MEDLINE:99357848].

\ \N \N \N 25091 IPR006644

In animals, cadherin domain-containing proteins are adhesion molecules that modulate a wide variety of processes including cell polarization and migration but they have also been identified in yeast and magnetotactic bacteria. Crystal structures have revealed that multiple cadherin domains form Ca²⁺-dependent rod-like structures with a conserved Ca²⁺-binding pocket at the domaindomain interface [MEDLINE:21906647].

\ \N \N \N 25081 IPR006634

TLC is a protein domain with at least 5 transmembrane -helices. Lag1p and Lac1pare essential for\ acyl-CoA-dependent ceramide synthesis [MEDLINE:21551514], TRAM is a subunit\ of the translocon and the CLN8\ gene is mutated in Northern epilepsy syndrome. Proteins containing this domain may possess\ multiple functions such as\ lipid trafficking, metabolism, or sensing. Trh homologues possess additional\ homeobox domains [MEDLINE:99091901].

\ \ \N \N \N 25082 IPR006635

This domain identifies a small family of protein with no known function which are found exclusively in bacteria.

\ \N \N \N 25083 IPR006636

This describes a heat shock chaperonin-binding motif found in the stress-inducible phosphoprotein STI1. Both N- and C-termini of STI1 are capable of binding heat shock proteins [MEDLINE:97153154] and the domain is found both singly and duplicated in other proteins.

\ \N \N \N 25084 IPR006637

This hydrophobic repeat is found in a number of Chlostridium proteins. It contains a conserved tryptophan residue.

\ \N \N \N 25085 IPR006638

This domain is found in MoaA, NifB, PqqE, coproporphyrinogenIII oxidase, biotin synthase\ and MiaB families, and includes a representative in the eukaryotic elongator\ subunit, Elp-3. Some\ members of the family are methyltransferases [MEDLINE:21127964].

\ \ \N \N \N 25086 IPR006639

Signal peptide peptidase (SPP) catalyzes intramembrane proteolysis of some signal peptides after they have been cleaved from a preprotein. In humans, SPP activity is required to generate signal sequence-derived human lymphocyte antigen-E epitopes that are\ recognized by the immune system, and to process hepatitis C virus core protein. A polytopic\ membrane protein with sequence motifs characteristic of the presenilin-type aspartic proteases has been identified. SPP and potential eukaryotic\ homologs may represent a family of aspartic proteases that promote intramembrane proteolysis to release biologically important\ peptides.

\ \ \N \N \N 25076 IPR006629

LPS-induced tumour necrosis factor factor (LITAF) is induced in mamalian cells following treatment with lipopolysaccharide. The LITAF domain is a possible membrane-associated motif which contains an N-terminal CXXC kuckle followed by a long (25 amino acid) hydrophobic region and a C-terminal (H)XCXXC knuckle. Both of these knuckles are highly characteristic of Zn²⁺ binding domains and the N-terminal region of one LITAF domian containing portien is thought to bind the intracellular molecule Nedd4 which suggests that the hydrophobic region does not span the membrane. It may instead insert into the membrane bringing togethr the N- and C-terminal CXXC knuckles to form a compact Zn²⁺ binding structure [MEDLINE:21588055].

\ \N \N \N 25077 IPR006630

Human Ro ribonucleoproteins (RNPs) are composed of one of the four small Y RNAs and at least two proteins, Ro60 and La. The La protein is a 47 kDa polypeptide that frequently acts as an autoantigen in systemic lupus erythematosus and Sjogren's syndrome. Homologous proteins have been identified in yeast and LA domain containing proteins are found in a wide range of organismsexcept the Archae, bacteria and viruses. They are of unknown function and in\ a number of cases have been suggested to be RNA-binding proteins.

\ \ \N \N \N 25078 IPR006631

These are domains of unknown function found in Drosophila melanogaster proteins of unknownfunction.

\ \ \N \N \N 25079 IPR006632

BAR proteins are a unique class of adaptor proteins characterized by a common N-terminal fold of undetermined function termed the BAR domain. This set of adaptors, which includes the mammalian proteins amphiphysin and Bin1 and the yeast proteins\ Rvs167 and Rvs161, has been implicated in diverse cellular processes, including synaptic vesicle endocytosis, actin regulation,\ differentiation, cell survival, and tumorigenesis.

\ \ \N \N \N 25080 IPR006633

The CASH domain is shared by many carbohydrate-binding proteins and sugar hydrolases. The CASH domain is characterized by internal repetitions of glycines and hydrophobicresidues that correspond to the repetitive units of a predicted or observed right-handed -helix structure of the pectate lyase superfamily. The basic structural unit of\ this family consists of three -strands that form a single turn of the -helix. Each turn contains ~20 amino acids, and is normally repeated between 7 and 11 times to\ form the elongated helix structure. The repeats show a low degree of sequence identity when compared with each other. The region of homology with\ the CASH domain corresponds to the core region of the -helix, covering from the second to the sixth repeat [MEDLINE:21841630].

\ \ \N \N \N 25070 IPR006623

Repeats found in the Mus musculus and Homo sapiens THEG (testicularhaploid expressed gene) proteins and several Drosophila melanogaster proteins\ [MEDLINE:21098470].

\ \ \N \N \N 25071 IPR006624

Tectonins I and II are two dominant proteins in the nuclei and nuclear matrix from plasmodia of Physarum polycephalum which encode 217 and 353 amino acids, respectively. Tectonin I\ is homologous to the C-terminal two-thirds of tectonin II. Both proteins contain six tandem repeats that are each 33-37 amino acids in\ length and define a new consensus sequence. Homologous repeats are found in L-6, a bacterial lipopolysaccharide-binding lectin from\ horseshoe crab hemocytes. The repetitive sequences of the tectonins and L-6 are reminiscent of the WD repeats of the -subunit of\ G proteins, suggesting that they form -propeller domains. The tectonins may be lectins that\ function as part of a transmembrane signaling complex during phagocytosis [MEDLINE:98165848].

\ \ \ \N \N \N 25075 IPR006628

Pur- is a highly conserved, eukaryotic sequence-specific DNA- and RNA-binding protein involved in diverse cellular and viral functions including transcription, replication, and cell growth. Pur- has a modular structure with alternating three basic aromatic class I and\ two acidic leucine-rich class II repeats in the central region of the protein [MEDLINE:93078769].

Homologous DNA/RNA-binding repeats have been identifed in PUR-/gamma and in hypothetical\ proteins from spirochetes and the\ Bacteroides-Cytophaga-Flexibacter bacteria.

\ \ \N \N \N 25074 IPR006627

The mammalian TEF and the Drosophila scalloped genes belong to a conserved family of transcriptional factors that possesses a TEA/ATTS DNA-binding domain. Transcriptional activation by these proteins likely requires interactions with specific coactivators. In\ Drosophila, Scalloped (Sd) interacts with Vestigial (Vg) to form a complex, which binds DNA through the Sd TEA/ATTS domain.\ The Sd-Vg heterodimer is a key regulator of wing development, which directly controls several target genes and is able to induce wing\ outgrowth when ectopically expressed. The human protein, TONDU, contains a short domain homologous to the domain of Vg required for interaction with\ Sd. TONDU specifically interacts with a domain conserved in all the mammalian TEF factors [MEDLINE:99449576].

\ \ \N \N \N 25072 IPR006625

PhBP is the insect pheromone/odorant binding protein domain [MEDLINE:95337092].

\ \N \N \N 25073 IPR006626

The tertiary structures of pectate lyases andrhamnogalacturonase A show a stack of parallel strands that are coiled into a large helix. Each coil of the helix represents\ a structural repeat that, in\ some homologues, can be recognised from sequence information alone.\ Conservation of\ asparagines might be connected with asparagine-ladders that contribute to the\ stability of the fold.\ Proteins containing these repeats most often are enzymes with polysaccharide\ substrates [MEDLINE:98393515].

\ \ \N \N \N 25063 IPR006615

This domain is found in eukaryotic ubiquitin-specific proteases.

\ \N \N \N 25064 IPR006616

This repeat of unknown function is found in Drosophila proteins.

\ \N \N \N 25065 IPR006617

This repeat of unknown function is found in Drosophila melanogaster proteins.

\ \N \N \N 25066 IPR006619

This is a family of animal peptidoglycan recognition proteins homologous to Bacteriophage T3lysozyme [MEDLINE:98374308]. The bacteriophage molecule, but not its moth\ homologue, has been shown to have\ N-acetylmuramoyl-L-alanine amidase activity. One member of this family, Tag7,\ is a cytokine [MEDLINE:98325081].

\ \ protein binding activity ; GO:0005515 \N \N 25067 IPR006620

Mammalian prolyl 4-hydroxylase catalyses the posttranslational formation of 4- hydroxyproline in -xaa-pro-gly-sequences in\ collagens and other proteins.\ Prokaryotic\ enzymes might\ catalyse hydroxylation of antibiotic peptides. These are\ 2-oxoglutarate-dependent dioxygenases,\ requiring 2-oxoglutarate and dioxygen as cosubstrates and ferrous iron as a\ cofactor [MEDLINE:21174434].

\ \ oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, 2-oxoglutarate as one donor, and incorporation of one atom each of oxygen into both donors ; GO:0016706 \N protein metabolism ; GO:0019538 25068 IPR006621

This is the N-terminal domain of Caenorhabditis elegans NRF-6 (Nose Resistant toFluoxetine-4) and NDG-4 (resistant to nordihydroguaiaretic\ acid-4) proteins; the domain is also present in several other worm and fly\ proteins. NRF-6 and NDG-4 are multipass transmembrane proteins which may act together in a complex to function to\ transport fluoxetine across the hypodermal barrier to the inside of the animal, where it can then act on\ neuromuscular targets to induce muscle contraction.The complex may more generally play a role in regulation of membrane transport in C. elegans [MEDLINE:99417954].

\ \ \N \N \N 25069 IPR006622

The CDGSH-type zinc finger is found in proteins from a wide range of organisms with the\ exception of fungi. Its precise function is unknown.

\ \ \N \N \N 25053 IPR006605

Nidogen, an invariant component of basementmembranes, is a multifunctional protein that\ interacts with most other major basement membrane proteins. The crystal\ structure of the mouse nidogen-1 G2 fragment, which contains binding sites for\ collagen IV\ and perlecan has been reported [MEDLINE:21320924]. The structure is composed of an\ EGF-like domain and an 11-stranded -barrel with a central helix. The -barrel domain has unexpected\ similarity to green\ fluorescent protein. A large surface patch on the -barrel is strikingly\ conserved in all\ metazoan nidogens. Site-directed mutagenesis demonstrates that the conserved\ residues are\ involved in perlecan binding.

\ \ \N \N \N 25054 IPR006606

This repeat of unknown function has been found in Ciona intestinalis (sea squirt) COS41.4 protein,Caenorhabditis elegans R01H10.6 protein and Drosophila melanogaster CG1126\ protein.

\ \ \N \N \N 25055 IPR006607

This tandem repeat of no known function has been found in Drosophila melanogaster CG14066 (La related protein), Homosapiens KIAA0731 protein and Caenorhabditis elegans R144.7 protein. These\ proteins are of unknown function.

\ \ \N \N \N 25056 IPR006608

This repeat is found in Drosophila melanogaster CG4713 protein, Caenorhabditiselegans Y37H9A.3 protein and Homo sapiens FLJ20241 protein. These proteins are\ of unknown function.

\ \ \N \N \N 25057 IPR006609

This domain of unknown function is present in proteins of Drosophila melanogaster (CG14681, CG12492,CG6217), Caenorhabditis elegans H06A10.1 and Arabidopsis thaliana MBG8.9.

\ \ \N \N \N 25058 IPR006610

This domain of unknown function has been found in a number of Drosophila melanogasterproteins.

\ \ \N \N \N 25059 IPR006611

This cysteine-rich domain has currently only been identified in Drosophila proteins.

\ \N \N \N 25060 IPR006612

This zinc finger domain is widespread in Drosophila species, Mus\ musculus, homosapiens and has been reported in Caenorhabditis elegans.

\ \ \N \N \N 25061 IPR006613

The dysferlin gene is mutated in limb girdle muscular dystrophy. A DysF domain of unknown function has been identifed as homologous to two domains in dysferlin [MEDLINE:21588055]. Interestingly, these two copies are not arranged in tandem, as is most usual with repeats. Rather, one DysFdomain is inserted within a second DysF domain. For this reason, the Dys domain is described in two parts: the N-terminal region (DysFN) and\ the C-terminal\ region (DysFC, IPR006614). The nesting of homologous domains one-within-another might be considered to reflect exacting constraints on binding sites, or else might\ represent a serendipitous event.

\ \ \ \ \ \ \N \N \N 25062 IPR006614

The dysferlin gene is mutated in limb girdle muscular dystrophy. A DysF domain of unknown function has been identifed as homologous to two domains in dysferlin [MEDLINE:21588055]. Interestingly, these two copies are not arranged in tandem, as is most usual with repeats. Rather, one DysFdomain is inserted within a second DysF domain. For this reason, the Dys domain is described in two parts: the N-terminal region (DysFN, IPR006613) and\ the C-terminal\ region (DysFC). The nesting of homologous domains one-within-another might be considered to reflect exacting constraints on binding sites, or else might\ represent a serendipitous event.

\ \ \ \ \N \N \N 25049 IPR006601

This domain of unknown function has been found a group of Drosophila proteins. A number of theseproteins are expressed\ in nonneuronal auxiliary cells within two nested subsets of chemosensory sensilla on the\ front legs of male Drosophila melanogaster, suggesting they may be involved\ in pheromone response [MEDLINE:21900713]. These proteins are predicted to have a single transmembrane domain\ at their amino terminus, probably to serve as a signal peptide, suggesting that they are soluble and secreted.

\ \ \N \N \N 25050 IPR006602

This domain of unknown function occurs in some nucleoside diphosphate kinases.

\ \ \N \N \N 25051 IPR006603

This repeated motif of unknown function has been found between the transmembrane helices of cystinosin, yeastERS1 and mannose-P-dolichol utilization defect\ 1. The positioning of this repeat suggests that it may be\ associated with the glycosylation machinery.

\ \ \N \N \N 25052 IPR006604

A disulphide knot is a domain defined by a number of critical cysteine residues. The domain isfound in varying copy numbers (from one to five in Drosophila proteins), but always N-terminal to trypsin-like serine protease domains. Disulphide knots have previously been suggested to be important for dimerisation, and they appear to consist of an internal ring of 8 amino acids joined by di-sulphide bonds, at least one of which passes through the centre of the ring to form the "knot" [MEDLINE:21308468].

The CLIP domain is present in horseshoe crab proclotting enzyme N-terminal domain,\ Drosophila Easter and silkworm\ prophenoloxidase-activating enzyme [MEDLINE:99167513]. It may be\ responsible for mediating specific protein-protein interactions, and as such is useful for regulating cascades of serine protease activities.

\ \ \N \N \N 25048 IPR006600

Centromere Protein B (CENP-B) is a DNA-binding protein localized to the centromere, which is suggested to organize arrays of centromere satellite DNA into a higher order structure which then directs centromere formation and kinetochore assembly in mammalian chromosomes. Within the N-terminal 125 residues, there is a\ DNA-binding domain, which binds to a corresponding 17bp CENP-B box sequence. In the C-terminal 59 residues, CENP-B has a\ dimerization domain. CENP-B dimers either bind two separate DNA molecules or alternatively, they may bind two CENP-B boxes on\ one DNA molecule, with the intervening stretch of DNA forming a loop structure. The CENP-B DNA-binding domain consists of two\ repeating units, RP1 and RP2. RP1 has been shown to consist of four helices in a helix- turn-helix structure [MEDLINE:98119825].

\ \

This DNA-binding domain has also been identified in mouse jerky and eukaryotic\ transposases but not in any archael, bacteriaa or plant proteins.

\ \ \N \N \N 25045 IPR006597

Sel1-like repeats are tetratricopeptide repeat sequences originally identified in a Caenorhabditis elegans receptor molecule which is a key negative regulator of the Notch pathway [MEDLINE:96304591]. Mammalian homologues have since been identified although these mainly pancreatic proteins have yet to have a function assigned.

\ \N \N \N 25042 IPR006594

A sequence motif, LisH, has been identified in the products of genes mutated in Miller-Dieker lissencephaly, Treacher Collins, oral-facial-digital type 1 and contiguous syndrome ocular albinism with late onset sensorineural deafness syndromes. An\ additional homologous motif was detected in a gene product fused to the fibroblast growth factor receptor type 1 in patients with an\ atypical stem cell myeloproliferative disorder. In total, over 100 eukaryotic intracellular proteins are shown to possess a LIS1\ homology (LisH) motif, including several katanin p60 subunits, muskelin, tonneau, LEUNIG, Nopp140, aimless and numerous WD\ repeat-containing -propeller proteins [MEDLINE:21592410].

It is suggested that LisH motifs contribute to the regulation of microtubule dynamics, either\ by mediating dimerization, or else by binding cytoplasmic dynein heavy chain or microtubules directly. The predicted secondary\ structure of LisH motifs, and their occurrence in homologues of Gbeta -propeller subunits, suggests that they are analogues of\ Ggamma subunits, and might associate with the periphery of -propeller domains.

\ \ \N \N \N 25047 IPR006599

Cyclase-associated protein (CAP) is a conserved two-domain protein that helps to activate the catalytic activity of adenylyl cyclase in the cyclase-bound state through interaction with Ras, which binds to the cyclase in a different region. With its other domain, CAP can\ bind monomeric actin and therefore also carries a cytoskeletal function. The protein is thus involved in Ras/cAMP-dependent signal\ transduction and most likely serves as an adapter protein translocating the adenylyl cyclase complex to the actin cytoskeleton. [MEDLINE:92199347], [MEDLINE:95051124].

Structurally, CAP is a protein of 474 to 551 residues. The N- and C-terminal domains of CAP are connected by an intermediate section which contains a proline-rich region. In the yeast protein, this domain has\ been further divided into the P1 and P2 regions. While the P1 region is constituted by a 14 amino-acid sequence of unknown function, the P2 region exhibits a\ consensus SH3-binding motif (PXXP) and is necessary to target CAP to cortical actin patches. Dictyostelium CAP is a phosphatidylinositol 4,5-biphosphate (PIP2) regulated G-actin sequestering protein, which is present in the cytosol and shows\ enrichment at plasma-membrane regions. The cortical translocation is mediated by the N-terminal domain [MEDLINE:22238044].

The CARP domain has been found as a tandem repeat in the C-terminal of many CAPs and also in the X-linked retinitis\ pigmentosa 2 gene product.

\ \ \N \N \N 25046 IPR006598

Cryptococcus neoformans is a pathogenic fungus which most commonly affects the central nervous system and causes fatal meningoencephalitis primarily in patients with AIDS. This fungus produces a thick extracellular polysaccharide capsule which is well\ recognized as a virulence factor. CAP10 is required for capsule\ formation and virulence [MEDLINE:99412261].

\ \ \N \N \N 25038 IPR006590

A major role in the regulation of eukaryotic protein-coding genes is played by the gene-specific transcriptional regulators, which recruit the RNA polymerase II holoenzyme to the specific promoter. The Rpb4 and Rpb7 subunits of yeast RNA polymerase II form a heterodimeric complex essential for promoter-directed transcription\ initiation. The Rpb4-Rpb7 complex is not required\ for stable recruitment of polymerase to active preinitiation complexes, suggesting that Rpb4-Rpb7 mediates an essential step\ subsequent to promoter binding [MEDLINE:21167816].

This represents a domain present in DNA-directed RNA polymerase II subunit, Rpb4 (EC: 2.7.7.6).

\ \ \N \N \N 25044 IPR006596

PINc describes a large group of domains which are predicted to play a role in nucleotide-binding, potentially being found in RNases.

PINc domains in nematode SMG-5 and yeast NMD4p are predicted to be involved in the posttranscriptional gene silencing pathway known as RNA interference (RNAi). In an early step in RNAi, the\ initiating dsRNA is cleaved into small interfering RNAs (siRNAs), 2123 nucleotides long, by the enzyme Dicer. After processing by Dicer, siRNAs\ associate with a multicomponent complex called the RNA-induced silencing complex that recognizes\ and cleaves the cognate message [MEDLINE:22307569].

\ \ \N \N \N 25043 IPR006595

This -helical motif of unknown function is commonly found C-terminal to the LisH motif (IPR006594).

\ \N \N \N 25041 IPR006593

Cytochrome b561 recycles ascorbate for the generation of norepinephrine by dopamine--hydroxylase in the chromaffin vesicles of the adrenal gland. It is a transmembrane heme protein with the two heme groups being bound to conserved histidine residues. A cytochrome\ b561 homologue, termed Dcytb, is an iron-regulated ferric reductase in the duodenal mucosa. Other homologues of these are also likely to\ be ferric reductases. This domain of unknown function is common to these proteins.

\ \ \N \N \N 25040 IPR006592

The task of transcribing nuclear genes is shared between three RNA polymerases in eukaryotes: RNA polymerase (pol) I synthesizes\ the large rRNA, pol II synthesizes mRNA and pol III synthesizes tRNA and 5S rRNA. Pol I transcription is localised to discrete sites called nucleoli; these can be likened to ribosome\ factories, in which rRNA is synthesised by pol I in the fibrillar centres and then processed and assembled into ribosomes in\ the surrounding granular regions.

This entry describes the N-terminal domain of RNA polymerase I subunit A.

\ \ \N \N \N 25039 IPR006591

DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four\ ribonucleoside triphosphates as substrates. Each class of RNA polymerase is assembled from 9 to 15\ different polypeptides.

\ \

Rbp10 (RNA polymerase CX) is a domain found in RNA polymerase subunit 10; present in RNA\ polymerase I, II and III.

\ \ \N \N \N 25035 IPR006587

Vaults are highly conserved ubiquitous ribonucleoprotein particles with an undefined function. Three protein species (p240/TEP1, p193/VPARP, and p100/MVP) and a small RNA comprise the 13-MDa vault particle. The expression of the unique 100-kDa major\ vault protein is sufficient to form the basic vault structure [MEDLINE:22287445].

\ \

This entry describes the vault protein inter--trypsin domain

\ \ \N \N \N 25036 IPR006588

The PAW domain of unknown function is found in peptide N glycanase (PNGase, EC: 3.5.1.52) and in a number of hypothetical proteins.

\ \N \N \N 25037 IPR006589

Alpha amylase is classified as family 13 (CAZY:GH_13) of the\ glycosyl hydrolases. The structure is an 8 stranded / barrel\ containing the active site, interrupted by a ~70 a.a. calcium-binding domain\ protruding between strand 3 and helix 3, and a carboxyl-terminal Greek key -barrel domain.

\ \ alpha-amylase activity ; GO:0004556 \N carbohydrate metabolism ; GO:0005975 25029 IPR006581

Yeast Vps10p is a receptor for sorting and transport of the soluble vacuolar hydrolase carboxypeptidase Y to the lysosome-like vacuole. [MEDLINE:21922808]. In mammalian cells, proteins containing this domain are involved in the transport of lipoproteins and sorting of endosomal proteins. They may also act as receptors for some neuropeptides.

The N terminus of murine brain SorCS contains two putative\ cleavage sites for the convertase furin which mark the beginning of the VPS10\ domain, which is followed by\ a module of imperfect leucine-rich repeats and a transmembrane domain. The\ short\ intracellular C-terminus contains consensus signals for rapid\ internalization. The identified\ putative binding motifs for SH2 and SH3 domains are unique in the family of\ VPS10 domain\ receptors. SorCS is predominantly expressed in brain, but also in heart,\ liver, and kidney.\ SorCS transcripts detected by in situ hybridization in the murine central\ nervous system point\ to a neuronal expression [MEDLINE:20068769], [MEDLINE:99262692].

\ \ protein transporter activity ; GO:0008565 membrane ; GO:0016020 intracellular protein transport ; GO:0006886 25030 IPR006582

MD is a domain of unknown function found in a number of Caenorhabditis elegans proteins.

\ \N \N \N 25031 IPR006583

CW is a domain associated with a number of Caenorhabditis eleganshypothetical proteins.

\ \ \N \N \N 25032 IPR006584

This entry represents a type IV cellulose binding domain. It is a sub-domain of the carbohydrate-binding module, family 6 (CAZY:GH_6).

\ carbohydrate binding activity ; GO:0030246 \N \N 25033 IPR006585

Lectins, a group of proteins that bind to cell surface carbohydrates and play important roles in innate immunity, are widely usedexperimentally to distinguish cell types and to induce cell proliferation. Eel serum lectins have been useful as anti-H\ hemagglutinins and also in lectin histochemistry as fucose-binding lectins (fucolectins). The fucose-binding lectins are secretory proteins and have unique structures among the lectins, exhibiting only\ weak similarities to frog pentraxin, horseshoe crab tachylectin-4, and fly fw protein [MEDLINE:20490760].

This domain of unknown function has been identified in all the Japanese eel (Anguilla japonica) fucolectins and at least one frog pentraxin.

\ \ \ \N \N \N 25034 IPR006586

An ADAM is a transmembrane protein that contains a disintegrin and metalloprotease domain. All members of the ADAM family display a common domain organization - a pro-domain, the metalloprotease, disintigrin, cysteine-rich, epidermal-growth factor like, and transmembrane domains and a C-terminal cytoplasmic tail. They possess four potential functions: proteolysis, cell adhesion, cell fusion, and cell signaling. Members\ of the ADAM family are responsible for the proteolytic cleavage of transmembrane proteins and release of their extracellular domain [MEDLINE:21034239], [MEDLINE:22401628].

\ \

This domain is the ADAM cysteine-rich domain which is not found in any plant, archae,\ bacteria or virus proteins. The cysteine-rich domain complements the binding capacity of the disintegrin\ domain, and perhaps imparts specificity to disintegrin domain-mediated interactions.

\ \ \N \N \N 25023 IPR006575

The RWD eukaryotic domain is found in RING finger (IPR001841) containing proteinsand DEXDc-like helicases (IPR001841/>) subfamily\ related to the ubiquitin-conjugating enzymes domain (IPR000608).

\ \ \N \N \N 25024 IPR006576

BRK is a domain of unknown function present in association with CHROMO domain (IPR000953).

\ \N \N \N 25025 IPR006577

UAS is a domain of unknown function found in FAF1 proteins (FAS-associated factor 1) and in otherproteins, many of which are described as having no known function.

\ \ \N \N \N 25026 IPR006578

MADF is related to the Myb DNA-binding domain (IPR001005) The retroviral oncogene v-myb, and itscellular counterpart c-myb, are nuclear DNA-binding proteins that specifically recognize the sequence YAAC(G/T)G.

\ \ \N \N \N 25027 IPR006579

This domain is present in proteins found exclusively in the arthropods, including a number of Drosophilaspecies, the silk moth and the gypsy moth. These proteins are possibly\ involved in RNA binding or single strand DNA binding.

\ \ \N \N \N 25028 IPR006580

ZnF_TTF is a zinc finger domain found in transposases and transcription\ factors. It is present in eukaryotic proteins but has not been identified in any from fungi and nematodes.

\ \ \N \N \N 25021 IPR006573

NEUZ is a domain of unknown function found in neuralized proteins, i.e. proteins involved in the specification of the neuroblast during cellular differentiation.

\ \N \N \N 25022 IPR006574

PRY is a domain associated with SPRY domains. The SPRY domain (IPR003877) is of unknown function however distant homologues are domains in butyrophilin/marenostrin/pyrin. Ca2+-release from the\ sarcoplasmic or endoplasmic reticulum, the intracellular Ca2+ store, is\ mediated by the ryanodine receptor (RyR) and/or the inositol trisphosphate\ receptor (IP3R).

The proteins identified by the PRY domain, clearly fall into 3 sets which can be defined by their combination of signatures:

This group contains an immunoglobulin domain N-terminal to the PRY and butyrophilin domains. Butyrophilins are glycoproteins that are expressed on the apical surfaces of secretory cells in lactating mammary tissue and which may function in the secretion of milk-fat droplets.
This group contain a RING-finger domain N-terminal to the PRY domain. The RING-finger is a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc, and is probably involved in mediating protein-protein interactions. There are two different variants, the C3HC4-type and a C3H2C3-type, which is clearly related despite the different cysteine/histidine pattern. The latter type is sometimes referred to as 'RING-H2 finger' is not found associated with this group of proteins.

\ \

This set of proteins are described as TRIM (TRIpartite Motif) family members and are involved in cellular compartmentalisation [MEDLINE:21231161]. The TRIM family sequences are defined by a Ring finger domain, a B-box type1 (B1) and a B-box type 2 (B2) followed by a coiled-coil (CC) region [MEDLINE:93032140]. Genes belonging to this family are implicated in a variety of processes such as development and cell growth and are involved in human disease.

\ \

Many of these proteins, if not all of those with the PRY domain have a number of C-terminal signatures, SPRY, RFP-like (B30.2) and butyrophilin domain. The B30.2-like domain is a well conserved C-terminal domain of 160-170 amino acids which is found in nuclear and cytoplasmic proteins, as well as transmembrane and secreted proteins. The function of the B30.2-like domain is not known, but the cytoplasmic B30.2-like domain of butyrophilin has been shown to interact with xanthine oxidase [MEDLINE:99083436].

\ \

The third set of proteins have the C-terminal signatures but have no N-terminal RING-finger or immunoglobulin domain signatures. These proteins have not been functionally described.

\ \ \N \N \N 25017 IPR006569

RPR is a domain of unknown function present in proteins which are involved in regulation ofnuclear pre-mRNA.

\ \ \N \N \N 25018 IPR006570

SPK is a domain of unknown function found in SET and PHD domain containing proteins and proteinkinases.

\ \ \N \N \N 25019 IPR006571

TLDc is a domain of unknown function found in TBC (IPR000195) domain containing proteins.

\ \N \N \N 25020 IPR006572

This domain represents a zinc finger found in DBF-like proteins, present in all eukaryotes except Nematodes\ and plants. Proteins containing this domain may be regulators of DNA replication and cell cycle, for example Cdc7/Dbf4 is a protein kinase that is required for the initiation of DNA replication in eukaryotes during\ G1/S cell cycle transition PUB00005329, and may play a role role in checkpoint function and in the maintenance of genomic integrity [MEDLINE:21166004].

\ \ zinc ion binding activity ; GO:0008270 \N \N 25013 IPR006565

This bromodomain is found in eukaryotic transcription factors and PHD domain containing proteins (IPR001965).

\ \N \N \N 25014 IPR006566

This domain of unknown function is found in FBox (IPR001810) containing plant proteins.

\ \N \N \N 25015 IPR006567

PUG is a domain in protein kinases, N-glycanases and other nuclear proteinsfound in eukaryotes.

\ \ \N \N \N 25016 IPR006568

PSP is a proline-rich domain of unknown function found in spliceosome associated proteins.

\ \ \N \N \N 25006 IPR006558

The LamG-like jellyroll fold domain is associated with proteins of largely unknownfunction found in the metazoa and bacteria, but not in other organisms. The purpose of this fold is unknown.

\ \ \N \N \N 25007 IPR006559

This domain of unknown function is found in short gastrulation protein and in chordin. Xenopus chordinand Drosophila short gastrulation genes encode homologous proteins functioning\ in\ dorsal-ventral axis formation [MEDLINE:95112345].

\ \ \N \N \N 25008 IPR006560

This domain, Associated With SET, of unknown function is found in eukaryotic proteins of unknown function. This domain, as the name suggests, is often found in association with the SET domain (IPR001214), suggesting a role in gene regulation by methylation of lysine residues in histones and other proteins.

\ \N \N \N 25009 IPR006561

This domain is found in proteins containing the double-stranded RNA-binding motif, DSRM (IPR001159). This domain is foundexclusively in the metazoa.

\ \ \N \N \N 25010 IPR006562

This domain of unknown function is found in helicases and other DNA-binding proteins.

\ \N \N \N 25011 IPR006563

This domain in found exclusively in plant proteins, associated with HOX domains which may suggest these proteins arehomeodomain transcription factors.

\ \ \N \N \N 25012 IPR006564

This entry describes a plant mutator transposase zinc finger.

\ \ \N \N \N 25002 IPR006554

This domain of unknown function is found in the Xeroderma pigmentosum group D (XPD) proteins which belong to a family of ATP-dependent helicases characterised by a 'D-E-A-H' motif . This resembles the 'D-E-A-D-box' of other known helicases, which represents a special version of the B motif of ATP-binding proteins. In XPD,\ His replaces the second Asp. The DEAD box helicases are involved in\ various aspects of RNA metabolism, including nuclear transcription, pre-mRNA splicing, ribosome biogenesis,\ nucleocytoplasmic transport, translation, RNA decay and organellar gene expression.

\ \ \N \N \N 25003 IPR006555

This domain of unknown function is found at the C-terminal of some ATP-dependent helicases characterised by a 'D-E-A-H' motif . This resembles the 'D-E-A-D-box' of other known helicases,\ a special version of the B motif of ATP-binding proteins however His replaces the second Asp. The DEAD\ box helicases are involved in various aspects of RNA metabolism, including nuclear transcription, pre-mRNA splicing,\ ribosome biogenesis, nucleocytoplasmic transport, translation, RNA decay and organellar gene expression.

\ \ \N \N \N 24999 IPR006551

These proteins catalyze the dephosphorylation of DNA 3'-phosphates. It is believed that this activity is important for the repair of single-strand breaks in DNA caused by radiation or oxidative damage. This region is often [MEDLINE:99377055], [MEDLINE:99377056], but not always linked to a DNA 5'-kinase domain [MEDLINE:21226750], [MEDLINE:21264590]. As is common in this superfamily, DNA 3-phosphatase is magnesium dependent. A difference between this enzyme and other HAD-superfamily phosphatases is in the third conserved catalytic motif which usually contains two conserved aspartate residues believed to be involved in binding the magnesium ion. Here, the second aspartate is usually replaced by an arginine residue which may indicate an interaction with the phosphate backbone of the substrate. Alternatively, there is an additional conserved aspartate downstream of the usual site which may indicate a slightly different fold in this region.

\ \N \N \N 25005 IPR006557

The GIT helical motif is found as a tandem repeat in the GIT family of ADP-ribosylation factorGTPase-activating proteins, and in yeast\ Spa2 scaffold protein and Sph1 [MEDLINE:20357364]. The ADP-ribosylation factor\ GTPase-activating proteins interact with other signal transduction proteins, suggesting the motif may play a role in these interactions. This group of proteins is not found in plants, bacteria,\ or the archae.

\ \ \N \N \N 25004 IPR006556

This domain of unknown function is present in a number of proteins, includingP47, FAF1 (Fas-associated factor 1), Drosophila eyc, yeast\ Shp1p and undulin 2. Many of these proteins also contain the UBX domain C-terminal to the FAF domain (IPR001012). This domain is found in many eukaryotic proteins\ [MEDLINE:96102221].

\ \ \N \N \N 25000 IPR006552

This is a domain of unknown function which is found in multiple repeats in some proteins.

\ \N \N \N 25001 IPR006553

This is a cysteine-containing, leucine-rich repeat which is wide spread amongsteukaryotes proteins but does not appear to be found in archae, bacteria or viruses.

\ \ \N \N \N 24998 IPR006550

These sequences represent the metazoan 5'-polynucleotide-kinase-3'-phosphatase, PNKP, which is believed to be involved in repair of oxidative DNA damage. Removal of 3'-phosphates is essential for the further processing of the break by DNA polymerases [MEDLINE:99377055], [MEDLINE:99377056]. The central phosphatase domain is a member of the IIIA subfamily (IPR006549. Outside of the phosphatase domain is a P-loop ATP-binding motif associated with the kinase activity. The entry for the mouse homolog appears to be missing a large piece of sequence corresponding to the first conserved catalytic motif of the phosphatase domain as well as the conserved threonine of the second motif. Either this is a sequencing artifact or this may represent a pseudo- or non-functional gene.

\ \N \N \N 24996 IPR006548

These sequences represent the ELAV/HuD subfamily of splicing factors found in metazoa. HuD stands for the human paraneoplastic encephalomyelitis antigen D of which there are 4 variants in human [MEDLINE:92005711]. ELAV stands for the Drosophila Embryonic lethal abnormalvisual protein [MEDLINE:89072740]. ELAV-like splicing factors are also known in human as HuB (ELAV-like protein 2), HuC (ELAV-like protein 3, Paraneoplastic cerebellar degeneration-associated antigen) and HuR (ELAV-like protein 1). These genes are most closely related to the sex-lethal subfamily of splicing factors found in Dipteran insects (IPR006546).

\ \N \N \N 24997 IPR006549

This subfamily falls within the haloacid dehalogenase (HAD) superfamily of aspartate-nucleophile hydrolases. The Class III subfamilies are characterized by the lack of any domains located either between the first and second conserved catalytic motifs (as in the Class I subfamilies) or between the second and third conserved catalytic motifs (as in the Class II subfamilies) of the superfamily domain. The IIIA subfamily contains five major clades: histidinol-phosphatase [MEDLINE:86174354], histidinol-phosphatase-related protein, DNA 3-phosphatase and sequences related to YqeG and YrbI.

\ \ \N \N \N 24992 IPR006544

These P-type ATPases form a distinct clade but the substrate of their pumping activity has yet to be determined. This clade has been designated type V [MEDLINE:98080613].

\ \N \N \N 24993 IPR006545

This group of proteins contains a conserved domain, which is common to all eyes absent (EYA) homologs. Metazoan EYAs also contain a variable N-terminal domain consisting largely of low-complexity sequences.

\ \N \N \N 24994 IPR006546

These sequences describe the sex-lethal family of splicing factors found in Dipteran insects. The sex-lethal phenotype, however, may be limited to the Melanogasters and closely related species [MEDLINE:20115421]. In Drosophila the protein acts as an inhibitor of splicing. This subfamily is most closely related to the ELAV/HUD subfamily of splicing factors (IPR006548).

\ \N \N \N 24995 IPR006547

The nitrate reductase enzyme complex allows bacteria to use nitrate as an electron acceptor during anaerobic growth. The enzyme complex consists of a tetramer that has an , and 2 gamma subunits. The and subunits have catalytic activity and the gamma subunits attach the enzyme to the membrane and are b-type cytochromes that receive electrons from the quinone pool and transfers them to the subunit. The sequences in this family are the subunit for nitrate reductase I (narH) and nitrate reductase II (narY) for gram positive and gram negative bacteria. A few thermophiles and archaea also match the model. A number of the sequences in this set are experimentally characterized, these include: E.Coli NarH (P11349 from Bacillus subtilis, and related proteins from Psuedomonas fluorescens, Paracoccus denitrificans, and Halomonas halodenitrificans.

\ \N \N \N 24990 IPR006542

These are a family of small (about 115 amino acids) uncharacterized proteins with N-terminal signal sequences, found exclusively in Gram-positive organisms. Most genomes that have any members of this family have at least two members.

\ \N \N \N 24991 IPR006543

This is a group of authentic histidinol-phosphate phosphatases which are sometimes found as stand-alone entities and sometimes as fusions with imidazoleglycerol-phosphate dehydratase. Additionally, a family of proteins including YaeD from Escherichia coli and various other proteins are closely related but may not have the same substrate specificity. This protein is a member of the haloacid-dehalogenase (HAD) superfamily of aspartate-nucleophile hydrolases. This superfamily is distinguished by the presence of three motifs: an N-terminal motif containing the nucleophilic aspartate, a central motif containing a conserved serine or threonine, and a C-terminal motif containing a conserved lysine (or arginine) and conserved aspartates. More specifically, the region modelled here is a member of subfamily III of the HAD-superfamily by virtue of lacking a "capping" domain in either of the two common positions, between motifs 1 and 2, or between motifs 2 and 3.

\ \N \N \N 24987 IPR006539

These sequences represent the P-type ATPase responsible for transporting phospholipids from one leaflet of bilayer membranes to the other [MEDLINE:97256755]. These ATPases are found only in eukaryotes.

\ \N \N \N 24988 IPR006540

These sequences represent bacteriocins related to lactococcin 972 [MEDLINE:20055640]. Members tend to be found in association with a seven transmembrane putative immunity protein.

\ \N \N \N 24989 IPR006541

These sequences represent a family of integral membrane proteins, most of which are about 650 residues in size and predicted to span the membrane seven times. Nearly half of the members of this family are found in association with a member of the lactococcin 972 family of bacteriocins (IPR006540. Others may be associated with uncharacterized proteins that may also act as bacteriocins. Although this protein is suggested to be an immunity protein, and the bacteriocin is suggested to be exported by a Sec-dependent process, the role of this protein is unclear.

\ \N \N \N 24985 IPR006537

These sequences are related to the Pseudomonas denitrificans CobS gene product, which is a cobalt chelatase subunit of MW ~37kDa [MEDLINE:93054361] that functions in cobalamin biosynthesis. Cobalamin (vitamin B12) can be synthesized via several pathways, including an aerobic pathway (found in Pseudomonas denitrificans) and an anaerobic pathway (found in P. shermanii and Salmonella typhimurium). These pathways differ in the point of cobalt insertion during corrin ring formation [MEDLINE:97061032]. There are apparently a number of variations on these two pathways, where the major differences seem to be concerned with the process of ring contraction [MEDLINE:21083208]. Confusion regarding the functions of enzymes found in the aerobic vs. anaerobic pathways has arisen because nonhomologous genes in these different pathways were given the same gene symbols. Thus, cobS in the aerobic pathway (P. denitrificans) is not a homolog of cobS in the anaerobic pathway (S. typhimurium). It should be noted that E. coli synthesizes cobalamin only when it is supplied with the precursor cobinamide, which is a complex intermediate. Additionally, all E. coli cobalamin synthesis genes (cobU, cobS and cobT) were named after their Salmonella typhimurium homologs which function in the anaerobic cobalamin synthesis pathway [MEDLINE:96062218]. The aerobic pathway cobalt chelatase is a heterotrimeric, ATP-dependent enzyme that catalyzes cobalt insertion during cobalamin biosynthesis. The other two subunits are the P. denitrificans CobT (IPR006538 CobN/magnesium chelatase) proteins.

\ \N \N \N 24986 IPR006538

This family of proteins contains the Pseudomonas denitrificans CobT gene product, which is a cobalt chelatase subunit, with a MW ~70 kDa [MEDLINE:93054361], that functions in cobalamin biosynthesis. Cobalamin (vitamin B12) can be synthesized via several pathways, including an aerobic pathway (found in Pseudomonas denitrificans) and an anaerobic pathway (found in P. shermanii and Salmonella typhimurium). These pathways differ in the point of cobalt insertion during corrin ring formation [MEDLINE:97061032]. There are apparently a number of variations on these two pathways, where the major differences seem to be concerned with the process of ring contraction [MEDLINE:21083208]. Confusion regarding the functions of enzymes found in the aerobic vs. anaerobic pathways has arisen because nonhomologous genes in these different pathways were given the same gene symbols. Thus, cobT in the aerobic pathway (P. denitrificans) is not a homolog of cobT in the anaerobic pathway (S. typhimurium). It should be noted that E. coli synthesizes cobalamin only when it is supplied with the precursor cobinamide, which is a complex intermediate. Additionally, all E. coli cobalamin synthesis genes (cobU, cobS and cobT) were named after their Salmonella typhimurium homologs which function in the anaerobic cobalamin synthesis pathway [MEDLINE:96062218]. The aerobic pathway cobalt chelatase is a heterotrimeric, ATP-dependent enzyme that catalyzes cobalt insertion during cobalamin biosynthesis. The other two subunits are the P. denitrificans CobS (IPR006537 CobN/magnesium chelatase) proteins.

\ \N \N \N 24983 IPR006535

Sequences in this subfamily include the human heterogeneous nuclear ribonucleoproteins (hnRNP) R [MEDLINE:98083170], Q [MEDLINE:21458434] and APOBEC-1 complementation factor (aka APOBEC-1 stimulating protein) [MEDLINE:20347895]. These proteins contain three RNA recognition domains and a somewhat variable C-terminal domain.

\ \N \N \N 24984 IPR006536

Included in this family of heterogeneous ribonucleoproteins are PTB (polypyrimidine tract binding protein [MEDLINE:21664105]) and hnRNP-L [MEDLINE:95347585]. These proteins contain four RNA recognition motifs.

\ \N \N \N 24981 IPR006533

These sequences represent the Vgr family of proteins, associated with some classes of Rhs elements. This model does not include a large octapeptide repeat region, VGXXXXXX, found in the Vgr of Rhs classes G and E [MEDLINE:98361897].

\ \N \N \N 24982 IPR006534

These sequences represent the plasma membrane proton efflux P-type ATPase found in plants, fungi, protozoa, slime molds and archaea. The best studied representative is from yeast [MEDLINE:93167622].

\ \N \N \N 24972 IPR006524

These sequences represent a family of phage proteins, including ArpU, called a putative autolysin regulatory protein. ArpU was described as a regulator of cellular muramidase-2 of Enterococcus hirae but appears to have been cloned from a prophage. This family appears related to the RinA family of bacteriophage transcriptional activators and to some sporulation-specific sigma factors. This group of sequences could be a phage transcriptional activator family.

\ \N \N \N 24973 IPR006525

These sequences represent a family similar in sequence and probably homologous to a large family of cysteine proteinase inhibitors, or cystatins, as described by IPR000010. Cystatins may help plants resist attack by insects.

\ \N \N \N 24974 IPR006526

These sequences contain a conserved sequence region of about 60 amino acids found in over 40 predicted proteins of Plasmodium falciparum. It is not found elsewhere, including closely related species such as Plasmodium yoelii. No member of this family has been functionally characterized.

\ \N \N \N 24975 IPR006527

This domain occurs in a diverse superfamily of genes in Arabidopsis thaliana. Most examples are found C-terminal to an F-box (IPR001810. Some members have two copies of this domain.

\ \N \N \N 24976 IPR006528

This family of sequences are identified by a region of about 110 amino acids found exclusively in phage-related proteins, internally or toward the C terminus. One member, gp7 of phage SPP1, appears to be involved in head morphogenesis.

\ \N \N \N 24977 IPR006529

These splicing factors consist of an N-terminal arginine-rich low complexity domain followed by three tandem RNA recognition motifs. The well-characterized members of this family are auxilliary components of the U2 small nuclear ribonuclearprotein splicing factor (U2AF). These proteins are closely related to the CC1-like subfamily of splicing factors (IPR006509). Members of this subfamily are found in plants, metazoa and fungi.

\ \N \N \N 24978 IPR006530

These sequences contain two tandem copies of a 21-residue extracellular repeat that is found in Gram-negative, Gram-positive, and animal proteins. The repeat is named for a YD dipeptide, the most strongly conserved motif of the repeat. These repeats appear in general to be involved in binding carbohydrate; the chicken teneurin-1 YD-repeat region has been shown to bind heparin [MEDLINE:99276585], [MEDLINE:95020608], [MEDLINE:90094253].

\ \N \N \N 24979 IPR006531

These sequences form a family of phage (and bacteriocin) proteins related to the phage P2 V gene product, which forms the small spike at the tip of the tail [MEDLINE:96036485]. Homologs in general are annotated as baseplate assembly protein V. At least one member is encoded within a region of Pectobacterium carotovorum (Erwinia carotovora) described as a bacteriocin, a phage tail-derived module able to kill bacteria closely related to the host strain.

\ \N \N \N 24980 IPR006532

The proteins contain three RNA recognition motifs and have been characterized as poly-pyrimidine tract binding proteins associated with RNA splicing factors [MEDLINE:21869987], [MEDLINE:20072282], [MEDLINE:20132233]. In the case of PUF60, in complex with p54, and in the presence of U2AF, it facilitates association of U2 snRNP with pre-mRNA [MEDLINE:20072282].

\ \N \N \N 24968 IPR006520

These sequences contain a domain of about 125 amino acids, toward the N-terminus. They represent a family of proteins from temperate phage of a number of Gram-positive bacteria. These phage proteins range in length from 230 to 525 amino acids.

\ \N \N \N 24969 IPR006521

These sequences represent the family of phage P2 protein I and related tail proteins from a number of temperate phage of Gram-negative bacteria.

\ \N \N \N 24970 IPR006522

These sequences describe protein S of phage P2, suggested experimentally to act in tail completion and stable head joining, and related proteins from a number of phages.

\ \N \N \N 24971 IPR006523

These sequences represent a family of phage proteins, including RinA, a transcriptional activator in staphylococcal phage phi 11. This family shows similarity to ArpU, a phage-related putative autolysin regulator, and to some sporulation-specific sigma factors [MEDLINE:93163038].

\ \N \N \N 24964 IPR006516

This set of sequences represent a family of phage and plasmid replication proteins. In bacteriophage IKe and related phage, the full-length protein is designated gene II protein. A much shorter protein of unknown function, translated from a conserved in-frame alternative initiator, is designated gene X protein. Members of this family also include plasmid replication proteins.

\ \N \N \N 24965 IPR006517

This domain in the C-terminal region of a set of phage proteins are typically about 400-500 amino acids in length, although some members are considerably shorter. An article on Methanobacterium phage Psi-M2 ([MEDLINE:99009353]) calls the member from that phage, ORF9, a putative large terminase subunit, and ORF8 a candidate terminase small subunit. Most proteins in this family have an apparent P-loop nucleotide-binding sequence toward the N terminus.

\ \N \N \N 24966 IPR006518

These sequences are full-length and part-length members of the RHS (retrotransposon hot spot) family in Trypanosoma brucei and Trypanosoma cruzi. Members of this family are frequently interrupted by non-LTR retrotransposons inserted at exactly the same relative position.

\ \N \N \N 24967 IPR006519

\ \ \

Ribosomal protein L11 is one of the proteins from the large ribosomal subunit. In Escherichia coli, L11 \ is known to bind directly to the 23S rRNA. It belongs to a family of ribosomal proteins which, on the \ basis of sequence similarities [MEDLINE:90356373], PUB00005071, groups bacteria, plant chloroplast, read \ algal chloroplast, cyanelle and archaeabacterial L11; and mammalian, plant and yeast L12 (YL15). L11 is \ a protein of 140 to 165 amino-acid residues. In Escherichia coli, the C-terminal half of L11 has been \ shown PUB00005071 to be in an extended and loosely folded conformation and is likely to be buried \ within the ribosomal structure. This set of sequences represents bacterial, chloroplast, and most mitochondrial forms of 50S ribosomal protein L11.

\ \ \N \N \N 24960 IPR006513

These are sequences from gamma proteobacteria that are related to the E. coli protein, YtfJ.

\ \N \N \N 24961 IPR006514

These sequences contain an uncharacterised domain found in both Arabidopsis thaliana (at least 10 copies) and Oryza sativa. Most member proteins have only a short stretch of sequence N-terminal to this domain, but one has a long N-terminal extension that includes a protein kinase domain (IPR000719).

\ \N \N \N 24962 IPR006515

These eukaryotic proteins recognize the poly-A of mRNA and consist of four tandem RNA recognition domains at the N terminus followed by a PABP-specific domain at the C terminus. The protein is involved in the transport of mRNAs from the nucleus to the cytoplasm [MEDLINE:98250751]. There are four paralogs in Homo sapiens which are expressed in testis [MEDLINE:22272378], platelets (Q13310\ \ \ [MEDLINE:96069385]), broadly expressed (Q13310/>\ \ \ \ [MEDLINE:98250751]) and of unknown tissue range (Q15097).

\ \ \N \N \N 24963 IPR006516

\ \N \N \N 24957 IPR006510

These sequernces contain a putative zinc finger domain found predominantly in plants. Arabidopsis thaliana has at least 10 distinct members. Proteins containing this domain, including LRP1 PUB00005329, generally share the same size, about 300 amino acids, and architecture. This 43-residue domain, and a more C-terminal companion domain of similar size, appear as tightly conserved islands of sequence similarity. The remainder consists largely of low-complexity sequence. Several animal proteins have regions with matching patterns of Cys, Gly, and His residues. But are excluded from this family because of their low similarity.

\ \ \N \N \N 24958 IPR006511

These sequences contain a tightly conserved small domain found in LRP1 [MEDLINE:95375539] and related plant proteins. This family also contains a well-conserved adjacent N-terminal putative zinc finger domain (IPR006510). The remaining sequence is highly divergent, and of low-complexity.

\ \N \N \N 24959 IPR006512

These sequences contain a domain that is duplicated in HI0035 of Haemophilus influenzae, in YidE and YbjL of E. coli, andin a number of other putative transporters. Member proteins may have 0, 1, or 2 copies of the TrkA-C potassium uptake domain (IPR006037). The domain contains several apparent transmembrane regions and is proposed here to act in transport.

\ \ \N \N \N 24956 IPR006509

These sequences represent a subfamily of RNA splicing factors including the Pad-1 protein (N. crassa), CAPER (M. musculus) and CC1.3 (H.sapiens). All are characterized by an N-terminal arginine-rich, low complexity domain followed by three (or in the case of 4 H. sapiens paralogs, two) RNA recognition domains. These splicing factors are closely related to the U2AF splicing factor family (IPR006529).

\ \N \N \N 24943 IPR006496

This set of protein sequences represent a family of at least four proteins in Plasmodium falciparum. An interesting feature is five perfectly conserved Trp residues.

\ \N \N \N 24944 IPR006497

This set of protein sequences, defined by an N-terminal domain, represent phage lambda replication protein O and other homologous phage proteins.

\ \N \N \N 24945 IPR006498

The tails of some phage are contractile. These sequences represent the tail tube, or tail core, protein of the contractile tail of phage P2, and homologous proteins from other phage.

\ \N \N \N 24946 IPR006499

These sequences represent a group of paralogous families in plasmodium species alternately annotated as reticulocyte binding protein, 235-kDa family protein and rhoptry protein. Rhoptry protein is localized on the cell surface and is extremely large (although aparrently lacking in repeat structure) and is important for the process of invasion of the RBCs by the parasite [MEDLINE:21436155], [MEDLINE:20104007]. These proteins are found in Plasmodium falciparum, Plasmodium vivax and Plasmodium yoelii.

\ \N \N \N 24947 IPR006500

These sequences form a clade within a larger family of proteins from viruses of bacteria and animals. Members of the family that contain this domain are found in phage and the plasmids of bacteria and archaea.

\ \N \N \N 24948 IPR006501

These sequences contain a plant domain of about 200 amino acids, characterized by four conserved cysteine residues. The functional importance of these residues has been studied in a pectinesterase inhibitor from Kiwi. The cysteine residues form two disulfide bonds: first to second and third to fourth [MEDLINE:20341134]. Roughly half the members of this family have an adjacent C-terminal pectinesterase domain (IPR000070), suggesting that the pairing of the enzymatic domain and the cysteine domain reflect a conserved regulatory mechanism for this enzyme family.

\ \N \N \N 24949 IPR006502

This group of sequences are defined by a domain found toward the C-terminus of a number of uncharacterised plant proteins. The domain is strongly conserved (greater than 30 % sequence identity between most pairs of members) but flanked by highly divergent regions including stretches of low-complexity sequence.

\ \N \N \N 24950 IPR006503

This set of sequences describe a small family of uncharacterized proteins only found so far in and gamma proteobacteria and in the Cyanobacterium Nostoc sp. PCC 7120. The gene for this protein is associated with nitrogenase genes. This family shows sequence similarity to glutaredoxin-dependent arsenate reductase that converts arsentate to arsenite for disposal.

\ \N \N \N 24954 IPR006507

These are putative membrane proteins from and gamma proteobacteria, each making up their own clade. The two clades have less than 25% identity between them.

\ \N \N \N 24955 IPR006508

These sequences represent a clade within the pseudouridine synthase superfamily (IPR006145 ]; only Neisseria does not appear to have an RluA homolog. It is presumed that these sequences function as pseudouridine synthases, although perhaps with different specificity.

\ \N \N \N 24951 IPR006504

These sequences are a part of the Arsenate reductase family of sequences. The family includes a glutaredoxin-dependent arsenate reductase that works together with an arsenite exporter. It also includes an uncharacterized family associated with nitrogenase system genes in a number of phylogenetically distant species. The function of this group of sequences seems unlikely to be arsenate reductase, although that assignment has been given to a number of members of this family.

\ \N \N \N 24952 IPR006505

These sequences represent an uncharacterized family of proteins from a number of phage of Gram-positive bacteria. This protein contains a P-loop motif, G/A-X-X-G-X-G-K-T near its amino end. The function of these proteins is unknown.

\ \N \N \N 24953 IPR006506

These sequences represent a hypothetical equivalog of gamma proteobacteria, which includes HI0040.

\ \N \N \N 24930 IPR006477

This group of sequences identifies a large paralogous family of variant antigens from several Plasmodium species (P. yoelii, P. berghei and P. chabaudi). It is not believed that there are any orthologs of this family in P. falciparum.

\ \N \N \N 24931 IPR006478

This group of sequences describe a subset of formate dehydrogenase chains found mainly in the archaea but also in and gamma proteobacteria and a small number of gram positive bacteria. The chain contains domains for molybdopterin dinucleotide binding and molybdopterin oxidoreductase. The holo-enzyme also contains and gamma subunits. The enzyme catalyzes the oxidation of formate (produced from pyruvate during anaerobic growth) to carbon dioxide with the concomitant release of two electrons and two protons. The enzyme's purpose is to allow growth on formate in some circumstances [MEDLINE:87008493] and, in the case of FdhH in gamma proteobacteria, to pass electrons to hydrogenase (by which process acid is neutralized) [MEDLINE:97190104]. The subunit of a version of nitrate reductase is closely related.

\ \N \N \N 24932 IPR006479

This group of sequences represent one of more than 30 families of phage proteins, all lacking detectable homology with each other, known or believed to act as holins. Holins act in cell lysis by bacteriophage. Members of this family are found in phage PBSX and phage SPP1, among others.

\ \N \N \N 24933 IPR006480

This group of sequences describe one of the many mutually dissimilar families of holins, phage proteins that act together with lytic enzymes in bacterial lysis. This family includes, besides phage holins, the protein TcdE/UtxA involved in toxin secretion in Clostridium difficile and related species [MEDLINE:21337673].

\ \N \N \N 24934 IPR006481

This group of sequences represent one of a large number of mutually dissimilar families of phage holins. Holins act against the host cell membrane to allow lytic enzymes of the phage to reach the bacterial cell wall. This family includes the product of the S gene of phage lambda.

\ \N \N \N 24935 IPR006482

This protein is found in at least five species that contain CRISPR loci being found exclusively next to other cas proteins. Its function is unknown.

\ \N \N \N 24936 IPR006483

This CRISPR-associated HD domain found in a number of proteins tends to be found near CRISPR repeats, either separately or as the N-terminal region of Cas3, the helicase-containing CRISPR-associated protein. CRISPR loci appear to be mobile elements with a wide host range.

\ \N \N \N 24937 IPR006485

Phage proteins for bacterial lysis typically include a membrane-disrupting protein, or holin, and one or more cell wall degrading enzymes that reach the cell wall because of holin action. Holins are found in a large number of mutually non-homologous families.

\ \N \N \N 24938 IPR006486

A single high-scoring gene was identified in the complete genome of P. falciparum as well as a single gene from P. chaboudi. There are no obvious homologs to these genes in any non-Plasmodium organism. These observations suggest an expansion of this family in yoelii from a common Plasmodium ancestor gene (present in a single copy in falciparum).

\ \N \N \N 24939 IPR006487

This group of sequences represent members of the family of phage lambda minor tail protein L.

\ \N \N \N 24940 IPR006490

This is a set of proteins that share low levels of sequence similarity but similar lengths and similar patterns of charged, hydrophobic, and Gly/Pro residues. All members (except one attributed to mouse embryo cDNA) belong to phage of Gram-positive bacteria. Several are identified as phage major tail proteins.

\ \N \N \N 24941 IPR006493

This family is represented by BlyA, a small holin found in Borrelia circular plasmids that prove to be temperate phage [MEDLINE:20528331]. This protein was previously proposed to be a hemolysin. BlyA is small (67 residues) and contains two largely hydrophobic helices and a highly charged C terminus.

\ \N \N \N 24942 IPR006495

This group of sequences represent the acyl carrier protein (gamma subunit) of the holoenzyme citrate lyase (EC: 4.1.3.6) composed of (EC: 2.8.3.10), (EC: 4.1.3.34), and acyl carrier protein subunits in a stoichiometric relationship of 6:6:6. Citrate lyase is an enzyme which converts citrate to oxaloacetate. In bacteria, this reaction is involved in citrate fermentation. The acyl carrier protein covalently binds the coenzyme of citrate lyase. The set contains an experimentally characterized member from Leuconostoc mesenteroides [MEDLINE:98117048]. The sequences come from a wide range of Gram-positive bacteria. For Gram-negative bacteria, it appears that only sequences from the gamma proteobacteria are included.

\ \N \N \N 24929 IPR006476

This group of sequences are defined by an uncharacterized plant-specific domain 57 residues in length. It is found toward the N terminus of most proteins that contain it. Examples include at least 10 proteins from Arabidopsis thaliana and at least one from Oryza sativa. The function of the proteins are unknown.

\ \N \N \N 24928 IPR006475

This group of sequences represent the subunit of the holoenzyme citrate lyase (EC: 4.1.3.6) composed of (EC: 2.8.3.10), (EC: 4.1.3.34), and acyl carrier protein subunits in a stoichiometric relationship of 6:6:6. Citrate lyase is an enzyme which converts citrate to oxaloacetate. In bacteria, this reaction is involved in citrate fermentation. The subunit catalyzes the reaction (3S)-citryl-CoA = acetyl-CoA + oxaloacetate. The group contains an experimentally characterized member from Leuconostoc mesenteroides [MEDLINE:98117048]. The group contains sequences from a wide range of Gram-positive bacteria. For Gram-negative bacteria, it appears that only the sequences from gamma proteobacteria are present.

\ \N \N \N 24926 IPR006473

This group of sequences are characterized by a cysteine protease domain found in proteins of bacteria that include plant pathogens (Pseudomonas syringae), root nodule bacteria, and intracellular pathogens (e.g. Yersinia pestis, Haemophilus ducreyi, Pasteurella multocida, Chlamydia trachomatis) of animal hosts. The domain features a catalytic triad of Cys, His, and Asp. Sequences can be extremely divergent outside of a few well-conserved motifs. YopT, a virulence effector protein of Yersinia pestis, cleaves and releases host cell Rho GTPases from the membrane, thereby disrupting the actin cytoskeleton. Members of the family from pathogenic bacteria are likely to be pathogenesis factors [MEDLINE:22057504].

\ \N \N \N 24927 IPR006474

This family of Cas3 sequences exhibit a highly conserved core region. The proteins are found in association with CRISPR repeat elements in a broad range of bacteria and Archaea [MEDLINE:21950952]. Cas3 appears to be a helicase, containing a DEAD/DEAH box region and conserved C-terminal domain. Some but not all members have an N-terminal HD domain region (IPR006674), these sequences are not included within this group.

\ \N \N \N 24923 IPR006470

The sequences in this group represent the subunit of the gamma-proteobacterial formate dehydrogenase. This subunit contains four 4Fe-4S clusters and is involved in transmitting electrons from the subunit (IPR006443) chains as well.

\ \N \N \N 24924 IPR006471

These sequences represent the gamma chain of the gamma proteobacteria (and Aquifex aolicus) formate dehydrogenase. This subunit is integral to the cytoplasmic membrane, consisting of 4 transmembrane helices, and receives electrons from the subunit. The entire Escherichia coli formate dehydrogenase N (nitrate-inducible form) has been crystallized and its structure determined PUB00009870. The gamma subunit contains two cytochromes, heme b(P) and heme b(C) near the periplasmic and cytoplasmic sides of the membrane respectively. The electron acceptor quinone binds at the cytoplasmic heme histidine ligand. NiFe-hydrogenase and thiosulfate reductase contain homologous gamma subunits, and these are found in this group.

\ \N \N \N 24925 IPR006472

These sequences, from both Gram-positive and Gram-negative bacteria, represent the subunit of the holoenzyme citrate lyase composed of (EC: 2.8.3.10), , and acyl carrier protein subunits in a stoichiometric relationship of 6:6:6. Citrate lyase is an enzyme which converts citrate to oxaloacetate. In bacteria, this reaction is involved in citrate fermentation. The subunit catalyzes the reaction Acetyl-CoA + citrate = acetate + (3S)-citryl-CoA. The protein from Lactococcus lactis subsp. lactis has been experimentally characterized [MEDLINE:75108063].

\ \ \N \N \N 24922 IPR006469

This is a clade of ABC porter genes with relatively weak homology compared to its neighbor clades, the molybdate (IPR006229 and Pasteurella multocida which are involved in the biosynthesis and/or control of nitrogenase. It would be reasonable to presume that NifC acts as a molybdate porter since the most common form of nitrogenase is a molybdoenzyme. Several other sequences falling within this group are annotated as molybdate porters and one, from Halobacterium, is annotated as a sulfate porter. There is presently no experimental evidence to support annotations with this degree of specificity.

\ \N \N \N 24920 IPR006467

This clade of sequences is closely related to MiaB, a modifier of isopentenylated adenosine-37 of certain eukaryotic and bacterial tRNAs (see IPR006463.

\ \N \N \N 24921 IPR006468

The nitrate reductase enzyme complex allows bacteria to use nitrate as an electron acceptor during anaerobic growth. The enzyme complex consists of a tetramer that has an , and 2 gamma subunits. The and subunits have catalytic activity and the gamma subunits attach the enzyme to the membrane. The gamma subunit is a b-type cytochrome that receives electrons from the quinone pool and transfers them to the subunit. This model is specific for the subunit for nitrate reductase I (narG) and nitrate reductase II (narZ) for Gram-positive and Gram-negative bacteria. A number of sequences from thermophiles and archaea are found in this group of sequences.

\ \N \N \N 24919 IPR006466

This clade of sequences is closely related to MiaB, a modifier of isopentenylated adenosine-37 of certain eukaryotic and bacterial tRNAs (see IPR006463.

\ \N \N \N 24914 IPR006461

This group of sequences are described by a region of about 170 amino acids found at the C terminus of a family of plant proteins. These proteins have highly divergent N-terminal regions rich in low complexity sequence. PSI-BLAST reveals no clear similarity to any characterized protein. At least 12 distinct members are found in Arabidopsis thaliana.

\ \N \N \N 24915 IPR006462

These sequences comprise a paralogous family of hypothetical proteins in Arabidopsis thaliana. No homologs are detected from other species. Length heterogeneity within the family is attributable partly to a 21-residue repeat present in from zero to three tandem copies. The proteins have no known function.

\ \N \N \N 24916 IPR006463

These sequences are homologs of the MiaB enzyme responsible for the modification of the isopentenylated adenine-37 base of most bacterial and eukaryotic tRNAs that read codons beginning with uracil (all except tRNA(I,V) Ser). Adenine-37 is next to the anticodon on the 3 side in these tRNAs, and lack of modification at this site leads to an increased spontaneous mutation frequency. Isopentenylated A-37 is modified by methylthiolation at position 2, either by MiaB alone or in concert with a separate methylase yet to be discovered (MiaC?) [MEDLINE:20042346], [MEDLINE:21950802], [MEDLINE:21213886].

\ \N \N \N 24917 IPR006464

Members belong to the GCN5-related N-acetyltransferase (GNAT) superfamily.

\ \N \N \N 24918 IPR006465

The name of this type of amylase is based on the characterization of an glucoamylase family enzyme from Thermoactinomyces vulgaris. The T. vulgaris enzyme was expressed in E. coli and, like other glucoamylases, it releases -D-glucose from starch. However, unlike previously characterized glucoamylases, this T. vulgaris amylase hydrolyzes maltooligosaccharides (maltotetraose, maltose) more efficiently than starch [MEDLINE:21432651], indicating this enzyme belongs to a class of glucoamylase-type enzymes with oligosaccharide-metabolizing activity.

\ \N \N \N 24905 IPR006453

This family describes a small protein of about 100 amino acids found in bacteriophage and in bacterial prophage regions. Examples include gp9 of phage HK022 and gp16 of phage SPP1. The function of these proteins is not known.

\ \N \N \N 24906 IPR006454

These sequences represent one of several families of proteins associated with the formation of prokaryotic S-layers. Members of this family are found in archaeal species, including Pyrococcus horikoshii (split into two tandem reading frames), Methanococcus jannaschii, and related species. Some local similarity can be found to other S-layer protein families.

\ \N \N \N 24907 IPR006454

\ \N \N \N 24908 IPR006455

These represent a group of sequences that contain a homoebox domain that differs substantially from the typical homoebox domain described in IPR001356.

\ \N \N \N 24909 IPR006456

This group of sequences described by a 54-residue domain found in the N-terminal region of plant proteins, the vast majority of which contain a ZF-HD class homeobox domain toward the C terminus. The region between the two domains typically is rich in low complexity sequence. The companion ZF-HD homeobox domain is described in IPR006455.

\ \N \N \N 24910 IPR006457

This domain is found tandemly duplicated in a most members of a paralogous family in the archaeon Methanosarcina acetivorans str. C2A. This domain is clearly related to the central region of a family of archaeal S-layer proteins described in IPR006454.

\ \N \N \N 24911 IPR006458

This group of sequences contain an uncharacterized domain of about 70 residues found exclusively in plants, generally toward the C terminus of proteins of 200 to 350 amino acids in length. At least 14 such proteins are found in Arabidopsis thaliana. Other regions of these proteins tend to consist largely of low-complexity sequence. Function is not known.

\ \N \N \N 24912 IPR006459

This group of sequences is described by a region of ~160 residues found exclusively in plant proteins, generally as the near complete length of the protein. At least 24 different members are found in Arabidopsis thaliana. Members have four predicted transmembrane regions. The family is not functionally characterized.

\ \N \N \N 24913 IPR006460

\ \N \N \N 24902 IPR006450

This group of sequences represents small (~100 amino acids) proteins found in phage and in putative prophage regions of a number of bacterial genomes. The function of these sequences is unknown.

\ \N \N \N 24903 IPR006451

These sequences are largely uncharacterised archaeal proteins which include those from Methanosarcina acetivorans and Sulfolobus solfataricus. The group also contains sequences from the Gram-positive bacterium Clostridium perfringens and the Cyanobacterium Nostoc sp. All the sequences display weak relatedness to the characterized eukaryotic glycogen debranching enzyme of S. cerevisiae.

\ \N \N \N 24904 IPR006452

This family of sequences describe an accessory protein required for the assembly of formate dehydrogenase of certain proteobacteria although not present in the final complex [MEDLINE:91008993]. The exact nature of the function of FdhE in the assembly of the complex is unknown, but considering the presence of selenocysteine, molybdopterin, iron-sulfur clusters and cytochrome b556, it is likely to be involved in the insertion of cofactors.

\ \N \N \N 24899 IPR006447

This group described by a DNA-binding domain is restricted to (but common in) plant proteins, many of which also contain a response regulator domain. The domain appears related to the Myb-like DNA-binding domain [MEDLINE:20117515], [MEDLINE:95045433].

\ \N \N \N 24900 IPR006448

This group of sequences describe the distinct family of phage (and integrated prophage) putative terminase small subunit sequnces. Members tend to be encoded by the gene adjacent to the phage terminase large subunit gene.

\ \N \N \N 24901 IPR006449

This family of sequences describe farnesyl-diphosphate farnesyltransferase, also known as squalene synthase, as found in eukaryotes. This family is related to phytoene synthases. Tentatively identified archaeal homologs lack the C-terminal predicted transmembrane region universally conserved among members of this family and therefore are not included in this group.

\ farnesyl-diphosphate farnesyltransferase activity ; GO:0004310 integral to membrane ; GO:0016021 lipid biosynthesis ; GO:0008610 24892 IPR006440

The characterized member of this family is the death-on-curing (DOC) protein of phage P1. It is part of a two protein operon with prevents-host-death (phd) that forms an addiction module. DOC lacks homology to analogous addiction module post-segregational killing proteins involved in plasmid maintenance. These modules work as a combination of a long lived poison (e.g. this protein) and a more abundant but shorter lived antidote. Members of this family have a well-conserved central motif HxFx[ND][AG]NKR. A similar region, with K replaced by G, is found in the huntingtin interacting protein (HYPE) family [MEDLINE:94016561] ].

\ \ \N \N \N 24893 IPR006441

This family represents the major capsid protein component of the heads (capsids) of bacteriophage P2 and related phage. This sequences represent one of several analogous families lacking detectable sequence similarity. The gene encoding this component is typically located in an operon encoding the small and large terminase subunits, the portal protein and the prohead or maturation protease.

\ \N \N \N 24894 IPR006442

This family of proteins is characterized by a region of about 55 amino acids toward the N-terminal end of bacterial proteins which are themselves only 85 amino acids, or thereabouts, in length. The best-characterized member is prevent-host-death (phd) of bacteriophage P1, the antidote partner of death-on-curing (doc) (IPR006440) in an addiction module. Addiction modules prevent plasmid curing by killing the host cell as the longer-lived killing protein persists while the gene for the shorter-lived antidote is lost. Note, however, that relatively few members of this family appear to be plasmid or phage-encoded. Also, there is little overlap, except for phage P1 itself, of species with this family and with the doc family.

\ \N \N \N 24898 IPR006446

This subfamily is composed of sequences from the gamma proteobacteria that function as L-rhamnosyltransferases in the synthesis of their respective surface polysaccharides. Rhamnolipids are glycolipids containing mono- or di- L-rhamnose molecules. Rhamnolipid synthesis occurs by sequential glycosyltransferase reactions involving two distinct rhamnosyltransferase enzymes. In Pseudomonas aeruginosa, the synthesis of mono-rhamnolipids is catalyzed by rhamnosyltransferase 1, and proceeds by a glycosyltransfer reaction catalyzed by rhamnosyltransferase 2 to yield di-rhamnolipids [MEDLINE:21260078].

\ \N \N \N 24896 IPR006444

This family represents the major capsid protein component of the heads (capsids) of bacteriophage HK97, phi-105, P27, and related phage. This group represent one of several analogous families lacking detectable sequence similarity. The gene encoding this component is typically located in an operon encoding the small and large terminase subunits, the portal protein and the prohead or maturation protease.

\ \N \N \N 24897 IPR006445

This group describes an uncharacterized family of proteins found in prophage regions of a number of bacterial genomes, including Haemophilus influenzae, Xylella fastidiosa, Salmonella typhi, and Enterococcus faecalis. Distantly related proteins can be found in the prophage-bearing plasmids of Borrelia burgdorferi.

\ \N \N \N 24895 IPR006443

This family of sequences describe a subset of formate dehydrogenase chains found mainly in proteobacteria but also in Aquifex aeolicus. The chain contains domains for molybdopterin dinucleotide binding and molybdopterin oxidoreductase. The holo-enzyme also contains and gamma subunits of 32 and 20 kDa. The enzyme catalyzes the oxidation of formate (produced from pyruvate during anaerobic growth) to carbon dioxide with the concomitant release of two electrons and two protons. The electrons are utilized mainly in the nitrate respiration by nitrate reductase [MEDLINE:88318439]. In Escherichia coli and Salmonella typhi, there are two forms of the formate dehydrogenase, one induced by nitrate which is strictly anaerobic (fdn), and one incuced during the transition from aerobic to anaerobic growth (fdo). This subunit is one of only three proteins in Escherichia coli which contain selenocysteine [MEDLINE:92042178].

\ formate dehydrogenase activity ; GO:0008863 cytoplasm ; GO:0005737 cellular respiration ; GO:0045333 24890 IPR006438

This family represent a small and phylogenetically curious clade of sequences. Sequences are found from Halobacterium (an archaeon), Nostoc and Synechococcus (cyanobacteria) and Phytophthora (a stramenophile eukaryote). These appear to be members of the haloacid dehalogenase (HAD) superfamily of aspartate-nucleophile hydrolases by general homology and the conservation of all of the recognized catalytic motifs. The variable domain is found in between motifs 1 and 2, indicating membership in subfamily I and phylogeny and prediction of the helical nature of the variable domain (by PSI-PRED) indicate membership in subfamily IA.

\ \N \N \N 24891 IPR006439

This family represents part of one structural subfamily of the Haloacid Dehalogenase (HAD) superfamily of aspartate-nucleophile hydrolases. The superfamily is defined by the presence of three short catalytic motifs [MEDLINE:95055742]. The subfamilies are defined [MEDLINE:21488076] based on the location and the observed or predicted fold of a so-called capping domain [MEDLINE:20412918], or the absence of such a domain. Subfamily I consists of sequences in which the capping domain is found in between the first and second catalytic motifs. Subfamily II consists of sequences in which the capping domain is found between the second and third motifs. Subfamily III sequences have no capping domain in either of these positions. The Subfamily IA and IB capping domains are predicted by PSI-PRED to consist of an helical bundle. Subfamily I encompasses such a wide region of sequence space (the sequences are highly divergent) that modelling it with a single HMM is impossible, resulting in an overly broad description which allows in many unrelated sequences. Subfamily IA and IB are separated based on an apparent phylogenetic bifurcation. Subfamily IA is still too broad to model, but can be further subdivided into large chunks based on phylogenetic trees. Of the three motifs defining the HAD superfamily, the third has three variant forms [MEDLINE:21488076]: (1) hhhhsDxxx(x)(D/E), (2) hhhhssxxx(x)D and (3) hhhhDDxxx(x)s where _s_ refers to a small amino acid and _h_ to a hydrophobic one. All three of these variants are found in subfamily 1A.

\ \ \N \N \N 24888 IPR006436

This family describes the type II glyceraldehyde-3-phosphate dehydrogenases which are limited to archaea. These enzymes catalyze the interconversion of 1,3-diphosphoglycerate and glyceraldehyde-3-phosphate, a central step in glycolysis and gluconeogenesis. In archaea, either NAD or NADP may be utilized as the cofactor.

\ glyceraldehyde 3-phosphate dehydrogenase activity ; GO:0008943 cytoplasm ; GO:0005737 glycolysis ; GO:0006096 24889 IPR006437

This group of sequences represent a highly divergent family of the large subunit of phage terminase. All members are encoded by phage genomes or within prophage regions of bacterial genomes. This is a distinct family from the phage terminase family represented by IPR005021.

\ \N \N \N 24885 IPR006433

This family describes the prohead protease of HK97 and related phage. It is generally encoded next to the gene for the capsid protein that it processes, and in some cases\ may be fused to it. This family does not show similarity to the prohead protease of\ phage T4 (IPR005082).

\ \ \N \N \N 24886 IPR006434

This family is a small group of metazoan sequences. The sequences from mouse are annotated as pyrimidine 5-nucleotidases, apparently in reference to HSPC233, the human homolog. However, no such annotation can currently be found for this gene. This group of sequences was found during searches for members of the haloacid dehalogenase (HAD) superfamily. All of the conserved catalytic motifs [MEDLINE:95055742] are found. The placement of the variable domain between motifs 1 and 2 indicates membership in subfamily I of the superfamily, but these sequences are sufficiently different from any of the branches (IA, IPR006388) of that subfamily as to constitute a separate branch to now be called IE. Considering that the closest identifiable hit outside of the noise range is to a phosphoserine phosphatase, this group may be considered to be most closely allied to subfamily IB.

\ \N \N \N 24887 IPR006435

This group describes a clade of sequences limited to the gamma proteobacteria. This group is a member of the haloacid dehalogenase (HAD) superfamily of aspartate-dependent hydrolases and all of the conserved catalytic motifs are present [MEDLINE:95055742]. Although structurally similar to subfamily IA in that the variable domain is predicted to consist of five consecutive helices (by PSI-PRED), it is sufficiently divergent to warrant being regarded as a separate sub-family (IF).

\ \N \N \N 24883 IPR006431

This group are characterized by a relatively well-conserved region near the C terminus of the tape measure protein of a lambda and related phage. This protein, which controls phage tail length, is typically about 1000 residues in length. Both low-complexity sequence and insertion/deletion events appear common in this family. Mutational studies suggest a ruler or template role in the determination of phage tail length. Similar behavior is attributed to proteins from distantly related or unrelated families in other phage.

\ \N \N \N 24884 IPR006432

These sequences represent a family of phage minor structural proteins. The protein is suggested to be the head-tail connector, or portal protein, on the basis of its position in the phage gene order, its presence in mature phage, its size, and its conservation across a number of complete genomes of tailed phage that lack other candidate portal proteins. Several other known portal protein families lack clear homology to this family and to each other [MEDLINE:20117992].

\ \N \N \N 24880 IPR006428

This group of sequences represent one of several distantly related families of phage portal protein. This protein forms a hole, or portal, that enables DNA passage during packaging and ejection. It also forms the junction between the phage head (capsid) and the tail proteins. It functions as a dodecamer of a single polypeptide of average mol. wt. of 40-90 KDa.

\ \N \N \N 24881 IPR006429

\ \N \N \N 24882 IPR006430

\ \N \N \N 24874 IPR006422

This group of sequences represent the small clade of dehydrogenases in gamma-proteobacteria which utilize NAD+ to oxidize erythrose-4-phosphate (E4P) to 4-phospho-erythronate, a precursor for the de novo synthesis of pyridoxine via 4-hydroxythreonine and D-1-deoxyxylulose [MEDLINE:95270598]. This enzyme activity appears to have evolved from glyceraldehyde-3-phosphate dehydrogenase, whose substrate differs only in the lack of one carbon relative to E4P. It is possible that some of the GAPDH enzymes may prove to be bifunctional in certain species.

\ \N \N \N 24875 IPR006423

This group of sequences represents a set of bacterial lipoproteins belonging to a larger acid phosphatase family, which in turn belongs to the haloacid dehalogenase (HAD) superfamily of aspartate-dependent hydrolases. Members are found on the outer membrane of Gram-negative bacteria and the cytoplasmic membrane of Gram-positive bacteria. Most members have classic lipoprotein signal sequences. A critical role of this 5'-nucleotidase in Haemophilus influenzae is the degradation of external riboside in order to allow transport into the cell. An earlier suggested role in hemin transport is no longer current. This enzyme may also have other physiologically significant roles.

\ \N \N \N 24876 IPR006424

This group of sequences represent glyceraldehyde-3-phosphate dehydrogenase (GAPDH), the enzyme responsible for the interconversion of 1,3-diphosphoglycerate and glyceraldehyde-3-phosphate, a central step in glycolysis and gluconeogenesis. Forms exist which utilize NAD (EC: 1.2.1.12), NADP (EC: 1.2.1.13) or either (EC: 1.2.1.59). In some species, NAD- and NADP- utilizing forms exist, generally being responsible for reactions in the anabolic and catabolic directions respectively [MEDLINE:20261518]. An additional form of gap gene is found in gamma proteobacteria and is responsible for the conversion of erythrose-4-phosphate (E4P) to 4-phospho-erythronate in the biosynthesis of pyridoxine [MEDLINE:95270598]. This pathway of pyridoxine biosynthesis appears to be limited, however, to a relatively small number of bacterial species although it is prevalent among the gamma-proteobacteria [MEDLINE:21040647]. This enzyme is described by IPR006422).

\ \N \N \N 24877 IPR006425

Glucan 1,4--glucosidase catalyzes the hydrolysis of terminal 1,4-linked -D-glucose residues from non-reducing ends of polysaccharides, releasing a -D-glucose monomer. Some forms of this enzyme can hydrolyze terminal 1,6- and 1,3--D-glucosidic bonds in polysaccharides as well.

\ \N \N \N 24878 IPR006426

These sequences represent glutamine-hydrolysing asparagine synthase. The group have a poorly conserved C-terminal extension while bacterial members of the family tend to have a long, poorly conserved insert lacking from archaeal and eukaryotic sequences. Multiple isozymes have been demonstrated, such as in Bacillus subtilis.

\ asparagine synthase (glutamine-hydrolyzing) activity ; GO:0004066 \N asparagine biosynthesis ; GO:0006529 24879 IPR006427

\ \N \N \N 24868 IPR006416

This group encompasses the copper and cadmium-type heavy metal transporting P-type ATPases as well as those which cannot be assigned to one or other of the groups.

\ P-type ATPase activity ; GO:0015662 integral to membrane ; GO:0016021 metal ion transport ; GO:0030001 24869 IPR006417

The NadR protein of E. coli and closely related bacteria is both enzyme and regulatory protein. The first 60 or so amino acids, N-terminal region is\ a DNA-binding helix-turn-helix domain (IPR001387) responsible for repressing the nadAB\ genes of NAD de novo biosynthesis. The NadR homologs in Mycobacterium\ tuberculosis, Haemophilus influenzae, and others appear to lack the repressor domain.\ NadR has recently been shown to act as an enzyme of the salvage pathway of NAD\ biosynthesis, nicotinamide-nucleotide adenylyltransferase; members of this family are\ presumed to share this activity. \ E. coli NadR has also been found to regulate the import of its substrate, nicotinamide\ ribonucleotide, but it is not known if the other members of this family share that activity.

\ \ \N \N \N 24870 IPR006418

This family of archaeal proteins exhibits NAD salvage biosynthesis enzyme nicotinamide-nucleotide adenylyltransferase (EC: 2.7.7.1) activity. In some cases, the enzyme was tested and found also to have the activity of nicotinate-nucleotide adenylyltransferase (EC: 2.7.7.18), an enzyme of NAD de novo biosynthesis, although with a higher Km. In some archaeal species, a number of proteins which are uncharacterized with respect to activity, are also present.

\ nicotinamide-nucleotide adenylyltransferase activity ; GO:0000309 cytoplasm ; GO:0005737 nicotinamide adenine dinucleotide biosynthesis ; GO:0009435 24871 IPR006419

The PnuC protein of Escherichia coli is membrane protein responsible for nicotinamide mononucleotide transport, subject to regulation by interaction with the NadR (also called NadI) protein (see IPR006417). The extreme N- and C-terminal regions are poorly conserved.

\ \N \N \N 24872 IPR006420

This family describes NadN of Haemophilus influenzae and a small number of close homologs in pathogenic, Gram-negative bacteria. NadN is a periplasmic enzyme that cleaves NAD (nicotinamide adenine dinucleotide) to NMN (nicotinamide mononucleotide) and AMP. The NMN must be converted by a 5-nucleotidase to nicotinamide riboside for import. NadN belongs a large family of 5-nucleotidases and has NMN 5-nucleotidase activity for NMN, AMP, etc.

\ \N \N \N 24873 IPR006421

Glycogen debranching enzyme possesses two different catalytic activities; oligo-1,4-->1,4-glucantransferase (EC: 2.4.1.25) and amylo-1,6-glucosidase (EC: 3.2.1.33). Site-directed mutagenesis studies in Saccharomyces cerevisiae [MEDLINE:21369917] indicate that the transferase and glucosidase activities are independent and located in different regions of the polypeptide chain. Proteins in this family belong to the larger -amylase family. The family contains eukaryotic proteins.

\ \N \N \N 24861 IPR006409

These sequences describe glycerol-3-phosphate cytidyltransferase, also called CDP-glycerol pyrophosphorylase. A closely related protein assigned a different function experimentally is a human ethanolamine-phosphate cytidylyltransferase (EC: 2.7.7.14). Glycerol-3-phosphate cytidyltransferase acts in pathways of teichoic acid biosynthesis. Teichoic acids are substituted polymers, linked by phosphodiester bonds, of glycerol, ribitol, etc. An example is poly(glycerol phosphate), the major teichoic acid of the Bacillus subtilis cell wall. Most but not all species encoding proteins in this family are Gram-positive bacteria.

\ \N \N \N 24862 IPR006410

These sequences represent an uncharacterized domain present in roughly eight hypothetical proteins of the malaria parasite Plasmodium falciparum.

\ \N \N \N 24863 IPR006411

Members of this family are class II examples of the glycolytic enzyme fructose-bisphosphate aldolase (FBA). They represent one of two deeply split, architecturally distinct clades of the family that includes class II fructose-bisphosphate aldolases, tagatose-bisphosphate aldolases, and related uncharacterized proteins. This family is well-conserved and includes characterized FBA from Saccharomyces cerevisiae, Escherichia coli, and Corynebacterium glutamicum.

\ fructose-bisphosphate aldolase activity ; GO:0004332 \N glycolysis ; GO:0006096 24864 IPR006412

Members of this family are class II examples of the enzyme fructose-bisphosphate aldolase, an enzyme both of glycolysis and (in the opposite direction) of the Calvin cycle of CO2 fixation. A deep split separates the tightly conserved yeast/Escherichia coli/Mycobacterium subtype (all species lacking the Calvin cycle) represented by IPR006411 from a broader group of aldolases that includes both tagatose- and fructose-bisphosphate aldolases. This family represents a distinct, elongated, very well conserved subtype within the latter group. Most species with this aldolase subtype have the Calvin cycle.

\ fructose-bisphosphate aldolase activity ; GO:0004332 \N glycolysis ; GO:0006096 24865 IPR006413

This family describes the P-type ATPase responsible for translocating calcium ions across the golgi membrane of fungi and animals [MEDLINE:89324047], [MEDLINE:99365310], and is of particular importance in the sarcoplasmic reticulum of skeletal and cardiac muscle in vertebrates [MEDLINE:99365310]. The calcium P-type ATPases have been characterized as Type IIA based on a phylogenetic analysis which distinguishes this group from the Type IIB PMCA calcium pump [MEDLINE:98080613] represented by IPR006408.

\ calcium-transporting ATPase activity ; GO:0005388 integral to membrane ; GO:0016021 calcium ion transport ; GO:0006816 24866 IPR006414

Initially described as a calcium efflux ATPase [MEDLINE:92362601], more recent work has shown that the Schizosaccharomyces pombe CTA3 gene is in fact a potassium ion efflux pump [MEDLINE:21930277]. These sequences form the clade which represents the fungal P-type ATPases which are responsible for potassium and sodium efflux. The degree to which these pumps show preference for sodium or potassium varies. This group of ATPases has been classified by phylogentic analysis as type IID [MEDLINE:98080613].

\ P-type ATPase activity ; GO:0015662 integral to membrane ; GO:0016021 cation transport ; GO:0006812 24867 IPR006415

This group describes the magnesium translocating P-type ATPase found in a limited number of bacterial species and best described in Salmonella typhimurium, which contains two isoforms [MEDLINE:93015809]. These transporters are active in low external Mg2+ concentrations and pump the ion into the cytoplasm. The magnesium ATPases have been classified as type IIIB by a phylogenetic analysis [MEDLINE:98080613].

\ magnesium-importing ATPase activity ; GO:0015444 integral to membrane ; GO:0016021 magnesium ion transport ; GO:0015693 24856 IPR006404

These sequences describe the P-type ATPase primarily responsible for translocating cadmium ions (and other closely-related divalent heavy metals such as cobalt, mercury, lead and zinc) across biological membranes. These transporters are found in prokaryotes and plants. Experimentally characterized members include P37617) are well separated, and thus the copper-ATPases can be typed as IB1 and the cadmium-ATPases as IB2.

\ \N \N \N 24857 IPR006405

A deep split separates two related families of proteins, one of which includes experimentally characterized examples of nicotinate phosphoribosyltransferase, the first enzyme of NAD salvage biosynthesis. This entry represents the other family. Members have a different (longer) spacing of several key motifs and have an additional C-terminal domain of up to 100 residues. One argument suggesting that this family represents the same enzyme is that no species has a member of both families. Another is that the gene encoding this protein is located near other NAD salvage biosynthesis genes in Nostoc and in at least four different Gram-positive bacteria. NAD and NADP are ubiquitous in life. Most members of this family are from Gram-positive bacteria. An additional set of mutually closely related archaeal sequences score between the trusted and noise cutoffs.

\ \N \N \N 24858 IPR006406

This family represents nicotinate phosphoribosyltransferase, the first enzyme in the salvage pathway of NAD biosynthesis from nicontinate (niacin). Members are primarily proteobacterial but also include yeasts and Methanosarcina acetivorans. A related family, apparently non-overlapping in species distribution, is IPR006405. Members of that family differ in substantially in sequence and have a long C-terminal extension missing from this family, but are proposed also to act as nicotinate phosphoribosyltransferase.

\ nicotinate phosphoribosyltransferase activity ; GO:0004516 \N nicotinate nucleotide biosynthesis ; GO:0019357 24859 IPR006407

This family describes the glycogen branching enzymes which are responsible for the transfer of chains of approximately 7 (1--4)-linked glucosyl residues to other similar chains (in new (1--6) linkages) in the biosynthesis of glycogen.

\ \ 1,4-alpha-glucan branching enzyme activity ; GO:0003844\ \N \N glycogen biosynthesis ; GO:0005978 24860 IPR006408

This family describes the P-type ATPase responsible for translocating calcium ions across the plasma membrane of eukaryotes [MEDLINE:99365031], out of the cell. In some organisms, this type of pump may also be found in vacuolar membranes [MEDLINE:20264032]. In humans and mice, at least, there are multiple isoforms of the PMCA pump with overlapping but not redundant functions. Accordingly, there are no human diseases linked to PMCA defects, although alterations of PMCA function do elicit physiological effects [MEDLINE:21638245]. The calcium P-type ATPases have been characterized as Type IIB based on a phylogenetic analysis which distinguishes this group from the Type IIA SERCA calcium pump [MEDLINE:98080613].

\ \N \N \N 24849 IPR006397

This family represents glyoxylate carboligase, also called tartronate-semialdehyde synthase. It releases CO2 while synthesizing a single molecule of tartronate semialdehyde from two molecules of glyoxylate. It is a thiamine pyrophosphate-dependent enzyme, closely related in sequence to the large subunit of acetolactate synthase. In the D-glycerate pathway, part of allantoin degradation in the Enterobacteriaceae, tartronate semialdehyde is converted to D-glycerate and then 3-phosphoglycerate, a product of glycolysis and entry point in the general metabolism.

\ tartronate-semialdehyde synthase activity ; GO:0009028 \N glyoxylate catabolism ; GO:0009436 24850 IPR006398

These sequences represent 2-hydroxy-3-oxopropionate reductase (EC: 1.1.1.60), also called tartronate semialdehyde reductase. It follows glyoxylate carboligase and precedes glycerate kinase in D-glycerate pathway of glyoxylate degradation. The eventual product, 3-phosphoglycerate, is an intermediate of glycolysis and is readily metabolized. Tartronic semialdehyde, the substrate of this enzyme, may also come from other pathways, such as D-glucarate catabolism [MEDLINE:20225875], [MEDLINE:20069628].

\ \N \N \N 24851 IPR006399

These archaeal proteins, bacterial riboflavin biosynthesis chain, catalyze the final step in riboflavin biosynthesis. However, it is more similar in sequence to 6,7-dimethyl-8-ribityllumazine synthase, which catalyzes the previous reaction and which (in bacteria) is called the riboflavin synthase chain.

\ riboflavin synthase activity ; GO:0004746 \N vitamin B2 biosynthesis ; GO:0009231 24852 IPR006400

Squalene hopene cyclase (SHC) is an essential prokaryotic gene in hopanoid (triterpenoid) biosynthesis. SHC is an integral membrane protein that directly cyclizes squalene into hopanoid products [MEDLINE:97442532].

\ \ intramolecular transferase activity, transferring other groups ; GO:0016870 \N hopanoid biosynthesis ; GO:0019746 24853 IPR006401

These sequences represent a specific reductase of riboflavin biosynthesis in the archaea, diaminohydroxyphosphoribosylaminopyrimidine reductase. It should not be confused with bacterial 5-amino-6-(5-phosphoribosylamino)uracil reductase. The intermediate 2,5-diamino-6-hydroxy-4-(5-phosphoribosylamino)pyrimidine in riboflavin biosynthesis is reduced first and then deaminated in both archaea and fungi, opposite to the order in bacteria. The subsequent deaminase is not presently known and is not closely homologous to the deaminase domain fused to the reductase domain, which is similar to this protein but found in most bacteria.

\ \N \N \N 24854 IPR006402

This group of sequences represent part of one structural subfamily of the Haloacid Dehalogenase (HAD) superfamily of aspartate-nucleophile hydrolases (IPR005834 ]: (1) hhhhsDxxx(x)D, (2) hhhhssxxx(x)D and (3) hhhhDDxxx(x)s where _s_ refers to a small amino acid and _h_ to a hydrophobic one. All three of these variants are found in subfamily IA.

\ \ \N \N \N 24855 IPR006403

This model describes the P-type ATPase primarily responsible for translocating copper ions across biological membranes. These transporters are found in\ prokaryotes and eukaryotes. This model encompasses those species which pump\ copper ions out of cells or organelles (efflux pumps such as CopA of Escherichia coli\ [MEDLINE:20105527]) as well as those which pump the ion into cells or organelles either for the purpose\ of supporting life in extremely low-copper environments (for example CopA of\ Enterococcus hirae [MEDLINE:93286122]) or for the specific delivery of copper to a biological complex\ for which it is a necessary component (for example FixI of Bradyrhizobium japonicum,\ or CtaA and PacS of Synechocystis [MEDLINE:21282897]). The substrate specificity of these\ transporters may, to a varying degree, include silver ions (for example, CopA from\ Archaeoglobus fulgidus [MEDLINE:21850708]). \ Copper transporters from this family are well known as the genes which are mutated\ in two human disorders of copper metabolism, Wilson's and Menkes' diseases [MEDLINE:94378325]. \ The sequences contributing to the seed of this model are all experimentally\ characterized. \ The copper P-type ATPases have been characterized as Type IB based on a\ phylogenetic analysis which combines the copper-translocating ATPases with the\ cadmium-translocating species [MEDLINE:98080613]. This family and that describing the\ cadmium-ATPases (IPR006404) are well separated, and thus we further type the\ copper-ATPases as IB1 (and the cadmium-ATPases as IB2). \

\ \ \N \N \N 24844 IPR006391

These sequences describe the P-type ATPase subunit of the complex responsible for translocating potassium ions across biological membranes in microbes. In Escherichia coli and other species, this complex consists of the proteins KdpA, KdpB, KdpC and KdpF. KdpB is the ATPase subunit, while KdpA is the potassium-ion translocating subunit [MEDLINE:90239122]. The function of KdpC is unclear, although it has been suggested to couple the ATPase subunit to the ion-translocating subunit [MEDLINE:99077600], while KdpF serves to stabilize the complex [MEDLINE:20076462]. The potassium P-type ATPases have been characterized as Type IA based on a phylogenetic analysis which places this clade closest to the heavy-metal translocating ATPases (Type IB) [MEDLINE:98080613]. Others place this clade closer to the Na+/K+ antiporter type (Type IIC) based on physical characteristics [MEDLINE:90239122].

\ potassium-transporting ATPase activity ; GO:0008556 integral to membrane ; GO:0016021 potassium ion transport ; GO:0006813 24845 IPR006393

These sequences represent sepiapterin reductase, a member of the short chain dehydrogenase/reductase family. The enzyme catalyzes the last step in the biosynthesis of tetrahydrobiopterin. A similar enzyme in Bacillus cereus was isolated for its ability to convert benzil to (S)-benzoin, a property sepiapterin reductase also shares.

\ \N \N \N 24846 IPR006394

These sequences represent the S (sigma) subunit of methylaspartate mutase (glutamate mutase), a cobalamin-dependent enzyme that catalyzes the first step in a pathway of glutamate fermentation.

\ intramolecular transferase activity, transferring other groups ; GO:0016870 \N glutamate fermentation ; GO:0019670 24847 IPR006395

These sequences describe methylaspartate ammonia-lyase, also called -methylaspartase (EC: 4.3.1.2). It follows methylaspartate mutase (composed of S and E subunits) in one of several possible pathways of glutamate fermentation.

\ \N \N \N 24848 IPR006396

These sequences represent the E (epsilon) subunit of methylaspartate mutase (glutamate mutase), a cobalamin-dependent enzyme that catalyzes the first step in a pathway of glutamate fermentation.

\ intramolecular transferase activity, transferring other groups ; GO:0016870 \N glutamate fermentation ; GO:0019670 24833 IPR006380

This family of sequences represent sucrose phosphate phosphohydrolase (SPP) from plants and cyanobacteria. SPP is a member of the Class IIB subfamily of the haloacid dehalogenase (HAD) superfamily of aspartate-nucleophile hydrolases. SPP catalyzes the final step in the biosynthesis of sucrose, a critically important molecule for plants. Sucrose phosphate synthase (SPS), the prior step in the biosynthesis of sucrose contains a domain which exhibits considerable similarity to SPP albeit without conservation of the catalytic residues. The catalytic machinery of the synthase resides in another domain. It seems likely that the phosphatase-like domain is involved in substrate binding, possibly binding both substrates in a "product-like" orientation prior to ligation by the synthase catalytic domain.

\ \N \N \N 24834 IPR006381

This small group of proteins is a member of the IIB subfamily of the haloacid dehalogenase (HAD) superfamily of aspartate-nucleophile hydrolases (IPR005834). Nothing is known about the function of this group of proteins, however given that the other known enzymes of the IIB subfamily are sugar phosphatases or mutases, it would not be unreasonable to predict that these also acts on sugars.

\ \N \N \N 24835 IPR006382

This group of Archaeal sequences is most closely related to the sucrose-phosphate phosphatases (SPP) from plants and cyanobacteria. If it should be shown that the proteins in this family possess sucrose-phosphatase activity then SPP would represent a broad family of functionally related proteins.

\ \N \N \N 24836 IPR006383

This group represents a subfamily of the haloacid dehalogenase superfamily of aspartate-nucleophile hydrolases. Subfamily IA, B, C and D are distinguished from the rest of the superfamily by the presence of a variable domain between the first and second conserved catalytic motifs. In subfamilies IA and IB, this domain consists of an -helical bundle. It was necessary to model these two subfamilies separately, breaking them at an apparent phylogenetic bifurcation, so that the resulting model(s) are not so broadly defined that members of subfamily III (which lack the variable domain) are included.

\ \N \N \N 24837 IPR006384

This group of sequences belong to the IB subfamily of the haloacid dehalogenase (HAD) superfamily of aspartate-nucleophile hydrolases. With exceptions from Bacillus subtilis and Clostridium acetabutylicum, the members of this group are all eukaryotic, spanning metazoa, plants and fungi.

\ \N \N \N 24838 IPR006385

This group of sequences belong to the IB subfamily of the haloacid dehalogenase (HAD) superfamily of aspartate-nucleophile hydrolases. The sequences are all bacterial. The IB subfamily includes the enzyme phosphoserine phosphatase. Due to this relationship, several of these sequences have been annotated as "phosphoserine phosphatase related proteins," or "phosphoserine phosphatase-family enzymes." There is presently no evidence that any of the proteins in this family possess PSPase activity.

\ \N \N \N 24839 IPR006386

This group of sequences belong to the IB subfamily of the haloacid dehalogenase (HAD) superfamily of aspartate-nucleophile hydrolases. The sequences are all from archaeal species. The phylogenetically closest group of sequences to these are phosphoserine phosphatases. As there are no known archaeal phosphoserine phosphatases, it seems likely that this group of sequences represent the archaeal branch of PSPase.

\ \N \N \N 24840 IPR006387

This group of sequences are defined by a domain of about 61 residues in length with six well-conserved cysteine residues and six well-conserved aromatic sites. The domain can be found in tandem repeats, and is known so far only in Plasmodium falciparum. It is named for motifs of CPxxW and (less well conserved) WPC.

\ \N \N \N 24841 IPR006388

This group of sequences represent part of one structural subfamily of the Haloacid Dehalogenase (HAD) superfamily of aspartate-nucleophile hydrolases (IPR005834: (1) hhhhsDxxx(x)D, (2) hhhhssxxx(x)D and (3) hhhhDDxxx(x)s where s refers to a small amino acid and h to a hydrophobic one. All three of these variants are found in subfamily IA.

\ \N \N \N 24842 IPR006389

These sequences represent a family of proteins from the malaria parasite Plasmodium falciparum, several of which have been shown to be expressed specifically in the ring stage as well as the rodent parasite Plasmodium yoelii [MEDLINE:21036610]. A homolog from Plasmodium chabaudi was localized to the parasitophorous vacuole membrane [MEDLINE:94187800]. Members have an initial hydrophobic, Phe/Tyr-rich stretch long enough to span the membrane, a highly charged region rich in Lys, a second putative transmembrane region, and a second highly charged, low complexity sequence region. Some members have up to 100 residues of additional C-terminal sequence. These genes have been shown to be found in the sub-telomeric regions of both Plasmodium falciparum and Plasmodium yoelii chromosomes.

\ \N \N \N 24843 IPR006390

These sequences represent dihydropteroate synthase, the enzyme that catalyzes the second to last step in folic acid biosynthesis. The gene is usually designated folP (folic acid biosynthsis) or sul (sulfanilamide resistance).

\ dihydropteroate synthase activity ; GO:0004156 \N folic acid and derivative biosynthesis ; GO:0009396 24828 IPR006375

This enzyme is known to be bifunctional, as both mannose-6-phosphate isomerase (EC: 5.3.1.8) (PMI) and mannose-1-phosphate guanylyltransferase (EC: 2.7.7.22) in Pseudomonas aeruginosa, Xanthomonas campestris, and Gluconacetobacter xylinus. The literature on the enzyme from Escherichia coli attributes mannose-6-phosphate isomerase activity to an adjacent gene, but the present sequence has not been shown to lack the activity. The PMI domain lies at the C-terminal.

\ \N \N \N 24829 IPR006376

These sequences represent the CopA copper resistance protein family. CopA is related to laccase (benzenediol:oxygen oxidoreductase) and L-ascorbate oxidase, both copper-containing enzymes. Most members have a typical TAT (twin-arginine translocation) signal sequence with an Arg-Arg pair. Twin-arginine translocation is observed for a large number of periplasmic proteins that cross the inner membrane with metal-containing cofactors already bound. The combination of copper-binding sites and TAT translocation motif suggests a mechanism of resistance by packaging and export.

\ \N \N \N 24830 IPR006377

Catabolite control protein A is a LacI family global transcriptional regulator found in Gram-positive bacteria. CcpA is involved in repressing carbohydrate utilization genes [ex: -amylase (amyE), acetyl-coenzyme A synthase (acsA)] and in activating genes involved in transporting excess carbon from the cell [e.g. acetate kinase (ackA), -acetolactate synthase (alsS)]. Additionally, disruption of CcpA in Bacillus megaterium, Staphylococcus xylosus, Lactobacillus casei and Lactocacillus pentosus also decreases growth rate, which suggests CcpA is involved in the regulation of other metabolic pathways.

\ \N \N \N 24831 IPR006378

This family of sequences includes both the members of the sucrose-phosphate phosphatase (SPP) family, encompassing plants and cyanobacteria, as well as those archaeal sequences which are the closest relatives. It remains to be shown whether these archaeal sequences catalyze the same reaction as SPP.

\ \N \N \N 24832 IPR006379

This subfamily falls within the Haloacid Dehalogenase (HAD) superfamily of aspartate-nucleophile hydrolases. The Class II subfamilies are characterized by a domain that is located between the second and third conserved catalytic motifs of the superfamily domain. The IIB subfamily is distinguished from the IIA subfamily (IPR006357) by homology and the predicted secondary structure of this domain by PSI-PRED. The IIB subfamilys Class II domain has the following predicted structure: Helix-Sheet-Sheet-(Helix or Sheet)-Helix-Sheet-(variable)-Helix-Sheet-Sheet. The IIB subfamily consists of trehalose-6-phosphatase, plant and cyanobacterial sucrose-phosphatase and a closely related group of bacterial and archaeal sequences, eukaryotic phosphomannomutase, a large subfamily of Cof-like hydrolases, containing many closely related bacterial sequences, a hypothetical equivalog containing the Escherichia coli YedP protein, as well as two other small clusters whose relationship to the other groups is unclear.

\ \N \N \N 24824 IPR006371

A fairly deep split separates this polyprenyltransferase subfamily from the set of mitochondrial and proteobacterial 4-hydroxybenzoate polyprenyltransferases, described in IPR006370, it is likely that this family of sequences represent 4-hydroxybenzoate polyprenyltransferase, a critical enzyme of ubiquinone biosynthesis, in the Archaea, Gram-positive bacteria, Aquifex aeolicus, and the Chlamydias.

\ \N \N \N 24825 IPR006372

These are a subfamily of a large family of polyprenyltransferases that also includes 4-hydroxybenzoate octaprenyltransferase and protoheme IX farnesyltransferase (heme O synthase). Members of this family are found exclusively in photosynthetic organisms, including a single copy in Arabidopsis thaliana.

\ \N \N bacteriochlorophyll biosynthesis ; GO:0030494 24826 IPR006373

These sequences represent the rifin branch of the rifin/stevor family of predicted variant surface antigens as found in Plasmodium falciparum.

\ \N \N \N 24827 IPR006374

These sequences represent the stevor branch of the rifin/stevor family of predicted variant surface antigens as found in Plasmodium falciparum.

\ \N \N \N 24822 IPR006369

This family describes protoheme IX farnesyltransferase, also called heme O synthase, an enzyme that creates an intermediate in the biosynthesis of heme A. Prior to the description of its enzymatic function, this protein was often called a cytochrome o ubiquinol oxidase assembly factor.

\ protoheme IX farnesyltransferase activity ; GO:0008495 integral to membrane ; GO:0016021 heme biosynthesis ; GO:0006783 24823 IPR006370

These sequences are a family of integral membrane proteins that condense para-hydroxybenzoate with any of several polyprenyldiphosphates. Heterologous expression studies suggest that for, many but not all members, the activity seen (e.g. octaprenyltransferase in Escherichia coli) reflects available host isoprenyl pools rather than enzyme specificity. A fairly deep split by both clustering (UPGMA) and phylogenetics (NJ tree) separates this group (mostly Proteobacterial and mitochondrial), with several characterized members, from another group (mostly archaeal and Gram-positive bacterial) lacking characterized members IPR006371\ \ \ [MEDLINE:20545437].

\ \ prenyltransferase activity ; GO:0004659 integral to membrane ; GO:0016021 biosynthesis ; GO:0009058 24817 IPR006364

These sequences represent precorrin-2 C20-methyltransferase, one of several closely related S-adenosylmethionine-dependent methyltransferases involved in cobalamin (vitamin B12) biosynthesis.

\ S-adenosylmethionine-dependent methyltransferase activity ; GO:0008757 \N \N 24818 IPR006365

These sequences represent the enzyme precorrin-6Y C5,15-methyltransferase (decarboxylating), designated EC: 2.1.1.132, which performs both methylation and decarboxylation during cobalamin (vitamin B12) biosynthesis. These activities are assigned to consecutive loci in Salmonella typhimurium cbiE (methylase) and cbiT (decarboxylase). This fused enzyme is termed CobL or CbiET.

\ precorrin-6Y C5,15-methyltransferase (decarboxylating) activity ; GO:0046025 \N vitamin B12 biosynthesis ; GO:0009236 24819 IPR006366

This domain is found in a family of sequences that represent enzymes, or enzyme domains, with uroporphyrin-III C-methyltransferase activity. This enzyme catalyzes the first step committed to the\ biosynthesis of either siroheme or cobalamin (vitamin B12) rather than protoheme\ (heme). Cobalamin contains cobalt while siroheme contains iron. Siroheme is a cofactor\ for nitrite and sulfite reductases and therefore plays a role in cysteine biosynthesis; many\ members of this family are CysG, siroheme synthase, with an additional N-terminal\ domain and with additional oxidation and iron insertion activities.

\ \ \N \N \N 24820 IPR006367

This group represent a subfamily of CysG N-terminal region-related sequences. All sequences in the seed alignment for this model are N-terminal regions of known or predicted siroheme synthases. The C-terminal region of each is uroporphyrin-III C-methyltransferase (EC: 2.1.1.107), which catalyzes the first step committed to the biosynthesis of either siroheme or cobalamin (vitamin B12) rather than protoheme (heme). Functionally these sequences complete the process of oxidation and iron insertion to yield siroheme. Siroheme is a cofactor for nitrite and sulfite reductases, so siroheme synthase is CysG of cysteine biosynthesis in some organisms.

\ \N \N \N 24821 IPR006368

This family represent GDP-mannose 4,6-dehydratase, also known as GDP-D-mannose dehydratase. This enzyme converts GDP-mannose to GDP-4-dehydro-6-deoxy-D-mannose, the first of three steps for the conversion of GDP-mannose to GDP-fucose in animals, plants, and bacteria. In bacteria, GDP-L-fucose acts as a precursor of surface antigens such as the extracellular polysaccharide colanic acid of Escherichia coli. Excluded from this family are members of the clade that are poorly related because of highly dervied (phylogenetically long-branch) sequences, e.g. Aneurinibacillus thermoaerophilus Gmd, described as a bifunctional GDP-mannose 4,6-dehydratase/GDP-6-deoxy-D-lyxo-4-hexulose reductase [MEDLINE:21101933].

\ GDP-mannose 4,6-dehydratase activity ; GO:0008446 \N biosynthesis ; GO:0009058 24815 IPR006362

These sequences represent precorrin-4 C11-methyltransferase, one of two methyltransferases commonly referred to as precorrin-3 methylase (the other is precorrin-3B C17-methyltransferase, EC: 2.1.1.131). This enzyme participates in the pathway toward the biosynthesis of cobalamin and related products.

\ precorrin-4 C11-methyltransferase activity ; GO:0046026 \N biosynthesis ; GO:0009058 24816 IPR006363

These sequences represent precorrin-3B C17-methyltransferase, one of two methyltransferases commonly referred to as precorrin-3 methylase (the other is precorrin-4 C11-methyltransferase, EC: 2.1.1.133). This enzyme participates in the pathway toward the biosynthesis of cobalamin and related products. Members of this family may appear as fusion proteins with other enzymes of cobalamin biosynthesis.

\ methyltransferase activity ; GO:0008168 \N vitamin B12 biosynthesis ; GO:0009236 24811 IPR006358

This family of sequences represent the prokaryotic transcription elongation factor GreB. GreA and GreB transcription elongation factors allow RNA transcription to continue past template-encoded arresting sites. Among the Proteobacteria, distinct clades of GreA and GreB are found. GreB differs functionally in that it releases larger oligonucleotides.

\ \N \N \N 24812 IPR006359

The GreA and GreB transcription elongation factors enable RNA transcription to continue past template-encoded arresting sites. Among the Proteobacteria, distinct clades of GreA and GreB are found. GreA differs functionally in that it releases smaller oligonucleotides. Because members of the family outside the Proteobacteria resemble GreA more closely than GreB, the GreB clade (IPR006358) forms a plausible outgroup and the remainder of the GreA/B family, included in this family, is designated GreA. In the Chlamydias and some spirochetes, the conserved region of these proteins is found as the C-terminal region of a much larger protein.

\ \N \N \N 24813 IPR006360

This family is closely related to, yet is distinct from, uroporphyrinogen decarboxylase (EC: 4.1.1.37). It includes two isozymes from Methanosarcina barkeri of methylcobalamin--coenzyme M methyltransferase. It also includes a chloromethane utilization protein, CmuA, which transfers the methyl group of chloromethane to a corrinoid protein [MEDLINE:20575224], [MEDLINE:96184544].

\ methyltransferase activity ; GO:0008168 \N methanogenesis ; GO:0015948 24814 IPR006361

This family of sequences represent uroporphyrinogen decarboxylase (HemE), which converts uroporphyrinogen III to coproporphyrinogen III. This step takes the pathway toward\ protoporphyrin IX, a common precursor of both heme and chlorophyll, rather than\ toward precorrin 2 and its products.

\ \ uroporphyrinogen decarboxylase activity ; GO:0004853 \N porphyrin biosynthesis ; GO:0006779 24805 IPR006352

This family describes GlmM, phosphoglucosamine mutase, also designated MrsA and YhbF in Escherichia coli [MEDLINE:96132879], UreC in Helicobacter pylori [MEDLINE:97315217], and femR315 or FemD in Staphlococcus aureus [MEDLINE:97431478]. It converts glucosamine-6-phosphate to glucosamine-1-phosphate as part of the pathway toward UDP-N-acetylglucosamine for peptidoglycan and lipopolysaccharides.

\ \N \N \N 24806 IPR006353

These sequences, all eukaryotic, are members of the Class IIA subfamily of the haloacid dehalogenase superfamily of aspartate-nucleophile hydrolases (IPR005834).

\ \N \N \N 24807 IPR006354

These sequences are all members of the Class IIA subfamily of the haloacid dehalogenase superfamily of aspartate-nucleophile hydrolases (IPR005834). The sequences are all from the Gram-positive (low-GC) bacteria.

\ \N \N \N 24808 IPR006355

These sequences are all members of the IIA subfamily of the haloacid dehalogenase superfamily of aspartate-nucleophile hydrolases. The sequences are all from multicellular eukaryotes (metazoa).

\ \N \N \N 24809 IPR006356

These sequences are all members of the Class IIA subfamily of the haloacid dehalogenase superfamily of aspartate-nucleophile hydrolases (IPR005834). The sequences are restricted to the Gram-negative and primarily proteobacteria. Only one sequence has been annotated as other than "hypothetical." That one, from Brucella, is annotated as related to NagD, but only by sequence similarity and should be treated with some scepticism.

\ \N \N \N 24810 IPR006357

These sequences form one of the structural subclasss of the Haloacid Dehalogenase (HAD) superfamily of aspartate-nucleophile hydrolases. The superfamily is defined by the presence of three short catalytic motifs [MEDLINE:95055742]. The classes are defined [MEDLINE:21488076] based on the location and the observed or predicted fold of a so-called "capping domain" [MEDLINE:20412918], or the absence of such a domain. Class I consists of sequences in which the capping domain is found in between the first and second catalytic motifs. Class II consists of sequences in which the capping domain is found between the second and third motifs. Class III sequences have no capping domain in either of these positions. The Class IIA capping domain is predicted to consist of a mixed - fold with the basic pattern: Helix-Helix-Helix-Sheet-Helix-Loop-Sheet-Helix-Sheet-Helix. Presently, this subfamily covers the eukaryotic phosphoglycolate phosphatase, as well as four further subfamilies covering closely related sequences in eukaryotes, in Gram-positive bacteria and in Gram-negative bacteria. The Escherishia coli NagD gene and the Bacillus subtilus AraL gene are members of this subfamily but are not members of the any of the presently defined equivalogs within it. NagD is part of the NAG operon responsible for N-acetylglucosamine metabolism [MEDLINE:90274974]. The function of this gene is unknown. Genes from several organisms have been annotated as NagD, or NagD-like. However, without data on the presence of other members of this pathway, (such as in the case of Yersinia pestis) these assignments should not be given great weight. The AraL gene is similar, it is part of the L-arabinose operon, but the function is unknown [MEDLINE:97237725]. A gene from Halobacterium has been annotated as AraL, but no other Ara operon genes have been annotated. Many of the genes in this subfamily have been annotated as "pNPPase" "4-nitrophenyl phosphatase" or "NPPase". These all refer to the same activity versus a common lab test compound used to determine phosphatase activity. There is no evidence that this activity is physiologically relevant.

\ \N \N \N 24802 IPR006349

This family of sequences represent 2-phosphoglycolate phosphatase which is limited to the eukaryotic lineage. PGP is an essential enzyme in the glycolate salvage pathway in higher organisms (photorespiration in plants). Phosphoglycolate results from the oxidase activity of RubisCO in the Calvin cycle when concentrations of carbon dioxide are low relative to oxygen. In mammals, PGP is found in many tissues, notably in red blood cells where P-glycolate is and important activator of the hydrolysis of 2,3-bisphosphoglycerate, a major modifier of the oxygen affinity of hemoglobin. The PGPase enzyme described here is a member of the Haloacid dehalogenase superfamily of hydrolase enzymes (IPR005834. The Homo sapiens sequence maps to chromosome 22. There is indeed a related gene on chromosome 16 (and it is expressed, since EST's are found) which shows 46% identity and 59% positives by BLAST2 (E=1e-66). Presumably, these two genes are isoforms and have the same catalytic function while being expressed in different tissues and may be differently regulated. The sequence from Caenorhabditis elegans, is only supported by sequence similarity. This family is closely related to a family of bacterial sequences including the Escherichia coli NagD and Bacillus subtilus AraL genes which are characterized by the ability to hydrolyze para-nitrophenylphosphate (pNPPases or NPPases). The Chlamydomonas reinhardtii PGPase does not catalyze this reaction and so presumably these two groups have different functions and substrate specificities. Many of the genes in this family have been annotated as pNPPases due to this association.

\ \N \N \N 24803 IPR006350

These sequences represent a subfamily of endonucleases containing the endo/excinuclease amino terminal domain, IPR000305 are often termed GIY-YIG endonucleases after N-terminal conserved motifs. The sequences are encoded by open reading frames found in group I introns in both phage and mitochondria. The closely related endonucleases of phage T4: segA, segB, segC, segD and segE, are not included in this family.

\ nuclease activity ; GO:0004518 intracellular ; GO:0005622 \N 24804 IPR006351

The enzymes in this family are all located in the operons for the biosynthesis of 3-amino-5-hydroxybenoic acid (AHBA), which is a precursor of several antibiotics including ansatrienin [MEDLINE:99203506], naphthomycin [MEDLINE:99203506], rifamycin [MEDLINE:21201076] and mitomycin [MEDLINE:99201491]. The role that this enzyme plays in this biosynthesis has not been elucidated. It is a member of the Haloacid dehalogenase superfamily (IPR005834), but it is unclear what purpose a PGPase or PGPase-like activity would serve in these biosyntheses. The family is restricted to the Gram-positive Actinobacteria.

\ \N \N \N 24799 IPR006344

This family describes the exodeoxyribonuclease V subunit, RecD. RecD is part of a RecBCD complex. C-terminal part of the protein matches a domain found in viral RNA helicase, superfamily 1, IPR000606.

\ exodeoxyribonuclease V activity ; GO:0008854 exodeoxyribonuclease V complex ; GO:0009338 \N 24800 IPR006345

These sequences represent a family similar to RecD, the exodeoxyribonuclease V chain of IPR006344. Members of this family, however, are not found in a context of RecB and RecC and are longer by about 200 amino acids at the amino end. Chlamydia muridarum has both a member of this family and a RecD.

\ \N \N \N 24801 IPR006346

This family of sequences represent 2-phosphoglycolate phosphatase which is limited to the prokaryotes. PGP is an essential enzyme in the glycolate salvage pathway in higher organisms (photorespiration in plants). Phosphoglycolate results from the oxidase activity of RubisCO in the Calvin cycle when concentrations of carbon dioxide are low relative to oxygen. In Ralstonia (Alcaligenes) eutropha and Rhodobacter sphaeroides, the PGP gene (CbbZ) is located on an operon along with other Calvin cycle enzymes including RubisCO [MEDLINE:94042908], [MEDLINE:97158658]. The only other pertinent experimental evidence concerns the gene from Escherichia coli [MEDLINE:20037583]. The in vitro activity of the Ralstonia and Escherichia enzymes was determined with crude cell extracts of strains containing PGP on expression plasmids and compared to controls. In Escherichia coli, however, there does not appear to be a functional Calvin cycle (RubisCO is absent), although the Escherichia coli PGP gene (gph) is on the same operon (dam) with ribulose-5-phosphate-3-epimerase (rpe), a gene in the pentose-phosphate pathway (along with other, unrelated genes). The Escherichia coli enzyme is not expressed under normal laboratory conditions; the pathway to which it belongs has not been determined. In fact, the possibility exists, although unlikely, that this enzyme and others within this equivalog have as their physiological substrate another, closely related molecule. The protein from Xylella fastidiosa has no experimental evidence, but is a plant pathogen and thus may obtain phosphoglycolate from its host. This model has been restricted to encompass only proteobacteria as no related PGP has been verified outside of this clade. Sequences from Aquifex aeolicus and Treponema pallidum fall between the trusted and noise cutoffs. Just below the noise cutoff is a gene which is part of the operon for the biosynthesis of the blue pigment, indigoidine, from Erwinia (Pectobacterium) chrysanthemi, a plant pathogen [MEDLINE:21650660]. It does not seem likely, considering the proposed biosynthetic mechanism, that the dephosphorylation of phosphoglycolate or a closely related compound is required. Possibly, this gene is fortuitously located in this operon, or has an indirect relationship to the necessity for the biosynthesis of this compound. This enzyme is a member of the Haloacid Dehalogenase (HAD) superfamily of aspartate-nucleophile hydrolase enzymes (IPR005834).

\ phosphoglycolate phosphatase activity ; GO:0008967 \N \N 24788 IPR006333

Members of this family catalyze the oxidation of ubiquinol with the concomitant reduction of molecular oxygen to water. This acts as the terminal electron acceptor in the respiratory chain. Subunit II is responsible for binding and oxidation of the ubiquinone substrate. This sequence is closely related to QoxA, which oxidizes quinol in Gram-positive bacteria but which is in complex with subunits which utilize cytochromes a in the reduction of molecular oxygen. Slightly more distantly related is subunit II of cytochrome c oxidase which uses cytochrome c as the oxidant [MEDLINE:90293062].

\ \N \N \N 24789 IPR006334

These sequences represent glutamate--cysteine ligase, also known as gamma-glutamylcysteine synthetase, an enzyme in the biosynthesis of glutathione (GSH). GSH is one of several low molecular weight cysteine derivatives that can serve to protect against oxidative damage and participate in biosynthetic or detoxification reactions.

\ glutamate-cysteine ligase activity ; GO:0004357 \N glutathione biosynthesis ; GO:0006750 24790 IPR006335

This entry represents a family with an N-terminal region similar to proteobacterial glutamate-cysteine ligase (gamma-glutamylcysteine synthetase). The C-terminal region is homologous to cyanophycin synthetase of cyanobacteria, and (shown by PSI-BLAST) to D-alanine-D-alanine ligases. Cyanophycin is a storage molecule composed of arginine, aspartic acid, and some glutamic acid. Members of this family are found in Listeria and Enterococcus, Gram-positive lineages in which glutathione is produced [MEDLINE:96178963], and in proteobacterium Pasteurella multocida.

\ \N \N \N 24791 IPR006336

These sequences represent one of two highly dissimilar forms of glutamate--cysteine ligase (gamma-glutamylcysteine synthetase), an enzyme of glutathione biosynthesis. The other group is represented by IPR006334. This form is found in plants (with a probable transit peptide), root nodule and other bacteria, but not Escherichia coli and closely related species.

\ \N \N \N 24792 IPR006337

These proteins are related to a number of pyridoxal phosphate-dependent enzymes, and in particular to selenocysteine synthase (SelA), which converts Ser to selenocysteine on its tRNA. While resembling SelA, this protein is found only in species that have a better candidate SelA or else lack the other genes (selB, selC, and selD) required for selenocysteine incorporation.

\ \N \N \N 24793 IPR006338

This homodimeric, FAD-containing member of the pyridine nucleotide disulfide oxidoreductase family contains a C-terminal motif Cys-SeCys-Gly, where SeCys is selenocysteine encoded by TGA (in some sequence reports interpreted as a stop codon). In some members of this subfamily, Cys-SeCys-Gly is replaced by Cys-Cys-Gly. The reach of the selenium atom at the C-terminal arm of the protein is proposed to allow broad substrate specificity [MEDLINE:21173616], [MEDLINE:96234105].

\ oxidoreductase activity, acting on NADH or NADPH, disulfide as acceptor ; GO:0016654 \N electron transport ; GO:0006118 24794 IPR006339

This DNA-binding domain is found in proteins like AbrB, a transition state regulator in Bacillus subtilis, whose DNA-binding domain structure in solution was determined by NMR. The domain binds DNA as a dimer in what is termed a looped-hinge helix fold. Some members of the family have two copies of the domain in tandem. The domain is found usually at the N-terminus of a small protein.

\ \N \N \N 24795 IPR006340

Members of this family are uncharacterized proteins of about 180 amino acids from the Bacillus/Clostridium group of Gram-positive bacteria, found in no more than one copy per genome.

\ \N \N \N 24796 IPR006341

This is a family of small, glutamine and asparagine-rich peptides that store amino acids in the spores of Bacillus subtilis and related bacteria. Most members of the family have two copies of the spore protease (GPR) cleavage motif, typically EFASE in this family, separating three low-complexity repeats.

\ \N \N \N 24797 IPR006342

Members of this family are characterized by two well-conserved short regions separated by a variable region in both sequence and length. The first of the two regions is found in a large number of proteins outside this subfamily, a number of which have been characterized as methyltransferases. One member of the present family, FkbM, was shown to be required for a specific methylation in the biosynthesis of the immunosuppressant FK506 in Streptomyces strain MA6548 [MEDLINE:96359380].

\ \N \N \N 24798 IPR006343

These sequences contain a conserved domain. It is found in DnaD, part of Bacillus subtilis replication restart primosome, and of a number of phage-associated proteins. Members, both chromosomal or phage-associated, are found in the Bacillus/Clostridium group of Gram-positive bacteria [MEDLINE:21537173].

\ \N \N \N 24783 IPR006328

These proteins catalyze the hydrolytic dehalogenation of small L-2-haloalkanoic acids to yield the corresponding D-2-hydroxyalkanoic acids [MEDLINE:21297013]. They belong to the Haloacid Dehalogenase (HAD) superfamily of aspartate-nucleophile hydrolases (IPR005834), class (subfamily) I. Note that the Type I HAD enzymes have not yet been fully characterized, but clearly utilize a substantially different catalytic mechanism and are thus unlikely to be related.

\ hydrolase activity, acting on acid halide bonds, in C-halide compounds ; GO:0019120 \N metabolism ; GO:0008152 24784 IPR006329

These sequences describe AMP deaminase, a large, well-conserved eukaryotic protein involved in energy metabolism. Most members of the family have an additional, poorly alignable region of 150 amino acids or more N-terminal to the conserved domain which defines this group of sequences.

\ AMP deaminase activity ; GO:0003876 \N purine ribonucleoside monophosphate biosynthesis ; GO:0009168 24785 IPR006330

This family includes the experimentally verified adenosine deaminases of mammals and Escherichia coli. Other members of this family are predicted also to be adenosine deaminase, an enzyme of nucleotide degradation. This family is distantly related to AMP deaminase.

\ adenosine deaminase activity ; GO:0004000 \N purine ribonucleoside monophosphate biosynthesis ; GO:0009168 24786 IPR006331

Members of this family have been described as secreted proteins with growth factor activity and regions of adenosine deaminase homology in insects, molluscs, and vertebrates [MEDLINE:20363729].

\ \N \N \N 24787 IPR006332

Members of this family catalyze the oxidation of quinol with the concomitant reduction of molecular oxygen to water. This acts as the terminal electron acceptor in the respiratory chain. This subunit contains two transmembrane helices and a large external domain responsible for the binding and oxidation of quinol. QuoX is (presently) only found in Gram-positive bacteria of the Bacillus/Staphylococcus group [MEDLINE:92268053]. Like CyoA, the ubiquinol oxidase found in proteobacteria, the residues responsible for the ligation of Cu(a) and cytochrome c (found in the related cyt. c oxidases) are absent. Unlike CyoA, QoxA is in complex with a subunit I which contains cytochromes similar to the cytochrome c oxidases (as opposed to cytochromes b).

\ \N \N \N 24779 IPR006324

These sequences represent glutathione reductases of plants and some bacteria, including cyanobacteria.

\ glutathione reductase (NADPH) activity ; GO:0004362 \N glutathione metabolism ; GO:0006749 24780 IPR006325

This family of proteins are from the eukaryotic cytosol signal recognition particle protein component, SRP54. They are GTP-binding proteins; and are a component of the eukaryotic signal recognition particle, along with several other protein subunits and a 7S RNA. Some species, including Arabidopsis, have several closely related forms. The extreme C-terminal region is glycine-rich and lower in complexity and poorly conserved between species.

\ \N \N \N 24781 IPR006326

These sequences belong to the MGT (macroside glycosyltransferase) subfamily of the UDP-glucuronosyltransferase family. Members include a number of glucosyl transferases for macrolide antibiotic inactivation, but also include transferases of glucose-related sugars for macrolide antibiotic production.

\ \N \N \N 24782 IPR006327

These sequences represent the IIC component, or IIC region of a IIABC or IIBC polypeptide of a phosphotransferase system for carbohydrate transport. Members of this family belong to the fructose-specific subfamily of the broader family of PTS EIIC proteins. Members should be found as part of the same chain or in the same operon as fructose family IIA (IPR004715) protein regions. A number of bacterial species have members in two different branches of this subfamily, suggesting some diversity in substrate specificity of its members.

\ \N \N \N 24774 IPR006319

This family represents phosphoenolpyruvate synthase; also called pyruvate,water dikinase and PEP synthase. The member from Methanococcus jannaschii contains a large intein. This enzyme generates phosphoenolpyruvate (PEP) from pyruvate, hydrolyzing ATP to AMP and releasing inorganic phosphate in the process. The enzyme shows extensive homology to other enzymes that use PEP as substrate or product. This enzyme may provide PEP for gluconeogenesis, for PTS-type carbohydrate transport systems, or for other processes.

\ water pyruvate dikinase activity ; GO:0008986 \N gluconeogenesis ; GO:0006094 24775 IPR006320

These sequences, which are about 160 residues in length, are closely related to the fructose-specific phosphotransferase (PTS) system IIA component. It is a regulatory protein found only in species with a phosphoenolpyruvate-protein phosphotransferase (enzyme I of PTS systems) and an HPr-like phosphocarrier protein, but not all species have a IIC-like permease. Members of this family are found in Proteobacteria, Chlamydia, and the spirochete Treponema pallidum [MEDLINE:21142530], [MEDLINE:98196715].

\ \N \N \N 24776 IPR006321

These represent the PilT subfamily of proteins related to GspE, a protein involved in type II secretion (also called the General Secretion Pathway). PilT is an apparent cytosolic ATPase associated with type IV pilus systems. It is not required for pilin biogenesis, but is required for twitching motility and social gliding behaviors, shown in some species, powered by pilus retraction [MEDLINE:20445177]. Members of this family may be found in some species that do not have type IV pili but have related structures for DNA uptake and natural transformation.

\ \N \N \N 24777 IPR006322

These sequences represent one of two closely related subfamilies of glutathione reductase. Both are closely related to trypanothione reductase, and separate models are built so each of the three can describe proteins with conserved function. This model describes glutathione reductases of animals, yeast, and a number of animal-resident bacteria.

\ glutathione reductase (NADPH) activity ; GO:0004362 \N glutathione metabolism ; GO:0006749 24778 IPR006323

These sequences represent an enzyme that catalyzes the cleavage of the carbon phosphorous bond of a phosphonate. The mechanism depends on the substrate having a carbonyl one carbon away from the cleavage position. This enzyme is a member of the Haloacid Dehalogenase (HAD) superfamily of aspartate-nucleophile hydrolases, and contains a modified version of the conserved catalytic motifs of that superfamily: the first motif is usually DxDx(T/V), here it is DxAxT, and in the third motif the normal conserved lysine is instead an arginine. Additionally, the enzyme contains a unique conserved catalytic lysine (B. cereus pos. 53) which is involved in the binding and activation of the substrate through the formation of a Schiff base [MEDLINE:20412918]. The substrate of this enzyme is the product of 2-aminoethylphosphonate (AEP) transaminase, phosphonoacetaldehyde. This degradation pathway for AEP may be related to its toxic properties which are utilized by microorganisms as a chemical warfare agent.

\ \N \N \N 24771 IPR006316

These sequences represent a family of pyridoxal-phosphate dependent enzymes that are closely related to the subunit of tryptophan synthase.

\ \N \N \N 24772 IPR006317

These sequences represent the Proteobacterial and mitochondrial type of the Rieske [2Fe-2S] iron-sulfur subunit as found in ubiquinol-cytochrome c reductase. Not included in this group are the Rieske iron-sulfur protein as found in the cytochrome b6-f complex of the Cyanobacteria and chloroplasts. Most members of this family have a recognizable twin-arginine translocation (tat) signal sequence (DeltaPh-dependent translocation in chloroplast) for transport across the membrane with the 2Fe-2S group already bound. These signal sequences include a motif resembling RRxFLK before the transmembrane helix.

\ ubiquinol-cytochrome c reductase activity ; GO:0008121 ubiquinol-cytochrome c reductase complex ; GO:0045285 electron transport ; GO:0006118 24773 IPR006318

These sequences are a distinct clade of phophoenolpyruvate (PEP)-dependent enzymes. Most members are known or deduced to function as the phosphoenolpyruvate-protein phosphotransferase (or enzyme I) of PTS sugar transport systems. However, some species with both a member of this family and a homolog of the phosphocarrier protein HPr lack a IIC component able to serve as a permease. An HPr homolog designated NPr has been implicated in the regulation of nitrogen assimilation, which demonstrates that not all phosphotransferase system components are associated directly with PTS transport.

\ transferase activity, transferring phosphorus-containing groups ; GO:0016772 \N \N 24767 IPR006312

This family represents TatA and TatE. The Tat (twin-arginine translocation) system is a Sec-independent exporter for folded proteins, often with a redox cofactor already bound, across the bacterial inner membrane. Functionally equivalent systems are found in the chloroplast and some in archaeal species. The signal peptide recognized by the Tat system is modeled by IPR006311.

\ \N \N \N 24768 IPR006313

These sequences represent a small family of proteins with a typical Tat (twin-arginine translocation) signal sequence, suggesting that the family is exported in a folded state, perhaps with a bound redox cofactor. Members of this family form a subfamily of Dyp superfamily, a dye-decolorizing peroxidase from Geotrichum candidum that lacks any typical heme-binding site [MEDLINE:20208896].

\ \N \N \N 24769 IPR006314

A defined member of this superfamily is Dyp, a dye-decolorizing peroxidase that lacks a typical heme-binding region [MEDLINE:20208896]. A distinct, uncharacterized branch of this superfamily has a typical twin-arginine dependent signal sequence characteristic of exported proteins with bound redox cofactors.

\ \N \N \N 24770 IPR006315

This group of Gram-negative bacterial proteins, mostly found in pathogens and associated with virulence, contain a conserved C-terminal domain that integrates into the outer membrane and enables the N-terminal region to be delivered across the membrane. This C-terminal autotransporter domain is about 400 amino acids in length and includes the aromatic amino acid-rich OMP signal, typically ending with a Phe or Trp residue, at the extreme C-terminus.

\ \N \N \N 24758 IPR006303

These sequences represent the FliR protein of bacterial flagellar biosynthesis. It distinguishes FliR from the homologous proteins bacterial type III protein secretion systems, known by names such as YopT, EscT, and HrcT.

\ \N \N \N 24759 IPR006304

These sequences represent members of bacterial type III secretion systems homologous to the flagellar biosynthetic protein FliR (IPR006303).

\ \N \N \N 24760 IPR006305

These sequences represent FliQ, a protein involved in biosynthesis of bacterial flagella. A related family of proteins, excluded from this model, participate in bacterial type III protein secretion systems.

\ \N \N \N 24761 IPR006306

This is one of several families of proteins related to bacterial flagellar biosynthesis proteins and involved in bacterial type III protein secretion systems. This family is homologous to, but separate from, the flagellar biosynthetic protein FliQ.

\ \N \N \N 24762 IPR006307

This is one of several families of proteins related to bacterial flagellar biosynthesis proteins and involved in bacterial type III protein secretion systems. This family is homologous to, but distinguished from, the flagellar biosynthetic protein FlhB (IPR006136). This model may not identify all type III secretion system FlhB homologs.

\ \N \N \N 24763 IPR006308

These are the polypeptide chains of DNA polymerase III. Full-length homologs of this protein are restricted to the Gram-positive lineages, including the Mycoplasmas. This protein is designated chain and given the gene symbol polC, but is not a full-length homolog of other polC genes. The N-terminal region of about 200 amino acids is rich in low-complexity sequence and poorly alignable.

\ DNA-directed DNA polymerase activity ; GO:0003887 \N DNA replication ; GO:0006260 24764 IPR006309

These represent DnaQ, the DNA polymerase III epsilon subunit, as found in most Proteobacteria. It consists largely of an exonuclease region as described in IPR006055. In Gram-positive bacteria, closely related regions are found both in the Gram-positive type DNA polymerase III subunit and as an additional N-terminal domain of a DinG-family helicase. Both are not included in this set of sequences, as they are smaller proteins.

\ DNA-directed DNA polymerase activity ; GO:0003887 \N DNA replication ; GO:0006260 24765 IPR006310

These are a family of proteins in Gram-positive bacteria. The N-terminal region of about 200 amino acids resembles the epsilon subunit of E. coli DNA polymerase III and the homologous region of the Gram-positive type DNA polymerase III subunit. The epsilon subunit contains an exonuclease domain. The remainder of this protein family resembles a predicted ATP-dependent helicase, the DNA damage-inducible protein DinG of Escherichia coli.

\ \N \N \N 24766 IPR006311

Proteins assembled with various cofactors or by means of cytosolic molecular chaperones are poor candidates for translocation across the bacterial inner membrane by the standard general secretory (Sec) pathway. This entry describes a family of predicted long, non-Sec signal sequences and signal-anchor sequences (uncleaved signal sequences). All contain an absolutely conserved pair of arginine residues, in a motif approximated by (S/T)-R-R-X-F-L-K, followed by a membrane-spanning hydrophobic region. Members with small amino acid side chains at the -1 and -3 positions from the C terminus of the model should be predicted to be cleaved as are Sec pathway signal sequences. Members are almost exclusively bacterial, although the domain is also found in eukaryotic and archaeal sequences. A large fraction of the members of this family may have bound redox-active cofactors [MEDLINE:97093961], [MEDLINE:20117987].

\ \N \N \N 24751 IPR006296

This family describes homoserine-O-acetyltransferase, an enzyme of methionine biosynthesis. The family does not contain a number of homologs that appear to represent sequences derived from within the family but to have changed substantially.

\ homoserine O-acetyltransferase activity ; GO:0004414 \N methionine biosynthesis ; GO:0009086 24752 IPR006297

LepA (GUF1 in Saccaromyces) is a GTP-binding membrane protein related to EF-G and EF-Tu. Two types of phylogenetic tree, rooted by other GTP-binding proteins, suggest that eukaryotic homologs (including GUF1 of yeast) originated within the bacterial LepA family. The function of the proteins in this family are unknown.

\ \N \N \N 24753 IPR006298

This bacterial (and Arabidopsis) protein, termed TypA or BipA, is a GTP-binding protein. It is phosphorylated on a tyrosine residue under some cellular conditions. Mutants show altered regulation of some pathways, but the precise function is unknown.

\ \N \N \N 24754 IPR006299

These sequences represent FlgC, one of several components of bacterial flagella. FlgC is part of the basal body.

\ \N \N \N 24755 IPR006300

These sequences represent FlgB, one of several components of bacterial flagella. FlgB is part of the basal body.

\ \N \N \N 24756 IPR006301

These sequences describe the flagellar biosynthesis protein FlhA, one of a large number of genes associated with the biosynthesis of functional bacterial flagella. Homologs of many such proteins, including FlhA, function in type III protein secretion systems.

\ \N \N \N 24757 IPR006302

Members of this family are closely homologous to the flagellar biosynthesis protein FlhA and should all participate in type III secretion systems. Examples include InvA (Salmonella enterica), LcrD (Yersinia enterocolitica), HrcV (Xanthomonas), etc. Type III secretion systems resemble flagellar biogenesis systems, and may share the property of translocating special classes of peptides through the membrane.

\ \N \N \N 24749 IPR006294

These sequences represent 2',3'-cyclic-nucleotide 2'-phosphodiesterase; it is a bifunctional enzyme localized to the periplasm of Gram-negative bacteria. 2',3'-cyclic-nucleotide 2'-phosphodiesters are intermediates formed during the hydrolysis of RNA by the ribonuclease I, which is also found in the periplasm, and other enzymes of the RNAse T2 family. Bacteria are unable to transport 2',3'-cyclic-nucleotides into the cytoplasm. 2',3'-cyclic-nucleotide 2'-phosphodiesterase contains 2 active sites which catalyze the reactions that convert the 2',3'-cyclic-nucleotide into a 3'-nucleotide, which is then converted into nucleic acid and phosphate. Both final products can be transported into the cytoplasm. Thus, it has been suggested that 2',3'-cyclic-nucleotide 2'-phosphodiesterase has a scavenging function. Experimental evidence indicates that 2',3'-cyclic-nucleotide 2'-phosphodiesterase enables Yersinia enterocolitica O:8 to grow on 23-cAMP as a sole source of carbon and energy [MEDLINE:21097257].

\ \ 2',3'-cyclic-nucleotide 2'-phosphodiesterase activity ; GO:0008663\ \N \N nucleotide metabolism ; GO:0009117 24750 IPR006295

DNA primase synthesizes the RNA primers for the Okazaki fragments in lagging strand DNA synthesis. Members of this family are DNA primases from bacteriophage or bacteria. The C-terminal region of this family of proteins is poorly conserved between species. No sequence similarity can be detected between these proteins and the DNA primases from the Archaea or to either of the two subunits, p50 and p60, of the heterodimeric eukaryotic DNA primase IPR002755.

\ DNA primase activity ; GO:0003896 \N DNA replication, priming ; GO:0006269 24748 IPR006293

The ATP-dependent DNA helicase RecQ (EC: 3.6.1.-) is involved in genome maintenance [MEDLINE:22241622]. All homologues tested to date unwind paired DNA, translocating in a 3' to 5' direction and several have a preference for forked or 4-way DNA structures (e.g. Holliday junctions) or for G-quartet DNA. The yeast protein, Sgs1, is present in numerous foci that coincide with sites of de novo synthesis DNA, such as the replication fork, and protein levels peak during S-phase.

A model has been proposed for Sgs1p action in the S-phase checkpoint response, both as a 'sensor' for damage during replication and a 'resolvase' for structures that ariseat paused forks, such as the four-way 'chickenfoot' structure. The action of Sgs1p may serve to maintain the proper amount and integrity of ss DNA that is\ necessary for the binding of RPA (replication protein A, the eukaryotic ss DNA-binding protein)DNA pol complexes. Sgs1p would thus function by detecting (or resolving) aberrant DNA structures, and would thus\ contribute to the full activation of the DNA-dependent protein kinase, Mec1p and the effector kinase, Rad53p. Its ability to bind both the large subunit of RPA and the\ RecA-like protein Rad51p, place it in a unique position to resolve inappropriate fork structures that can occur when either the leading or lagging strand\ synthesis is stalled. Thus, RecQ helicases integrate checkpoint activation and checkpoint response.

\ \ ATP dependent DNA helicase activity ; GO:0004003 \N SOS response ; GO:0009432 24743 IPR006288

These sequences are the archaeal transcription factor S, a protein related in size and sequence to certain eukaryotic RNA polymerase small subunits, and in sequence and function to the much larger eukaryotic transcription factor IIS (TFIIS). Although originally suggested to be a subunit of the archaeal RNA polymerase, it elutes separately from active polymerase in gel filtration experiments and acts, like TFIIs, as an induction factor for RNA cleavage by RNA polymerase [MEDLINE:20239876].

\ \N \N \N 24744 IPR006289

These sequences represent the eukaryotic transcription elongation factor S-II. This protein allows stalled RNA transcription complexes to perform a cleavage of the nascent RNA and restart at the newly generated 3-prime end.

\ \N \N \N 24745 IPR006290

Members of this family contain a sensor histidine kinase domain (IPR003661). This group is separated phylogenetically from related proteins with similar architecture and contains a number of proteins associated with heavy metal resistance efflux systems for copper, silver, cadmium, and/or zinc.

\ \N \N \N 24746 IPR006291

Members of this family contain a response regulator receiver domain (IPR001789), its partner in the two-component response regulator system.

\ \N \N \N 24747 IPR006292

These proteins represent ribonuclease D, a 3-exonuclease shown to act on tRNA both in vitro and when overexpressed in vivo. Members of this family are restricted to the Proteobacteria; Aquifex, Mycobacteria and eukaryotes. Ribonuclease D is not essential in Escherichia coli but is deleterious when overexpressed. The precise biological role of ribonuclease D is still unknown.

\ ribonuclease activity ; GO:0004540 cytoplasm ; GO:0005737 tRNA processing ; GO:0008033 24735 IPR006280

These sequences represent the gamma subunit of a family of known and putative heterotetrameric sarcosine oxidases. Five operons of such oxidases are found in Mesorhizobium loti and three in Agrobacterium tumefaciens, a high enough copy number to suggest that not all members share the same function. The gamma subunit is the most divergent between operons of the four subunits. Sarcosine oxidase catalyzes the oxidative demethylation of sarcosine to glycine. The reaction converts tetrahydrofolate to 5,10-methylene-tetrahydrofolate. The enzyme is known in monomeric and heterotetrameric (,,gamma,delta) forms, this represents the heterotetrameric form.

\ sarcosine oxidase activity ; GO:0008115 \N tetrahydrofolate metabolism ; GO:0046653 24736 IPR006281

Sarcosine oxidase catalyzes the oxidative demethylation of sarcosine to glycine. The reaction converts tetrahydrofolate to 5,10-methylene-tetrahydrofolate. The enzyme is known in monomeric and heterotetrameric (,,gamma,delta) forms, this represents the monomeric form.

\ sarcosine oxidase activity ; GO:0008115 \N tetrahydrofolate metabolism ; GO:0046653 24737 IPR006282

This set of sequences comprise the strictly eukaryotic enzyme thiamine pyrophosphokinase, which converts thiamine (vitamin B1) into the enzyme cofactor thiamine pyrophosphate (TPP, coenzyme B1).

\ thiamin pyrophosphokinase activity ; GO:0004788 \N thiamin metabolism ; GO:0006772 24738 IPR006283

This family represents thiamine-monophosphate kinase, an enzyme that converts thiamine monophosphate into thiamine pyrophosphate (TPP, coenzyme B1), an enzyme cofactor. Thiamine monophosphate may be derived from de novo synthesis or from unphosphorylated thiamine, known as vitamin B1. Eukaryotes lack this enzyme, and add pyrophosphate from ATP to unphosphorylated thiamine in a single step.

\ thiamin-phosphate kinase activity ; GO:0009030 \N thiamin biosynthesis ; GO:0009228 24739 IPR006284

These are the glutathione synthetases found in Gram-negative bacteria. This gene does not appear to be present in genomes of Gram-positive bacteria. Glutathione synthetase has an ATP-binding domain in the COOH terminus and catalyzes the second step in the glutathione biosynthesis pathway: ATP + gamma-L-glutamyl-L-cysteine + glycine = ADP + phosphate + glutathione. Glutathione is a tripeptide that functions as a reductant in many cellular reactions.

\ glutathione synthase activity ; GO:0004363 \N glutathione biosynthesis ; GO:0006750 24740 IPR006285

This is a family of eukaryotic proteins found in animals, plants, and yeasts that includes Apg7p (YHR171W) from Saccharomyces cerevisiae and GSA7 from Pichia pastoris. Members are about 650 to 700 residues in length and include a central domain of about 150 residues shared with the ThiF/MoeB/HesA family of proteins. A low level of similarity to ubiquitin-activating enzyme E1 is described in a paper on peroxisome autophagy mediated by GSA7, and is the basis of the name ubiquitin activating enzyme E1-like protein. Members of the family appear to be involved in protein lipidation events analogous to ubiquitination and required for membrane fusion events during autophagy.

\ \N \N \N 24741 IPR006286

The member of this family from Pyrococcus horikoshii has been solved to 2 Angstrom resolution. It is an ATP-independent intracellular protease that crystallizes as a hexameric ring. Cys-101 is proposed as the active site residue in a catalytic triad with the adjacent His-102 and a Glu residue from an adjacent monomer. A member of this family from Bacillus subtilis, GSP18, has been shown to be expressed in response to several forms of stress. A role in the degradation of small peptides has been suggested. This family is contained in a larger one of the thiamine biosynthesis protein ThiJ and its homologs.

\ \N \N \N 24742 IPR006287

These sequences represent the DJ-1 clade of the so-called ThiJ/PfpI family of proteins. PfpI, represented by IPR006286 refers to a locus near thiD and thiM in E. coli, unlike the gene represented here. Current public annotation reflects ThiJ/ThiD bifunctional activity, apparently a property of ThiD and not of this locus.

\ \N \N \N 24734 IPR006279

These sequences represent the delta subunit of a family of known and putative heterotetrameric sarcosine oxidases. Five operons of such oxidases are found in Mesorhizobium loti and three in Agrobacterium tumefaciens, a high enough copy number to suggest that not all members share the same function. Sarcosine oxidase catalyzes the oxidative demethylation of sarcosine to glycine. The reaction converts tetrahydrofolate to 5,10-methylene-tetrahydrofolate. The enzyme is known in monomeric and heterotetrameric (,,gamma,delta) forms, this represents the heterotetrameric form.

\ sarcosine oxidase activity ; GO:0008115 \N tetrahydrofolate metabolism ; GO:0046653 24733 IPR006278

These sequences represent the subunit of a family of known and putative heterotetrameric sarcosine oxidases. Five operons of such oxidases are found in Mesorhizobium loti and three in Agrobacterium tumefaciens, a high enough copy number to suggest that not all members share the same function. The model is designated as subfamily rather than equivalog for this reason. Sarcosine oxidase catalyzes the oxidative demethylation of sarcosine to glycine. The reaction converts tetrahydrofolate to 5,10-methylene-tetrahydrofolate. The enzyme is known in monomeric and heterotetrameric (,,gamma,delta) forms, this represents the heterotetrameric form.

\ sarcosine oxidase activity ; GO:0008115 \N tetrahydrofolate metabolism ; GO:0046653 24730 IPR006275

Carbamoyl-phosphate synthase (CPSase) catalyzes the first committed step in pyrimidine, arginine, and urea biosynthesis. In general, it is a glutamine-dependent enzyme, EC: 6.3.5.5, termed CPSase II in eukaryotes. An exception is the mammalian mitochondrial urea-cycle form, CPSase I, in which the glutamine amidotransferase domain active site Cys on the small subunit has been lost, and the enzyme is ammonia-dependent. In both CPSase I and the closely related, glutamine-dependent CPSase III (allosterically activated by acetyl-glutamate) demonstrated in some other vertebrates, the small and large chain regions are fused in a single polypeptide chain. This group of sequences represent the large chain of glutamine-hydrolysing carbamoyl-phosphate synthases, or the corresponding regions of larger, multifunctional proteins, as found in all domains of life, and CPSase I forms are considered exceptions within the family. In several thermophilic species (Methanobacterium thermoautotrophicum, Methanococcus jannaschii, Aquifex aeolicus), the large subunit appears split, at different points, into two separate genes.

\ carbamoyl-phosphate synthase activity ; GO:0004086 \N nitrogen metabolism ; GO:0006807 24731 IPR006276

This group represents cobalamin-independent methionine synthase. A family of uncharacterized archaeal proteins having substantial homology to the C-terminal region of this family, are not included in this group, though they are contained in a larger family of vitamin-B12 independent methionine synthase.

\ \ 5-methyltetrahydropteroyltriglutamate-homocysteine S-methyltransferase activity ; GO:0003871\ \N \N methionine biosynthesis ; GO:0009086 24732 IPR006277

This set of sequences describes the subunit of a family of known and putative heterotetrameric sarcosine oxidases. Five operons of such oxidases are found in Mesorhizobium loti and three in Agrobacterium tumefaciens, a high enough copy number to suggest that not all members share the same function. Sarcosine oxidase catalyzes the oxidative demethylation of sarcosine to glycine. The reaction converts tetrahydrofolate to 5,10-methylene-tetrahydrofolate. The enzyme is known in monomeric and heterotetrameric (,,gamma,delta) forms, this represents the heterotetrameric form.

\ sarcosine oxidase activity ; GO:0008115 \N tetrahydrofolate metabolism ; GO:0046653 24724 IPR006269

These sequences describe 2-dehydro-3-deoxyphosphooctonate aldolase. Alternate names include 3-deoxy-d-manno-octulosonic acid 8-phosphate and KDO-8 phosphate synthetase. It catalyzes the aldol condensation of phosphoenolpyruvate with D-arabinose 5-phosphate. In Gram-negative bacteria, this is the first step in the biosynthesis of 3-deoxy-D-manno-octulosonate, part of the oligosaccharide core of lipopolysaccharide.

\ \ 2-dehydro-3-deoxyphosphooctonate aldolase activity ; GO:0008676\ \N cytoplasm ; GO:0005737 metabolism ; GO:0008152 24725 IPR006270

The sequences represented in this group are identified by a domain which consists of the N-terminal half of a family of Streptococcal proteins that contain a signal peptide and then up to five repeats of a region that includes a His-X-X-His-X-His (histidine triad) motif. Additional copies of the repeats are found in more poorly conserved regions. Members of this family from Streptococcus pneumoniae are suggested to cleave human C3, and the member PhpA has been shown in vaccine studies to be a protective antigen in mice [MEDLINE:21246685].

\ \N \N \N 24726 IPR006271

These sequences represent a variant form of the serine biosynthesis enzyme phosphoserine aminotransferase, as found in a small number of distantly related species, including Caulobacter crescentus, Mesorhizobium loti, and the archaeon Methanosarcina barkeri.

\ phosphoserine aminotransferase activity ; GO:0004646 \N biosynthesis ; GO:0009058 24727 IPR006272

These sequences represent a putative variant form of the serine biosynthesis enzyme phosphoserine aminotransferase, as found in Mycobacterium tuberculosis and related high-GC Gram-positive bacteria.

\ phosphoserine aminotransferase activity ; GO:0004646 \N biosynthesis ; GO:0009058 24728 IPR006273

This group of sequences are a distinct clade of orotate phosphoribosyltransferases. Members include the experimentally determined example from Thermus aquaticus and additional examples from Caulobacter crescentus, Helicobacter pylori, Mesorhizobium loti, and related species.

\ orotate phosphoribosyltransferase activity ; GO:0004588 \N pyrimidine base biosynthesis ; GO:0019856 24729 IPR006274

This group of sequences represent the whole of the small chain of the glutamine-dependent form (EC: 6.3.5.5) of carbamoyl phosphate synthase, CPSase II. The C-terminal domain has glutamine amidotransferase activity. Note that the sequence from the mammalian urea cycle form has lost the active site Cys, resulting in an ammonia-dependent form, CPSase I (EC: 6.3.4.16). CPSases of pyrimidine biosynthesis, arginine biosynthesis, and the urea cycle may be encoded by one or by several genes, depending on the species.

\ carbamoyl-phosphate synthase activity ; GO:0004086 \N nitrogen metabolism ; GO:0006807 24718 IPR006263

Cytidine deaminase is a homodimeric zinc metalloprotein found in Arabidopis and some Proteobacteria. A related, homotetrameric form with a much smaller subunit is found most bacteria and in animals, IPR006262. Both types may act on deoxycytidine as well as cytidine.

\ cytidine deaminase activity ; GO:0004126 \N cytidine metabolism ; GO:0046087 24719 IPR006264

These sequences represent 3-phosphoshikimate-1-carboxyvinyltransferase (aroA), which catalyzes the sixth of seven steps in the shikimate pathway of the biosynthesis of chorimate. Chorismate is last common precursor of all three aromatic amino acids.

\ \ 3-phosphoshikimate 1-carboxyvinyltransferase activity ; GO:0003866\ \N \N aromatic amino acid family biosynthesis, shikimate pathway ; GO:0016089 24720 IPR006265

This family of sequences represent 3-dehydroquinate synthase, the enzyme catalyzing the second of seven steps in the shikimate pathway of chorismate biosynthesis.\ Chorismate is the last common intermediate in the biosynthesis of all three\ aromatic amino acids.

\ \ \ 3-dehydroquinate synthase activity ; GO:0003856\ \N \N aromatic amino acid family biosynthesis, shikimate pathway ; GO:0016089 24721 IPR006266

This subfamily of the adenylate kinase superfamily contains examples of UMP-CMP kinase, as well as others proteins with unknown specificity, some currently designated adenylate kinase. All known\ members are eukaryotic.

\ \ phosphotransferase activity, phosphate group as acceptor ; GO:0016776 \N \N 24722 IPR006267

Members of this family are adenylate kinase, EC: 2.7.4.3. This clade is found only in eukaryotes and includes human adenylate kinase isozyme 1 (myokinase). Within the adenylate kinase superfamily, this set appears specifically closely related to a subfamily of eukaryotic UMP-CMP kinases (IPR006266.

\ adenylate kinase activity ; GO:0004017 cytoplasm ; GO:0005737 ATP metabolism ; GO:0046034 24723 IPR006268

These sequences are one of at least three types of phospho-2-dehydro-3-deoxyheptonate aldolase (DAHP synthase). This enzyme catalyzes the first of 7 steps in the biosynthesis of chorismate, that last common precursor of all three aromatic amino acids and of PABA, ubiquinone and menaquinone. Some members of this family, including an experimentally characterized member from Bacillus subtilis, are bifunctional, with a chorismate mutase domain N-terminal to this region. The member of this family from Synechocystis PCC 6803, CcmA, was shown to be essential for carboxysome formation. However, no other candidate for this enzyme is present in that species, chorismate biosynthesis does occur, other species having this protein lack carboxysomes but appear to make chorismate, and a requirement of CcmA for carboxysome formation does not prohibit a role in chorismate biosynthesis.

\ \N \N \N 24714 IPR006259

Adenylate kinase (EC: 2.7.4.3) converts ATP + AMP to ADP + ADP, that is, uses ATP as a phosphate donor for AMP. Most members of this family are known or believed to be adenylate kinase. However, some members accept other nucleotide triphosphates as donors, may be unable to use ATP, and may fail to complement adenylate kinase mutants. An example of a nucleoside-triphosphate--adenylate kinase (EC: 2.7.4.10) is Q9UIJ7, a GTP:AMP phosphotransferase.

\ phosphotransferase activity, phosphate group as acceptor ; GO:0016776 \N \N 24715 IPR006260

This sequences in this set all contain a conserved C-terminal domain which is characteristic of TonB and is homologs. TonB is an energy-transducer for TonB-dependent receptors of Gram-negative bacteria. Most members are designated as TonB or TonB-related proteins, but a few represent the paralogous TolA protein. Several bacteria have up to four TonB paralogs. In nearly every case, a proline-rich repetitive region is found N-terminal to this domain; these low-complexity regions are highly divergent and cannot readily be aligned. The region is suggested to span the periplasm.

\ \N \N \N 24716 IPR006261

DeoxyGTP triphosphohydrolase (dgt) releases inorganic triphosphate, an unusual reaction product, from GTP. Its activity has been called limited to the Enterobacteriaceae, although homologous sequences are detected elsewhere. This finding casts doubt on whether the activity is shared in other species. In several of these other species, the homologous gene is found in an apparent operon with dnaG, the DNA primase gene. The enzyme from E. coli was shown to bind coopertatively to single stranded DNA. The biological role of dgt is unknown [MEDLINE:98083057].

\ \N \N \N 24717 IPR006262

Cytidine deaminase is a small homotetrameric zinc metalloprotein. It is found in humans and most bacteria. A related homodimeric form, IPR006263 and in Arabidopsis. Both types may act on deoxycytidine as well as cytidine.

\ cytidine deaminase activity ; GO:0004126 \N cytidine metabolism ; GO:0046087 24713 IPR006258

These sequences represent dihydrolipoamide dehydrogenase, a flavoprotein that acts in a number of ways. It is the E3 component of dehydrogenase complexes for pyruvate, 2-oxoglutarate, 2-oxoisovalerate, and acetoin. It can also serve as the L protein of the glycine cleavage system. This family includes a few members known to have distinct functions (ferric leghemoglobin reductase and NADH:ferredoxin oxidoreductase) but that may be predicted by homology to act as dihydrolipoamide dehydrogenase as well. The motif GGXCXXXGCXP near the N-terminus contains a redox-active disulfide.

\ dihydrolipoamide dehydrogenase activity ; GO:0004148 \N glycolysis ; GO:0006096 24707 IPR006252

These sequences represent plant malate synthase and one of two bacterial forms, designated malate synthase A. This enzyme and isocitrate lyase are the two characteristic enzymes of the glyoxylate shunt. The shunt enables the cell to use acetyl-CoA to generate increased levels of TCA cycle intermediates for biosynthetic pathways such as gluconeogenesis.

\ malate synthase activity ; GO:0004474 \N glyoxylate cycle ; GO:0006097 24708 IPR006253

These sequnces represent the G isozyme of malate synthase. Isocitrate synthase and malate synthase form the glyoxylate shunt, which generates additional TCA cycle intermediates.

\ malate synthase activity ; GO:0004474 \N glyoxylate cycle ; GO:0006097 24709 IPR006254

Isocitrate lyase and malate synthase are the enzymes of the glyoxylate shunt, a pathway associated with the TCA cycle.

\ \ isocitrate lyase activity ; GO:0004451 \N glyoxylate cycle ; GO:0006097 24710 IPR006255

These sequences describe the TCA cycle 2-oxoglutarate system E2 component, dihydrolipoamide succinyltransferase. It is closely related to the pyruvate dehydrogenase E2 component, dihydrolipoamide acetyltransferase. Members include the mitochondrial and Gram-negative bacterial forms. Mycobacterial candidates are highly derived, differ in having and extra copy of the lipoyl-binding domain at the N-terminus and are generally excluded from this group of sequences as are all examples of dihydrolipoamide acetyltransferase.

\ dihydrolipoamide S-succinyltransferase activity ; GO:0004149 oxoglutarate dehydrogenase complex ; GO:0045252 tricarboxylic acid cycle ; GO:0006099 24711 IPR006256

This group of sequences are a subset of pyruvate dehydrogenase complex dihydrolipoamide acetyltransferase specifically close by both phylogenetic and percent identity (UPGMA) trees. Members contain two or three copies of the lipoyl-binding domain. Escherichia coli AceF is included in this set while mitochondrial and some other bacterial forms are excluded.

\ dihydrolipoamide S-acetyltransferase activity ; GO:0004742 pyruvate dehydrogenase complex ; GO:0045254 glycolysis ; GO:0006096 24712 IPR006257

This group of sequences represent one of several closely related clades of the dihydrolipoamide acetyltransferase subunit of the pyruvate dehydrogenase complex. It includes sequences from mitochondria and from and branches of the proteobacteria, as well as from some other bacteria, but not the Gram-positive bacteria.

\ dihydrolipoamide S-acetyltransferase activity ; GO:0004742 pyruvate dehydrogenase complex ; GO:0045254 glycolysis ; GO:0006096 24703 IPR006248

These sequences represent mitochondrial forms of the TCA cycle enzyme aconitate hydratase, also known as aconitase and citrate hydro-lyase.

\ aconitate hydratase activity ; GO:0003994 mitochondrion ; GO:0005739 tricarboxylic acid cycle ; GO:0006099 24704 IPR006249

These sequences represent one form of the TCA cycle enzyme aconitate hydratase, also known as aconitase and citrate hydro-lyase. It is found in bacteria, archaea, and in the eukaryotic cytosol. It has been shown to act also as an iron-responsive element binding protein in animals and may have the same role in other eukaryotes [MEDLINE:20283661].

\ \N \N \N 24705 IPR006250

These sequences represent a small family of proteins homologous and likely functionally equivalent to aconitase 1. Members are found, so far in the anaerobe Clostridium acetobutylicum, in the microaerophilic, early-branching bacterium Aquifex aeolicus, and in the halophilic archaeon Halobacterium sp. NRC-1. No member is experimentally characterized.

\ \N \N \N 24706 IPR006251

These sequences represent a subfamily of proteins consisting of aconitase, homoaconitase, 3-isopropylmalate dehydratase, and uncharacterized proteins. The majority of the members of this family have been designated as 3-isopropylmalate dehydratase large subunit (LeuC) in microbial genome annotation, but the only characterized member is Thermus thermophilus homoaconitase, an enzyme of a non-aspartate pathway of Lysine biosynthesis.

\ hydro-lyase activity ; GO:0016836 \N amino acid metabolism ; GO:0006520 24698 IPR006243

These sequences in this family represent PsaA. The core proteins of photosystem I are PsaA and PsaB, homologous integral membrane proteins that form a heterodimer. The heterodimer binds the electron-donating chlorophyll dimer P700, as well as chlorophyll, phylloquinone, and 4FE-4S electron acceptors.

\ \N \N \N 24699 IPR006244

These sequences in this family represent PsaB. The core proteins of photosystem I are PsaA and PsaB, homologous integral membrane proteins that form a heterodimer. The heterodimer binds the electron-donating chlorophyll dimer P700, as well as chlorophyll, phylloquinone, and 4FE-4S electron acceptors.

\ \N \N \N 24700 IPR006245

This family of sequences represents the allophycocyanin subunit.The and subunits of allophycocyanin form heterodimers, six of which associate into larger aggregates as part of the phycobilisome, a light-harvesting complex of phycobiliproteins and linker proteins. Other, homologous phyobiliproteins include allophycocyanin chain and the phycocyanin and phycoerythrin and chains.

\ \N \N \N 24701 IPR006246

These sequences in this family represent the phycocyanin subunit. Other, homologous phyobiliproteins of the phycobilisome include phycocyanin chain and the allophycocyanin and phycoerythrin and chains. Not included are the closely related phycoerythrocyanin subunit sequences.

\ \N \N \N 24702 IPR006247

These sequences describe the phycocyanin subunit. Other, homologous phycobiliproteins of the phycobilisome include phycocyanin chain and the allophycocyanin and phycoerythrin and chains. Not included are the closely related phycoerythrocyanin subunit sequences.

\ \N \N \N 24693 IPR006238

This group of sequences represent cystathionine -lyase (alternate name: -cystathionase), one of several pyridoxal-dependent enzymes of cysteine, methionine, and homocysteine metabolism. This enzyme is involved in the biosynthesis of Met from Cys.

\ \N \N \N 24694 IPR006239

Sulfate is incorporated into 3-phosphoadenylylsulfate, PAPS, for utilization in pathways such as methionine biosynthesis. Transfer of sulfate from PAPS to an acceptor leaves adenosine 3'-5'-bisphosphate, APS. In plants these sequences represent a form of the enzyme, 3'(2'),5'-bisphosphate nucleotidase, which removes the 3'-phosphate from APS to regenerate AMP and help drive the cycle. Sensitivity of this essential enzyme to sodium and other metal ions results is responsible for characterization of this enzyme as a salt tolerance protein [MEDLINE:99222627]. Some members of this family are active also as inositol 1-monophosphatase.

\ \ 3'(2'),5'-bisphosphate nucleotidase activity ; GO:0008441\ \N \N sulfur metabolism ; GO:0006790 24695 IPR006240

\ \N \N \N 24696 IPR006241

These sequences describe the subunit of cytochrome b559 which is about 40 residues in length. It is homologous to the N-terminal half of the subunit, a protein of about 83 residues. Cytochrome b559 is associated with photosystem II.

\ \N \N \N 24697 IPR006242

The gene modD for a member of this family is found with molybdenum transport genes modABC in Rhodobacter capsulatus. However, disruption of modD causes only a 4-fold (rather than 500-fold for modA, modB, modC) change in the external molybdenum concentration required to suppress an alternative nitrogenase. ModD proteins are highly similar to nicotinate-nucleotide pyrophosphorylase (also called quinolinate phosphoribosyltransferase). Their function is unknown.

\ \N \N \N 24688 IPR006233

Cystathionine -lyase (alternate name: -cystathionase) is one of several pyridoxal-dependent enzymes of cysteine, methionine, and homocysteine metabolism. This enzyme is involved in the biosynthesis of Met from Cys.

\ cystathionine beta-lyase activity ; GO:0004121 cytoplasm ; GO:0005737 amino acid metabolism ; GO:0006520 24689 IPR006234

These sequences represent O-succinylhomoserine sulfhydrylase, one of several related pyridoxal phosphate-dependent enzymes of cysteine and methionine metabolism. This enzyme is part of an alternative pathway of homocysteine biosynthesis, a step in methionine biosynthesis.

\ other carbon-oxygen lyase activity ; GO:0016839 \N methionine biosynthesis ; GO:0009086 24690 IPR006235

This family of sequences is a distinct clade of the Cys/Met metabolism pyridoxal phosphate-dependent enzyme superfamily. Members include examples of OAH/OAS sulfhydrylase, an enzyme with activity both as O-acetylhomoserine (OAH) sulfhydrylase (EC: 4.2.99.10) and O-acetylserine (OAS) sulphydrylase (EC: 4.2.99.8). An alternate name for OAH sulfhydrylase is homocysteine synthase.

\ other carbon-oxygen lyase activity ; GO:0016839 \N amino acid metabolism ; GO:0006520 24691 IPR006236

This group of sequences represent the long form of D-3-phosphoglycerate dehydrogenase, they include the serA gene of one pathway of serine biosynthesis. Shorter forms not in this group include SerA from Escherichia coli.

\ phosphoglycerate dehydrogenase activity ; GO:0004617 \N serine biosynthesis ; GO:0006564 24692 IPR006237

This family of sequences is a methionine gamma-lyase subset of a family of PLP-dependent trans-sulfuration enzymes. The member from the parasite Trichomonas vaginalis is described as catalyzing gamma- and - eliminations and gamma-replacement reactions on methionine, cysteine, and some derivatives. Likewise, the enzyme from Pseudomonas degrades cysteine as well as methionine.

\ methionine gamma-lyase activity ; GO:0018826 \N amino acid metabolism ; GO:0006520 24686 IPR006231

The membrane-associated enzyme, malate:quinone-oxidoreductase, is an alternative to the better-known NAD-dependent malate dehydrogenase as part of the TCA cycle. The reduction of a quinone rather than NAD+ makes the reaction essentially irreversible in the direction of malate oxidation to oxaloacetate. Both forms of malate dehydrogenase are active in E. coli; disruption of this form causes less phenotypic change. In some bacteria, this form is the only or the more important malate dehydrogenase [MEDLINE:20545431].

\ malate dehydrogenase (acceptor) activity ; GO:0008924 \N tricarboxylic acid cycle ; GO:0006099 24687 IPR006232

Glycoside hydrolase family 32 comprises enzymes with several known activities; invertase (EC: 3.2.1.26); inulinase; levanase (EC: 3.2.1.7); exo-inulinase (EC: 3.2.1.7); sucrose:sucrose 1-fructosyltransferase (EC: 3.2.1.7); and fructan:fructan 1-fructosyltransferase (EC: 2.4.1.100). This subfamily represents sucrose-6-phosphate hydrolase.

\ \ beta-fructofuranosidase activity ; GO:0004564 cytoplasm ; GO:0005737 carbohydrate metabolism ; GO:0005975 24680 IPR006225

This is the RluD subfamily of pseudouridine synthases. In Escherichia coli, RluD (SfhB) modifies uridine to pseudouridine at 23S RNA.

\ pseudouridylate synthase activity ; GO:0004730 \N \N 24681 IPR006226

This is a family of hypothetical proteins with no known function that is mainly restricted to Mycobacterium tuberculosis. No similar sequences have been found outside of Mycobacteria.

\ \N \N \N 24682 IPR006227

This family includes a number of hydrogenase related proteins, belonging to peptidase family M52. They are possibly involved in the processing of the large subunit of hydrogenase. The frhD branch has been shown experimentally to have protease activity and be required for hydrogenase maturation [MEDLINE:91002562].

\ \N \N \N 24683 IPR006228

This represents the N-terminal region of polycystin, a member of the Polycystin Cation Channel (PCC) family (TC:1.A.5). Polycystin is a huge protein of 4303aa. Its repeated leucine-rich (LRR) segment is found in many proteins. It contains 16 polycystic kidney disease (PKD) domains, one LDL-receptor class A domain, one C-type lectin family domain, and 16-18 putative transmembrane regions in positions between residues 2200 and 4100. Polycystin-L has been shown to be a cation (Na⁺, K⁺ and Ca²⁺) channel that is activated by Ca²⁺. Two members of the PCC family (polycystin 1 and 2) are mutated in autosomal dominant polycystic kidney disease, and polycystin-L is deleted in mice with renal and retinal defects.

\ \N \N \N 24684 IPR006229

These sequences represent the modB permease subunit of the molybdate-transporting ABC-type transport system. This system has been characterized in Escherichia coli [MEDLINE:95394784], Staphylococcus carnosus [MEDLINE:99345912], Rhodobacter capsulatus [MEDLINE:93259949] and Azotobacter vinlandii [MEDLINE:95394849].

\ \ \N \N \N 24685 IPR006230

This small family includes, so far, an uncharacterized protein from Escherichia coli O157:H7 and GlmL from Clostridium tetanomorphum and Clostridium cochlearium. GlmL is located between the genes for the two subunits, epsilon (GlmE) and sigma (GlmS), of the coenzyme-B12-dependent glutamate mutase (methylaspartate mutase), the first enzyme in a pathway of glutamate fermentation. Members shows significant sequence similarity to the hydantoinase branch of the hydantoinase/oxoprolinase family (IPR002821.

\ \N \N \N 24674 IPR006219

Members of the 3-deoxy-D-arabino-heptulosonate 7-phosphate (DAHP) synthetase family EC: 4.1.2.15 catalyse the first step in aromatic amino acid biosynthesis from chorismate. Class I includes bacterial and yeast enzymes; class II includes higher plants and various microorganisms (see IPR002480.

The first step in the common pathway leading to the biosynthesis of aromatic compounds is the stereospecific condensation of phosphoenolpyruvate (PEP) and D-erythrose-4-phosphate (E4P) giving rise to 3-deoxy-D-arabino-heptulosonate-7-phosphate (DAHP). This reaction is catalyzed by DAHP synthase, a metal-activated enzyme, which in microorganisms is the target for negative-feedback regulation by pathway intermediates or by end products. In Escherichia coli there are three DAHP synthetase isoforms, each specifically inhibited by one of the three aromatic amino acids. The crystal structure of the phenylalanine-regulated form of DAHP synthetase shows the fold as is a (/)8 barrel with several additional strands and helices [MEDLINE:99354419].

\ \ \ 2-dehydro-3-deoxyphosphoheptonate aldolase activity ; GO:0003849\ \N \N aromatic amino acid family biosynthesis ; GO:0009073 24675 IPR006220 Anthranilate synthase (ASase) is a tetrameric protein comprising two copies each of components I and II [MEDLINE:89255120]. The protein catalyses the first step in \ the tryptophan biosynthetic pathway, namely the conversion of chorismate \ and an ammonium ion to anthranilate. Component I obtains this ion from \ ammonia, whereas component II obtains the ion from glutamine using the \ glutamine amidotransferase (GATase) activity [MEDLINE:82216842].

In some bacteria, such as\ E.coli, component II can be much larger than in other organisms, due to the\ presence of phosphoribosyl-anthranilate transferase (PRTase) activity. \ This is the second step in tryptophan biosynthesis and results in the \ addition of 5-phosphoribosyl-1-pyrophosphate to anthranilate to create \ N-5'-phosphoribosyl-anthranilate. Some studies have suggested that the \ larger component II could have arisen by gene fusion, a hypothesis \ supported by the fact that the two activities are found in discrete domains \ that are physically separated in the 3D model.

\ \ \ \N \N \N 24676 IPR006221

This entry presents the glutamine amidotransferase domain or peptide of the tryptophan-biosynthetic pathway enzyme anthranilate synthase or of the folate biosynthetic pathway enzyme para-aminobenzoate synthase. In at least one case, a single polypeptide from Bacillus subtilis was shown to have both functions.

\ anthranilate synthase activity ; GO:0004049 \N metabolism ; GO:0008152 24677 IPR006222 This is a family of glycine cleavage T-proteins, part of the glycine cleavage multienzyme complex (GCV) found in bacteria and the mitochondria\ of eukaryotes. GCV catalyses the catabolism of glycine in eukaryotes.\ The T-protein is an aminomethyl transferase EC: 2.1.2.10\ that catalyses the following reaction:\

\
(6S)-tetrahydrofolate + S-aminomethyldihydrolipoylprotein = (6R)-5,10-methylenetetrahydrofolate + NH₃ + dihydrolipoylprotein\

\ \ \N \N \N 24678 IPR006223

This is a subfamily of glycine cleavage T proteins, part of the glycine cleavage multienzyme complex (GCV) found in bacteria and the mitochondria\ of eukaryotes. GCV catalyses the catabolism of glycine in eukaryotes.\ The T-protein is an aminomethyl transferase EC: 2.1.2.10\ that catalyses the following reaction:\

\
(6S)-tetrahydrofolate + S-aminomethyldihydrolipoylprotein = (6R)-5,10-methylenetetrahydrofolate + NH₃ + dihydrolipoylprotein\

\ \ aminomethyltransferase activity ; GO:0004047 \N glycine catabolism ; GO:0006546 24679 IPR006224 Pseudouridine synthases (EC: 4.2.1.70) are responsible for synthesis of pseudouridine from uracil in 23S rRNA. The following proteins, which seem to belong to the Rlu family of pseudouridine\ synthases [MEDLINE:98325071] have been shown to share regions of similarities:\ E. coli and Haemophilus influenzae ribosomal large subunit\ pseudouridine synthase A (gene rluA) and C (gene rluC); E. coli protein and homologs in other bacteria large subunit pseudouridine synthase D (gene rluD); yeast DRAP deaminase (gene RIB2); E. coli hypothetical protein yqcB and HI1435, the corresponding Haemophilus influenzae protein; Haemophilus influenzae hypothetical protein HI0042; Aquifex aeolicus hypothetical protein AQ_1758;\ Bacillus subtilis hypothetical proteins yhcT, yjbO and ylyB; Helicobacter pylori hypothetical proteins HP0347, HP0745 and HP0956; Mycoplasma genitalium hypothetical proteins MG209 and MG370; Synechocystis strain PCC 6803 hypothetical proteins slr1592 and slr1629; and yeast hypothetical proteins YDL036c and YGR169c.\ \ pseudouridylate synthase activity ; GO:0004730 \N \N 24671 IPR006216 Cytochrome b559 is an essential component of photosystem II complex from oxygenic photosynthetic organisms [MEDLINE:91266888]. It is an integral thylakoid membrane\ protein composed of two subunits,

(gene psbE) (IPR006217) and

(gene psbF), each\ of which contains a histidine residue located in a transmembrane region. The\ two histidines coordinate the heme iron of cytochrome b559.\ \ \N photosystem II reaction center ; GO:0009539 electron transport ; GO:0006118 24672 IPR006217

This is subunit of cytochrome b559. Cytochrome b559 is an essential component of photosystem II complex from oxygenic photosynthetic organisms [MEDLINE:91266888]. It is an integral thylakoid membrane\ protein composed of two subunits, (gene psbE) and (gene psbF), each\ of which contains a histidine residue located in a transmembrane region. The\ two histidines coordinate the heme iron of cytochrome b559.

\ \ \N photosystem II reaction center ; GO:0009539 electron transport ; GO:0006118 24673 IPR006218 Members of the 3-deoxy-D-arabino-heptulosonate 7-phosphate (DAHP) synthetase family EC: 4.1.2.15 catalyse the first step in aromatic amino acid biosynthesis from chorismate. Class I includes bacterial and yeast enzymes; class II includes higher plants and various microorganisms (see IPR002480.

\ \ aldolase activity ; GO:0016228 \N biosynthesis ; GO:0009058 24667 IPR006212

The furin-like cysteine rich region has been found in a variety of proteins from eukaryotes that are involved in the mechanism of signal transduction by receptor tyrosine kinases, which involves receptor aggregation [MEDLINE:92038942].

\ \N \N \N 24668 IPR006213

Bax inhibitor-1 (BI-1) (gene TEGT) [MEDLINE:96015061] is a suppressor of apoptosis that interacts with BCL2 and BCL-X. These are proteins of about 25 kDa which seem to contain seven transmembrane domains.

\ \ \N \N \N 24669 IPR006214

This family of proteins of unknown function contains a subset of Bax inhibitor-1 proteins.

\ \N \N \N 24670 IPR006215

Family 27 (CAZY:GH_27) encompasses -galactosidases and -N-\ acetylgalactosaminidases in which two conserved Asp residues may be involved in the catalytic\ mechanism. \ Alpha-galactosidase (melibiase) catalyses the hydrolysis of melibiose into\ galactose and glucose [MEDLINE:95242831]. In man, deficiency in the enzyme results in\ Fabry's disease (X-linked sphingolipidosis). Alpha-N-acetylgalactosaminidase\ catalyses the hydrolysis of terminal non-reducing N-acetyl-D-galactosamine\ residues in N-acetyl--D-galactosaminides [MEDLINE:91072392]. Deficiency in this enzyme \ results in Schindler and Kanzaki diseases.

This group identifies specifically melibiase.

\ \ alpha-galactosidase activity ; GO:0004557 \N carbohydrate metabolism ; GO:0005975 24663 IPR006208

This domain is found at the C-terminal of glycoprotein hormones and various extracellular proteins. It is believed to be involved in disulfide-linked dimerisation.

\ \N \N \N 24664 IPR006209 A sequence of about thirty to forty amino-acid residues long found in the sequence of epidermal growth factor (EGF)has been shown PUB00001077, PUB00001077, [MEDLINE:84117505], [MEDLINE:91145344], [MEDLINE:85063790], PUB00004964 to be present, in a more\ or less conserved form, in a large number of other, mostly animal proteins. The list of proteins currently known to\ contain one or more copies of an EGF-like pattern is large and varied. The functional significance of EGF domains in\ what appear to be unrelated proteins is not yet clear. However, a common feature is that these repeats are found in\ the extracellular domain of membrane-bound proteins or in proteins known to be secreted (exception: prostaglandin\ G/H synthase). The EGF domain includes six cysteine residues which have been shown (in EGF) to be involved in disulfide\ bonds. The main structure is a two-stranded

-sheet followed by a loop to a C-terminal short two-stranded sheet.\ Subdomains between the conserved cysteines vary in length.\ \ \N \N \N 24665 IPR006210

Epidermal growth factors and transforming growth factors belong to a general class of proteins that share a repeat pattern involving a number of conserved Cys residues. Growth \ factors are involved in cell recognition and division [MEDLINE:90321281]. The repeating \ pattern, especially of cysteines (the so-called EGF repeat), is thought to be important \ to the 3D structure of the proteins, and hence its recognition by receptors and other \ molecules. The type 1 EGF signature includes six conserved cysteines believed to be \ involved in disulphide bond formation. The EGF motif is found frequently in nature, \ particularly in extracellular proteins.

\ \ \N \N \N 24666 IPR006211 The furin-like cysteine rich region has been found in a variety of proteins from eukaryotes that are involved in the mechanism of signal transduction by receptor tyrosine kinases, which involves receptor aggregation [MEDLINE:92038942].\ ATP binding activity ; GO:0005524 membrane ; GO:0016020 transmembrane receptor protein tyrosine kinase signaling pathway ; GO:0007169 24659 IPR006204

The galacto- (EC: 2.7.1.6), homoserine (EC: 2.7.1.39), mevalonate (EC: 2.7.1.36) and phosphomevalonate (EC: 2.7.4.2) kinases contain, in their N-terminal section, a conserved Gly/Ser-rich region which is probably involved in the binding of ATP [MEDLINE:91117228], [MEDLINE:20031459]. This group of kinases has been called 'GHMP' (from the first letter of their substrates).

\ \N \N \N 24660 IPR006205

Mevalonate kinase (EC: 2.7.1.36) is well-characterized among the Eukaryotes, where it plays a role in the synthesis of isopentanyl pyrophosphate, a common intermediate for a number of pathways including cholesterol biosynthesis. It is also involved in mevalonate catabolism. Close homologs are found in the Archaea. A single candidate bacterial example is found in the Lyme disease spirochete Borrelia burgdorferi, but is not necessarily the same biosynthetic enzyme.

\ ATP binding activity ; GO:0005524 cytoplasm ; GO:0005737 biosynthesis ; GO:0009058 24661 IPR006206

Mevalonate kinase (EC: 2.7.1.36) and galactokinases (EC: 2.7.1.6) belong to this family. Mevalonate kinase may be a regulatory site in the cholesterol biosynthetic pathway. It is also involved in mevalonate catabolism. Galactokinase takes part in the first reaction of galactose metabolism by converting galactose to galactose-1-phosphate.

\ phosphotransferase activity, alcohol group as acceptor ; GO:0016773 cytoplasm ; GO:0005737 metabolism ; GO:0008152 24662 IPR006207 Four recent crystal structures of growth factors--nerve growth factor, transforming growth factor-

, platelet-derived growth factor, and human chorionic gonadotropin--from four separate superfamilies revealed that these proteins are structurally related and share a common overall topology [MEDLINE:93258805]. These proteins have very little sequence homology, but they all have an unusual arrangement of six cysteines linked to form a "cystine-knot" conformation. The active forms of these proteins are dimers, either homo- or heterodimers [MEDLINE:95392154]. Because of their shape, there appears to be an intrinsic requirement for the cystine-knot growth factors to form dimers. This extra level of organization increases the variety of structures built around this simple structural motif [MEDLINE:96082952].\ \N \N \N 24657 IPR006202

\ \

This entry presents the extracellular ligand binding domain of these ion channels. This domain forms a pentameric arrangement in the known structure.

\ \ extracellular ligand-gated ion channel activity ; GO:0005230 membrane ; GO:0016020 transport ; GO:0006810 24658 IPR006203 The galacto- (EC: 2.7.1.6), homoserine (EC: 2.7.1.39), mevalonate (EC: 2.7.1.36) and phosphomevalonate (EC: 2.7.4.2) kinases contain, in their N-terminal section, a conserved Gly/Ser-rich region which is probably involved in the binding of ATP [MEDLINE:91117228], [MEDLINE:20031459]. This group of kinases has been called 'GHMP' (from the first letter of their substrates).\ ATP binding activity ; GO:0005524 \N \N 24656 IPR006201

\ \

This InterPro entry represents the GABA-A, nicotinic, glycine, and 5HT3 receptors.

\ \ \ extracellular ligand-gated ion channel activity ; GO:0005230 membrane ; GO:0016020 transport ; GO:0006810 24654 IPR006199

Serine proteases are ubiquitous, being found in viruses, bacteria and eukaryotes and include proteins with exopeptidase, endopeptidase, oligopeptidase and omega-peptidase activity. Over 20 families (denoted S1 - S27) of serine protease have been identified, these being grouped into 6 clans (SA, SB, SC, SE, SF and SG) on the basis of structural similarity and other functional evidence [MEDLINE:95147689]. Structures are known for at least four of the clans (SA, SB, SC and SE): these appear to be totally unrelated, suggesting at least four evolutionary origins of serine peptidases.

There are, however, similarities in the reaction mechanisms of several peptidases. Chymotrypsin, subtilisin and carboxypeptidase C clans have a catalytic triad of serine, aspartate and histidine in common: serine acts as a nucleophile, aspartate as an electrophile, and histidine as a base. The geometric orientations of the catalytic residues are similar between families, despite different protein folds [MEDLINE:95147689]. The linear arrangements of the catalytic residues commonly reflect clan relationships. For example the catalytic triad in the chymotrypsin clan (SA) is ordered HDS, DHS in the subtilisin clan (SB) and SDH in the carboxypeptidase clan (SC) [MEDLINE:95147689], [MEDLINE:93176119].

This is the DNA binding domain of the LexA SOS regulon\ repressor which prevents expression of DNA repair proteins in bacteria.\ The aligned region contains a variant form of the helix-turn-helix DNA\ binding motif [MEDLINE:94357165].\ This domain usually at the N terminus is found associated with IPR006198.

\ \ repressor lexA activity ; GO:0008992 \N proteolysis and peptidolysis ; GO:0006508 24655 IPR006200

This entry is a subfamily of the peptidase S24 family that consists of LexA proteins.The lexA protein represses around 20 genes of the cellular SOS response to\ DNA damage in Escherichia coli\ \ \ \ [MEDLINE:95147689]. Damage to cellular DNA results in inactivation of\ lexA, allowing transcription of the genes involved in DNA repair [MEDLINE:95147689]. In\ E.coli, this derepression of the DNA repair system is affected by the recA\ protein, which binds to lexA upon interaction with single-stranded\ DNA [MEDLINE:95147689]. This results in inactivation of lexA by proteolytic cleavage,\ disrupting the DNA-binding capabilities of lexA [MEDLINE:95147689]. Although initially\ thought to be mediated by recA, it has been found that the cleavage of lexA\ is an autolytic event catalysed by the presence of recA [MEDLINE:95147689].

The lexA protein consists of around 200 amino acids, of which the first 90\ form the DNA-binding domain [MEDLINE:95147689]. The remaining residues form the protease\ domain, Ser-119 and Lys-156 being the active residues.

\ \ repressor lexA activity ; GO:0008992 \N proteolysis and peptidolysis ; GO:0006508 24651 IPR006196

The S1 domain of around 70 amino acids, originally identified in ribosomal protein S1, is found in a large number of RNA-associated proteins. It has been\ shown that S1 proteins bind RNA through their S1 domains with some degree of\ sequence specificity. This type of S1 domain is found in translation initiation factor 1.

\ The solution structure of one S1 RNA-binding domain from Escherichia coli\ polynucleotide phosphorylase has been determined [MEDLINE:97160844]. It displays some\ similarity with the cold shock domain (CSD) (IPR002059). Both the S1\ and the CSD domain consist of an antiparallel barrel of the same topology\ with 5 strands. This fold is also shared by many other proteins of\ unrelated function and is known as the OB fold. However, the S1 and CSD\ fold can be distinguished from the other OB folds by the presence of a short\ 3(10) helix at the end of strand 3. This unique feature is likely to form a\ part of the DNA/RNA-binding site.

\ \ \N \N \N 24652 IPR006197

The lexA protein represses around 20 genes of the cellular SOS response to\ DNA damage in E.coli\ \ \ \ [MEDLINE:95147689]. Damage to cellular DNA results in inactivation of\ lexA, allowing transcription of the genes involved in DNA repair [MEDLINE:95147689]. In\ E.coli, this derepression of the DNA repair system is effected by the recA\ protein, which binds to lexA upon interaction with single-stranded\ DNA [MEDLINE:95147689]. This results in inactivation of lexA by proteolytic cleavage,\ disrupting the DNA-binding capabilities of lexA [MEDLINE:95147689]. Although initially\ thought to be mediated by recA, it has been found that the cleavage of lexA\ is an autolytic event catalysed by the presence of recA [MEDLINE:95147689].

\ \

\ \ serine-type peptidase activity ; GO:0008236 \N proteolysis and peptidolysis ; GO:0006508 24653 IPR006198

The lexA protein consists of around 200 amino acids, of which the first 90\ form the DNA-binding domain IPR006199\ \ \ \ [MEDLINE:95147689]. The remaining residues form the protease\ domain, Ser-119 and Lys-156 being the active residues.

This entry presents the C-terminal domain of LexA repressor and other proteins of S24 peptidase family.

\ \ serine-type peptidase activity ; GO:0008236 \N proteolysis and peptidolysis ; GO:0006508 24650 IPR006195

The aminoacyl-tRNA synthetases (EC: 6.1.1.-) catalyse the attachment of an amino acid to its cognate transfer RNA molecule in a highly specific two-step reaction. These proteins differ widely in size and oligomeric state, and have limited sequence homology [MEDLINE:90370122]. The 20 aminoacyl-tRNA synthetases are divided into two classes, I and II. Class I aminoacyl-tRNA synthetases contain a characteristic Rossman fold and are mostly monomeric, while class II aminoacyl-tRNA synthetases share an anti-parallel -sheet formation, flanked by -helices [MEDLINE:93372080], and are mostly dimeric or multimeric. In reactions catalysed by the class I aminoacyl-tRNA synthetases,the aminoacyl group is coupled to the 2'-hydroxyl of the tRNA, while, in\ class II reactions, the 3'-hydroxyl site is preferred. The synthetases specific for arginine, cysteine, glutamic acid, glutamine, isoleucine, leucine, methionine, tyrosine, tryptophan and valine belong to class I synthetases.\ The synthetases specific for alanine, asparagine, aspartic acid, glycine, histidine, lysine, phenylalanine, proline, serine, and threonine belong to class-II synthetases [Bairoch A. List of aminoacyl-tRNA synthetases http://ca.expasy.org/cgi-bin/lists?aatrnasy.txt].

\ \

The 10 class I synthetases are considered to have in common the catalytic domain structure based on the Rossmann fold, which is totally different from the class II catalytic domain structure. The class I synthetases are further divided into three subclasses, a, b and c, according to sequence homology. No conserved structural features for tRNA recognition by class I synthetases have been established.

\ \

Class-II tRNA synthetases do not share a high degree of similarity, however at least three conserved regions are present [MEDLINE:94099781], [MEDLINE:91272282], [MEDLINE:91305088].

\ \

This entry recognizes all\ class-II enzymes except for heterodimeric glycyl-tRNA synthetases IPR006194 and alanyl-\ tRNA synthetases IPR006194/>.

\ \ ATP binding activity ; GO:0005524 \N amino acid activation ; GO:0006418 24646 IPR006190

Antifreeze proteins (AFPs) are defined by their ability to bind ice and prevent it from growing. In this way they function in both freeze-resistance\ and freeze-tolerance strategies of organisms that live at sub-zero\ temperatures and require protection from ice growth. In fish, five AFP types\ have been described that are remarkably diverse in their 3D structures. They\ have completely dissimilar folds and no sequence homology. Type III AFPs found\ in eel pounts are 65-residue proteins with a compact globular fold formed from\ short strands, which presents a flat ice binding surface. These proteins\ are homologous to the C-terminal region of mammalian and prokaryotic sialic\ acid synthase (SAS; gene neuB), which has been called AFP-like domain [MEDLINE:22162998].\ The similarity is greatest in the protein core and the flat ice-binding\ region. SAS is involved in the condensation of phosphoenolpyruvate with N-\ acetylmannosamine derivatives to generate N-acetylneuraminic acid, an\ intermediate used for the sialylation of glycoconjugates. The function of the\ AFP-like domain in SAS is not known, but it has been proposed that it could be\ involved in sugar binding.

\ \ \N \N \N 24647 IPR006191

A conserved domain of about 70 amino acid residues has been found in a number of proteins that transport or detoxify heavy metals. This domain\ contains two conserved cysteines that could be involved in the binding of\ these metals. The domain has been termed Heavy-Metal-Associated (HMA).

\ Structure solution of the fourth HMA domain of the Menkes copper-transporting\ ATPase shows a well defined structure comprising a four-stranded antiparallel -sheet and two helices packed in an - sandwich fold [MEDLINE:98100082]. This fold is common to other domains and is classified\ as "ferredoxin-like".

\ \ \N \N \N 24648 IPR006193

\ \

Class-II tRNA synthetases do not share a high degree of similarity, however at least three conserved regions are present [MEDLINE:94099781], [MEDLINE:91272282], [MEDLINE:91305088].

\ \

This is a specific profile for Alanyl-transfer RNA synthetase.

\ \ ATP binding activity ; GO:0005524 \N alanyl-tRNA aminoacylation ; GO:0006419 24649 IPR006194

\ \

Class-II tRNA synthetases do not share a high degree of similarity, however at least three conserved regions are present [MEDLINE:94099781], [MEDLINE:91272282], [MEDLINE:91305088].

\ \

This is a specific profile for heterodimeric glycyl-transfer RNA synthetase.

\ \ ATP binding activity ; GO:0005524 \N glycyl-tRNA aminoacylation ; GO:0006426 24644 IPR006188

\ \ \

\ \

\ \ \ structural molecule activity ; GO:0005198 tight junction ; GO:0005923 \N 24645 IPR006189

The CHASE domain is an extracellular domain of 200-230 amino acids, which is found in transmembrane receptors from bacteria, lower eukaryotes and plants.\ It has been named CHASE (Cyclases/Histidine kinases Associated Sensory\ Extracellular) because of its presence in diverse receptor-like proteins with\ histidine kinase and nucleotide cyclase domains. The CHASE domain always\ occurs N-terminally in extracellular or periplasmic locations, followed by an\ intracellular tail housing diverse enzymatic signaling domains such as\ histidine kinase (IPR005467), adenyl cyclase, GGDEF-type nucleotide\ cyclase and EAL-type phosphodiesterase domains, as well as non-enzymatic\ domains such PAS (IPR005467/>), GAF (IPR003018), phosphohistidine and response\ regulatory domains. The CHASE domain is predicted to bind\ diverse low molecular weight ligands, such as the cytokinin-like adenine\ derivatives or peptides, and mediate signal transduction through the\ respective receptors [MEDLINE:21474767].

\ The CHASE domain has a predicted + fold, with two extended helices on both boundaries and two central helices separated by sheets. The termini are less conserved compared with the central part of the\ domain, which shows strongly conserved motifs.

\ \ \N \N \N 24643 IPR006187

\ \ \

\ \

\ \ structural molecule activity ; GO:0005198 tight junction ; GO:0005923 \N 24642 IPR006186

Protein phosphorylation plays a central role in the regulation of cell functions [MEDLINE:88107662], causing the activation or inhibition of many enzymes involved in various biochemical pathways [MEDLINE:91092406]. Kinases and phosphatases are the enzymes responsible for this, and may themselves \ be subject to control through the action of hormones and growth factors [MEDLINE:88107662]. Serine/threonine\ (S/T) phosphatases (EC: 3.1.3.16) catalyse the dephosphorylation of phosphoserine and phosphothreonine residues. In \ mammalian tissues four different types of PP have been identified and are known as PP1, PP2A, PP2B and \ PP2C. Except for PP2C, these enzymes are evolutionary related. The catalytic regions of the proteins are\ well conserved and have a slow mutation rate, suggesting that major changes in these regions are highly \ detrimental [MEDLINE:88107662].

Protein phosphatase-1 (PP1) and protein phosphatase-2A (PP2A) have a broad \ specificity and there are two closely related isoforms of each, and . PP2A is a trimeric enzyme \ that consists of a core composed of a catalytic subunit associated with a 65 kDa regulatory subunit and a \ third variable subunit. Protein phosphatase-2B (PP2B or calcineurin), a calcium-dependent enzyme whose \ activity is stimulated by calmodulin, is composed of two subunits the catalytic A-subunit and the \ calcium-binding B-subunit. The specificity of PP2B is restricted. Other serine/threonine specific protein \ phosphatases that have been characterized include mammalian phosphatase-X (PP-X), and Drosophila \ phosphatase-V (PP-V), which are closely related but yet distinct from PP2A; yeast phosphatase PPH3, which \ is similar to PP2A, but with different enzymatic properties; and Drosophila phosphatase-Y (PP-Y), and yeast\ phosphatases Z1 and Z2 which are closely related but yet distinct from PP1.

\ \ hydrolase activity ; GO:0016787 \N \N 24641 IPR006184

6-Phosphogluconate dehydrogenase (EC: 1.1.1.44) (6PGD) is an oxidative carboxylase that catalyses the decarboxylating reduction of 6-phosphogluconate into ribulose 5-phosphate in the presence of NADP. This reaction is a component of the hexose mono-phosphate shunt and pentose phosphate pathways (PPP) [MEDLINE:90299831], [MEDLINE:84057760]. Prokaryotic and eukaryotic 6PGD are proteins of about 470 amino acids whose sequences are highly conserved [MEDLINE:92065803]. The protein is a homodimer in which the monomers act independently [MEDLINE:84057760]: each contains a large, mainly -helical domain and a smaller -- domain, containing a mixed parallel and anti-parallel 6-stranded sheet [MEDLINE:84057760]. NADP is bound in a cleft in the small domain, the substrate binding in an adjacent pocket [MEDLINE:84057760].

This family represents the C-terminal all- domain of 6-phosphogluconate dehydrogenase. The domain contains two structural repeats of 5 helices each. The NAD-binding domain is described in IPR006115.

\ \ phosphogluconate dehydrogenase (decarboxylating) activity ; GO:0004616 \N pentose-phosphate shunt ; GO:0006098 24638 IPR006181 D-amino acid oxidase (EC: 1.4.3.3) (DAMOX or DAO) is an FAD flavoenzyme that catalyzes the oxidation of neutral and basic D-amino acids into their corresponding keto acids. DAOs have been characterized \ and sequenced in fungi and vertebrates where they are known to be located in the peroxisomes. D-aspartate \ oxidase (EC: 1.4.3.1) (DASOX) [MEDLINE:92291057] is an enzyme, structurally related to DAO, which catalyzes \ the same reaction but is active only toward dicarboxylic D-amino acids. In DAO, a conserved histidine \ has been shown [MEDLINE:91201275] to be important for the enzyme's catalytic activity.\ \ D-amino acid oxidase activity ; GO:0003884 \N electron transport ; GO:0006118 24639 IPR006182 This bacterial family includes proteins that are related to the YscJ lipoprotein, and the amino terminus of FliF, the flagellar M-ring protein. The members of the YscJ family are thought to be involved in secretion of several proteins. The FliF protein ring is thought to be part of the export apparatus for flagellar proteins, based on the similarity to YscJ proteins [MEDLINE:99160439].\ \N \N \N 24640 IPR006183

6-Phosphogluconate dehydrogenase (EC: 1.1.1.44) (6PGD) is an oxidative carboxylase that catalyses the decarboxylating reduction of 6-phosphogluconate into ribulose 5-phosphate in the presence of NADP. This reaction is a component of the hexose mono-phosphate shunt and pentose phosphate pathways (PPP) [MEDLINE:90299831], [MEDLINE:84057760]. Prokaryotic and eukaryotic 6PGD are proteins of about 470 amino acids whose sequence are highly conserved [MEDLINE:92065803]. The protein is a homodimer in which the monomers act independently [MEDLINE:84057760]: each contains a large, mainly -helical domain and a smaller -- domain, containing a mixed parallel and anti-parallel 6-stranded sheet [MEDLINE:84057760]. NADP is bound in a cleft in the small domain, the substrate binding in an adjacent pocket [MEDLINE:84057760].

\ phosphogluconate dehydrogenase (decarboxylating) activity ; GO:0004616 \N pentose-phosphate shunt ; GO:0006098 24637 IPR006180

3-hydroxyacyl-CoA dehydrogenase (EC: 1.1.1.35) (HCDH) [MEDLINE:88068574] is an enzyme involved in fatty acid metabolism, it catalyzes the reduction of 3-hydroxyacyl-CoA to 3-oxoacyl-CoA. Most eukaryotic cells have 2 fatty-acid -oxidation systems, one located in mitochondria and the other in peroxisomes. In peroxisomes 3-hydroxyacyl-CoA dehydrogenase forms, with enoyl-CoA hydratase (ECH) and 3,2-trans-enoyl-CoA isomerase (ECI) a multifunctional enzyme where the N-terminal domain bears the hydratase/isomerase activities and the C-terminal domain the dehydrogenase activity. There are two mitochondrial enzymes: one which is monofunctional and the other which is, like its peroxisomal counterpart, multifunctional.

In Escherichia coli (gene fadB) and Pseudomonas fragi (gene faoA) HCDH is part of a multifunctional enzyme which also contains an ECH/ECI domain as well as a 3-hydroxybutyryl-CoA epimerase domain [MEDLINE:90370500].

The other proteins structurally related to HCDH are:

Bacterial 3-hydroxybutyryl-CoA dehydrogenase (EC: 1.1.1.157) which reduces 3-hydroxybutanoyl-CoA to acetoacetyl-CoA [MEDLINE:95095030].
Eye lens protein lambda-crystallin [MEDLINE:89008448], which is specific to lagomorphes (such as rabbit).

\ \ \N \N \N 24636 IPR006179

5'-nucleotidases (EC: 3.1.3.5) [MEDLINE:92344608] are enzymes that catalyze the hydrolysis ofphosphate esterified at carbon 5' of the ribose and deoxyribose portions of\ nucleotide molecules. 5'-nucleotidase is a ubiquitous enzyme found in a wide\ variety of species and which occurs in different cellular locations. The extracellular 5'-nucleotidase from mammals and electric ray isozyme is a homodimeric disulfide-bonded glycoprotein attached to the membrane by a GPI-anchor, and requires zinc for its activity. Vibrio parahaemolyticus 5'-nucleotidase (gene nutA) is bound to the membrane by a lipid chain, and requires chloride and magnesium ions for its activity. It is involved in degrading extracellular 5'-nucleotides for nutritional needs.

\ \

Periplasmic bacterial 5'-nucleotidase (gene ushA), also known\ as UDP-sugar hydrolase (EC: 3.6.1.45), can degrade UDP-glucose and other nucleotide diphosphate sugars. It produces sugar-1-phosphate which can then be used by the cell. UshA seems to require cobalt for its activity.\ 5'-Nucleotidases are evolutionary related to the periplasmic bacterial 2',3'-cyclic-nucleotide 2'-phosphodiesterase (EC: 3.1.4.16) (gene cpdB), which catalyzes two consecutive reactions: it first converts 2',3'-cyclic-nucleotide to 3'-nucleotide and then acts as a 3'-nucleotidase; and mosquito apyrase (EC: 3.6.1.5) (ATP-diphosphohydrolase) [MEDLINE:95148604], which catalyzes the hydrolysis of ATP into AMP and facilitates hematophagy by preventing ADP-dependent platelet aggregation in the host.

\ \

CD73 (also called ecto-5'-nucleotidase) possesses the enzymatic activity of a 5'-nucleotidase and catalyses the dephosphorylation of purine and pyrimidine ribo- and deoxyribonucleoside monophosphates to their corresponding nucleosides. Triggering of lymphocyte CD73 with mAb causes phosphorylation and dephosphorylation of certain, yet unknown protein substrates [MEDLINE:97167694]. A possible function for CD73 is to regulate the availability of adenosine for interaction with cell surface adenosine receptor by converting AMP to adenosine. In common with other GPI anchored surface proteins CD73 can mediate costimulatory signals in T cell activation [MEDLINE:89381313].

\ \

CD molecules are leucocyte antigens on cell surfaces. CD antigens nomenclature is updated at http://www.ncbi.nlm.nih.gov/PROW/guide/45277084.htm \

\ \ hydrolase activity ; GO:0016787 \N nucleotide catabolism ; GO:0009166 24632 IPR006175

This domain is found in endoribonuclease, that is active on single-stranded mRNA and inhibits protein synthesis by cleavage of mRNA [MEDLINE:99296592]. Previously it was thought to inhibit protein synthesis initiation [MEDLINE:96102067]. This endoribonuclease may also be involved in the regulation of purine biosynthesis [MEDLINE:99329090].

\ \N \N \N 24633 IPR006176

There are two major regions of similarity in the sequences of proteins of the HCDH family, the first one located in the N-terminal, corresponds to the NAD-binding site, the second one is located in the center of the sequence. This represents the C-terminal domain which is also found in lambda crystallin. Some proteins include two copies of this domain.

\ \ \N \N \N 24634 IPR006177

Staphylococcal enterotoxins and streptococcal pyrogenic exotoxins belongto a family of related toxins [MEDLINE:90239565], [MEDLINE:90024957] that share the ability to bind to\ the major histocompatibility complex proteins of their hosts. A more\ distant relative of the family is the Staphylococcus aureus toxic shock\ syndrome toxin, which shares only a low level of sequence similarity\ with this group. \

\ \ \N \N \N 24635 IPR006178

Allergen 1 from the domestic cat, Felis domesticus, is an important agentin human allergic reactions [MEDLINE:84265679]. The protein is expressed in saliva and \ sebaceous glands. The complete primary structure of Fel dI has been \ determined. The allergen is composed of two polypeptide chains, which\ have been shown to be encoded by different genes. The protein exists as \ a heterotetramer of non-covalently linked disulphide-linked heterodimers of \ chains 1 and 2. Fel dI chain 1 shares sequence similarity with rabbit \ uteroglobin; chain 2 is a glycoprotein with N-linked oligosaccharides [MEDLINE:92052157].

\ \ \N \N \N 24631 IPR006174

The NusB protein is involved in the regulation of rRNA biosynthesisby transcriptional antitermination. The antitermination proteins of Escherichia coli are recruited in the replication cycle of\ bacteriophage lambda, where they play an important role in switching from the\ lysogenic to the lytic cycle. The solution structure indicates that the protein folds into an /-helical\ topology consisting of six helices; the arginine-rich N-terminus appears to be\ disordered [MEDLINE:98336198].

\ \ \N \N \N 24626 IPR006169

Several proteins have recently been shown to contain the 5 structural motifs characteristicof GTP-binding proteins [MEDLINE:93080583]. These include murine DRG protein; GTP1 protein\ from Schizosaccharomyces pombe; OBG protein from Bacillus subtilis; and several others.\ Although the proteins contain GTP-binding motifs and are similar to each other, they do\ not share sequence similarity to other GTP-binding proteins, and have thus been classed\ as a novel group, the GTP1/OBG family. As yet, the functions of these proteins is uncertain,\ but they have been shown to be important in development and normal cell metabolism\ [MEDLINE:93216121], [MEDLINE:89155435].

\ \ \N \N \N 24627 IPR006170

The olfactory receptors of terrestrial animals exist in an aqueous environment, yet detect odorants that are primarily hydrophobic. The aqueous solubility of hydrophobic odorants is thought to be greatly enhanced via odorant binding proteins which exist in the extracellular fluid surrounding the odorant receptors [MEDLINE:91186129]. This family is composed of pheromone binding proteins (PBP), which are male-specific and associate with pheromone-sensitive neurons and general-odorant binding proteins (GOBP).

\ odorant binding activity ; GO:0005549 \N transport ; GO:0006810 24628 IPR006171

This is a conserved region from DNA primase. This corresponds to the Toprim domain common to DnaG primases, topoisomerases, OLD family nucleases and RecR proteins [MEDLINE:97238688] ]. Both DnaG motifs IV and V are present in the alignment, the DxD (V) motif may be involved in Mg2+ binding and mutations to the conserved glutamate (IV) completely abolish DnaG type primase activity. DNA primase EC: 2.7.7.6 is a nucleotidyltransferase it synthesizes the oligoribonucleotide primers required for DNA replication on the lagging strand of the replication fork; it can also prime the leading stand and has been implicated in cell division [MEDLINE:94124015]. This family also includes the atypical archaeal A subunit from type II DNA topoisomerases [MEDLINE:98391745]. Type II DNA topoisomerases catalyse the relaxation of DNA supercoiling by causing transient double strand breaks.

\ nucleic acid binding activity ; GO:0003676 \N DNA modification ; GO:0006304 24629 IPR006172

DNA is the biological information that instructs cells how to exist in anordered fashion: accurate replication is thus one of the most important\ events in the life cycle of a cell. This function is performed by DNA-\ directed DNA-polymerases (EC: 2.7.7.7) by adding nucleotide triphosphate (dNTP) residues \ to the 5'-end of the growing chain of DNA, using a complementary DNA chain \ as a template. Small RNA molecules are generally used as primers for chain \ elongation, although terminal proteins may also be used for the de novo synthesis of a DNA chain. \ Even though there \ are 2 different methods of priming, these are mediated by 2 very similar \ polymerases classes, A and B, with similar methods of chain elongation.

A number of DNA polymerases have been grouped\ under the designation of DNA polymerase family B.\ Six regions of similarity (numbered from I to VI) are found in all or a subset\ of the B family polymerases. The most conserved region (I) includes a conserved\ tetrapeptide with two aspartate residues. Its function is not yet known.\ However, it has been suggested [MEDLINE:89057522] that it may be involved in binding a\ magnesium ion. All sequences in the B\ family contain a characteristic DTDS motif, and possess many functional\ domains, including a 5'-3' elongation domain, a 3'-5' exonuclease domain [MEDLINE:96292335],\ a DNA binding domain, and binding domains for both dNTP's and pyrophosphate [MEDLINE:98437631].

\ \ \ 3'-5' exonuclease activity ; GO:0008408\ DNA-directed DNA polymerase activity ; GO:0003887 \N DNA replication ; GO:0006260 24630 IPR006173

Staphylococcus aureus is a Gram-positive coccus that grows in clusters or pairs, and is the major cause of nosocomial infections due to its multiple \ antibiotic resistant nature [MEDLINE:87057222]. Patients who are immunocompromised (e.g., \ those suffering from third degree burns or chronic illness) are at risk \ from deep staphylococcal infections, such as osteomyelitis and pneumonia.\ Most skin infections are also caused by this bacterium.

\ \ Many virulence mechanisms are employed by Staphylococci to induce \ pathogenesis: these can include polysaccharide capsules and exotoxins [MEDLINE:87057222].\ One of the major virulence exotoxins is toxic shock syndrome toxin (TSST),\ which is secreted by the organism upon successful invasion. It causes a\ major inflammatory response in the host via superantigenic properties,\ and is the causative agent of toxic shock syndrome.

The structure of the TSST protein was originally determined to 2.5A by means\ of X-ray crystallography [MEDLINE:94150598]. The N- and C-terminal domains both contain\ regions involved in MHC class II association; the C-terminal domain is also\ implicated in binding the T-cell receptor. Overall, the structure \ resembles that of Staphylococcal enterotoxin B (SEB), but differs in its\ N-terminus and in the degree to which a long central helix is covered by \ surface loops [MEDLINE:94092653]. The region around the carboxyl end of this helix is \ proposed to govern the superantigenic properties of TSST. An adjacent\ region along this helix is thought to be critical in the ability of TSST\ to induce toxic shock syndrome. Most recently, the structures of five \ mutants of TSST have been determined to 1.95A [MEDLINE:97337442]. The mutations are in \ the central -helix, and allow mapping of portions of TSST involved in\ superantigenicity and lethality.

\ \ \N \N \N 24624 IPR006167

All proteins in this family, for which functions are known, are components in a multiprotein endonuclease complex, usually made up of Rad1 and Rad10 homologues. This complex is used\ primarily for nucleotide excision repair but also for some aspects of recombinational repair in\ some species. Most Archaeal species also have homologues of these genes, but the function of\ the Archaeal proteins is not known, so are not included in this family.

\ \ endonuclease activity ; GO:0004519 \N DNA repair ; GO:0006281 24625 IPR006168 NAD-dependent glycerol-3-phosphate dehydrogenase (EC: 1.1.1.8) (GPD) catalyzes the reversible reduction of dihydroxyacetone phosphate to glycerol-3-phosphate. It is a cytoplasmic protein, active as a homodimer [MEDLINE:89296935], each monomer containing an N-terminal NAD binding site [MEDLINE:81003924]. In insects, it acts in conjunction with a mitochondrial

-glycerophosphate oxidase in the

-glycerophosphate cycle, which is essential for the production of energy used in insect flight [MEDLINE:89296935].\ glycerol-3-phosphate dehydrogenase (NAD+) activity ; GO:0004367 glycerol-3-phosphate dehydrogenase complex ; GO:0009331 glycerol-3-phosphate metabolism ; GO:0006072 24620 IPR006163

Phosphopantetheine (or pantetheine 4' phosphate) is the prosthetic group of acyl carrier proteins (ACP) in some multienzyme complexes where it serves as a 'swinging arm' for the attachment of activated fatty acid and amino-acid groups [MEDLINE:66047462].

The amino-terminal region of the ACP proteins is well defined and consists of four helices arranged in a right-handedbundle held together by interhelical hydrophobic interactions. The Asp-Ser-Leu (DSL)motif is conserved in all of the ACP sequences, and the 4'-PP prosthetic group is covalently linked\ via a phosphodiester bond to the serine residue. The DSL sequence is present at the amino terminus of helix II, a domain of the protein referred to as the recognition helix and which is responsible for the\ interaction of ACPs with the enzymes of type II fatty acid synthesis [MEDLINE:21975158].

\ \ \N \N \N 24621 IPR006164

The Ku heterodimer is composed of Ku70 and Ku80, 70 kDa and 80 kDa subunits of an ATP-dependent DNA helicase, which contribute to genomic integrity through its ability to bind DNA double-strand breaks and facilitate repair by the non-homologous end-joining pathway. This is the central DNA-binding -barrel domain and is found in both the Ku70 and Ku80 proteins. Ku makes no contacts with DNA bases and few with the\ sugar-phosphate backbone, but it fits sterically to major and minor groove contours so as to position the DNA helix in a defined path\ through the protein ring formed by the heterodimer [MEDLINE:21376142].

\ \ \ \ ATP dependent DNA helicase activity ; GO:0004003 nucleus ; GO:0005634 double-strand break repair via nonhomologous end-joining ; GO:0006303 24622 IPR006165

The Ku heterodimer is composed of Ku70 and Ku80, 70 kDa and 80 kDa subunits of an ATP-dependent DNA helicase, which contribute to genomic integrity through its ability to bind DNA double-strand breaks, single-strand gaps, and noncomplementary segments and facilitate repair by the\ non-homologous end-joining pathway.

Ku forms a ring to encircle duplex DNA. Unlike the uniform, symmetrical protein rings observed in replication processivity factors27, the Ku ring is designed\ with an expansive base that cradles DNA, and a very narrow bridge (strand J on each subunit) that acts as a barrier to\ promiscuous binding to unbroken DNA. The folds of Ku70 and Ku80 are closely related and the two form a\ quasi-symmetrical molecule, indicating that they diverged from an ancestral homodimer. The low level of sequence identity (15%) among residues that contribute to the dimer interface should ensure\ heterodimer formation and preclude Ku7070 or Ku8080 homodimer formation. Ku70 and Ku80 share a three-domain\ topology comprising an amino-terminal / domain, a central -barrel domain and a helical C-terminal arm. In\ addition, the subunits have divergent C-terminal regions: the 19K DNA-PK recruitment element of Ku80, which\ is absent from the crystal structure, and a 5K region of Ku70, present in the crystals, identified previously as a SAP domain [MEDLINE:21385640]

\ \ ATP dependent DNA helicase activity ; GO:0004003 nucleus ; GO:0005634 double-strand break repair via nonhomologous end-joining ; GO:0006303 24623 IPR006166 This domain is predicted to be a nuclease domain, and is found in DNA repair proteins and proteins involved in recombination events during meiosis in Drosophila melanogaster.\ nuclease activity ; GO:0004518 \N DNA metabolism ; GO:0006259 24617 IPR006160 Members of this family may be short chain fatty acid transporters although there has been no experimental characterisation of this function.\ short-chain fatty acid transporter activity ; GO:0015635 membrane ; GO:0016020 short-chain fatty acid transport ; GO:0015912 24618 IPR006161

This is a family of conserved hypothetical proteins of no clearly defined function, although they may act as short chain fatty acid transporters.

\ short-chain fatty acid transporter activity ; GO:0015635 membrane ; GO:0016020 short-chain fatty acid transport ; GO:0015912 24619 IPR006162

\ \ \N \N \N 24616 IPR006159

Methylmalonyl-CoA mutase (EC: 5.4.99.2) catalyzes a reversible isomerization between L-methylmalonyl-CoA and succinyl-CoA. The enzyme uses an adenosylcobalamin cofactor.\ It may be a homodimer, as in mitochondrion, or a heterodimer with partially homologous chain that does not bind the adenosylcobalamin cofactor, as in Propionibacterium\ freudenreichii.

This entry describes the\ C-terminal domain of these enzymes.

\ \ \N \N \N 24613 IPR006156

Dihydroneopterin aldolase (EC: 4.1.2.25) catalyzes the conversion of 7,8-dihydroneopterin to 6-hydroxymethyl-7,8-dihydropterin in the biosynthetic pathway of\ tetrahydrofolate. The enzyme form a homo-octamers. Aldolase can use L-threo-dihydroneopterin and\ D-erythro-dihydroneopterin as substrates for the formation of 6-hydroxymethyldihydropterin, but it can also catalyze the epimerization\ of carbon 2' of dihydroneopterin and dihydromonapterin at appreciable velocity [MEDLINE:98316300].

\ \ dihydroneopterin aldolase activity ; GO:0004150 \N folic acid and derivative metabolism ; GO:0006760 24614 IPR006157

Dihydroneopterin aldolase EC: 4.1.2.25 catalyses the conversion of 7,8-dihydroneopterin to 6-hydroxymethyl-7,8-dihydropterin in the biosynthetic pathway of tetrahydrofolate. In the opportunistic pathogen Pneumocystis carinii, dihydroneopterin aldolase function is expressed as the N-terminal portion of the multifunctional folic acid synthesis protein (Fas). This region encompasses two domains, FasA and FasB, which are 27% amino acid\ identical. FasA and FasB also share significant amino acid sequence similarity with bacterial dihydroneopterin aldolases.

This region consists of two\ tandem sequences each homologous to folB and which form tetramers [MEDLINE:98376447].

\ \ dihydroneopterin aldolase activity ; GO:0004150 \N folic acid and derivative metabolism ; GO:0006760 24615 IPR006158

Glutamate mutase is an adenosylcobamide (coenzyme B12) dependent enzyme that catalyzes the reversible rearrangement of (2S)-glutamate to (2S,3S)-3-methylaspartate. The enzyme from Clostridium tetanomorphum comprises two subunits and in its active form appears to be an 2 2 tetramer. The smaller subunit, termed MutS, has been characterized as the B12-binding component. This domain is found in several enzymes, such as glutamate mutase, methionine synthase and methylmalonyl-CoA mutase.

The core structure consists of 5 parallel -sheets, surrounded by 4-5 helices. The fold of the domain resembles that of the nucleotide-binding proteins (a Rossman fold). Upon binding B12, important\ elements of the binding site appear to become structured, including an -helix that\ forms on one side of the cleft accommodating the nucleotide 'tail' of the cofactor [MEDLINE:21975158].

\ \ \N \N \N 24611 IPR006154

Toprim is a conserved region from DNA primase, DnaG primases, topoisomerases, OLD family nucleases and RecR proteins. The fold of the TOPRIM domain resembles a Rossman-like nucleotide binding fold, with a central -sheet formed by 4 parallel -strands flanked by 3 -helices. Only 5 residues are conserved across all TOPRIM domain, 2 of these are glycines which may play a structural role, the other 3 are acidic residues that are present in 2 conserved sequence motifs. These may have a metal binding function [MEDLINE:20334715]

The TOPRIM domain may form a shallow groove on these molecules and play a role in the binding of double-helical DNA/RNA hybrids.

\ \ nucleic acid binding activity ; GO:0003676 \N DNA modification ; GO:0006304 24612 IPR006155 Human genes containing triplet repeats can markedly expand in length, leadingto neuropsychiatric disease. Expansion of triplet repeats explains the\ phenomenon of anticipation, i.e. the increasing severity or earlier age of\ onset in successive generations in a pedigree [MEDLINE:93315145].\ A novel gene containing CAG repeats has been identified and mapped to\ chromosome 14q32.1, the genetic locus for Machado-Joseph disease (MJD).\ Normally, the gene contains 13-36 CAG repeats, but most clinically diagnosed\ patients and all affected members of a family with the clinical and \ pathological diagnosis of MJD show expansion of the repeat number, from \ 68-79 [MEDLINE:95179166]. Similar abnormalities in related genes may give rise to diseases\ similar to MJD. \ MJD is a neurodegenerative disorder characterised by cerebellar ataxia, \ pyramidal and extra-pyramidal signs, peripheral nerve palsy, external \ ophtalmoplegia, facial and lingual fasciculation and bulging. The disease\ is autosomal dominant, with late onset of symptoms, generally after the\ fourth decade.\ \ \N \N \N 24606 IPR006149

The EB domain has no known function. It is found in several Caenorhabditis elegans proteins. The domain contains 8 conserved cysteines that probably form four disulphide bridges and is found associated with kunitz domains IPR002223

\ \N \N \N 24607 IPR006150

The Worm-specific repeat type 1 is found in several Caenorhabditis elegans proteins. The region contains several conserved cysteines that probably form disulphide bridges and is often found associated with kunitz domains IPR002223

\ \N \N \N 24608 IPR006151

This family contains both shikimate and quinate dehydrogenases. Shikimate 5-dehydrogenase (EC: 1.1.1.25) catalyses the conversion of shikimate to 5-dehydroshikimate. This reaction is part of the shikimate pathway which is involved in the biosynthesis of aromatic amino acids.Quinate 5-dehydrogenase catalyses the conversion of quinate to 5-dehydroquinate. This reaction is part of the quinate pathway where quinic acid is exploited as\ a source of carbon in prokaryotes and microbial eukaryotes.\ Both the shikimate and quinate pathways share two common pathway metabolites, 3-dehydroquinate and dehydroshikimate.

\ \ shikimate 5-dehydrogenase activity ; GO:0004764 cytoplasm ; GO:0005737 aromatic amino acid family biosynthesis, shikimate pathway ; GO:0016089 24609 IPR006152

Shikimate 5-dehydrogenase (EC: 1.1.1.25) catalyses the conversion of shikimate to 5-dehydroshikimate. This reaction is part of the shikimate pathway which is involved in the biosynthesis of aromatic amino acids.

\ \ shikimate 5-dehydrogenase activity ; GO:0004764 cytoplasm ; GO:0005737 aromatic amino acid family biosynthesis, shikimate pathway ; GO:0016089 24604 IPR006147

Allergies are hypersensitivity reactions of the immune system to specific substances called allergens (such as pollen, stings, drugs, or food) that, in most people, result in no symptoms. A nomenclature system has been established for antigens (allergens) that cause IgE-mediated atopic allergies in humans [WHO/IUIS Allergen Nomenclature Subcommittee King T.P., Hoffmann D., Loewenstein H., Marsh D.G., Platts-Mills T.A.E.,\ Thomas W. Bull. World Health Organ. 72:797-806(1994)]. This nomenclature system is defined by a designation that is composed of\ the first three letters of the genus; a space; the first letter of the\ species name; a space and an arabic number. In the event that two species\ names have identical designations, they are discriminated from one another\ by adding one or more letters (as necessary) to each species designation.

The allergens in this family include allergens with the following designations: Fel d 1.

\ \ \

Allergen 1 from the domestic cat, Felis domesticus, is an important agent\ in human allergic reactions [MEDLINE:84265679]. The protein is expressed in saliva and \ sebaceous glands. The complete primary structure of Fel dI has been \ determined [MEDLINE:92052157]. The allergen is composed of two polypeptide chains, which\ have been shown to be encoded by different genes . The protein exists as \ a heterotetramer of non-covalently linked disulphide-linked heterodimers of \ chains 1 and 2. Fel dI chain 1 shares sequence similarity with rabbit\ uteroglobin and chain 2 is a glycoprotein with N-linked oligosaccharides [MEDLINE:92052157].\ \ Androgen-binding protein in house mice belongs to this group.

\ \ \N \N \N 24610 IPR006153

The monovalent Cation:Proton antiporter-1 (CPA1) family is a large family of proteins derived from Gram-positive and Gram-negative bacteria, blue green bacteria, yeast, plants and animals. \ Transporters from eukaryotes have been functionally characterized, and all of these\ catalyze Na+:H+ exchange. Their primary physiological functions may be in

cytoplasmic pH regulation, extruding the H+ generated during metabolism, and

salt\ tolerance (in plants), due to Na+ uptake into vacuoles.

Na⁺/H⁺ exchange proteins eject protons from cells, effectively eliminating excess acid from actively metabolising cells. Na⁺/H⁺ exchange activity is also crucial for the regulation of cell volume, and for the reabsorption of NaCl across renal, intestinal, and other epithelia. These antiports exchange Na⁺ for H⁺ in an electroneutral manner, and this activity is carried out by a family of Na⁺/H⁺ exchangers, or NHEs, which are known to be present in both prokaryotic and eukaryotic cells. In mammalian cells, Na⁺/H⁺ exchange activity is found in both the plasma membrane and inner mitochondrial membrane. To date, six mammalian isoforms have been identified (designated NHE1-NHE6) [MEDLINE:97426369], [MEDLINE:98175963]. These exchangers are highly-regulated (glyco)phosphoproteins, which, based on their primary structure, appear to contain 10-12 membrane-spanning regions (M) at the N-terminus and a large cytoplasmic region at the C-terminus. The transmembrane regions M3-M12 share identity with other members of the family. The M6 and M7 regions are highly conserved. Thus, this is thought to be the region that is involved in the transport of sodium and hydrogen ions. The cytoplasmic region has little similarity throughout the family. There is some evidence that the exchangers may exist in the cell membrane as homodimers, but little is currently known about the mechanism of their antiport [MEDLINE:98196852].

\ \ \ solute:hydrogen antiporter activity ; GO:0015299 integral to membrane ; GO:0016021 regulation of pH ; GO:0006885 24605 IPR006148 This family contains 6-phosphogluconolactonase (EC: 3.1.1.31), Glucosamine-6-phosphate isomerase (EC: 3.5.99.6), and Galactosamine-6-phosphate isomerase. 6-phosphogluconolactonase is the enzyme responsible for the hydrolysis of 6-phosphogluconolactone to 6-phosphogluconate, the second step in the pentose phosphate pathway. Glucosamine-6-phosphate isomerase (or Glucosamine 6-phosphate deaminase) is the enzyme responsible for the conversion of D-glucosamine 6-phosphate into D-fructose 6-phosphate [MEDLINE:96363670]. It is the last specific step in the pathway for N-acetylglucosamine (GlcNAC) utilization in bacteria such as Escherichia coli (gene nagB) or in fungi such as Candida albicans (gene NAG1).A region located in the central part of Glucosamine-6-phosphate isomerase contains a conserved histidine which has been shown [MEDLINE:96363670], in nagB, to be important for the pyranose ring-opening step of the catalytic mechanism.\ \ \N \N carbohydrate metabolism ; GO:0005975 24603 IPR006146

5'-nucleotidases (EC: 3.1.3.5) are enzymes that catalyze the hydrolysis of phosphate esterified at carbon 5' of the ribose and deoxyribose portions of nucleotide molecules. 5'-nucleotidase is a ubiquitous enzyme found in a wide variety of species\ and which occurs in different cellular locations. All these proteins share regions of sequence similarity, this signature pattern is located in the N-\ terminal section of these enzymes and contains a perfectly\ conserved pentapeptide.

\ \ hydrolase activity, acting on ester bonds ; GO:0016788 \N nucleotide catabolism ; GO:0009166 24602 IPR006145 Pseudouridine synthases (EC: 4.2.1.70) are responsible for synthesis of pseudouridine from uracil in 23S rRNA.Proteins belonging to the family of pseudouridine synthases have been shown to share regions of\ similarities [MEDLINE:98325071]. These include E. coli and Haemophilus influenzae ribosomal large subunit\ pseudouridine synthase A (gene rluA), C (gene rluC) and D (gene rluD); yeast DRAP deaminase\ (gene RIB2); E. coli hypothetical protein yqcB and HI1435, the corresponding Haemophilus influenzae protein;\ Bacillus subtilis hypothetical proteins yhcT, yjbO and ylyB; Helicobacter pylori hypothetical proteins HP0347;\ HP0745 and HP0956; Mycoplasma genitalium hypothetical proteins MG209 and MG370; Synechocystis strain\ PCC 6803 hypothetical proteins slr1592 and slr1629; yeast hypothetical proteins YDL036c, YGR169c and\ SpAC18B11.02c; and C. elegans hypothetical protein K07E8.7. These are proteins of from 21 to 50 Kd which\ contain a number of conserved regions in their central section. This family includes members of both the Rsu and Rlu families.\ \ \N \N \N 24600 IPR006143

Gram-negative bacteria produce a number of proteins which are secreted into the growth medium by a mechanism that does not require a cleaved N-terminal signal sequence. These proteins, while having different functions, require the help of two or more proteins for their secretion across the cell envelope. These secretion proteins include members belonging to the ABC transporter family (see the relevant entry IPR003439 of the following members:

\ Gene Species Protein which is exported\ ---- ---------------------- --------------------------------------------\ hlyD Escherichia coli Hemolysin\ appD A.pleuropneumoniae Hemolysin\ lcnD Lactococcus lactis Lactococcin A\ lktD A.actinomycetemcomitans Leukotoxin\ Pasteurella haemolytica\ rtxD A.pleuropneumoniae Toxin-III\ cyaD Bordetella pertussis Calmodulin-sensitive adenylate cyclase-\ hemolysin (cyclolysin)\ cvaA Escherichia coli Colicin V\ prtE Erwinia chrysanthemi Extracellular proteases B and C\ aprE Pseudomonas aeruginosa Alkaline protease\ emrA Escherichia coli Drugs and toxins\ yjcR Escherichia coli Unknown\

The secretion proteins are evolutionary related and consist of from 390 to 480 amino acid residues. They seem to be anchored in the inner membrane by a N-terminal transmembrane region. Their exact role in the secretion process is not yet known.

\ \ protein transporter activity ; GO:0008565 membrane ; GO:0016020 protein secretion ; GO:0009306 24601 IPR006144

Gram-negative bacteria produce a number of proteins which are secreted into the growth medium by a mechanism that does not require a cleaved N-terminal\ signal sequence. These proteins, while having different functions, require the\ help of two or more proteins for their secretion across the cell envelope.

The secretion proteins are evolutionary related and consist of from 390 to 480 amino\ acid residues. They seem to be anchored in the inner membrane by a N-terminal\ transmembrane region. The C-terminal section of these proteins is the best conserved region.

\ \ protein transporter activity ; GO:0008565 membrane ; GO:0016020 protein secretion ; GO:0009306 24597 IPR006140

A number of NAD-dependent 2-hydroxyacid dehydrogenases which seem to be\ specific for the D-isomer of their substrate have been shown to be\ functionally and structurally related. All contain a glycine-rich\ region located in the central section of these enzymes, this region corresponds to the NAD-binding domain. The catalytic domain is described in IPR006139

\ \ oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor ; GO:0016616 \N serine biosynthesis ; GO:0006564 24598 IPR006141

Inteins, or protein introns, are parts of protein sequences that are post-translationally excised, their flanking regions (exteins) being\ spliced together to yield an additional protein product [MEDLINE:95276640],[MEDLINE:94218231]. This\ process is believed to be self-catalysed, apparently initiating at\ the C-terminal splice junction, where a conserved asparagine residue\ mediates the nucleophilic attack of the peptide bond between it and its\ neighbouring residue. Most inteins consist of two domains: One is involved in autocatalytic splicing, and the other is an endonuclease\ that is important in the spread of inteins [MEDLINE:22201712].

In most cases the intein seems to be an endonuclease. It has been proposed that the splicing initiates at the C-terminal splice junction. The delta-nitrogen group of a conserved asparagine residue makes a nucleophilic attack on the peptide bond that links this asparagine to the next residue. The next residue (a Cys, Ser or Thr) is then free to attack the peptide bond at the N-terminal splice junction by a transpeptidation reaction that releases the intein and creates a new peptide bond. Such a mechanism is briefly schematized in the following figures.

\ 1) Primary translation product\ \ +---------------+ +-------------+ +--------------+\ NH2-| Extein 1 x--y Intein N--z Extein 2 |-COOH\ +---------------+ +-------------+ +--------------+\ \ 2) Breakage of the peptide bond at the C-terminal splice junction by\ nucleophilic attack of the asparagine.\ \ +---------------+ +-------------+ +--------------+\ NH2-| Extein 1 x--y Intein N NH2-z Extein 2 |-COOH\ +---------------+ +-------------+ +--------------+\ \ 3) Transpeptidation to produce the final products.\ \ +---------------+ +-------------+ +--------------+\ NH2-| Extein 1 x--z Extein 2 |-COOH NH2-y Intein N\ +---------------+ +-------------+ +--------------+\

Inteins are difficult to identify from sequence data because they lie in the same reading frame as the spliced protein and they are characterised by only a few short conserved motifs [MEDLINE:95276640]: two of these are similar to the nonapeptide LAGLIDADG, which is diagnostic of certain homing endonucleases (mutation of one such motif causes loss of endonucleic activity, but not of the protein splicing function); another includes the C' splice site, mutations in which disable protein function.

\ \ \N \N protein splicing ; GO:0016539 24599 IPR006142

\ \ Inteins are\ between 134 and 608 amino acids long, and they are found in members of all three domains of life: eukaryotes, bacteria, and archaea, although most frequently in archaea. Inteins\ are found in proteins with diverse functions, including metabolic enzymes, DNA and RNA polymerases, proteases, ribonucleotide reductases, and the vacuolar-type\ ATPase. However, enzymes involved in DNA replication and repair appear to dominate. Inteins are found in conserved regions of conserved proteins and can be regarded as parasitic genetic elements [MEDLINE:22201712]. Inteins are difficult to identify from sequence data because they lie in\ the same reading frame as the spliced protein and they are characterised\ by only a few short conserved motifs [MEDLINE:95276640]: two of these are similar to\ the nonapeptide LAGLIDADG, which is diagnostic of certain homing\ endonucleases (mutation of one such motif causes loss of endonucleic\ activity, but not of the protein splicing function); another includes the\ C' splice site, mutations in which disable protein function.

\ \ \N \N protein splicing ; GO:0016539 24596 IPR006139

A number of NAD-dependent 2-hydroxyacid dehydrogenases which seem to be specific for the D-isomer of their substrate have been shown to be functionally and structurally related. The catalytic domain contains a number of conserved charged residues which may play a role in the catalytic mechanism. The NAD-binding domain is described in IPR006140

\ \ oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor ; GO:0016616 \N serine biosynthesis ; GO:0006564 24593 IPR006136

The flhB and flhA genes constitute an operon called flhB operon on the Salmonella typhimurium chromosome. They, together with FliI and FliH, may constitute the export apparatus of flagellin, the component protein of flagellar filament. The flhB gene encodes a highly\ hydrophobic polypeptide with several\ potential membrane-spanning segments, suggesting that it may be an integral membrane protein [MEDLINE:95095932].

\ \ \N membrane ; GO:0016020 protein secretion ; GO:0009306 24595 IPR006138 Respiratory-chain NADH dehydrogenase (EC: 1.6.5.3) (also known as complex I or NADH-ubiquinone oxidoreductase) is an oligomeric enzymatic complex\ located in the inner mitochondrial membrane which also seems to exist in\ the chloroplast and in cyanobacteria (as a NADH-plastoquinone oxidoreductase).\

Among the 25 to 30 polypeptide subunits of this bioenergetic enzyme complex\ there is one with a molecular weight of 20 kDa (in mammals) [MEDLINE:92249573], which is a\ component of the iron-sulfur (IP) fragment of the enzyme. It seems to bind a\ 4Fe-4S iron-sulfur cluster. The 20 kDa subunit has been found to be nuclear encoded, as a precursor form with a transit peptide in mammals, and\ in Neurospora crassa. It is \ mitochondrial encoded in Paramecium (gene psbG)\ and chloroplast encoded in various higher plants (gene ndhK or psbG).

\ \ NADH dehydrogenase (ubiquinone) activity ; GO:0008137 \N oxidative phosphorylation, NADH to ubiquinone ; GO:0006120 24592 IPR006135

Secretion of virulence factors in Gram-negative bacteria involves transportation of the protein across two membranes to reach the cell \ exterior. There have been four secretion systems described in \ animal enteropathogens such as Salmonella and Yersinia, with further \ sequence similarities in plant pathogens like Ralstonia and Erwinia [MEDLINE:97125927].

\ \ The type III secretion system is of great interest, as it is used to \ transport virulence factors from the pathogen directly into the host cell \ [MEDLINE:99269264] and is only triggered when the bacterium comes into close contact with\ the host. The protein subunits of the system are very similar to those of \ bacterial flagellar biosynthesis [MEDLINE:20032050]. However, while the latter forms a\ ring structure to allow secretion of flagellin and is an integral part of\ the flagellum itself, type III subunits in the outer membrane\ translocate secreted proteins through a channel-like structure.

\ \ It is believed that the family of type III inner membrane proteins are \ used as structural moieties in a complex with several other subunits [MEDLINE:98284147]. \ One such set of inner membrane proteins, labeled "S" here for nomenclature \ purposes, includes the Salmonella and Shigella SpaS, the Yersinia YscU, \ Rhizobium Y4YO, and the Erwinia HrcU genes. The flagellar protein FlhB \ also shares similarity, probably due to evolution of the type III secretion\ system from the flagellar biosynthetic pathway.

\ \ \N membrane ; GO:0016020 protein secretion ; GO:0009306 24594 IPR006137

Respiratory-chain NADH dehydrogenase (EC: 1.6.5.3) (also known as complex I or NADH-ubiquinone oxidoreductase) is an oligomeric enzymatic complex\ located in the inner mitochondrial membrane which also seems to exist in\ the chloroplast and in cyanobacteria (as a NADH-plastoquinone oxidoreductase).

\ \ NADH dehydrogenase (ubiquinone) activity ; GO:0008137 \N oxidative phosphorylation, NADH to ubiquinone ; GO:0006120 24591 IPR006134

DNA is the biological information that instructs cells how to exist in an ordered fashion: accurate replication is thus one of the most important events in the life cycle of a cell. This function is performed by DNA- directed DNA-polymerases EC: 2.7.7.7)\ by adding nucleotide triphosphate (dNTP) residues to the 5'-end of the growing chain of DNA, using a complementary DNA\ chain as a template. Small RNA molecules are generally used as primers for chain elongation, although terminal proteins\ may also be used for the de novo synthesis of a DNA chain. Even though there are 2 different methods of priming, these are\ mediated by 2 very similar polymerases classes, A and B, with similar methods of chain elongation. \ \ A number of DNA polymerases have been grouped under the designation of DNA polymerase family B. Six regions\ of similarity (numbered from I to VI) are found in all or a subset of the B family polymerases. The most conserved region (I)\ includes a conserved tetrapeptide with two aspartate residues. Its function is not yet known, however, it has been suggested\ that it may be involved in binding a magnesium ion. All sequences in the B family contain a characteristic DTDS motif, and\ possess many functional domains, including a 5'-3' elongation domain, a 3'-5' exonuclease domain [MEDLINE:96292335], a DNA binding domain,\ and binding domains for both dNTP's and pyrophosphate [MEDLINE:98437631].

This region of DNA polymerase B appears to consist of more than one structural domain, possibly including elongation,\ DNA-binding and dNTP binding activities [MEDLINE:98437631].

\ \ DNA binding activity ; GO:0003677 \N \N 24589 IPR006132

This family contains two related enzymes:

Aspartate carbamoyltransferase (EC: 2.1.3.2) (ATCase) catalyzes the conversion\ of aspartate and carbamoyl phosphate to carbamoylaspartate, the second step\ in the de novo biosynthesis of pyrimidine nucleotides [MEDLINE:86278215]. In prokaryotes\ ATCase consists of two subunits: a catalytic chain (gene pyrB) and a\ regulatory chain (gene pyrI), while in eukaryotes it is a domain in a multi-\ functional enzyme (called URA2 in yeast, rudimentary in Drosophila, and CAD\ in mammals [MEDLINE:93256915]) that also catalyzes other steps of the biosynthesis of\ pyrimidines.
Ornithine carbamoyltransferase (EC: 2.1.3.3) (OTCase) catalyzes the conversion\ of ornithine and carbamoyl phosphate to citrulline. In mammals this enzyme\ participates in the urea cycle [MEDLINE:89302060] and is located in the mitochondrial\ matrix. In prokaryotes and eukaryotic microorganisms it is involved in the\ biosynthesis of arginine. In some bacterial species it is also involved in the\ degradation of arginine [MEDLINE:87246664] (the arginine deaminase pathway).

\ It has been shown [MEDLINE:84272730] that these two enzymes are evolutionary related. The\ predicted secondary structure of both enzymes are similar and there are some\ regions of sequence similarities. One of these regions includes three\ residues which have been shown, by crystallographic studies [MEDLINE:84248054], to be\ implicated in binding the phosphoryl group of carbamoyl phosphate and may also play a role in trimerization of the molecules [MEDLINE:99254050]. The carboxyl-terminal, aspartate/ornithine-binding domain is is described by IPR006131 . \

\ \ carboxyl- and carbamoyltransferase activity ; GO:0016743 \N amino acid metabolism ; GO:0006520 24590 IPR006133

DNA is the biological information that instructs cells how to exist in an ordered fashion: accurate replication is thus one of the most important events in the life cycle of a cell. This function is performed by DNA- directed DNA-polymerases EC: 2.7.7.7)\ by adding nucleotide triphosphate (dNTP) residues to the 5'-end of the growing chain of DNA, using a complementary DNA\ chain as a template. Small RNA molecules are generally used as primers for chain elongation, although terminal proteins\ may also be used for the de novo synthesis of a DNA chain. Even though there are 2 different methods of priming, these are\ mediated by 2 very similar polymerases classes, A and B, with similar methods of chain elongation. \ \ A number of DNA polymerases have been grouped under the designation of DNA polymerase family B. Six regions\ of similarity (numbered from I to VI) are found in all or a subset of the B family polymerases. The most conserved region (I)\ includes a conserved tetrapeptide with two aspartate residues. Its function is not yet known. However, it has been suggested\ that it may be involved in binding a magnesium ion. All sequences in the B family contain a characteristic DTDS motif, and\ possess many functional domains, including a 5'-3' elongation domain, a 3'-5' exonuclease domain [MEDLINE:96292335], a DNA binding domain,\ and binding domains for both dNTP's and pyrophosphate [MEDLINE:98437631].

This domain has 3' to 5' exonuclease activity and adopts a ribonuclease H type fold [MEDLINE:96292335].

\ \ \ 3'-5' exonuclease activity ; GO:0008408\ \N \N \N 24588 IPR006131

This family contains two related enzymes:

Aspartate carbamoyltransferase (EC: 2.1.3.2) (ATCase) catalyzes the conversion\ of aspartate and carbamoyl phosphate to carbamoylaspartate, the second step\ in the de novo biosynthesis of pyrimidine nucleotides [MEDLINE:86278215]. In prokaryotes\ ATCase consists of two subunits: a catalytic chain (gene pyrB) and a\ regulatory chain (gene pyrI), while in eukaryotes it is a domain in a multi-\ functional enzyme (called URA2 in yeast, rudimentary in Drosophila, and CAD\ in mammals [MEDLINE:93256915]) that also catalyzes other steps of the biosynthesis of\ pyrimidines.
Ornithine carbamoyltransferase (EC: 2.1.3.3) (OTCase) catalyzes the conversion\ of ornithine and carbamoyl phosphate to citrulline. In mammals this enzyme\ participates in the urea cycle [MEDLINE:89302060] and is located in the mitochondrial\ matrix. In prokaryotes and eukaryotic microorganisms it is involved in the\ biosynthesis of arginine. In some bacterial species it is also involved in the\ degradation of arginine [MEDLINE:87246664] (the arginine deaminase pathway).

\ It has been shown [MEDLINE:84272730] that these two enzymes are evolutionary related. The\ predicted secondary structure of both enzymes are similar and there are some\ regions of sequence similarities. One of these regions includes three\ residues which have been shown, by crystallographic studies [MEDLINE:84248054], to be\ implicated in binding the phosphoryl group of carbamoyl phosphate and is described by IPR006132. The carboxyl-terminal, aspartate/ornithine-binding domain is connected to the amino-terminal\ domain by two

-helices, which comprise a hinge between domains [MEDLINE:99254050].

\ \ carboxyl- and carbamoyltransferase activity ; GO:0016743 \N amino acid metabolism ; GO:0006520 24587 IPR006130

This family contains two related enzymes:

Aspartate carbamoyltransferase (EC: 2.1.3.2) (ATCase) catalyzes the conversion\ of aspartate and carbamoyl phosphate to carbamoylaspartate, the second step\ in the de novo biosynthesis of pyrimidine nucleotides [MEDLINE:86278215]. In prokaryotes\ ATCase consists of two subunits: a catalytic chain (gene pyrB) and a\ regulatory chain (gene pyrI), while in eukaryotes it is a domain in a multi-\ functional enzyme (called URA2 in yeast, rudimentary in Drosophila, and CAD\ in mammals [MEDLINE:93256915]) that also catalyzes other steps of the biosynthesis of\ pyrimidines.
Ornithine carbamoyltransferase (EC: 2.1.3.3) (OTCase) catalyzes the conversion\ of ornithine and carbamoyl phosphate to citrulline. In mammals this enzyme\ participates in the urea cycle [MEDLINE:89302060] and is located in the mitochondrial\ matrix. In prokaryotes and eukaryotic microorganisms it is involved in the\ biosynthesis of arginine. In some bacterial species it is also involved in the\ degradation of arginine [MEDLINE:87246664] (the arginine deaminase pathway).

\ \ carboxyl- and carbamoyltransferase activity ; GO:0016743 \N amino acid metabolism ; GO:0006520 24583 IPR006126

Staphylococcal enterotoxins and streptococcal pyrogenic exotoxins constitute a family of biologically and structurally related toxins produced by Staphylococcus aureus and Streptococcus pyogenes\ \ \ [MEDLINE:90024957], [MEDLINE:90239565]. These toxins share the ability to bind to the major histocompatibility complex proteins of their hosts. A more distant relative of the family is the Staphylococcus aureus toxic shock syndrome toxin (TSST-1), which shares only a low level of sequence similarity with this group.

This family is identified by a well conserved\ region of enterotoxins and pyrogenic exotoxins, but which does not pick up TSST-1.

\ \ toxin activity ; GO:0015070 extracellular ; GO:0005576 pathogenesis ; GO:0009405 24586 IPR006129

The Streptococcus pneumoniae psaA gene encodes a protein with significant similarity to previously-reported Streptococcal proteins, SsaB (80% similarity) and FimA (92.3% similarity), from Streptococcus sanguis and Streptococcus parasanguis\ \ \ [MEDLINE:94086122]. These homologues are associated with bacterial adhesion, and PsaA may play a similar role [MEDLINE:94086122].

The SsaB protein has a putative hydrophobic 19-amino-acid signal sequence yielding a 32,620-Mr secreted protein [MEDLINE:91147187]. SsaB is hydrophilic and appears not to have a hydrophobic membrane anchor in its C-terminal region. A high degree of similarity exists between S.sanguis ssaB and type 1 fimbrial genes [MEDLINE:91147187]. Comparison of the gene products reveals close similarity of the two proteins. It is thought that ssaB adhesion may play a role in oral colonisation by binding either to a receptor on saliva or to a receptor on Actinomyces.

This sub-family is described by from conserved regions spanning the full alignment\ length, focusing on those sections that characterise the adhesin B\ precursors but distinguish them from the rest of the adhesin family.

\ \ \N \N cell adhesion ; GO:0007155 24585 IPR006128

This family includes the adhesins and related periplasmic binding proteins.

\ \ \N \N cell adhesion ; GO:0007155 24584 IPR006127

This is a family of periplasmic solute binding proteins such as TroA P96116 that interacts with an ATP-binding cassette transport system in Treponema pallidum and plays a role in the transport of zinc across the cytoplasmic membrane of the bacterium.

\ \ binding activity ; GO:0005488 periplasmic space (sensu Gram-negative Bacteria) ; GO:0030288 \N 24582 IPR006125

\ \ The structure of the TSST protein was originally determined to 2.5A by means\ of X-ray crystallography [MEDLINE:94150598]. The N- and C-terminal domains both contain\ regions involved in MHC class II association; the C-terminal domain is also\ implicated in binding the T-cell receptor. Overall, the structure \ resembles that of Staphylococcal enterotoxin B (SEB), but differs in its\ N-terminus and in the degree to which a long central helix is covered by \ surface loops [MEDLINE:94092653]. The region around the carboxyl end of this helix is \ proposed to govern the superantigenic properties of TSST. An adjacent\ region along this helix is thought to be critical in the ability of TSST\ to induce toxic shock syndrome. Most recently, the structures of five \ mutants of TSST have been determined to 1.95A [MEDLINE:97337442]. The mutations are in \ the central -helix, and allow mapping of portions of TSST involved in\ superantigenicity and lethality.

\ \ toxin activity ; GO:0015070 extracellular ; GO:0005576 pathogenesis ; GO:0009405 24581 IPR006124 This family unites alkaline phosphatase, N-acetylgalactosamine-4-sulfatase, and cerebroside sulfatase, enzymes with known\ three-dimensional structures, with phosphopentomutase,\ 2,3-bisphosphoglycerate-independent phosphoglycerate mutase, phosphoglycerol\ transferase, phosphonate monoesterase, streptomycin-6-phosphate phosphatase, alkaline\ phosphodiesterase/nucleotide pyrophosphatase PC-1, and several closely related sulfatases. This family is also related to alkaline phosphatase IPR001952\ \ \ \ [MEDLINE:99180418].\ The most conserved residues are\ probably involved in metal binding and catalysis.\ \ heavy metal binding activity ; GO:0005505 \N \N 24578 IPR006121

Proteins that transport heavy metals in micro-organisms and mammals share similarities in their sequences and structures.

These proteins provide an important focus for research, some being involved in bacterial resistance to toxic metals, such as lead and cadmium, while others are involved in inherited human syndromes, such as Wilson's and Menke's diseases [MEDLINE:94378325].

A conserved 30-residue domain has been found in a number of these heavy metal transport or detoxification proteins [MEDLINE:94378325]. The domain, which has been termed Heavy-Metal-Associated (HMA), contains two conserved cysteines that are probably involved in metal binding.

\ \ heavy metal binding activity ; GO:0005505 \N heavy metal ion transport ; GO:0006823 24580 IPR006123

Staphylococcal enterotoxins and streptococcal pyrogenic exotoxins constitute a family of biologically and structurally related toxins produced by Staphylococcus aureus and Streptococcus pyogenes\ \ \ [MEDLINE:90024957], [MEDLINE:90239565]. These toxins share the ability to bind to the major histocompatibility complex proteins of their hosts. A more distant relative of the family is the Staphylococcus aureus toxic shock syndrome toxin, which shares only a low level of sequence similarity with this group.

All of these toxins share a similar two-domain fold (N and C-terminal domains) with a long -helix in the middle of the molecule, a\ characteristic -barrel known as the "oligosaccharide/oligonucleotide fold" at the N-terminal domain and a -grasp motif at the C-terminal domain. Each superantigen possesses slightly different binding mode(s) when it interacts with MHC class II molecules or the T-cell receptor [MEDLINE:98181012].

The -grasp domain has some structural similarities to the -grasp motif present in immunoglobulin-binding\ domains, ubiquitin, 2Fe-2 S ferredoxin and translation initiation factor 3 as identified by the SCOP database.

\ \ toxin activity ; GO:0015070 extracellular ; GO:0005576 pathogenesis ; GO:0009405 24579 IPR006122

Proteins that transport heavy metals in micro-organisms and mammals share similarities in their sequences and structures.

\ \ copper ion binding activity ; GO:0005507 \N copper ion transport ; GO:0006825 24576 IPR006119

Site-specific recombination plays an important role in DNA rearrangement in prokaryotic organisms. Two types of site-specific recombination are known to occur:

Recombination between inverted repeats resulting in the reversal of a DNA segment.
Recombination between repeat sequences on two DNA molecules resulting in their cointegration, or between repeats on one DNA molecule resulting in the excision of a DNA fragment.

Site-specific recombination is characterized by a strand exchange mechanism that requires no DNA synthesis or high energy cofactor; the phosphodiester bond energy is conserved in a phospho-protein linkage during strand cleavage and re-ligation.

Two unrelated families of recombinases are currently known [MEDLINE:86220123]. The first, called the 'phage integrase' family, groups a number of bacterial phage and yeast plasmid enzymes. The second [MEDLINE:88201676], called the 'resolvase' family, groups enzymes which share the following structural characteristics: an N-terminal catalytic and dimerization domain that contains a conserved serine residue involved in the transient covalent attachment to DNA, and a C-terminal helix-turn-helix DNA-binding domain IPR006120.

\ \ recombinase activity ; GO:0000150 \N DNA recombination ; GO:0006310 24577 IPR006120

Site-specific recombination plays an important role in DNA rearrangement in prokaryotic organisms. Two types of site-specific recombination are known to occur:

Recombination between inverted repeats resulting in the reversal of a DNA segment.
Recombination between repeat sequences on two DNA molecules resulting in their cointegration, or between repeats on one DNA molecule resulting in the excision of a DNA fragment.

Two unrelated families of recombinases are currently known [MEDLINE:86220123]. The first, called the 'phage integrase' family, groups a number of bacterial phage and yeast plasmid enzymes. The second [MEDLINE:88201676], called the 'resolvase' family, groups enzymes which share the following structural characteristics: an N-terminal catalytic and dimerization domain that contains a conserved serine residue involved in the transient covalent attachment to DNA IPR006119, and a C-terminal helix-turn-helix DNA-binding domain.

\ \ recombinase activity ; GO:0000150 \N DNA recombination ; GO:0006310 24574 IPR006117

\ \

Three distinct classes of 2-5A synthetases have been described that correspond to proteins of 40-46 Kd, 69-71 Kd, and 100\ Kd. The 40 and 46 Kd forms are produced by alternative splicing of the same gene. The 69 and 71 Kd forms are also\ produced by alternative splicing of a gene and consist of two adjacent homologous domains whose sequences are highly\ similar to that of the 40/46 Kd forms. The sequence of the 100 Kd form is not yet known.

This domain corresponds to a highly conserved\ region located in the C-terminal part of 2-5A synthetase proteins or domains. The proposed ATP-binding domain is described in IPR006116.

\ \ transferase activity ; GO:0016740 \N immune response ; GO:0006955 24575 IPR006118

Site-specific recombination plays an important role in DNA rearrangement in prokaryotic organisms. Two types of site-specific recombination are known to occur:

Recombination between inverted repeats resulting in the reversal of a DNA segment.
Recombination between repeat sequences on two DNA molecules resulting in their cointegration, or between repeats on one DNA molecule resulting in the excision of a DNA fragment.

Two unrelated families of recombinases are currently known [MEDLINE:86220123]. The first, called the 'phage integrase' family, groups a number of bacterial, phage and yeast plasmid enzymes. The second [MEDLINE:88201676], called the 'resolvase' family, groups enzymes which share the following structural characteristics: an N-terminal catalytic and dimerization domain that contains a conserved serine residue involved in the transient covalent attachment to DNA, and a C-terminal helix-turn-helix DNA-binding domain.

The resolvase family is currently known to include the following proteins:

DNA invertase from Salmonella typhimurium (gene hin). Hin can invert a 900 bp DNA fragment adjacent to a gene for one of the flagellar antigens.
DNA invertase from Escherichia coli (gene pin).
DNA invertase from Bacteriophage Mu (gene gin), P1 and P7 (gene cin).
Resolvases from transposons Tn3, Tn21, Tn501, Tn552, Tn917, Tn1546, Tn1721, Tn2501 and Tn1000 (known as gamma-delta resolvase).
Resolvase from Clostridium perfringens plasmid pIP404.
Resolvase from Escherichia coli plasmid R46.
Resolvase from Escherichia coli plasmid RP4 (gene parA).
A putative recombinase from Bacillus subtilis (gene cisA) [MEDLINE:90130265] which plays an important role in sporulation by catalyzing the recombination of genes spoIIIC and spoIVCB to form polymerase sigma-K factor.
Uvp1, a protein from Escherichia coli plasmid pR which cooperates with the mucAB genes in the DNA repair process and could be a resolvase [MEDLINE:89384434].

Generally, proteins from the resolvase family have 180 to 200 amino-acid residues, excepting cisA which is much larger (500 residues).

\ \ recombinase activity ; GO:0000150 \N DNA recombination ; GO:0006310 24573 IPR006116

2'-5'-oligoadenylate synthetases constitute a family of interferon-induced enzymes that bind double-stranded RNA (dsRNA) and polymerize ATP into 2'-5' linked oligomers of adenosine (pppA(2'p5'A)n) (2-5A) of various lengths. The 2-5A\ molecules activate a latent ribonuclease (Rnase L) that then cleaves single-stranded RNAs; as a result protein synthesis and\ virus growth are inhibited. Thus 2-5A synthetases play an important role in the antiviral action of interferons.\ \ Three distinct classes of 2-5A synthetases have been described that correspond to proteins of 40-46 kDa, 69-71 kDa, and 100\ kDa. The 40 and 46 kDa forms are produced by alternative splicing of the same gene. The 69 and 71 kDa forms are also\ produced by alternative splicing of a gene and consist of two adjacent homologous domains whose sequences are highly\ similar to that of the 40/46 kDa forms. The sequence of the 100 kDa form is not yet known.

This domain spans a\ region rich in glycine residues which has been proposed [MEDLINE:92250658] to be part of the\ ATP-binding site. The C-terminal domain is described in IPR006117.

\ \ transferase activity ; GO:0016740 \N immune response ; GO:0006955 24572 IPR006115

6-Phosphogluconate dehydrogenase (EC: 1.1.1.44) (6PGD) is an oxidative carboxylase that catalyses the decarboxylating reduction of 6-phosphogluconate into ribulose 5-phosphate in the presence of NADP. This reaction is a component of the hexose mono-phosphate shunt and pentose phosphate pathways (PPP) [MEDLINE:90299831], [MEDLINE:84057760]. Prokaryotic and eukaryotic 6PGD are proteins of about 470 amino acids whose sequence are highly conserved [MEDLINE:92065803]. The protein is a homodimer in which the monomers act independently [MEDLINE:84057760]: each contains a large, mainly -helical domain and a smaller -- domain, containing a mixed parallel and anti-parallel 6-stranded sheet [MEDLINE:84057760]. NADP is bound in a cleft in the small domain, the substrate binding in an adjacent pocket [MEDLINE:84057760].

This family represents the NAD binding domain of 6-phosphogluconate dehydrogenase which adopts a Rossman fold. The C-terminal domain is described in IPR006114.

\ phosphogluconate dehydrogenase (decarboxylating) activity ; GO:0004616 \N pentose-phosphate shunt ; GO:0006098 24569 IPR006111 In eukaryotes, there are three different forms of DNA-dependent RNA polymerases (EC: 2.7.7.6) transcribing different sets of genes. Each class of RNA polymerase is an assemblage of ten to twelve different polypeptides. In archaebacteria, there is generally a single form of RNA polymerase which also consist of an oligomeric assemblage of 10 to 13 polypeptides.A component of 14 to 18 kDa shared by all three forms of eukaryotic RNA polymerases and which has been sequenced in budding yeast (gene RPB6 or RPO26), in fission yeast (gene rpb6 or rpo15), in human and in African swine fever virus\ \ \ \ [MEDLINE:93324382] is evolutionary related [MEDLINE:94321350] to archaebacterial subunit K (gene\ rpoK). The archaebacterial protein is colinear with the C-terminal part of the eukaryotic subunit.\ \ DNA-directed RNA polymerase activity ; GO:0003899 \N transcription, DNA-dependent ; GO:0006351 24570 IPR006113

6-Phosphogluconate dehydrogenase (EC: 1.1.1.44) (6PGD) is an oxidative carboxylase that catalyses the decarboxylating reduction of 6-phosphogluconate into ribulose 5-phosphate in the presence of NADP. This reaction is a component of the hexose mono-phosphate shunt and pentose phosphate pathways (PPP) [MEDLINE:90299831], [MEDLINE:84057760]. Prokaryotic and eukaryotic 6PGD are proteins of about 470 amino acids whose sequence are highly conserved [MEDLINE:92065803]. The protein is a homodimer in which the monomers act independently [MEDLINE:84057760]: each contains a large, mainly -helical domain and a smaller -- domain, containing a mixed parallel and anti-parallel 6-stranded sheet [MEDLINE:84057760]. NADP is bound in a cleft in the small domain, the substrate binding in an adjacent pocket [MEDLINE:84057760].

This model does not specify whether the cofactor is NADP only, NAD only, or both.

\ \ phosphogluconate dehydrogenase (decarboxylating) activity ; GO:0004616 \N pentose-phosphate shunt ; GO:0006098 24567 IPR006109

NAD-dependent glycerol-3-phosphate dehydrogenase (EC: 1.1.1.8) (GPD) catalyzes the reversible reduction of dihydroxyacetone phosphate to glycerol-3-phosphate. It is a cytoplasmic protein, active as a homodimer [MEDLINE:89296935], each monomer containing an N-terminal NAD binding site [MEDLINE:81003924]. In insects, it acts in conjunction with a mitochondrial -glycerophosphate oxidase in the -glycerophosphate cycle, which is essential for the production of energy used in insect flight [MEDLINE:89296935].

\ oxidoreductase activity, acting on CH-OH group of donors ; GO:0016614 \N carbohydrate metabolism ; GO:0005975 24571 IPR006114

6-Phosphogluconate dehydrogenase (EC: 1.1.1.44) (6PGD) is an oxidative carboxylase that catalyses the decarboxylating reduction of 6-phosphogluconate into ribulose 5-phosphate in the presence of NADP. This reaction is a component of the hexose mono-phosphate shunt and pentose phosphate pathways (PPP) [MEDLINE:90299831], [MEDLINE:84057760]. Prokaryotic and eukaryotic 6PGD are proteins of about 470 amino acids whose sequence are highly conserved [MEDLINE:92065803]. The protein is a homodimer in which the monomers act independently [MEDLINE:84057760]: each contains a large, mainly -helical domain and a smaller -- domain, containing a mixed parallel and anti-parallel 6-stranded sheet [MEDLINE:84057760]. NADP is bound in a cleft in the small domain, the substrate binding in an adjacent pocket [MEDLINE:84057760].

This family represents the C-terminal all- domain of 6-phosphogluconate dehydrogenase. The domain contains two structural repeats of 5 helices each. The NAD-binding domain is described in IPR006115.

\ \ phosphogluconate dehydrogenase (decarboxylating) activity ; GO:0004616 \N pentose-phosphate shunt ; GO:0006098 24568 IPR006110

In eukaryotes, there are three different forms of DNA-dependent RNA polymerases (EC: 2.7.7.6) transcribing different sets of genes. Each class of RNA polymerase is an assemblage of ten to twelve different polypeptides. In archaebacteria, there is generally a single form of RNA polymerase which also consists of an oligomeric assemblage of 10 to 13 polypeptides. A component of 14 to 18 kDa shared by all three forms of eukaryotic RNA polymerases and which has been sequenced in budding yeast (gene RPB6 or RPO26), in fission yeast (gene rpb6 or rpo15), in human and in African swine fever virus is evolutionary related to the archaebacterial subunit K (gene rpoK). The archaebacterial protein is colinear with the C-terminal part of the eukaryotic subunit.

The structures of the omega subunit and RBP6, and the structures of the omega/' and RPB6/RPB1 interfaces, suggest a molecular mechanism for the function of omega and RPB6 in promoting RNAP assembly and/or stability. The conserved regions of omega and RPB6 form a compact structural domain that interacts simultaneously with conserved regions of the largest RNAP subunit and with the C-terminal tail following a conserved region of the largest RNAP subunit. The second half of the conserved region of omega and RPB6 forms an arc that projects away from the remainder of the structural domain and wraps over and around the C-terminal tail of the largest RNAP subunit, clamping it in a crevice, and threading the C-terminal tail of the largest RNAP subunit through the narrow gap between omega and RPB6 [MEDLINE:21107642].

\ \ DNA-directed RNA polymerase activity ; GO:0003899 \N transcription, DNA-dependent ; GO:0006351 24564 IPR006106

The seeds of cereals contain numerous serine proteases and -amylase inhibitors. These inhibitors can be grouped into families based on structural similarities. The cereal trypsin/-amylase inhibitor family [MEDLINE:91346619], PUB00004500 consists of proteins of about 120 amino acids which contain 10 cysteine residues, all of which are involved in disulfide bonds. Some of these inhibitors are specific to trypsin, others to -amylase, and a few are bifunctional. The schematic representation of the structure of these inhibitors is shown below:

\
                       +----------------------------+\
           +----------+|   +-+                      |\
           |          ||   | |                      |\
  xxCxxxxxxCxxxCxxxxxxCCxxxCxCxxxxxxxxxxxxxCxxxxxxxxCxxxxxxxCxxxx\
    |          |                           |                |\
    |          +---------------------------+                |\
    +-------------------------------------------------------+\
\
'C': conserved cysteine involved in a disulfide bond.\

The 3D structure of the bifunctional -amylase/trypsin inhibitor (RBI) from seeds of ragi (Eleusine coracana) has been determined in solution using multidimensional 1H and 15N NMR spectroscopy PUB00004500. The inhibitor forms a globular 4-helix motif with a simple 'up-and-down' topology, and includes a short anti-parallel -sheet [MEDLINE:95322379].

This family of proteins also contains a subfamily of seed allergenic protein from rice [MEDLINE:93144699].

\ \ serine protease inhibitor activity ; GO:0004867 \N \N 24566 IPR006108

There are two major region of similarities in the sequences of proteins of the HCDH family, the first one located in the N-terminal, corresponds to the NAD-binding site, the second one is located in the center of the sequence. This represents the C-terminal domain which is also found in lambda crystallin. Some proteins include two copies of this domain.

\ \ \N \N \N 24565 IPR006107

Glutamyl-tRNA(Gln) amidotransferase subunit B (EC: 6.3.5.-) [MEDLINE:98004482] is a microbial enzyme that furnishes a means for formation of correctly charged Gln-tRNA(Gln) through the transamidation of misacylated Glu-tRNA(Gln) in organisms which lack glutaminyl-tRNA synthetase. The reaction takes place in the presence of glutamine and ATP through an activated gamma-phospho-Glu-tRNA(Gln). The enzyme is composed of three subunits: A (an amidase), B and C. It also exists in eukaryotes as a protein targeted to the mitochondria.

\ \ \N \N \N 24562 IPR006104

Glycoside hydrolase family 2 CAZY:GH_2\ comprises enzymes with several known activities; -galactosidase (EC: 3.2.1.23) ; -mannosidase (EC: 3.2.1.25); -glucuronidase (EC: 3.2.1.31).

\ \

These enzymes contain a conserved glutamic acid residue which has been shown [MEDLINE:92283812], in Escherichia coli lacZ (P00722.

\ \ hydrolase activity, hydrolyzing O-glycosyl compounds ; GO:0004553 \N carbohydrate metabolism ; GO:0005975 24563 IPR006105

\
                       +----------------------------+\
           +----------+|   +-+                      |\
           |          ||   | |                      |\
  xxCxxxxxxCxxxCxxxxxxCCxxxCxCxxxxxxxxxxxxxCxxxxxxxxCxxxxxxxCxxxx\
    |          |                           |                |\
    |          +---------------------------+                |\
    +-------------------------------------------------------+\
\
'C': conserved cysteine involved in a disulfide bond.\

This family of proteins also includes a number of seed allergenic protein from rice (see IPR002411.

\ \ serine protease inhibitor activity ; GO:0004867 \N \N 24561 IPR006103

Glycoside hydrolase family 2 CAZY:GH_2\ comprises enzymes with several known activities; -galactosidase (EC: 3.2.1.23) ; -mannosidase (EC: 3.2.1.25); -glucuronidase (EC: 3.2.1.31).

\ \

These enzymes contain a conserved glutamic acid residue which has been shown [MEDLINE:92283812], in Escherichia coli lacZ (P00722), to be the general acid/base catalyst in the active site of the enzyme.

Beta-galactosidase from E. coli has a TIM-barrel-like core surrounded by four other largely domains [MEDLINE:94277211].

\ \ \ hydrolase activity, hydrolyzing O-glycosyl compounds ; GO:0004553 \N carbohydrate metabolism ; GO:0005975 24560 IPR006102

Glycoside hydrolase family 2 CAZY:GH_2\ comprises enzymes with several known activities; -galactosidase (EC: 3.2.1.23) ; -mannosidase (EC: 3.2.1.25); -glucuronidase (EC: 3.2.1.31).

\ \

This entry describes the immunoglobulin-like -sandwich domain [MEDLINE:94277211].

\ \ hydrolase activity, hydrolyzing O-glycosyl compounds ; GO:0004553 \N carbohydrate metabolism ; GO:0005975 24559 IPR006101

Glycoside hydrolase family 2 CAZY:GH_2\ comprises enzymes with several known activities; -galactosidase (EC: 3.2.1.23) ; -mannosidase (EC: 3.2.1.25); -glucuronidase (EC: 3.2.1.31).

\ \

\ \ \ hydrolase activity, hydrolyzing O-glycosyl compounds ; GO:0004553 \N carbohydrate metabolism ; GO:0005975 24558 IPR006100

Methylmalonyl-CoA mutase (EC: 5.4.99.2) (MCM) [MEDLINE:90365682] is an adenosylcobalamin (vitamin B12) dependent enzyme that catalyzes the isomerization between methylmalonyl-CoA and succinyl-CoA. MCM is involved in various catabolic or biosynthetic pathways; for example in man it is involved in the degradation of several amino acids, odd-chain fatty acids and cholesterol via propionyl-CoA to the tricarboxylic acid cycle; while in some bacteria it is involved in the synthesis of propionate from tricarboxylic acid-cycle intermediates.

Deficiency of MCM in man causes an often fatal disorder of organic acid metabolism termed methylmalonic acidemia. The sequences of eukaryotic and prokaryotic MCM are rather well conserved. In eukaryotes MCM is located in the mitochondrial matrix and is a homodimer of a polypeptide chain of about 710 amino acids. In bacteria MCM is a dimer of two non-identical, yet structurally related chains. This family also includes an Escherichia coli protein (gene sbm) whose function is not yet known.

A small degree of similarity is said [MEDLINE:90324235] to exist between MCM and the large subunit of the adenosylcobalamin-dependent enzyme ethanolamine ammonia-lyase, but this similarity is so weak that these two type of enzymes can not be detected by a single pattern.

This sub-family is described by a conserved region which is located\ in the central part of these sequences.

\ \ methylmalonyl-CoA mutase activity ; GO:0004494 \N metabolism ; GO:0008152 24557 IPR006099

\ \ methylmalonyl-CoA mutase activity ; GO:0004494 \N metabolism ; GO:0008152 24556 IPR006098

This describes the N-terminal domain.

\ \ methylmalonyl-CoA mutase activity ; GO:0004494 \N metabolism ; GO:0008152 24555 IPR006097

Glutamate, leucine, phenylalanine and valine dehydrogenases are structurally and functionally related. They contain a Gly-rich region containing a conserved Lys residue, which has been implicated in the catalytic activity, in each case a reversible oxidative deamination reaction.

Glutamate dehydrogenases (EC: 1.4.1.2, EC: 1.4.1.3, and EC: 1.4.1.4) (GluDH) are enzymes that catalyze the NAD- and/or NADP-dependent reversible deamination of L-glutamate into -ketoglutarate [MEDLINE:93049342], [MEDLINE:93301933]. GluDH isozymes are generally involved with either ammonia assimilation or glutamate catabolism. Two separate enzymes are present in yeasts: the NADP-dependent enzyme, which catalyses the amination of -ketoglutarate to L-glutamate; and the NAD-dependent enzyme, which catalyses the reverse reaction [MEDLINE:85234567] - this form links the L-amino acids with the Krebs cycle, which provides a major pathway for metabolic interconversion of -amino acids and - keto acids [MEDLINE:88217927].

Leucine dehydrogenase (EC: 1.4.1.9) (LeuDH) is a NAD-dependent enzyme that catalyzes the reversible deamination of leucine and several other aliphatic amino acids to their keto analogues [MEDLINE:89166517]. Each subunit of this octameric enzyme from Bacillus sphaericus contains\ 364 amino acids and folds into two domains, separated by a deep cleft. The\ nicotinamide ring of the NAD+ cofactor binds deep in this cleft, which is thought to\ close during the hydride transfer step of the catalytic cycle.

\ \ \ oxidoreductase activity ; GO:0016491 \N amino acid metabolism ; GO:0006520 24554 IPR006096

\ \ \ oxidoreductase activity ; GO:0016491 \N amino acid metabolism ; GO:0006520 24553 IPR006095

\ \ \ oxidoreductase activity ; GO:0016491 \N amino acid metabolism ; GO:0006520 24552 IPR006094

Various enzymes use FAD as a co-factor, most of these enzymes are oxygen-dependent oxidoreductases, containing a covalently bound FAD group which is attached to a histidine via an 8--(N3-histidyl)-riboflavin linkage. One of the enzymes Vanillyl-alcohol oxidase (VAO, EC: 1.1.3.38) has a solved structure, the alignment includes the FAD binding site, called the PP-loop, between residues 99-110 [MEDLINE:20556311]. The FAD molecule is covalently bound in the known\ structure, however the residue that links to the FAD is not in the alignment. VAO catalyses the oxidation of a wide\ variety of substrates, ranging from aromatic amines to 4-alkylphenols.

\ \ \N \N electron transport ; GO:0006118 24550 IPR006092

Mammalian Co-A dehydrogenases (EC: 1.3.99.3) are enzymes that catalyse the first step in each cycle of -oxidation in mitochondion. Acyl-CoA dehydrogenases [MEDLINE:88151871], [MEDLINE:89380240], [MEDLINE:94308174] catalyze the ,-dehydrogenation of acyl-CoA thioesters to the corresponding trans 2,3-enoyl CoA-products with concommitant reduction of enzyme-bound FAD. Reoxidation of the flavin involves transfer of electrons to ETF (electron transfering flavoprotein). These enzymes are homodimers containing one molecule of FAD.

The monomeric enzyme is folded into three domains of approximately equal size. The N-terminal and the C-terminal are mainly -helices packed together, and the middle domain consists of two orthogonal -sheets. The flavin ring is buried in the crevise between two -helical domains and the -sheet of one subunit, and the adenosine pyrophosphate moiety is stretched into the subunit junction with one formed by two C-terminal domains [MEDLINE:93361479].

The N-terminal domain of Acyl-CoA dehydrogenase is an all- domain, on dimerisation, the N-terminal of one molecule extends into the other dimer and lies on the surface of the molecule.

\ acyl-CoA dehydrogenase activity ; GO:0003995 \N electron transport ; GO:0006118 24551 IPR006093

Other members of this family include

D-lactate\ dehydrogenase, this enzyme catalyses the conversion of D-lactate to pyruvate using FAD as a co-factor;
mitomycin\ radical oxidase, this enzyme oxidizes the reduced form of mitomycins and is involved in mitomycin resistance.
MurB, an UDP-N-acetylenolpyruvoylglucosamine reductase enzyme EC: 1.1.1.158. This enzyme is involved in the\ biosynthesis of peptidoglycan [MEDLINE:96419135]

\ \ oxidoreductase activity ; GO:0016491 \N electron transport ; GO:0006118 24549 IPR006091

The central domain of Acyl-CoA dehydrogenase has a -barrel fold.

\ acyl-CoA dehydrogenase activity ; GO:0003995 \N electron transport ; GO:0006118 24548 IPR006090

\ oxidoreductase activity ; GO:0016491 \N electron transport ; GO:0006118 24545 IPR006087 The SUR2-type hydroxylase/desaturase catalytic domain is present in a variety of proteins including C-4 methyl sterol oxidase, which is involved in cholesterol biosynthesis;

-carotene hydroxylase, which catalyses the hydroxylation of

-carotene to zeaxanthine; C-5 sterol desaturase, which introduces a C-5 double bond into the ring of ergosterol; and SUR2 (syringomycin response protein 2), which is involved in the response to syringomycin.\ enzyme activity ; GO:0003824 \N metabolism ; GO:0008152 24546 IPR006088

This family includes C-5 sterol desaturase and C-4 sterol methyl oxidase. Members of this family are involved in cholesterol biosynthesis and biosynthesis of a plant cuticular wax. These enzymes contain many conserved histidine residues. Members of this family are integral membrane proteins.

\ enzyme activity ; GO:0003824 \N metabolism ; GO:0008152 24547 IPR006089

Mammalian Co-A dehydrogenases (EC: 1.3.99.3) are enzymes that catalyse the first step in each cycle of -oxidation in mitochondion. Acyl-CoA dehydrogenases [MEDLINE:88151871], [MEDLINE:89380240], [MEDLINE:94308174] catalyze the ,-dehydrogenation of acyl-CoA thioesters to the corresponding trans 2,3-enoyl CoA-products with concommitant reduction of enzyme-bound FAD. Reoxidation of the flavin involves transfer of electrons to ETF (electron transfering flavoprotein) [MEDLINE:93361479]. These enzymes are homodimers containing one molecule of FAD.

\ acyl-CoA dehydrogenase activity ; GO:0003995 \N electron transport ; GO:0006118 24544 IPR006086

Xeroderma pigmentosum (XP) [MEDLINE:94212451] is a human autosomal recessive disease, characterized by a high incidence of sunlight-induced skin cancer. People's skin cells with this condition are hypersensitive to ultraviolet light, due to defects in the incision step of DNA excision repair. There are a minimum of seven genetic complementation groups involved in this pathway: XP-A to XP-G. XP-G is one of the most rare and phenotypically heterogeneous of XP, showing anything from slight to extreme dysfunction in DNA excision repair [MEDLINE:93219111], [MEDLINE:94266772]. XP-G can be corrected by a 133 Kd nuclear protein, XPGC [MEDLINE:94212451]. XPGC is an acidic protein that confers normal UV resistance in expressing cells [MEDLINE:94266772]. It is a magnesium-dependent, single-strand DNA endonuclease that makes structure-specific endonucleolytic incisions in a DNA substrate containing a duplex region and single-stranded arms [MEDLINE:94266772], [MEDLINE:94376899]. XPGC cleaves one strand of the duplex at the border with the single-stranded region [MEDLINE:94376899].

XPG belongs to a family of proteins that includes RAD2 from budding yeast and rad13 from fission yeast, which are single-stranded DNA endonucleases [MEDLINE:94376899], [MEDLINE:94067324]; mouse and human FEN-1, a structure-specific endonuclease; RAD2 from fission yeast and RAD27 from budding yeast; fission yeast exo1, a 5'-3' double-stranded DNA exonuclease that may act in a pathway that corrects mismatched base pairs; yeast DHS1, and yeast DIN7. Sequence alignment of this family of proteins reveals that similarities are largely confined to two regions. The first is located at the N-terminal extremity (N-region) and corresponds to the first 95 to 105 amino acids. The second region is internal (I-region) and found towards the C-terminus; it spans about 140 residues and contains a highly conserved core of 27 amino acids that includes a conserved pentapeptide (E-A-[DE]-A-[QS]). It is possible that the conserved acidic residues are involved in the catalytic mechanism of DNA excision repair in XPG. The amino acids linking the N- and I-regions are not conserved.

\ \ nuclease activity ; GO:0004518 \N DNA repair ; GO:0006281 24543 IPR006085

\ \ nuclease activity ; GO:0004518 \N DNA repair ; GO:0006281 24542 IPR006084

\ \ nuclease activity ; GO:0004518 \N DNA repair ; GO:0006281 24540 IPR006082

Phosphoribulokinase (PRK) EC: 2.7.1.19 catalyses the ATP-dependent phosphorylation of ribulose-5-phosphate to ribulose-1,5-phosphate, a key step in the pentose phosphate \ pathway where carbon dioxide is assimilated by autotrophic organisms [MEDLINE:91084479]. In \ general, plant enzymes are light-activated by the thioredoxin/ferredoxin system, while \ those from photosynthetic bacteria are regulated by a system that has an absolute \ requirement for NADH. Thioredoxin/ferredoxin regulation is mediated by the reversible\ oxidation/reduction of sulphydryl and disulphide groups. In the spinach enzyme (P09559) the \ participating residues are Cys-16 and Cys-55. Sequence analysis shows the first of these \ cysteines to be present in the ATP-binding site [MEDLINE:88087076]; neither is found in the \ bacterial sequences.

\ \ phosphoribulokinase activity ; GO:0008974 \N carbohydrate metabolism ; GO:0005975 24541 IPR006083

Uridine kinase (pyrimidine ribonucleoside kinase) is the rate-limiting enzyme in the pyrimidine\ salvage pathway. It catalyzes the following reaction:\

\
ATP + Uridine = ADP + UMP\

Pantothenate kinase (EC: 2.7.1.33) catalyzes the rate-limiting step in the biosynthesis of coenzyme A, the conversion of pantothenate to D-4'-phosphopantothenate in the presence of ATP.

\ \ kinase activity ; GO:0016301 \N biosynthesis ; GO:0009058 24539 IPR006081

Defensins are produced constitutively and/or in response to microbial products or proinflammatory cytokines. Some defensins are also called corticostatins (CS) because \ they inhibit corticotropin-stimulated corticosteroid production. The mechanism(s) by which microorganisms are killed and/or inactivated by defensins is not understood completely. However, it is generally believed that killing is a\ consequence of disruption of the microbial membrane. The polar topology of defensins, with spatially separated charged and hydrophobic regions, allows them to\ insert themselves into the phospholipid membranes so that their hydrophobic regions are buried within the lipid membrane interior and their charged (mostly cationic)\ regions interact with anionic phospholipid head groups and water. Subsequently, some defensins can aggregate to form 'channel-like' pores; others might bind to and cover the microbial membrane in a 'carpet-like' manner. The net outcome is the disruption of membrane integrity and function,\ which ultimately leads to the lysis of microorganisms. Some defensins are synthesized as propeptides which may be relevant to this process.

Human neutrophil-derived -defensins (HNPs) are\ capable of enhancing phagocytosis by mouse macrophages. HNP1-3 have been reported to increase the production of tumor necrosis factor (TNF) and IL-1, while decreasing the production of IL-10 by monocytes.\ Increased levels of proinflammatory factors (e.g. IL-1, TNF, histamine and prostaglandin D2) and suppressed levels of IL-10 at the site of microbial infection are likely to\ amplify local inflammatory responses. This might be further reinforced by the capacity of some human and rabbit -defensins to inhibit the production of\ immunosuppressive glucocorticoids by competing for the binding of adrenocorticotropic hormone to its receptor. Moreover, human -defensins can enhance\ or suppress the activation of the classical pathway of complement in vitro by binding to solid-phase or fluid-phase complement C1q, respectively. The\ capacity of defensins to enhance phagocytosis, promote neutrophil recruitment, enhance the production of proinflammatory cytokines, suppress anti-inflammatory\ mediators and regulate complement activation argues that defensins upregulate innate host inflammatory defenses against microbial invasion.

\ \ antimicrobial peptide activity ; GO:0003795 extracellular ; GO:0005576 defense response ; GO:0006952 24538 IPR006080

Defensins are 2-6 kDa, cationic, microbicidal peptides active against many Gram-negative and Gram-positive bacteria, fungi, and enveloped viruses [MEDLINE:96085805], containing three pairs of intramolecular disulfide bonds. On the basis of their size and pattern of\ disulfide bonding, mammalian defensins are classified into , and theta categories. Alpha-defensins, which have been identified in humans, monkeys and several\ rodent species, are particularly abundant in neutrophils, certain macrophage populations and Paneth cells of the small intestine. Every mammalian species\ explored thus far has -defensins. In cows, as many as 13 -defensins exist in neutrophils. However, in other species, -defensins are more often produced by\ epithelial cells lining various organs (e.g. the epidermis, bronchial tree and genitourinary tract). Theta-defensins are cyclic and have so far only been identified in primate\ phagocytes.

\ \ antimicrobial peptide activity ; GO:0003795 extracellular ; GO:0005576 defense response ; GO:0006952 24537 IPR006079

Lantibiotics are heavily-modified bacteriocin-like peptides from Gram- positive bacteria. They contain ,-unsaturated amino acids (dehydroalanine and dehydrobutyrine) and lanthionine or 3-methyllanthionine rings (collectively known as thioether rings). There are 2 types of lantibiotic:

Type A (which include nisin, subtilin, epidermin,\ gallidermin and Pep5) are strongly cationic and bactericidal - nisin, subtilin and Pep5 inhibit the growth of Gram-positive\ bacteria, probably by voltage-dependent pore formation in the cytoplasmic membrane, resulting in cellular efflux of\ electrolytes, amino acids and ATP;
Type B lantibiotics possess at most one positive charge and are not bactericidal.

This domain is found in both type A and type B molecules.

\ \ Gram-positive antibacterial peptide activity ; GO:0008224 \N defense response ; GO:0006952 24535 IPR006077

Vinculin is a eukaryotic protein that seems to be involved in theattachment of the actin-based microfilaments to the plasma membrane. Vinculin\ is located at the cytoplasmic side of focal contacts or adhesion plaques\ [MEDLINE:90284037]. In addition to actin, vinculin interacts with other structural\ proteins such as talin and -actinins.

Vinculin is a large protein of 116 kDa (about a 1000 residues). Structurally the protein consists of an acidic N-terminal domain of about 90 kDa separated from a basic C-terminal domain of about 25 kDa by a proline-rich region of about 50 residues. The central part of the N-terminal domain consists of a variable number (3 in vertebrates, 2 in Caenorhabditis elegans) of repeats of a 110 amino acids domain.

Alpha-catenins are evolutionary related to vinculin IPR001033\ \ \ \ [MEDLINE:92021009]. Catenins are proteins that associate with the cytoplasmic domain of a variety of cadherins. The association of catenins to cadherins produces a complex which is linked to the actin filament network, and which seems to be of primary importance for cadherins cell-adhesion properties. Three different types of catenins seem to exist: , , and gamma. Alpha-catenins are proteins of about 100 kDa which are evolutionary related to vinculin. In terms of their structure the most significant differences are the absence, in -catenin, of the repeated domain and of the proline-rich segment.

\ \ \N \N \N 24536 IPR006078

Type A (which include nisin, subtilin, epidermin,\ gallidermin and Pep5) are strongly cationic and bactericidal - nisin, subtilin and Pep5 inhibit the growth of Gram-positive\ bacteria, probably by voltage-dependent pore formation in the cytoplasmic membrane, resulting in cellular efflux of\ electrolytes, amino acids and ATP;
Type B lantibiotics possess at most one positive charge and are not bactericidal.

Gallidermin is a type A lantibiotic. Type A lantibiotics (which include nisin,\ subtilin, epidermin, gallidermin and Pep5) are strongly cationic and bactericidal.\ Nisin, subtilin, epidermin and gallidermin are likely to have evolved from a common\ ancestor [MEDLINE:89034093]. The sequences of lantibiotics do not adopt regular secondary\ structures because of their constituent thioether rings (four are found in gallidermin).\ Nevertheless, the rings may be important in providing rigid local structures, which\ could be essential for pore formation in membranes [MEDLINE:92032577].

\ \ Gram-positive antibacterial peptide activity ; GO:0008224 \N defense response ; GO:0006952 24532 IPR006074

A widespread family of GTP-binding proteins has been recently characterized[MEDLINE:93080583], [MEDLINE:93216121]. The function of the proteins that belong to this family is not yet known. They are polypeptides of about 40 to 48 kDa which contain the five small sequence\ elements characteristic of GTP-binding proteins [MEDLINE:91095015]. As a signature pattern was\ selected the region that correspond to the ATP/GTP B motif (also called G-3 in\ GTP-binding proteins).\

\ \ \N \N \N 24533 IPR006075

\ \ \N \N \N 24534 IPR006076 This family includes various FAD dependent oxidoreductases: Glycerol-3-phosphate dehydrogenase (EC: 1.1.99.5) , Sarcosine oxidase

subunit (EC: 1.5.3.1), D-alanine oxidase (EC: 1.4.99.1), D-aspartate oxidase (EC: 1.4.3.1).

D-amino acid oxidase (EC: 1.4.3.3) (DAMOX or DAO) is an FAD flavoenzyme that catalyzes the oxidation \ of neutral and basic D-amino acids into their corresponding keto acids. DAOs have been characterized \ and sequenced in fungi and vertebrates where they are known to be located in the peroxisomes. D-aspartate \ oxidase (EC: 1.4.3.1) (DASOX) [MEDLINE:92291057] is an enzyme, structurally related to DAO, which catalyzes \ the same reaction but is active only toward dicarboxylic D-amino acids. In DAO, a conserved histidine \ has been shown [MEDLINE:91201275] to be important for the enzyme's catalytic activity.

\ \ oxidoreductase activity ; GO:0016491 \N electron transport ; GO:0006118 24525 IPR006067

Sulphite and nitrite reductases are vital in the biosynthetic assimilation of sulphur and nitrogen, respectfully. They are both also important for the dissimilation of oxidized anions for energy transduction.

\ \N \N electron transport ; GO:0006118 24526 IPR006068

Members of this families are involved in Na+/K+, H+/K+, Ca++ and Mg++ transport.

\ P-type ATPase activity ; GO:0015662 membrane ; GO:0016020 cation transport ; GO:0006812 24527 IPR006069 The

Several uncharacterized proteins of from 20 to 46 kDa have been shown to contain a number of conserved regions in their N-terminal section. These include yeast protein SUA5 (P32579).

\ \N \N \N 24529 IPR006071

Proteins containing this domain are involved in the hydrogenase maturation process.

\ \N \N \N 24530 IPR006072

Pheromone binding proteins (PBPs) are abundant, secreted antennal proteins present in olfactory sensilla. They lie in the lymph that surrounds the dendrites of olfactory receptor neurons [MEDLINE:94266829]. The olfactory receptors of terrestrial animals exist in an\ aqueous environment, yet detect odorants that are primarily hydrophobic. The aqueous solubility of hydrophobic odorants is\ thought to be greatly enhanced via odorant binding proteins which exist in the extracellular fluid surrounding the odorant\ receptors [MEDLINE:91186129]. This family is composed of pheromone binding proteins (PBP), which are male-specific and associate with\ pheromone-sensitive neurons and general-odorant binding proteins (GOBP). GOBPs have been found in moth antennae,\ and share a high level of sequence similarity with the PBPs. They are believed to carry odorants rather than pheromones.\ This family is distinct from the vertebrate odorant-binding proteins (OBPs).

\ \ odorant binding activity ; GO:0005549 \N transport ; GO:0006810 24531 IPR006073 Several proteins have recently been shown to contain the 5 structural motifs characteristicof GTP-binding proteins [MEDLINE:93080583]. These include murine DRG protein; GTP1 protein\ from Schizosaccharomyces pombe; OBG protein from Bacillus subtilis; and several others.\ Although the proteins contain GTP-binding motifs and are similar to each other, they do\ not share sequence similarity to other GTP-binding proteins, and have thus been classed\ as a novel group, the GTP1/OBG family. As yet, the functions of these proteins is uncertain,\ but they have been shown to be important in development and normal cell metabolism\ [MEDLINE:93216121], [MEDLINE:89155435].\ \ \ \N \N \N 24522 IPR006064

These enzymes correspond to Agrobacterium rolC and were characterized along with rolB. RolB and rolC were originally classified as glycoside hydrolase family 40 and 41 respectively. RolB has subsequently been shown [MEDLINE:96170030] to have tyrosine phosphatase activity.

\ \N \N \N 24523 IPR006065

Family 41 encompasses cytokinin--glucosidases. These enzymes hydrolyse\ cytokinin glucosides, liberating free cytokinins [MEDLINE:92007732] and contribute to root-\ inducing activity [MEDLINE:94227335].

\ \ beta-glucosidase activity ; GO:0008422 \N carbohydrate metabolism ; GO:0005975 24524 IPR006066 Nitrite reductases and bacterial sulphite reductases catalyse the 6-electron reduction of nitrite (sulphite) toammonia (sulphide) PUB00003574, PUB00003574. On the basis of physiological function, 2 types of nitrite\ reductase can be defined: the assimilatory type, which is involved in nitrate assimilation (denitrification);\ and the dissimilatory type, which is responsible for nitrate respiration function. Assimilatory nitrite\ reductases contain a prosthetic group termed sirohaem (an iron tetra-hydroporphyrin of the isobacteriochlorin\ type, with 8 carboxylic acid-containing peripheral sidechains), and an iron-sulphur cluster. Similarly, there\ are 2 types of sulphite reductase: the assimilatory type, which participate in the synthesis of \ sulphur-containing compounds; and the dissimilatory type, which are terminal reductases in the reduction of sulphate.\ Assimilatory sulphite reductases can catalyse 6-electron reduction without the formation of free intermediates,\ while dissimilatory reductases can produce trithionate and thiosulphate in addition to sulphide. Both types of\ reductase contain sirohaem and iron-sulphur clusters PUB00003574. A region of sequence similarity, about 80\ amino acids long, is shared by assimilatory nitrite PUB00003574 and sulphite reductases [MEDLINE:91139599],\ [MEDLINE:89359425]. Four conserved Cys residues are suggested to be involved in binding the sirohaem group and/or the\ iron-sulphur center [MEDLINE:89359425].\ \ \N \N electron transport ; GO:0006118 24520 IPR006062 Histidine is formed by several complex and distinct biochemical reactions catalysed by eight enzymes. Proteinsinvolved in steps 4 and 6 of the histidine biosynthesis pathway are contained in one family. These enzymes are called\ His6 and His7 in eukaryotes and HisA and HisF in prokaryotes. HisA is a phosphoribosylformimino-5-aminoimidazole\ carboxamide ribotide isomerase (EC: 5.3.1.16), involved in the fourth step of histidine biosynthesis. The bacterial HisF\ protein is a cyclase which catalyzes the cyclization reaction that produces D-erythro-imidazole glycerol phosphate during\ the sixth step of histidine biosynthesis. The yeast His7 protein is a bifunctional protein which catalyzes an \ amido-transferase reaction that generates imidazole-glycerol phosphate and 5-aminoimidazol-4-carboxamide. The latter is the\ ribonucleotide used for purine biosynthesis. The enzyme also catalyzes the cyclization reaction that produces \ D-erythro-imidazole glycerol phosphate, and is involved in the fifth and sixth steps in histidine biosynthesis.\ \ \N \N histidine biosynthesis ; GO:0000105 24521 IPR006063

1-(5-phosphoribosyl)-5-[(5-phosphoribosylamino)methylideneamino] imidazole-4-carboxamide isomerase (EC: 5.3.1.16), also known as Phosphoribosylformimino-5-aminoimidazole carboxamide ribotide isomerase or HisA, catalyses the fourth step in histidine biosynthesis. HisA from Lactococcus lactis was found to be inactive [MEDLINE:93322317].The putative HisA from Thermotoga maritima, is a conspicuous outlier to the set of all other HisA, including experimental HisA from the bacterium E. coli and the Archaeaon Methanococcus voltae. Neighbor joining shows HisA from Thermotoga maritima to be within the HisA family (with HisF as an outgroup) but with a long branch.

\ \ \ 1-(5-phosphoribosyl)-5-[(5-phosphoribosylamino)methylideneamino)imidazole-4-carboxamide isomerase activity ; GO:0003949\ \N \N histidine biosynthesis ; GO:0000105 24517 IPR006059

Bacterial high affinity transport systems are involved in active transport of solutes across the cytoplasmic membrane. The protein components of these traffic systems include one or two transmembrane protein components, one or two membrane-associated ATP-binding proteins and a high affinity periplasmic solute-binding protein. In Gram-positive bacteria, which are surrounded by a single membrane and therefore have no periplasmic region, the equivalent proteins are bound to the membrane via an N-terminal lipid anchor. These homologue proteins do not play an integral role in the transport process per se, but probably serve as receptors to trigger or initiate translocation of the solute through the membrane by binding to external sites of the integral membrane proteins of the efflux system. In addition at least some solute-binding proteins function in the initiation of sensory transduction pathways.

On the basis of sequence similarities, the vast majority of these solute-binding proteins can be grouped [MEDLINE:93330183]\ into eight families of clusters, which generally correlate with the nature of the solute bound. Family 1 currently \ includes the periplasmic proteins maltose/maltodextrin-binding proteins of Enterobacteriaceae (gene malE) [MEDLINE:95156492] \ and Streptococcus pneumoniae malX; multiple oligosaccharide binding protein of Streptococcus mutans (gene msmE); E. coli \ glycerol-3-phosphate-binding protein; Serratia marcescens iron-binding protein (gene sfuA) and the homologous proteins \ (gene fbp) from Haemophilus influenzae and Neisseria; and E. coli thiamine-binding protein (gene tbpA).

\ \ transporter activity ; GO:0005215 \N transport ; GO:0006810 24518 IPR006060

Maltodextrin binding protein (MBP) is the primary component of bacterial\ high-affinity active transport and chemotaxis [MEDLINE:95156492]. It is a monomeric\ protein, with 2 globular domains separated by a 2- or 3-stranded hinge.\ MBP binds and transports linear oligosaccharides (of up to 7 glucosyl\ units), as well as 2 cyclic maltodextrins which, although binding\ tightly, cannot be transported nor initiate a chemotactic response [MEDLINE:94002045].\ It is thought that the hinge region is critical for the correct \ functioning of MBP, not just in the binding and recognition of sugars,\ but also in allowing and maintaining the integrity of initiation of\ both active transport and chemotaxis [MEDLINE:93041761].\

\ \ maltose transporter activity ; GO:0005363 \N maltose transport ; GO:0015768 24519 IPR006061

Bacterial high affinity transport systems are involved in active transport of solutes across the cytoplasmic membrane.The protein components of these traffic systems include one or two transmembrane protein components, one or two\ membrane-associated ATP-binding proteins and a high affinity periplasmic solute-binding protein. In gram-positive\ bacteria which are surrounded by a single membrane and have therefore no periplasmic region the equivalent proteins\ are bound to the membrane via an N-terminal lipid anchor. These homolog proteins do not play an integral role in the\ transport process per se, but probably serve as receptors to trigger or initiate translocation of the solute through the\ membrane by binding to external sites of the integral membrane proteins of the efflux system. In addition at least some\ solute-binding proteins function in the initiation of sensory transduction pathways.

On the basis of sequence similarities, the vast majority of these solute-binding proteins can be grouped [MEDLINE:93330183]\ into eight families of clusters, which generally correlate with the nature of the solute bound. Family 1 currently \ includes the periplasmic proteins maltose/maltodextrin-binding proteins of Enterobacteriaceae (gene malE) [MEDLINE:95156492] \ and Streptococcus pneumoniae malX; multiple oligo-saccharide binding protein of Streptococcus mutans (gene msmE); E. coli \ glycerol-3-phosphate-binding protein; Serratia marcescens iron-binding protein (gene sfuA) and the homologous proteins \ (gene fbp) from Haemophilus influenzae and Neisseria; and E. coli thiamine-binding protein (gene tbpA).

\ \ transporter activity ; GO:0005215 \N transport ; GO:0006810 24512 IPR006054

All proteins in this family for which functions are known are components of the DNA polymerase III complex (epsilon subunit).

\ DNA-directed DNA polymerase activity ; GO:0003887 \N DNA replication ; GO:0006260 24513 IPR006055 This family includes a variety of exonuclease proteins, such as ribonuclease T [MEDLINE:93281412] and the epsilon subunit of DNA polymerase III. Ribonuclease T is responsible for the end-turnover of tRNA,and removes the terminal AMP residue from uncharged tRNA. DNA polymerase III is a complex, multichain enzyme responsible for most of the replicative synthesis in bacteria, and also exhibits 3' to 5' exonuclease activity.\ exonuclease activity ; GO:0004527 intracellular ; GO:0005622 \N 24514 IPR006056

This family includes proteins encoded by the yabJ gene from Bacillus subtilis that is required for adenine-mediated repression of purinebiosynthetic genes in vivo and codes for an acid-soluble, 14-kDa protein.\ The structure of this protein has been solved [MEDLINE:20027502] and the protein\ is found to form a homotrimer. The trimer has a deep cleft that is a probably \ ligand binding site and possibly forms an enzymatic active site. However the ligand and reaction are unknown.

\ \ \N \N \N 24515 IPR006057

Ferredoxins are iron-sulphur proteins that mediate electron transfer in a range of metabolic reactions [MEDLINE:93073713],[MEDLINE:89382659]; they fall into several subgroups according to the nature of their iron-sulphur cluster(s). One group,\ originally found in chloroplast membranes, has been termed 'chloroplast-type' or 'plant-type', and includes ferredoxins\ from plants, algae, archaebacteria, rhodobacter and a toluene degrading pseudomonas. Here, the active centre is a\ 2Fe-2S cluster, where the irons are tetrahedrally coordinated by both inorganic sulphurs and sulphurs provided by 4\ conserved Cys residues [MEDLINE:91214942]. In chloroplasts, 2Fe-2S ferredoxins function as electron carriers in the\ photosynthetic electron transport chain and as electron donors to various cellular proteins PUB00003104. In\ hydroxylating bacterial dioxygenase systems, they serve as intermediate electron-transfer carriers between\ reductase flavoproteins and oxygenase PUB00003104.

Several oxidoreductases contain redox domains similar to 2Fe-2S ferredoxins, including ferredoxin/ferredoxin \ reductase components of several bacterial aromatic di- and monooxygenases, phenol hydroxylase, methane \ monooxygenase, vanillate demethylase oxidoreductase, phthalate dioxygenase reductase, bacterial fumarate \ reductase iron-sulphur protein, eukaryotic succinate dehydrogenase and xanthine dehydrogenase. 3D structures \ are known for a number of 2Fe-2S ferredoxins [MEDLINE:91214942] and for the ferredoxin reductase/ferredoxin fusion protein \ phthalate dioxygenase reductase [MEDLINE:93088078]. The fold belongs to the + class, with 3 helices and 4 \ strands forming a barrel-like structure, and an extruded loop containing 3 of the 4 cysteinyl residues of the \ iron-sulphur cluster.

\ \ electron transporter activity ; GO:0005489 \N electron transport ; GO:0006118 24516 IPR006058

\ \ electron transporter activity ; GO:0005489 \N electron transport ; GO:0006118 24511 IPR006053

Tumor necrosis factor (TNF) (or cachectin) is a monocyte-derived cytotoxinthat has been implicated in tumour regression, septic shock and cachexia\ [MEDLINE:85242112], [MEDLINE:88165056]. The protein is synthesised as a prohormone with an unusually long \ and atypical signal sequence, which is absent from the mature secreted\ cytokine [MEDLINE:91097531]. A short hydrophobic stretch of amino acids serves to anchor \ the prohormone in lipid bilayers. Both the mature protein and a \ partially-processed form of the hormone are secreted after cleavage of the\ propeptide [MEDLINE:89380231].

\ \ tumor necrosis factor receptor ligand activity ; GO:0005164 membrane ; GO:0016020 immune response ; GO:0006955 24509 IPR006051

DNA photolyases are enzymes that bind to DNA containing pyrimidine dimers:on absorption of visible light, they catalyse dimer splitting into the\ constituent monomers, a process called photoreactivation [MEDLINE:84185762]. This is a DNA\ repair mechanism, repairing mismatched pyrimidine dimers induced by\ exposure to ultra-violet light [MEDLINE:86083177]. The precise mechanisms involved in\ substrate binding, conversion of light energy to the mechanical energy\ needed to rupture the cyclobutane ring, and subsequent release of the\ product are uncertain [MEDLINE:84185762]. Analysis of DNA lyases has revealed the presence\ of an intrinsic chromophore, all monomers containing a reduced FAD moiety,\ and, in addition, either a reduced pterin or 8-hydroxy-5-diazaflavin as a\ second chromophore [MEDLINE:86083177], [MEDLINE:90243674]. Either chromophore may act as the primary photon\ acceptor, peak absorptions occurring in the blue region of the spectrum\ and in the UV-B region, at a wavelength around 290nm [MEDLINE:90243674].

This entry represents the N-terminal part of the DNA photolyase FAD binding domain.

\ \ DNA photolyase activity ; GO:0003913 \N DNA repair ; GO:0006281 24510 IPR006052

The following cytokines can be grouped into a family on the basis of sequence, functional, and structural similarities [MEDLINE:93200072], [MEDLINE:92310561], PUB00001027:

Tumor Necrosis Factor (TNF) (also known as cachectin or TNF-) PUB00001027, [MEDLINE:91210229] is a cytokine which has a wide variety of functions. It can cause cytolysis of certain tumor cell lines; it is involved in the induction of cachexia; it is a potent pyrogen, causing fever by direct action or by stimulation of interleukin-1 secretion; finally, it can stimulate cell proliferation and induce cell differentiation under certain conditions.
Lymphotoxin- (LT-) and lymphotoxin- (LT-), two related cytokines produced by lymphocytes and which are cytotoxic for a wide range of tumor cells in vitro and in vivo [MEDLINE:93208881].
T cell antigen gp39 (CD40L), a cytokine which seems to be important in B-cell development and activation.
CD27L, a cytokine which plays a role in T-cell activation. It induces the proliferation of costimulated T cells and enhances the generation of cytolytic T cells.
CD30L, a cytokine which induces proliferation of T cells.
FASL, a cytokine involved in cell death [MEDLINE:94084792].
4-1BBL, a inducible T cell surface molecule that contributes to T-cell stimulation.
OX40L, a cytokine that co-stimulates T cell proliferation and cytokine production [MEDLINE:94357171].
TNF-related apoptosis inducing ligand (TRAIL), a cytokine that induces apoptosis [MEDLINE:96111955].
TNF- is synthesized as a type II membrane protein which then undergoes post-translational cleavage liberating the extracellular domain. CD27L, CD30L, CD40L, FASL, LT-, 4-1BBL and TRAIL also appear to be type II membrane proteins. LT- is a secreted protein.

All these cytokines seem to form homotrimeric (or heterotrimeric in the case of LT-/) complexes that are recognized by their specific receptors. The PROSITE pattern for this family is located in a -strand in the central section of the protein which is conserved across all members.

\ \ tumor necrosis factor receptor ligand activity ; GO:0005164 membrane ; GO:0016020 immune response ; GO:0006955 24508 IPR006050

This domain binds a light harvesting cofactor.

\ \ DNA photolyase activity ; GO:0003913 \N DNA repair ; GO:0006281 24507 IPR006048

Alpha amylase is classified as family 13 of the glycosyl hydrolases. The structure is an 8 stranded / barrel containing the active site, interrupted by a ~70 a.a. calcium-binding domain protruding between strand 3 and helix 3, and a carboxyl-terminal Greek key -barrel domain.

\ \ alpha-amylase activity ; GO:0004556 \N carbohydrate metabolism ; GO:0005975 24504 IPR006045

This family represents the conserved barrel domain of the 'cupin' superfamily ('cupa' is the Latin term for a small barrel). This family contains 11S and 7S plant seed storage proteins, and germins. Plant seed storage proteins provide the major nitrogen source for the developing plant.

\ nutrient reservoir activity ; GO:0045735 \N \N 24505 IPR006046

Glycoside hydrolase family 13 CAZY:GH_13).

Alpha-amylases are 1,4--D-glucan glucanohydrolases, which\ degrade both the branched and unbranched forms of starch by cleaving the\ internal -1,4 bonds connecting the glucose monomers. The products of\ these reactions are maltose and maltotriose, which are further degraded to\ glucose by maltases. One atom of calcium is required to bind to each protein\ molecule to allow it to function, but excess calcium can inhibit activity\ by binding to amino acids that are required for the catalytic activity\ of the enzyme.

\ \ alpha-amylase activity ; GO:0004556 \N carbohydrate metabolism ; GO:0005975 24506 IPR006047

Alpha amylase is classified as family 13 of the glycosyl hydrolases (CAZY:GH_13). The structure is an 8 stranded / barrel containing the active site, interrupted by a ~70 a.a. calcium-binding domain protruding between strand 3 and helix 3, and a carboxyl-terminal Greek key -barrel domain.

\ \ alpha-amylase activity ; GO:0004556 \N carbohydrate metabolism ; GO:0005975 24500 IPR006041

The allergens in this family include allergens with the following designations: Ole e 1.

\ \

A number of plant pollen proteins, whose biological function is not yet\ known, are structurally related [MEDLINE:94009049].\ These proteins are most probably secreted and consist of about 145 residues.\ There are six cysteines\ which are conserved in the sequence of these proteins. They seem to be\ involved in disulfide bonds.

\ \ \N \N \N 24501 IPR006042 A number of transport proteins which are involved in the uptake of xanthineor uracil are evolutionary related [MEDLINE:95238349].\ They are proteins of from 430 to 595 residues that seem to contain 12\ transmembrane domains.\ \ transporter activity ; GO:0005215 membrane ; GO:0016020 transport ; GO:0006810 24502 IPR006043

This family includes permeases for diverse substrates such as xanthine, uracil and vitamin C. However many members of this family are functionally uncharacterised and may transport other substrates. Members of this family have ten predicted transmembrane helices.

\ transporter activity ; GO:0005215 membrane ; GO:0016020 transport ; GO:0006810 24503 IPR006044 Plant seed storage proteins, whose principal function appears to be the majornitrogen source for the developing plant, can be classified, on the basis of\ their structure, into different families. 11-S are non-glycosylated proteins\ which form hexameric structures [MEDLINE:88166744], PUB00004572. Each of the subunits in the hexamer is\ itself composed of an acidic and a basic chain derived from a single precursor\ and linked by a disulfide bond. This structure is shown in the following\ representation.\

\ +-------------------------+\ | |\ xxxxxxxxxxxCxxxxxxxxxxxxxxxxxxxxxxNGxCxxxxxxxxxxxxxxxxxxxxxxx\ |------Acidic-subunit-------------||-----Basic-subunit------|\ |-----------------About-480-to-500-residues-----------------|\ \ 'C': conserved cysteine involved in a disulfide bond.\

\ \ Members of the 11-S family include pea and broad bean legumins, rape\ cruciferin, rice glutelins, cotton

-globulins, soybean glycinins, pumpkin\ 11-S globulin, oat globulin, sunflower helianthinin G3, etc.\ This family represents the precursor protein which is cleaved into \ the two chains. These proteins contain two

-barrel domains.\ This family is a member of the 'cupin' superfamily on the\ basis of their conserved barrel domain ('cupa' is the Latin term\ for a small barrel).\ \ nutrient reservoir activity ; GO:0045735 \N \N 24497 IPR006038

Uteroglobin [MEDLINE:89199637] is a protein that seems specific to lagomorphes (rabbit, hare,and pica) and which binds progesterone specifically and with high affinity. It\ may regulate progesterone concentrations reaching the blastocyst. Uteroglobin\ is also a potent inhibitor of phospholipase A2. It is a protein of 70 amino\ acids that form antiparallel disulfide-linked dimers. The progesterone-\ binding site is formed by a cavity between the monomeric subunits. A schematic\ representation of the location of the two disulfide bonds in the antiparallel\ dimer is shown below:\

\ NH2-xxCxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxCx-COOH\ | | \ COOH-xCxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxCxx-NH2\

\ \ The precise role of uteroglobin has still to be elucidated [MEDLINE:95288292].

\ \ \N \N \N 24498 IPR006039

\ NH2-xxCxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxCx-COOH\ | | \ COOH-xCxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxCxx-NH2\

\ \ The precise role of uteroglobin has still to be elucidated [MEDLINE:95288292].

\ \ \N \N \N 24499 IPR006040

The allergens in this family include allergens with the following designations: Ole e 1.

\ \

\ \ \N \N \N 24494 IPR006035 Arginase, which catalyses the conversion of arginine to urea and ornithine,is one of the five members of the urea cycle enzymes that convert ammonia\ to urea as the principal product of nitrogen excretion [MEDLINE:93170326]. There are\ several arginase isozymes: a liver isozyme takes part in the final step of\ the urea cycle in ureotelic animals [MEDLINE:87092419]; other isozymes take part in the\ first step of arginine degradation in various cell types (the kidney, small\ intestine and lactating mammary glands) [MEDLINE:85054621], and differ in catalytic,\ molecular and immunological properties [MEDLINE:87092419]. Deficiency in the liver isozyme\ leads to argininemia, which is usually associated with hyperammonemia [MEDLINE:87092419].\ \ enzyme activity ; GO:0003824 \N \N 24495 IPR006036 The NAD⁺-binding protein TrkA is a component of a low-affinity K⁺ uptake system in E.coli\ \ \ [MEDLINE:94018648]. Sequence analysis reveals that the protein consists of 2 tandemly arrayed halves that are 22% identical, a situation that might have arisen through gene duplication. TrkA also exhibits similarity to other E.coli proteins [MEDLINE:94357168], in particular KefC, a glutathione- regulated efflux protein [MEDLINE:91260444], and to various dehydrogenase proteins that possess NAD⁺ binding sites.\ \ cation transporter activity ; GO:0008324 \N potassium ion transport ; GO:0006813 24496 IPR006037

This domain is often found next to the TrkA-N domain. The exact function of this domain is unknown. It has been suggested that it may bind an unidentified ligand. The domain is predicted to adopt an all structure [MEDLINE:21189415].

\ cation transporter activity ; GO:0008324 \N potassium ion transport ; GO:0006813 24492 IPR006033

Two related families of asparaginase are designated type I and type II according to the terminology in E. coli, which has both: L-asparaginase I is a low-affinity enzyme found in the cytoplasm, while L-asparaginase II is a high-affinity secreted enzyme synthesized with a cleavable signal sequence. This family includes L-asparaginases related to type I of E. coli. Archaeal putative asparaginases are of this type but contain an extra ~ 80 residues in a conserved N-terminal region. These archaeal homologs are included in this family.

\ \ asparaginase activity ; GO:0004067 \N amino acid metabolism ; GO:0006520 24493 IPR006034 Asparaginase, which is found in various plant, animal and bacterial cells, catalyses the deamination of asparagine to yield aspartic acid and an ammonium ion, resulting in a depletion of free circulatory asparagine in plasma [MEDLINE:87106840]. The enzyme is effective in the treatment of human malignant lymphomas, which have a diminished capacity to produce asparagine synthetase: in order to survive, such cells absorb asparagine from blood plasma [MEDLINE:90170867], [MEDLINE:88243706] - if Asn levels have been depleted by injection of asparaginase, the lymphoma cells die. Glutaminase, a similar enzyme, catalyses the deaminination of glutamine to glutamic acid and an ammonium ion [MEDLINE:90170867]. Both enzymes are homotetramers [MEDLINE:87106840]: two threonine residues in the N-terminal half of the proteins are involved in the catalytic activity.\ \N \N amino acid metabolism ; GO:0006520 24489 IPR006030

The sequences of the molluscan rhodopsins depart from those of otherrhodopsins by virtue of bearing intra-cellular C-terminal tails, which are\ characterised by a repetitive Gln/Pro-rich motif [MEDLINE:88211878], [MEDLINE:98328743]. Although the\ precise function of the tail is unknown, it may be involved in the\ immobilisation of the protein in the membrane, or may be important in\ conferring the high degree of order found in the microvilli of the\ receptors (which itself may play a role in the detection of plane\ polarised light).

\ \ rhodopsin-like receptor activity ; GO:0001584 integral to membrane ; GO:0016021 vision ; GO:0007601 24490 IPR006031

This repeat is found in a wide variety of proteins and generally consists of the motif XYPPX where X can be any amino acid. The family includes annexin VII ANX7_DICDI, the carboxy tail of certain rhodopsins OPSD_LOLSU. This family also includes plaque matrix proteins, however this motif is embedded in a ten residue repeat in FP1_MYTED. The molecular function of this repeat is unknown. It is also not clear is all the members of this family share a common evolutionary ancestor due to its short length and biased amino acid composition.

\ \N \N \N 24491 IPR006032

\ \ \

Ribosomal protein S12 is one of the proteins from the small ribosomal subunit.\ In Escherichia coli, S12 is known to be involved in the translation initiation\ step. It is a very basic protein of 120 to 150 amino-acid residues. S12\ belongs to a family of ribosomal proteins which are grouped on the basis of sequence\ similarities. This protein is known typically as S12 in bacteria, S23 in eukaryotes and as either S12 or S23 in the Archaea. PUB00005070.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 24488 IPR006029

\ \

This domain represents four transmembrane helices of a variety of neurotransmitter-gated ion-channels.

\ \ neurotransmitter receptor activity ; GO:0030594 membrane ; GO:0016020 ion transport ; GO:0006811 24483 IPR006024

Vertebrate endogenous opioid neuropeptides are released by post-translational proteolytic cleavage of precursor proteins. The precursors consist of the following components: a signal sequence that precedes a conserved region of about 50 residues; a variable-length region; and the sequence of the neuropeptide itself. Three types of precursor are known: preproenkephalin A \ (gene PENK), which is processed to produce 6 copies of Met-enkephalin, plus \ Leu-enkephalin; preproenkephalin B (gene PDYN), which is processed to\ produce neoendorphin, dynorphin, leumorphin, rimorphin and Leu-enkephalin; \ and prepronocipeptin (gene PNOC), whose processing produces nociceptin\ (orphanin FQ) and two other potential neuropeptides.

Sequence analysis reveals that the conserved N-terminal region of the\ precursors contains 6 cysteines, which are probably involved in disulphide\ bond formation. It is speculated that this region might be important for \ neuropeptide processing [MEDLINE:96323281].

\ \ \N \N neuropeptide signaling pathway ; GO:0007218 24484 IPR006025

The majority of zinc-dependent metallopeptidases (with the notable exception\ of the carboxypeptidases) share a common pattern of primary structure [MEDLINE:89121072], [MEDLINE:91372401], PUB00005666\ in the part of their sequence involved in the binding of zinc, and can be\ grouped together as a superfamily,known as the metzincins, on the basis of\ this sequence similarity. They can be classified into around 40 distinct families PUB00005666.

\ \ \ zinc ion binding activity ; GO:0008270 \N proteolysis and peptidolysis ; GO:0006508 24485 IPR006026

The majority of zinc-dependent metallopeptidases (with the notable exceptionof the carboxypeptidases) share a common pattern of primary structure [MEDLINE:89121072], [MEDLINE:91372401], PUB00005666\ in the part of their sequence involved in the binding of zinc, and can be\ grouped together as a superfamily,known as the metzincins, on the basis of\ this sequence similarity. They can be classified into around 40 distinct families PUB00005666.

\ \ \ metallopeptidase activity ; GO:0008237 \N proteolysis and peptidolysis ; GO:0006508 24486 IPR006027 The NusB protein is involved in the regulation of rRNA biosynthesisby transcriptional antitermination. The antitermination proteins of Escherichia coli are recruited in the replication cycle of\ bacteriophage lambda, where they play an important role in switching from the\ lysogenic to the lytic cycle. The solution structure indicates that the protein folds into an

-helical\ topology consisting of six helices; the arginine-rich N-terminus appears to be\ disordered [MEDLINE:98336198].\ \ RNA binding activity ; GO:0003723 \N regulation of transcription, DNA-dependent ; GO:0006355 24487 IPR006028

\ \

\ \ \ GABA-A receptor activity ; GO:0004890 membrane ; GO:0016020 ion transport ; GO:0006811 24480 IPR006021 Staphylococcus aureus nuclease (SNase) homologues, previously thought to be restricted to bacteria and archaea, are also in eukaryotes. Staphylococcal nuclease has multidomain organization [MEDLINE:97157029]. The human cellular coactivator p100 contains\ four repeats, each of which is a SNase homologue. These repeats are unlikely to possess SNase-like activities as each lacks equivalent SNase catalytic residues, yet they may mediate p100's single-stranded DNA-binding function [MEDLINE:97194072].\ A variety of proteins including many that are still uncharacterised belong to this group.\ \ nuclease activity ; GO:0004518 \N \N 24481 IPR006022

Staphylococcus aureus nuclease (SNase) homologues, previously thought to be restricted to bacteria and archaea, are also in eukaryotes. Staphylococcal nuclease has multidomain organization [MEDLINE:97157029]. The human cellular coactivator p100 contains\ four repeats, each of which is a SNase homologue. These repeats are unlikely to possess SNase-like activities as each lacks equivalent SNase catalytic residues, yet they may mediate p100's single-stranded DNA-binding function [MEDLINE:97194072].\ A variety of proteins including many that are still uncharacterised belong to this group.

\ \ nuclease activity ; GO:0004518 \N \N 24482 IPR006023 Vertebrate endogenous opioid neuropeptides are released by post-translational proteolytic cleavage of precursor proteins. The precursors consist of the following components: a signal sequence that precedes a conserved region of about 50 residues; a variable-length region; and the sequence of the neuropeptide itself. Three types of precursor are known: preproenkephalin A \ (gene PENK), which is processed to produce 6 copies of Met-enkephalin, plus \ Leu-enkephalin; preproenkephalin B (gene PDYN), which is processed to\ produce neoendorphin, dynorphin, leumorphin, rimorphin and Leu-enkephalin; \ and prepronocipeptin (gene PNOC), whose processing produces nociceptin\ (orphanin FQ) and two other potential neuropeptides.\

\ \ \N \N neuropeptide signaling pathway ; GO:0007218 24475 IPR006016 The universal stress protein UspA P28242\ \ \ [MEDLINE:94203056] is a small cytoplasmic\ bacterial protein whose expression\ is enhanced when the cell is exposed to\ stress agents. UspA enhances the rate of cell survival during\ prolonged exposure to such conditions, and may provide a general\ "stress endurance" activity.\ The crystal structure of Haemophilus influenzae UspA [MEDLINE:21605726] reveals\ an

fold similar to that of the Methanococcus jannaschi\ MJ0577 protein, which binds ATP [MEDLINE:99079988], though UspA lacks ATP-binding\ activity.\ \ \N \N response to stress ; GO:0006950 24476 IPR006017 Caldesmon (CDM) is an actin- and myosin-binding protein implicated in theregulation of actomyosin interactions in smooth muscle and non-muscle cells,\ possibly acting as a bridge between myosin and actin filaments [MEDLINE:92209999]. CDM is\ believed to be an elongated molecule, with an N-terminal myosin/calmodulin-\ binding domain and a C-terminal tropomyosin/actin/calmodulin-binding domain,\ separated by a 40nm-long central helix [MEDLINE:92209999].\

A high-molecular-weight form of CDM is predominantly expressed in smooth\ muscles, while a low-molecular-weight form is widely distributed in non-\ muscle tissues and cells (the protein is not expressed in skeletal muscle\ or heart).

A short CDM has been cloned from a chicken gizzard library [MEDLINE:92042686]. The \ predicted protein contains 524 amino acids, with molecular mass ~60Kda.\ The expressed protein binds to F-actin and is retained on calmodulin-\ Sepharose in the presence of Ca²⁺ [MEDLINE:92042686]. Like the human non-muscle form [MEDLINE:92209999],\ this CDM is identical to the smooth muscle protein at its N- and C-termini,\ but is missing 232 amino acids from the centre. Lack of this central\ segment, which is thought to be helical, renders the non-muscle protein\ ~35nm shorter than smooth muscle CDM [MEDLINE:92042686].

\ \ myosin binding activity ; GO:0017022 \N muscle contraction ; GO:0006936 24477 IPR006018

This group of proteins includes two protein families: caldesmon and lymphocyte specific protein.

Caldesmon (CDM) is an actin- and myosin-binding protein implicated in the\ regulation of actomyosin interactions in smooth muscle and non-muscle cells,\ possibly acting as a bridge between myosin and actin filaments [MEDLINE:92209999]. CDM is\ believed to be an elongated molecule, with an N-terminal myosin/calmodulin-\ binding domain and a C-terminal tropomyosin/actin/calmodulin-binding domain,\ separated by a 40nm-long central helix [MEDLINE:92209999].

\ \ \N \N \N 24478 IPR006019 Shc proteins contain an SH2 domain and a phosphotyrosine interaction (PI) domain. These domains facilitate interaction with various activated\ tyrosine-phosphorylated receptors, including those of growth factors,\ insulin, cytokines and lymphocytes. The PI domain comprises 165 residues,\ 4 of which (Arg67, Arg175, Ser151 and Lys169 [MEDLINE:96234229]) are responsible for\ binding phosphotyrosine on a 'IIENPQYFSDA'(NPxPY) peptide [MEDLINE:95318073]. \

The PI domain has a similar structure to the insulin receptor substrate-1 \ PTB domain, a 7-stranded -sandwich, capped by a C-terminal helix.\ However, the PI domain contains an additional short N-terminal helix and a\ large insertion between strands 1 and 2, which forms a helix and 2 long\ connecting loops. The substrate peptide fits into a surface cleft formed\ from the C-terminal helix and strand 5 [MEDLINE:96185451].

\ \ \N \N intracellular signaling cascade ; GO:0007242 24479 IPR006020

The PI domain has a similar structure to the insulin receptor substrate-1 PTB domain, a 7-stranded -sandwich, capped by a C-terminal helix.\ However, the PI domain contains an additional short N-terminal helix and a\ large insertion between strands 1 and 2, which forms a helix and 2 long\ connecting loops. The substrate peptide fits into a surface cleft formed\ from the C-terminal helix and strand 5 [MEDLINE:96185451].

\ \ \N \N \N 24472 IPR006013 Marine teleosts from polar oceans can be protected from freezing in icy sea-water by serum antifreeze proteins (AFPs) or glycoproteins (AFGPs) [MEDLINE:97094988]:\ these function by binding to, and preventing the growth of, ice crystals\ within the fish. Despite functional similarity, the proteins are\ structurally diverse and include glycosylated and at least 3 non-\ glycosylated forms: the AFGP of nototheniids and cods are polymers of a\ tripeptide repeat, Ala-Ala-Thr, with a disaccharide attached to the\ threonine residue; type I AFPs are Ala-rich,

-helical peptides\ found in flounder and sculpin; type II AFPs of sea-raven, smelt and\ herring are Cys-rich proteins; and type III AFPs, found in eel pouts,\ are rich in

-structure [MEDLINE:97094988].\ \ antifreeze activity ; GO:0016172 \N cold acclimation ; GO:0009631 24473 IPR006014

This domain is found in type III antifreeze proteins as well as in a variety of enzymes. It is presumed to be involved in sugar binding in the enzyme proteins.

\ \N \N \N 24474 IPR006015

Transcriptional induction of the uspA gene of Escherichia coli occurswhen conditions cause growth arrest; cells deficient in UspA survive\ poorly in stationary phase [MEDLINE:98070599]. The product of uspA has been shown to be\ a cytoplasmic serine and threonine phosphoprotein. Members of the Usp\ family are predicted to be related to the MADS-box proteins and bind to DNA\ [MEDLINE:98070599]. Some members of the family contain 2 copies of the domain.

\ \

The structure of a UspA homologue from Methanococcus jannaschii from has \ been determined to 1.8Е resolution by using its selenomethionyl derivative\ and multiwavelength anomalous diffraction. The protein homodimerises in \ the crystal; each monomer adopts an open-twisted 5-stranded parallel -sheet with 2 helices on each side of the sheet [MEDLINE:99079988]. Although the structure\ co-crystallised with ATP, the function of the protein is unknown.

\ \ \ \N \N \N 24470 IPR006011

Syntaxins A and B are nervous system-specific proteins implicated in the docking of synaptic vesicles with the presynaptic plasma membrane. Syntaxins are a family of receptors for intracellular transport vesicles. Each target membrane may be\ identified by a specific member of the syntaxin family [MEDLINE:93386759].\ Members of the syntaxin family [MEDLINE:93262668], [MEDLINE:93258806] have a size ranging from\ 30 Kd to 40 Kd; a C-terminal extremity which is highly hydrophobic and anchors the protein on the cytoplasmic surface of cellular membranes; a central, well\ conserved region, which seems to be in a coiled-coil conformation.\

\ \ \N membrane ; GO:0016020 \N 24471 IPR006012 Syntaxins A and B are nervous system-specific proteins implicated in the docking of synaptic vesicles with the presynaptic plasma membrane. Syntaxins are a family of receptors for intracellular transport vesicles. Each target membrane may be\ identified by a specific member of the syntaxin family [MEDLINE:93386759].\ Members of the syntaxin family [MEDLINE:93262668], [MEDLINE:93258806] have a size ranging from\ 30 Kd to 40 Kd; a C-terminal extremity which is highly hydrophobic and anchors the protein on the cytoplasmic surface of cellular membranes; a central, well\ conserved region, which seems to be in a coiled-coil conformation.\

Epimorphin is related to neuronal and yeast vesicle\ targeting proteins.

\ \ protein transporter activity ; GO:0008565 membrane ; GO:0016020 intracellular protein transport ; GO:0006886 24466 IPR006007

One pathway for the assimilation of ammonia and glutamate biosynthesis involves glutamate synthase (EC: 1.4.1.13) which transfers the amide group of glutamine to 2-oxoglutarate to yield two molecules of glutamate. \ \

 2 L-glutamate + NADP+ = L-glutamine + 2-oxoglutarate + NADPH + H+

\ \ This family includes both glutatate synthase small subunit and closely related paralogs of unknown function from a number\ of gamma and

subdivision Proteobacteria, including Escherichia coli.

\ \

Many photosynthetic organisms including cyanobacteria can concentrate CO₂/HCO₃^- against a greater than ten-fold concentration gradient. In cyanobacteria, the CO₂\ concentrating mechanism involves:

CO₂ conversion to HCO₃^-
energy-dependent HCO₃^- transport, and
carbonic anhydrase-catalyzed formation of CO₂\ from HCO₃^- in the carboxysomes.

The gene believed to encode the transporter, possibly a Na⁺:HCO₃^- symporter, is designated ictB\ or ORF467 in Synechococcus sp. strain PCC 7942. The protein is 467 amino acyl residues long and possesses 10 putative transmembrane

-helical spanners.

\ \ \ \N \N \N 24467 IPR006008

Intracellular septation protein A is a family of proteins which are essential for both normal cell division and bacterial virulence and are believed to play a role in the septation process [MEDLINE:98427132].

\ \N integral to membrane ; GO:0016021 cell growth and/or maintenance ; GO:0008151 24468 IPR006009

The murG gene of Escherichia coli encodes the N-acetylglucosaminyltransferase, UDP-N-acetylglucosamine--N-acetylmuramyl-(pentapeptide) pyrophosphoryl-undecaprenol N-acetylglucosamine transferase, responsible for the final step in the formation of the lipid-linked disaccharide-pentapeptide subunit of peptidoglycan. The enzyme is peripherally associated with the inner face of the cytoplasmic membrane. Therefore, the peptidoglycan subunit is completely assembled before it traverses the cytoplasmic membrane.

\ transferase activity, transferring hexosyl groups ; GO:0016758 inner membrane ; GO:0019866 UDP-N-acetylgalactosamine biosynthesis ; GO:0019277 24469 IPR006010

Deoxythymidine diphosphate (dTDP)-4-keto-6-deoxy-d-hexulose 3, 5-epimerase (RmlC, EC: 5.1.3.13) is involved in the biosynthesis of dTDP-l-rhamnose, which is an essential component of the bacterial cell wall, converting\ dTDP-4-keto-6-deoxy-D-glucose to dTDP-4-keto-L-rhamnose.

The crystal structure of RmlC from Methanobacterium\ thermoautotrophicum was determined in the presence and absence of a substrate analogue. RmlC is a homodimer comprising a\ central jelly roll motif, which extends in two directions into longer -sheets. Binding of dTDP is stabilized by ionic interactions to the\ phosphate group and by a combination of ionic and hydrophobic interactions with the base. The active site, which is located in the\ center of the jelly roll, is formed by residues that are conserved in all known RmlC sequence homologues. The active site is lined with a number of charged residues and a number of residues with hydrogen-bonding potentials, which together comprise a potential network for substrate binding and catalysis. The active site is also lined with aromatic residues\ which provide favorable environments for the base moiety of dTDP and potentially for the sugar moiety of the\ substrate [MEDLINE:20387354].

\ \ dTDP-4-dehydrorhamnose 3,5-epimerase activity ; GO:0008830 \N cell wall biosynthesis (sensu Bacteria) ; GO:0009273 24462 IPR006003

The enzymes for catabolism of the pentitols D-arabinitol and ribitol include NAD-dependent pentose dehydrogenase (dalD and rbtD), ATP-dependent pentulose kinases (dalK and rbtK) and a pentose-specific ion symporter (dalT and rbtT). Ofthe two kinases (19.3% identity), DalK (487 aa) belongs to the family of short D-xylulokinases and RbtK (D-ribulokinase; 535 aa) to the family of long kinases [MEDLINE:98304087].

\ \ \ \N \N \N 24463 IPR006004

  2 L-glutamate + NADP⁺ = L-glutamine + 2-oxoglutarate + NADPH + H⁺.

\ \ \ \N \N \N 24464 IPR006005

  2 L-glutamate + NADP⁺ = L-glutamine + 2-oxoglutarate + NADPH + H⁺.

\ \

This describes a family in several archaeal and deeply branched bacterial\ lineages of a homotetrameric form of the NADPH-dependent or NADH-dependent glutamate synthase (EC: 1.4.1.13 and EC: 1.4.1.14 respectively) small subunit. There is no corresponding large subunit.

\ \ \ oxidoreductase activity, acting on the CH-NH2 group of donors, NAD or NADP as acceptor ; GO:0016639 \N glutamate biosynthesis ; GO:0006537 24465 IPR006006

  2 L-glutamate + NADP⁺ = L-glutamine + 2-oxoglutarate + NADPH + H⁺.

This model describes both glutatate synthase small subunit and closely related\ paralogs of unknown function from a number of gamma and subdivision\ Proteobacteria, including Escherichia coli.

\ \ \ oxidoreductase activity, acting on the CH-NH2 group of donors, NAD or NADP as acceptor ; GO:0016639 \N glutamate biosynthesis ; GO:0006537 24458 IPR005999

Glycerol kinase (EC: 2.7.1.30) is a bacterial sugar kinase which catalyzes the Mg-ATP-dependent phosphorylation of glycerol to yield glycerol 3-phosphate. The enzyme from Escherichia coli is an allosteric regulatory enzyme whose activity is inhibited by fructose 1,6-bisphosphate (FBP) and the glucose-specific phosphocarrier of the phosphoenolpyruvate:glycose phosphotransferase system, IIA(Glc), structural studies suggest a nucleophilic in-line transfer mechanism for the ATP-dependent phosphorylation of glycerol by glycerol kinase [MEDLINE:99294641].

\ glycerol kinase activity ; GO:0004370 \N glycerol-3-phosphate metabolism ; GO:0006072 24459 IPR006000

1-deoxy-D-xylulose 5-phosphate serves as a precursor for the biosynthesis of the vitamins thiamine and pyridoxal and for the formation of isopentenyl pyrophosphate and dimethylallyl pyrophosphate via the nonmevalonate pathway of terpenoid biosynthesis. D-xylulokinase (EC: 2.7.1.17) catalyzes the phosphorylation of 1-deoxy-D-xylulose at the hydroxy group of C-5. This reaction constitutes a potential salvage pathway for the generation of 1-deoxy-D-xylulose 5-phosphate from exogenous or endogenous 1-deoxy-D-xylulose as starting material for the biosynthesis of terpenoids, thiamine and pyridoxal.

\ xylulokinase activity ; GO:0004856 \N xylulose metabolism ; GO:0005997 24460 IPR006001

This family of proteins includes thermoresistant and thermosensitve isozymes of gluconate kinase (gluconokinase) in E. coli and other related proteins; members of this family are often named by similarity to the thermostable isozyme. These proteins show homology to shikimate kinases and adenylate kinases but not to gluconate kinases from the FGGY family of carbohydrate kinases (IPR000577).

\ kinase activity ; GO:0016301 \N carbohydrate metabolism ; GO:0005975 24461 IPR006002

Gluconate kinase (EC: 2.7.1.12) is an / structure consisting of a twisted parallel -sheet surrounded by -helices with overall topology similar to nucleoside monophosphate (NMP) kinases, such as adenylate kinase. Significant conformational changes are induced upon binding of ATP to the enzyme. The largest changes involve a hinge-bending motion of the NMP(bind) part and a motion of the LID with adjacent helices, which opens the cavity to the second substrate, gluconate. The opening of the active site cleft upon ATP binding is the opposite of what has been observed in the NMP kinase family so far, which usually close their active site to prevent fortuitous hydrolysis of ATP. The and gamma-phosphate groups of ATP bind in the predicted P-loop. A conserved lysine side-chain interacts with the gamma-phosphate group, and might promote phosphoryl transfer.\

 ATP + D-gluconate = ADP + 6-phospho-D-gluconate.

Gluconate-6-phosphate binds with its phosphate group in a similar position as the gamma-phosphate of ATP, consistent with inline phosphoryl transfer. [MEDLINE:22050861].

\ \ \ carbohydrate kinase activity ; GO:0019200 \N D-gluconate metabolism ; GO:0019521 24456 IPR005997

\ \ \

Ribosomal protein L30 is one of the proteins from the large ribosomal subunit. L30 belongs to a family of ribosomal proteins which, on the basis of sequence similarities, groups bacteria and archaea L30, yeast mitochondrial L33, and Drosophila , slime mould, fungal and mammalian L7 ribosomal proteins This family describes the eukaryotic 60S (cytosolic) ribosomal protein L7 and homologues that\ may or may not also be L7. Human, Drosophila, and Arabidopsis all have both a typical L7 and an L7-related protein. Members of this family average ~ 250 residues in length, somewhat longer than the archaeal L30P/L7E homolog (~ 155 residues) and much longer than the related bacterial/organellar form (~ 60 residues).

\ \ \ structural constituent of ribosome ; GO:0003735 large ribosomal subunit ; GO:0015934 protein biosynthesis ; GO:0006412 24457 IPR005998

\ \ \

Eukaryotic ribosomal protein, L7, contains an N-terminal bZIP DNA binding domain and a second, DNA-binding domain has been mapped to the 50 C-terminal amino acids of the protein [MEDLINE:99262132]. In addition to its role in translation, L7 has also been shown to be involved in nuclear-receptor mediated transcriptional control. There is no bacterial homologue of this protein.

\ \ transcription regulator activity ; GO:0030528 large ribosomal subunit ; GO:0015934 protein biosynthesis ; GO:0006412 24454 IPR005995

Phosphoglycerate mutase (PGM) enzymes catalyze the isomerization of phosphoglycerate substrates, a process essential for the metabolism of glucose and/or2,3-phosphoglycerate in nearly all organisms [MEDLINE:20416341]. At least two known, distinct classes of PGM enzymes were identified and one of them catalyzes the interconversion of 3-phosphoglycerate and 2-phosphoglycerate. This enzyme is known as monophosphoglycerate mutase (mPGM) (EC: 5.4.2.1). The mPGM enzymes are divided into two main groups, the ones dependent on 2,3-bisphosphoglycerate as a cofactor (dPGM) and the ones independent of 2,3-bisphosphoglycerate (iPGM). The iPGM enzymes are monomers and the mechanism of catalysis of this enzyme has also been elucidated and shown to involve a phosphoserine intermediate with a two-step catalytic process involving phosphatase and phosphotransferase activity.

\ \

The B. stearothermophilus iPGM enzyme consists of 511 residues (57 kDa) and its active form structure contains two Mn(II) ions. It is a monomer which contains two distinctly separated domains of approximately equal size which interact with one another through an extended surface area contact . There is a narrow cleft between these domains which is where the active site of the enzyme is located. This crystal structure also includes a 3-phosphoglycerate substrate as well as a catalytic, ordered water molecule bound in the active site of the enzyme. Both domains have a central -sheet surrounded by -helices on the outside. The active site contains residues from both domains. However, residues interacting with the Mn(II) ions and the phosphate group of 3-phosphoglycerate originate from one domain whereas residues interacting with the glycerate part of the substrate originate from the other domain.

\ \ \ phosphoglycerate mutase activity ; GO:0004619 \N glucose catabolism ; GO:0006007 24455 IPR005996

\ \ \

\ \ structural constituent of ribosome ; GO:0003735 large ribosomal subunit ; GO:0015934 protein biosynthesis ; GO:0006412 24449 IPR005990

Synonyms: Inosine-5'-monophosphate dehydrogenase, Inosinic acid dehydrogenase

IMP dehydrogenase (EC: 1.1.1.205,IMPDH) catalyzes the rate-limiting reaction of de novo GTP biosynthesis, the NAD-dependent reduction of IMP into XMP. \

                   Inosine 5-phosphate + NAD+ + H2O = xanthosine 5-phosphate + NADH

\ \

IMP dehydrogenase is associated with cell proliferation and is a possible target for cancer chemotherapy. Mammalian and bacterial IMPDHs are tetramers of identical chains. There are two IMP dehydrogenase isozymes in humans. IMP dehydrogenase nearly always contains a long insertion that has two CBS domains within it and adopts a TIM barrel structure.

\ \ \ IMP dehydrogenase activity ; GO:0003938 \N GMP biosynthesis ; GO:0006177 24450 IPR005991

This family of proteins, often annotated as a putative IMP dehydrogenase, are related to IMP dehydrogenase and GMP reductase and restricted to the high GC Gram-positive bacteria.

\ \N \N \N 24451 IPR005992

This family of proteins, often annotated as a putative IMP dehydrogenase, are related to IMP dehydrogenase and GMP reductase. Most species with a member of this family belong to the high GC Gram-positive bacteria.

\ \N \N \N 24452 IPR005993

Guanosine monophosphate reductase (EC: 1.7.1.7) catalyzes the irreversible and NADPH-dependent reductive deamination of GMP into IMP.

 NADPH + guanosine 5-phosphate = NADP+ + inosine 5-phosphate + NH3

\ \

It converts nucleobase, nucleoside and nucleotide derivatives of G to A nucleotides, and maintains intracellular balance of A and G nucleotides. A deep split separates two families of GMP reductase. This family includes both eukaryotic\ and some proteobacterial sequences.

\ \ \ GMP reductase activity ; GO:0003920 \N nucleotide metabolism ; GO:0009117 24453 IPR005994

Guanosine monophosphate reductase (EC: 1.7.1.7) catalyzes the irreversible and NADPH-dependent reductive deamination of GMP into IMP.

 NADPH + guanosine 5-phosphate = NADP+ + inosine 5-phosphate + NH3

\ \

\ \ \ \N \N \N 24443 IPR005984

Phospholamban (PLB) is a small protein (52 amino acids) that regulates the affinity of the cardiac sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) for calcium. PLB is present in cardiac myocytes, in slow-twitch and smooth muscle and is expressed also in aorta endothelial cells in which it could play a role in tissue relaxation. The phosphorylation/dephosphorylation of phospholamban removes and restores, respectively, its inhibitory activity on SERCA2a. It has in fact been shown that phospholamban, in its non-phosphorylated form, binds to SERCA2a and inhibits this pump by lowering its affinity for Ca²⁺, whereas the phosphorylated form does not exert the inhibition. PLB is phosphorylated at two sites, namely at Ser-16 for acAMP-dependent phosphokinase and at Thr-17 for a Ca²⁺/calmodulin-dependent phosphokinase, phosphorylation at Ser-16 being a prerequisite for the phosphorylation at Thr-17.

The structure of a 36-amino-acid-long N-terminal fragment of human phospholamban phosphorylated at Ser-16 and Thr-17 and Cys36Ser mutated was determined from nuclear magnetic resonance data. The peptide assumes a conformation characterized by two

-helices connected by an irregular strand, which\ comprises the amino acids from Arg-13 to Pro-21. The proline is in a trans conformation. The two phosphate groups on Ser-16 and Thr-17 are shown to interact preferably with the side chains of Arg-14 and Arg-13, respectively [MEDLINE:22074790].

\ \ \ ATPase inhibitor activity ; GO:0042030 membrane ; GO:0016020 calcium ion transport ; GO:0006816 24444 IPR005985

This is a small family of proteins believed to aid in the export of various class II bacteriocins, which are ribosomally-synthesized, non-lantibiotic bacterial peptide antibiotics. Members of this family are found in operons for pediocin PA-1 from Pediococcus acidilactici and brochocin-C from Brochothrix campestris.

\ drug transporter activity ; GO:0015238 \N drug transport ; GO:0015893 24445 IPR005986

Aspartate-semialdehyde dehydrogenase (EC: 1.2.1.11) catalyzes the second step in the common metabolic pathway to synthesize threonine and methionine from aspartic acid. Two closely related families of aspartate-semialdehyde dehydrogenase are found. They differ by a deep split in phylogenetic and percent identity trees and in gap patterns. This model represents a branch which is closely related to the USG-1 protein.

\ aspartate-semialdehyde dehydrogenase activity ; GO:0004073 \N threonine biosynthesis ; GO:0009088 24446 IPR005987

Ribonuclease T (EC: 3.1.13.-) is an enzyme found so far only in gamma-subdivision proteobacteria such as Escherichia coli and Xylella fastidiosa. Ribonuclease T is homologous to the DNA polymerase III chain. It can liberate AMP from the common C-C-A terminus of uncharged tRNA. It appears also to be involved in RNA maturation. It also acts as a 3' to 5' single-strand DNA-specific exonuclease; it is distinctive for its ability to remove residues near a double-stranded stem. Ribonuclease T is a high copy suppressor in E. coli of a U.V.-repair defect caused by deletion of three other single-stranded DNA exonucleases.

\ ribonuclease activity ; GO:0004540 \N RNA processing ; GO:0006396 24447 IPR005988

SV2 proteins are abundant synaptic vesicle proteins expressed in two major (SV2A and SV2B) and one minor isoform (SV2C) that resemble transporter proteins. SV2B knockout mice are phenotypically normal while SV2A- and SV2A/SV2Bdouble knockout mice exhibit severe seizures and die postnatally. Without SV2 proteins, presynaptic Ca²⁺ accumulation during consecutive action potentials causes abnormal increases in neurotransmitter release that destabilize synaptic circuits and induce epilepsy [MEDLINE:20088300].

\ \ \ transporter activity ; GO:0005215 membrane ; GO:0016020 transport ; GO:0006810 24448 IPR005989

These sucrose/proton symporters, found in plants, are from the Glycoside-Pentoside-Hexuronide (GPH)/cation symporter family. These proteins are predicted to have 12 transmembrane domains. Members may export sucrose (e.g. SUT1, SUT4) from green parts to the phloem for long-distance transport or import sucrose (e.g SUT2) to sucrose sinks such as the tap root of the carrot [MEDLINE:99063785].

\ sucrose transporter activity ; GO:0008515 inner membrane ; GO:0019866 sucrose transport ; GO:0015770 24440 IPR005981

Nearly all the members of this family are NodJ proteins which, together with NodI IPR005978, acts to export a variety of modified carbohydrate molecules as signals to plant hosts to establish root nodules. The family includes a highly divergent member from Azorhizobium caulinodans that is, nonetheless, associated with nodulation.

\ transporter activity ; GO:0005215 inner membrane ; GO:0019866 nodulation ; GO:0009877 24441 IPR005982

Reactive oxygen species (ROS) are known mediators of intracellular signaling cascades. Excessive production of ROS may, however, lead to oxidative stress, loss of cell function, and ultimately apoptosis or necrosis. A balance between oxidant and antioxidant intracellular systems is hence vital for cell function, regulation, and adaptation to diverse growth conditions. Thioredoxin reductase in conjunction with thioredoxin is a ubiquitous oxidoreductase system with antioxidant and redox regulatory roles. Thidoxin reductase (EC: 1.8.1.9) reduces oxidised thioredoxin in the presence of NADPH. Reduced thioredoxin serves as an electron donor for thioredoxin peroxidase which consequently reduces H₂O₂ to H₂O. In mammals, extracellular forms of Trx also have cytokine-like effects. Mammalian TrxR has a highly reactive active site selenocysteine residue resulting in a profound reductive capacity, reducing several substrates in addition to Trx.

\ thioredoxin reductase (NADPH) activity ; GO:0004791 cytoplasm ; GO:0005737 removal of superoxide radicals ; GO:0019430 24442 IPR005983

This entry represents the conserved core region of the subunit of voltage-gated potassium (Kv) channels in animals. Amino-terminal regions differ substantially, in part by alternative splicing, and are not included in the model. Four subunits form a complex with four subunit cytoplasmic (T1) regions, and the structure of the complex is solved. The subunit belongs to a family of NAD(P)H-dependent aldo-keto reductases, binds NADPH, and couples voltage-gated channel activity to the redox potential of the cell. Plant subunits and their closely related bacterial homologs (in Deinococcus radiudurans, Xylella fastidiosa, etc.) appear more closely related to each other than to animal forms. However, the bacterial species lack convincing counterparts the Kv subunit and the Kv homolog may serve as an enzyme. Cutoffs are set for this model such that yeast and plant forms and bacterial close homologues score between trusted and noise cutoff.

\ \ voltage-gated potassium channel activity ; GO:0005249 cytoplasm ; GO:0005737 potassium ion transport ; GO:0006813 24436 IPR005977

The enzyme responsible for nitrogen fixation, thenitrogenase, shows a high degree of conservation of structure, function, and amino acid sequence across wide phylogenetic ranges. All known Mo-nitrogenases consist of two components, component I (also called dinitrogenase, or Fe-Mo protein), an alpha2beta2 tetramer encoded by the nifD and nifK genes, and component II (dinitrogenase reductase, or Fe protein) a homodimer encoded by the nifH gene. Two operons, nifDK and nifEN, encode a tetrameric (alpha2beta2 and N2E2) enzymatic complex. Nitrogenase contains two unusual rare metal clusters; one of them is the iron molybdenum cofactor (FeMo-co), which is considered to be the site of dinitrogen reduction and whose biosynthesis requires the products of nifNE and of\ some other nif genes. It has been proposed that NifNE might serve as a scaffold upon\ which FeMo-co is built and then inserted into component I.

\ \ \ molybdenum-iron nitrogenase activity ; GO:0016734 \N nitrogen fixation ; GO:0009399 24437 IPR005978

ATP-binding cassette (ABC) transporters are multidomain membrane proteins, responsible for the controlled efflux and influx of substances (allocrites) across cellular membranes. They are minimally composed of four domains, with two transmembrane domains\ (TMDs) responsible for allocrite binding and transport and two nucleotide-binding domains\ (NBDs) responsible for coupling the energy of ATP hydrolysis to conformational changes\ in the TMDs. Both NBDs are capable of ATP hydrolysis, and inhibition of\ hydrolysis at one NBD effectively abrogates hydrolysis at the other. Hydrolysis\ at the two NBDs may occur in an alternative fashion although they appear substantially functionally\ symmetrical in terms of their binding to diverse nucleotides [MEDLINE:22392972].

Nodulation ABC transporter, NodI is required for normal nodulation by nitrogen-fixing root nodule bacteria such as Mesorhizobium loti. It is a member of the family of ABC transporter ATP binding proteins and works with NodJ IPR005981 This model does not recognize the highly divergent NodI from Azorhizobium caulinodans.

\ \ ATP binding activity ; GO:0005524 membrane ; GO:0016020 nodulation ; GO:0009877 24438 IPR005979

This family contains the light-dependent, NADPH-dependent form of protochlorophyllide reductase (EC: 1.3.1.33) which catalyses the reaction

  chlorophyllide A + NADP+ = protochlorophyllide + NADPH.

The enzyme belongs to the short chain alcohol dehydrogenase family.

\ protochlorophyllide reductase activity ; GO:0016630 chloroplast ; GO:0009507 photosynthesis, dark reaction ; GO:0019685 24439 IPR005980

NifB is a protein required for the biosynthesis of the iron-molybdenum (or iron-vanadium) cofactor used by the nitrogen-fixing enzyme nitrogenase. Archaeal homologs lack most of the C-terminal region and are excluded from this model.

\ \ \ \N \N nitrogen fixation ; GO:0009399 24430 IPR005971

Synonym: dark protochlorophyllide reductase

Protochlorophyllide reductase catalyzes the reductive formation of chlorophyllide from protochlorophyllide during biosynthesis of chlorophylls and bacteriochlorophylls. The light-independent (dark) form of protochlorophyllide reductase plays a key role in the ability of gymnosperms, algae, and photosynthetic bacteria to form chlorophyll in the dark. Genetic and sequence analyses have indicated that dark protochlorophyllide reductase consists of three protein subunits that exhibit significant sequence similarity to the three subunits of nitrogenase, which catalyzes the reductive formation of ammonia from dinitrogen. Dark protochlorophyllide reductase activity was shown to be dependent on the presence of all three subunits, ATP, and the reductant dithionite.

The BchL peptide (ChlL in chloroplast and cyanobacteria) is an ATP-binding iron-sulfur protein of the dark form protochlorophyllide reductase, an enzyme similar to nitrogenase [MEDLINE:20378986].

\ \ \ oxidoreductase activity, acting on iron-sulfur proteins as donors ; GO:0016730 \N photosynthesis, dark reaction ; GO:0019685 24431 IPR005972

\ \ \ molybdenum-iron nitrogenase activity ; GO:0016734 \N nitrogen fixation ; GO:0009399 24432 IPR005973

\ \ \ protein binding activity ; GO:0005515 \N nitrogen fixation ; GO:0009399 24433 IPR005974

This model represents the chains of various forms of the nitrogen-fixing enzyme nitrogenase: vanadium-iron, iron-iron, and molybdenum-iron. Most examples of NifD, the molybdenum-iron type nitrogenase chain, are excluded from this model and described instead by equivalog model IPR005972.

\ \ \ molybdenum-iron nitrogenase activity ; GO:0016734 \N nitrogen fixation ; GO:0009399 24434 IPR005975

\ \ \ protein binding activity ; GO:0005515 \N nitrogen fixation ; GO:0009399 24435 IPR005976

\ \ \ molybdenum-iron nitrogenase activity ; GO:0016734 \N nitrogen fixation ; GO:0009399 24428 IPR005969

Synonym: dark protochlorophyllide reductase

\ oxidoreductase activity, acting on iron-sulfur proteins as donors ; GO:0016730 \N photosynthesis, dark reaction ; GO:0019685 24429 IPR005970

Synonym: dark protochlorophyllide reductase

This enzyme describes the N subunit of the dark form protochlorophyllide reductase, a nitrogenase-like enzyme [MEDLINE:20378986].

\ \ oxidoreductase activity, acting on iron-sulfur proteins as donors ; GO:0016730 \N photosynthesis, dark reaction ; GO:0019685 24427 IPR005968

Despite its importance in cellular physiology, neither the de novo biosynthetic pathway nor the salvage systems for thiamine are fully understood in any organism.

\ \

The model describes thiamine ABC transporter, ATP-binding protein, believed to be involved in the specific translocation of thiamine and its phosphoesters across the inner membrane The protein belongs to the larger ABC transport system which consists of at least three components: the inner membrane permease; thiamine binding protein and an ATP-binding subunit. This protein is found so far only in Proteobacteria, and is found in complete genomes only if the ThiB and ThiP subunits are also found. It has been experimentally demonstrated that mutants in the various steps in the de novo synthesis of thiamine and its biologically active form, namely thiamine pyrophosphate can be exogenously supplemented with thiamine, thiamine monophosphate or thiamine pyrophosphate.

\ \ \ \ ATP-binding cassette (ABC) transporter activity ; GO:0004009 inner membrane ; GO:0019866 transport ; GO:0006810 24421 IPR005962

Tyrosine 3-monooxygenase (EC: 1.14.16.2), is a member of the family of tetrameric, biopterin-dependent aromatic amino acid hydroxylases found in metazoans. It is closely related to tetrameric phenylalanine-4-hydroxylase and tryptophan 5-monooxygenase, and more distantly related to the monomeric phenylalanine-4-hydroxylase found in some Gram-negative bacteria. It catalyses the first step in catecholamine biosynthesis.

 L-tyrosine + tetrahydropteridine + O2 = 3,4-dihydroxy-L-phenylalanine + dihydropteridine + H2O.

\ \ \ tyrosine 3-monooxygenase activity ; GO:0004511 \N catecholamine biosynthesis ; GO:0042423 24422 IPR005963

Tryptophan 5-monooxygenase (EC: 1.14.16.4) is a member of the family of tetrameric, biopterin-dependent aromatic amino acid hydroxylases found in metazoans. It is closely related to tetrameric phenylalanine-4-hydroxylase and tyrosine 3-monooxygenase, and more distantly related to the monomeric phenylalanine-4-hydroxylase found in some Gram-negative bacteria. It is the rate-limiting enzyme in the biosynthesis of serotonin in the central nervous system and catalyzes the first step of the synthesis of melatonin in the pineal gland.\

 L-tryptophan + tetrahydropteridine + O2 = 5-hydroxy-L-tryptophan + dihydropteridine + H2O

\ \ \ tryptophan 5-monooxygenase activity ; GO:0004510 \N serotonin biosynthesis ; GO:0042427 24423 IPR005964

This model describes the glucose/galactose transporter in bacteria (TC:2.A.1.7.2.

\ galactose/glucose (methylgalactoside) porter activity ; GO:0015613 inner membrane ; GO:0019866 glucose transport ; GO:0015758 24424 IPR005965

1-aminocyclopropane-1-carboxylate deaminase (EC: 3.5.99.7) is a pyridoxal phosphate-dependent enzyme which degrades 1-aminocyclopropane-1-carboxylateto ammonia and -ketoglutarate. In plants, the latter is a precursor of the ripening hormone ethylene. This model includes all members of this family for which the function has been demonstrated experimentally, but excludes a closely related family often annotated as putative members of this family.

\ \ \ \ 1-aminocyclopropane-1-carboxylate deaminase activity ; GO:0008660\ \N \N ethylene biosynthesis ; GO:0009693 24425 IPR005966

This is a family of pyridoxal phosphate-dependent enzymes closely related to (and often designated as) putative examples of 1-aminocyclopropane-1-carboxylate deaminase. However, the members of this family are less well conserved.

\ \ \N \N \N 24426 IPR005967

Thiamine pyrophosphate (TPP) is a required cofactor synthesized de novo in Salmonella typhimurium. The primary role for TPP is in central\ metabolism as an electron carrier and nucleophile for such enzymes as pyruvate dehydrogenase (EC: 1.2.4.1), acetolactate synthase (EC: 4.1.3.18), and -ketoglutarate dehydrogenase (EC: 1.2.4.2). Despite its importance in cellular physiology, neither the de novo biosynthetic pathway nor the salvage systems for thiamine are fully understood in any organism.

\ \

The thiamine ABC transporter, periplasmic binding protein in proteobacteria is believed to be involved in the specific translocation of thiamine and its phosphoesters across the inner membrane The protein belongs to the larger ABC transport system which consists of at least three components: the inner membrane permease; thiamine binding protein and an ATP-binding subunit. It has been experimentally demonstrated that mutants in the various steps in the de novo synthesis of thiamine and its biologically active form, namely thiamine pyrophosphate can be exogenously supplemented with thiamine, thiamine monophosphate or thiamine pyrophosphate.

\ \ ATP-binding cassette (ABC) transporter activity ; GO:0004009 periplasmic space (sensu Gram-negative Bacteria) ; GO:0030288 transport ; GO:0006810 24419 IPR005960

This family comprises the small, monomeric form of phenylalanine-4-hydroxylase (EC: 1.14.16.1), as found in a small number of Gram-negative bacteria. The enzyme irreversibly converts phenylalanine to tryosine and is known to be the rate-limiting step in phenylalanine catabolism in some systems.

 L-phenylalanine + tetrahydrobiopterin + O2 = L-tyrosine + dihydrobiopterin + H2O

This family of biopterin and metal-dependent hydroxylases is related to a family of longer, multimeric aromatic amino acid hydroxylases that have additional N-terminal regulatory sequences.

\ \ \ phenylalanine 4-monooxygenase activity ; GO:0004505 \N phenylalanine catabolism ; GO:0006559 24420 IPR005961

This family comprises the large, tetrameric form of phenylalanine-4-hydroxylase (EC: 1.14.16.1), as found in metazoans. The enzyme irreversibly converts phenylalanine to tryosine and is known to be the rate-limiting step in phenylalanine catabolism in some systems. It is closely related to\ metazoan tyrosine 3-monooxygenase and tryptophan 5-monoxygenase, and more distantly to monomeric phenylalanine-4-hydroxylases of some Gram-negative bacteria. The member of this family from Drosophila has been described as having both phenylalanine-4-hydroxylase and tryptophan 5-monoxygenase activity [MEDLINE:92156168]. However, a Drosophila member of the tryptophan 5-monoxygenase clade has subsequently been discovered.

\ \ \ phenylalanine 4-monooxygenase activity ; GO:0004505 \N phenylalanine catabolism ; GO:0006559 24412 IPR005953

This family comprises subunit C in F1/F0-ATP synthase, a membrane associated multisubunit complex found in bacteria and organelles of higher eukaryotes, namely,\ mitochondria and chloroplast. This enzyme is principally involved in the synthesis of ATP from\ ADP and inorganic phosphate by coupling the energy derived from the proton electrochemical\ gradient across the biological membrane. F1 and F0 represent two major clusters of subunits. The functional role of subunit c,\ which is the part of F0 cluster, has been delineated in in-vitro reconstitution experiments. Overall\ experimental proof exists that demonstrate the electrochemical gradient is converted into a\ rotational torque that leads to ATP synthesis.

\ \ hydrogen-translocating F-type ATPase activity ; GO:0016467 integral to membrane ; GO:0016021 ATP synthesis coupled proton transport ; GO:0015986 24413 IPR005954

This model describes histidinol phosphatase. All known examples in the scope of this model are bifunctional proteins with a histidinol phosphatase domain (EC: 3.1.3.15) followed by an imidazoleglycerol-phosphate dehydratase domain (EC: 4.2.1.19). These enzymatic domains catalyze theninth and seventh steps, respectively, of histidine biosynthesis.\

\ \ \ histidinol-phosphatase activity ; GO:0004401 cytoplasm ; GO:0005737 histidine biosynthesis ; GO:0000105 24414 IPR005955

Maleylacetoacetate isomerase is an enzyme of tyrosine and phenylalanine catabolism. It requires glutathione and belongs by homology to the zeta family of glutathione S-transferases. The enzyme (EC: 5.2.1.2) is described as active also on maleylpyruvate.

\ enzyme activity ; GO:0003824 cytoplasm ; GO:0005737 aromatic amino acid family metabolism ; GO:0009072 24415 IPR005956

4-hydroxyphenylpyruvate dioxygenase (EC: 1.13.11.27) oxidizes 4-hydroxyphenylpyruvate, a tyrosine and phenylalanine catabolite, to homogentisate. Homogentisate can undergo a further non-enzymatic oxidation and polymerization into brown pigments that protect some bacterial species from light. A similar process occurs spontaneously in blood and is hemolytic [MEDLINE:95093067]. In some bacterial species, this enzyme has been studied as a hemolysin.

\ \ 4-hydroxyphenylpyruvate dioxygenase activity ; GO:0003868\ \N \N aromatic amino acid family metabolism ; GO:0009072 24416 IPR005957

This family describes tyrosine aminotransferase (EC: 2.6.1.5) as found in animals and Trypanosoma cruzi. It is the first enzyme of a pathway of tyrosine degradation via homogentisate.

 L-tyrosine + 2-oxoglutarate = 4-hydroxyphenylpyruvate + L-glutamate.

\ Several plant enzyme designated as probable tyrosine aminotransferases are very closely related to an experimentally demonstrated nicotianamine aminotransferase, an enzyme in a siderophore (iron uptake chelator) biosynthesis pathway but are excluded from this family.

\ \ tyrosine aminotransferase activity ; GO:0004838 \N aromatic amino acid family metabolism ; GO:0009072 24417 IPR005958

This family of pyridoxal phosphate-dependent enzymes includes known examples of both tyrosine aminotransferase tyrosine aminotransferase (EC: 2.6.1.5) from animals and nicotianamine aminotransferase from barley.

\ transaminase activity ; GO:0008483 \N amino acid and derivative metabolism ; GO:0006519 24418 IPR005959

Fumarylacetoacetase aminotransferase (EC: 3.7.1.2) catalyzes the final step in the breakdown of tyrosine or phenylalanine to fumarate and acetoacetate.

 4-fumarylacetoacetate + H2O = acetoacetate + fumarate

\ \ \ fumarylacetoacetase activity ; GO:0004334 \N aromatic amino acid family metabolism ; GO:0009072 24408 IPR005949

Pyruvate formate-lyase EC: 2.3.1.54 (also known as formate C-acetyltransferase) is an enzyme which converts acetyl-CoA and formate to CoA and pyruvate.

 Acetyl-CoA + formate = CoA + pyruvate

In Escherichia coli, it uses a radical mechanism to reversibly cleave the C1-C2 bond of pyruvate using the Gly 734 radical and two cysteine residues (Cys 418, Cys 419) [MEDLINE:99436526].

This family comprises formate acetyltransferase 1. More distantly related putative formate acetyltransferases have also been identified, including formate acetyltransferase 2 from E. coli, which is excluded from this model.

\ \ \ formate C-acetyltransferase activity ; GO:0008861 cytoplasm ; GO:0005737 carbohydrate metabolism ; GO:0005975 24409 IPR005950

The model describes the molybdate ABC transporter periplasmic binding protein in bacteria and archae. Several of the periplasmic receptors constitute a diverse class of binding proteins that differ widely in size, sequence and ligand specificity. It has been shown experimentally by radioactive labeling that ModA represents a hydrophylioc periplasmic-binding protein in Gram-negative organisms and its counterpart in Gram-positive organisms is a lipoprotein. The other components of the system include ModB, an integral membrane protein and ModC, the ATP-binding subunit. Almost all of them display a common / folding motif and have similar tertiary structures consisting of two globular domains.

\ molybdate-transporting ATPase activity ; GO:0015412 periplasmic space (sensu Gram-negative Bacteria) ; GO:0030288 molybdate ion transport ; GO:0015689 24410 IPR005951

Rim protein (ABCR), is an ATP binding cassette (ABC)1 transporter found in vertebrate retinal photoreceptor cells. It is localized along the rim region of photoreceptor rod outer segment disc membranes and more recently has been found in human foveal and peripheral cone outer segments. Several studies have implicated ABCR in the retinoid cycle, possibly functioning as a retinal extruder or retinal-phosphatidylethanolamine flippase to facilitate the removal of all-trans-retinal from disc membranes following the photobleaching of rhodopsin [MEDLINE:21316539].

ABCR contains eight glycosylation sites. Four sites reside in a 600-amino acid exocytoplasmic domain of the N-terminal half between the first transmembrane segment H1 and the first multi-spanning membrane domain, and four sites are in a 275-amino acid domain of the C half between transmembrane segment H7 and the second multi-spanning membrane domain. This leads to a model in which each\ half has a transmembrane segment followed by a large exocytoplasmic domain, a multi-spanning membrane domain, and a nucleotide binding domain.

\ \ \ ATP-binding cassette (ABC) transporter activity ; GO:0004009 integral to plasma membrane ; GO:0005887 transport ; GO:0006810 24411 IPR005952

Most members of this family are phosphoglycerate mutase (EC: 5.4.2.1). This enzyme interconverts 2-phosphoglycerate and 3-phosphoglycerate.

  2-phospho-D-glycerate + 2,3-diphosphoglycerate = 3-phospho-D-glycerate + 2,3-diphosphoglycerate.

The enzyme is transiently phosphorylated on an active site histidine by 2,3-diphosphoglyerate, which is both substrate and product. Some members of this family have are phosphoglycerate mutase as a minor activity and act primarily as a bisphoglycerate mutase, interconverting 2,3-diphosphoglycerate and 1,3-diphosphoglycerate (EC: 5.4.2.4).

\ \ \ intramolecular transferase activity, phosphotransferases ; GO:0016868 \N glycolysis ; GO:0006096 24403 IPR005944

Proline iminopeptidase (Prolyl aminopeptidase, EC: 3.4.11.5) catalyzes the removal of the N-terminal proline from peptides. This family represents one of two related families of proline iminopeptidase containing the / fold. The fine specificities of the various members, including both the range of short peptides from which proline can be removed and whether other amino acids such as\ alanine can be also removed, may vary among members.

\ \ \ prolyl aminopeptidase activity ; GO:0016804 cytoplasm ; GO:0005737 \N 24404 IPR005945

\ \ \ prolyl aminopeptidase activity ; GO:0016804 cytoplasm ; GO:0005737 \N 24405 IPR005946

Synonyms: phosphoribosylpyrophosphate synthetase

Phosphoribosyldiphosphate synthetase (PRPPsase, EC: 2.7.6.1) catalyzes the transfer of an intact diphosphate (PP) group from ATP to\ ribose-5-phosphate (R-5-P), which results in the formation of AMP and 5-phospho-D-ribosyl--1-diphosphate (PRPP). \

 ATP + D-ribose 5-phosphate = AMP + 5-phospho--D-ribose 1-diphosphate

\ PRPP is an essential precursor for purine and pyrimidine nucleotides, both in the de novo synthesis and in the salvage pathway as well as in the synthesis of pyridine nucleotide coenzymes. The activity of PRPPsase is highly regulated. Besides competitive inhibition at the substrate binding\ sites, most PRPPsases are regulated in an allosteric manner, in which ADP generally acts as the most potent inhibitor. In some systems, close homologs lacking enzymatic activity exist and perform regulatory functions.

\ \ \ ribose-phosphate pyrophosphokinase activity ; GO:0004749 \N nucleotide biosynthesis ; GO:0009165 24406 IPR005947

Thiamine pyrophosphate (TPP)1 is a required cofactor synthesized de novo in Salmonella typhimurium. The primary role for TPP is in centralmetabolism as an electron carrier and nucleophile for such enzymes as pyruvate dehydrogenase (EC: 1.2.4.1), acetolactate synthase (EC: 4.1.3.18), and -ketoglutarate dehydrogenase (EC: 1.2.4.2). Despite its importance in cellular physiology, neither the de novo biosynthetic\ pathway nor the salvage systems for thiamine are fully understood in any organism.

\ \

The model describes thiamine ABC transporter, permease protein in bacteria, believed to be involved in the specific translocation of thiamine and its phosphoesters across the inner membrane The protein belongs to the larger ABC transport system which consists of at least three components:

the inner membrane permease

thiamine binding protein

an ATP-binding subunit.

It has been experimentally demonstrated that mutants in the various steps in the de novo synthesis of thiamine and its biologically active form, namely thiamine pyrophosphate can be exogenously supplemented with thiamine, thiamine monophosphate (TMP) or thiamine\ pyrophosphate (TPP).

\ \ \ transporter activity ; GO:0005215 inner membrane ; GO:0019866 transport ; GO:0006810 24407 IPR005948

Thiamine pyrophosphate 1 is a required cofactor synthesized de novo in Salmonella typhimurium. The primary role for TPP is in central\ metabolism as an electron carrier and nucleophile for such enzymes as pyruvate dehydrogenase (EC: 1.2.4.1), acetolactate synthase (EC: 4.1.3.18), and -ketoglutarate dehydrogenase (EC: 1.2.4.2). Despite its importance in cellular physiology, neither the de novo biosynthetic pathway nor the salvage systems for thiamine are fully understood in any organism.

\ \

The thiamine ABC transporter, periplasmic binding protein in bacteria is believed to be involved in the specific translocation of thiamine and its phosphoesters across the inner membrane. The protein belongs to the larger ABC transport system which consists of at least three components: the inner membrane permease; thiamine binding protein and an ATP-binding subunit. It has been experimentally demonstrated that mutants in the various steps in the de novo synthesis of thiamine and its biologically active form, namely thiamine pyrophosphate can be exogenously supplemented with thiamine, thiamine monophosphate (TMP) or thiamine pyrophosphate TPP.

\ \ \ transporter activity ; GO:0005215 periplasmic space (sensu Gram-negative Bacteria) ; GO:0030288 transport ; GO:0006810 24401 IPR005942

Daunorubicin resistance ABC transporter membrane protein is associated with the effux of the drug, daunorubicin. It functions as an ATP dependent antiporter. This transport system belongs to the larger ATP-Binding Cassette (ABC) transporter superfamily. The characteristic feature of these transporter is the obligatory coupling of ATP hydrolysis to substrate translocation. The minimal configuration of bacterial ABC transport system is

an ATPase or ATP binding subunit

an integral membrane protein

a hydrophilic polypeptide which probably functions as the substrate binding protein.

This family describes the daunorubicin resistance ABC transporter, membrane associated protein in bacteria and archaea. In eukaryotes proteins of similar function include p-glyco-proteins and multidrug resistance protein.

\ \N \N \N 24402 IPR005943

Daunorubicin resistance protein C confers the function of daunorubicin resistance. The protein seems to share strong sequence similarity to UvrA proteins, which are involved in excision repair of DNA. Disruption of drrC gene showed increased sensitivity upon exposure to duanorubicin, however it failed to complement uvrA mutants to exposure to UV irradiation. The mechanism on how it confers duanomycin resistance is unclear, but has been suggested to be different from DrrA and DrrB which are antiporters.

\ \N integral to membrane ; GO:0016021 \N 24395 IPR005936

FtsH is a membrane-anchored ATP-dependent protease that degrades misfolded or misassembled membrane proteins as well as a subset of cytoplasmic regulatory proteins. FtsH is a 647-residue protein of Mr = 71 000, with two putative transmembrane segments towards its N terminus which anchor the protein to themembrane, giving rise to a periplasmic domain of 70 residues and a cytoplasmic segment of 520 residues containing the ATPase and protease domains [MEDLINE:22032483].

\ \ \ metalloendopeptidase activity ; GO:0004222 membrane ; GO:0016020 protein catabolism ; GO:0030163 24396 IPR005937

Intracellular proteins, including short-lived proteins such as cyclin, Mos, Myc, p53, NF-kappaB, and IkappaB, are degraded by the ubiquitin-proteasome system. The 26S proteasome (a 2 MDa complex) is made up of two subcomplexes: the 20S proteasome and the regulatory complex. The former is a 700 kDa cylindrical protease complex consisting of four stacks of heptameric rings with 28 subunits (i.e., 7777) with molecular masses of about 20-35 kDa, whereas the latter is a 700-1000 kDa complex consisting of at least 18 subunits with molecular\ masses of 28-110 kDa, including 6 putative ATPases (Rpt1-Rpt6) and 12 non-ATPase subunits (Rpn1-12).

The ATPase p45/Sug1/Rpt6 may itself be phosphorylated within the proteosome. This phosphorylation event may play a key role in ATP-dependent proteolysis because a good correlation exists between the inhibition pattern of protein kinase inhibitors against the phosphorylation of p45 and that against the ATP-dependent proteolytic activity [MEDLINE:20582593].

\ \ \ hydrolase activity ; GO:0016787 cytoplasm ; GO:0005737 protein catabolism ; GO:0030163 24397 IPR005938

The ATPase Cdc48 is required for membrane fusion and protein degradation. It possesses chaperone-like activities and can functionally interact with Hsc70. Yeast CDC48 plays a role in cell division control whereas eukaryotic homologues are involved in the budding and transfer of membrane from the transitional endoplasmic reticulum to the Golgi apparatus.

\ hydrolase activity ; GO:0016787 \N cell growth and/or maintenance ; GO:0008151 24398 IPR005939

This is a family of largely hypothetical proteins of unknown function.

\ \ \ \N \N \N 24399 IPR005940

In many widely different species, including Escherichia coli, Thermotoga maritima, and Archaeoglobus fulgidus, this enzyme is a C-terminal part of a multifunctional protein together with glutamine amidotransferase; the fusion protein is designated anthranilate synthase component II (EC: 4.1.3.27).

\ \ anthranilate phosphoribosyltransferase activity ; GO:0004048 \N tryptophan biosynthesis ; GO:0000162 24400 IPR005941

Succinyl-diaminopimelate desuccinylase (EC: 3.5.1.18) hydrolyses N-succinyl-L,L-diaminopimelic acid which is required for the bacterial synthesis of lysine and meso-diaminopimelic acid.

This family comprises of a proteobacterial subset of succinyl-diaminopimelate desuccinylases.

\ \ \ succinyl-diaminopimelate desuccinylase activity ; GO:0009014 \N lysine biosynthesis via diaminopimelate ; GO:0009089 24390 IPR005931

The delta(1)-pyrroline-5-carboxylate synthetase (EC: 1.5.1.12) a mitochondrial inner membrane, ATP- and NADPH-dependent, bifunctional enzyme, catalyzes the reduction of glutamate to delta1-pyrroline-5-carboxylate, a critical step in the de novo biosynthesis of proline and ornithine. It is the rate-limiting enzyme in proline biosynthesis and is subject to feedback inhibition by proline.\

 1-pyrroline-5-carboxylate + NAD+ + H2O = L-glutamate + NADH

This model represents one of several related branches of delta-1-pyrroline-5-carboxylate dehydrogenase.

\ \ \ \ 1-pyrroline-5-carboxylate dehydrogenase activity ; GO:0003842\ \N mitochondrial matrix ; GO:0005759 proline biosynthesis ; GO:0006561 24391 IPR005932

 1-pyrroline-5-carboxylate + NAD+ + H2O = L-glutamate + NADH

This model represents one of several related branches of delta-1-pyrroline-5-carboxylate dehydrogenase.

\ \ \ \ 1-pyrroline-5-carboxylate dehydrogenase activity ; GO:0003842\ \N \N proline biosynthesis ; GO:0006561 24392 IPR005933

 1-pyrroline-5-carboxylate + NAD+ + H2O = L-glutamate + NADH

This model represents one of several related branches of delta-1-pyrroline-5-carboxylate dehydrogenase. Members of this branch include the C-terminal domain of the PutA bifunctional proline dehydrogenase / delta-1-pyrroline-5-carboxylate dehydrogenase.

\ \ \ \ 1-pyrroline-5-carboxylate dehydrogenase activity ; GO:0003842\ \N \N proline biosynthesis ; GO:0006561 24393 IPR005934

Galactose-1-phosphate uridylyltransferase (EC: 2.7.7.10) catalyzes one step in the conversion of galactose to glucose.

 UTP + -D-galactose 1-phosphate = diphosphate + UDP-galactose

\ \ \ UTP-hexose-1-phosphate uridylyltransferase activity ; GO:0003982 cytoplasm ; GO:0005737 galactose metabolism ; GO:0006012 24394 IPR005935

Synonyms: mevalonate diphosphate decarboxylase; pyrophosphomevalonate decarboxylase

Diphosphomevalonate decarboxylase (EC: 4.1.1.33) catalyzes the last step in the synthesis of isopentenyl diphosphate, an essential intermediate in isoprenoid biosynthesis via the mevalonate pathway.\

 ATP + (R)-5-diphosphomevalonate = ADP + phosphate + isopentenyl diphosphate + CO2

\ \ \ diphosphomevalonate decarboxylase activity ; GO:0004163 \N isoprenoid biosynthesis ; GO:0008299 24386 IPR005927

Tagatose 1,6-diphosphate aldolase (EC: 4.1.2.40) is part of the tagatose-6-phosphate pathway of galactose-6-phosphate degradation.

 D-tagatose 1,6-bisphosphate = glycerone phosphate + D-glyceraldehyde 3-phosphate

\ The genes coding for the enzymes of the tagatose 6-phosphate pathway have been found to be part of the lac operon together with the\ genes coding for the lactose-phosphotransferase system and the phospho-

-galactosidase in Lactococcus lactis, Staphlococcus aureus, and Streptococcus mutans. This family consists of proteins from Gram-positive bacteria.

\ \ \ tagatose-6-phosphate kinase activity ; GO:0009024 \N lactose catabolism via tagatose-6-phosphate ; GO:0019512 24387 IPR005928

6-phospho--galactosidase (EC: 3.2.1.85) is part of the tagatose-6-phosphate pathway of galactose-6-phosphate degradation.

 A 6-phospho--D-galactoside + H2O = an alcohol + 6-phospho-D-galactose

-galactosidase in Lactococcus lactis, Staphlococcus aureus, and Streptococcus mutans.

\ \ \ hydrolase activity, hydrolyzing O-glycosyl compounds ; GO:0004553 \N lactose catabolism via tagatose-6-phosphate ; GO:0019512 24388 IPR005929

L-ribulokinase (EC: 2.7.1.16) catalyzes the second step in arabinose catabolism.

 ATP + L-ribulose = ADP + L-ribulose 5-phosphate

\ \ \ L-ribulokinase activity ; GO:0008741 \N L-arabinose catabolism ; GO:0019572 24389 IPR005930

In the postabsorptive state, blood glucose concentration is kept constant by a combination of glycogenolysis and gluconeogenesis. During prolonged fasting, when hepatic glycogen is exhausted, gluconeogenesis becomes the only source of plasma glucose. Gluconeogenesis (the production of new glucose molecules) occurs mainly in liver and, to a small extent, in kidneys.

Pyruvate carboxylase (EC: 6.4.1.1), a member of the biotin-dependent enzyme family, catalyses the ATP-dependent carboxylation of pyruvate to oxaloacetate, thus playing a crucial role in gluconeogenesis.

 ATP + pyruvate + HCO3- = ADP + phosphate + oxaloacetate

\ Most well characterized forms of active enzyme consist of four identical subunits arranged in a tetrahedron-like structure. Each subunit contains three functional domains: the biotin carboxylation domain, the transcarboxylation domain and the biotin carboxyl carrier domain.

\ \ \ pyruvate carboxylase activity ; GO:0004736 cytoplasm ; GO:0005737 gluconeogenesis ; GO:0006094 24384 IPR005925

Members of this family include known and predicted examples of agmatinase (agmatine ureohydrolase, EC: 3.5.3.11) and members of archaea, for which no definitive agmatinase sequence has yet been made available. However, archaeal sequences are phylogenetically close to the experimentally verified B. subtilis sequence. One species of Halobacterium has been demonstrated in vitro to produce agmatine from arginine, but no putrescine from ornithine, suggesting that arginine decarboxylase and agmatinase, rather than arginase and ornithine decarboxylase, lead from arginine to polyamine biosynthesis.

\ agmatinase activity ; GO:0008783 \N polyamine biosynthesis ; GO:0006596 24385 IPR005926

Tagatose-6-phosphate kinase (EC: 2.7.1.144) is part of the tagatose-6-phosphate pathway of lactose degradation.

 ATP + D-tagatose 6-phosphate = ADP + D-tagatose 1,6-bisphosphate

-galactosidase in Lactococcus lactis, Staphlococcus aureus, and Streptococcus mutans.

\ \ \ tagatose-6-phosphate kinase activity ; GO:0009024 \N lactose catabolism via tagatose-6-phosphate ; GO:0019512 24379 IPR005920

Imidazolonepropionase (EC: 3.5.2.7) catalyzes the third step in histidine degradation.

 4-imidazolone-5-propanoate + H2O = N-formimino-L-glutamate

\ \ \ hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in cyclic amides ; GO:0016812 cytoplasm ; GO:0005737 histidine catabolism to glutamate and formamide ; GO:0019556 24380 IPR005921

Histidine ammonia-lyase (EC: 4.3.1.3) deaminates histidine to urocanic acid, the first step in histidine degradation. It is closely related to phenylalanine ammonia-lyase.

\ histidine ammonia-lyase activity ; GO:0004397 cytoplasm ; GO:0005737 histidine catabolism ; GO:0006548 24381 IPR005922

The ubiquitous higher plant enzyme phenylalanine ammonia-lyase (EC: 4.3.1.5) catalyzes the nonoxidative deamination of L-phenylalanine to trans-cinnamic acid.

\ ammonia-lyase activity ; GO:0016841 cytoplasm ; GO:0005737 phenylalanine catabolism ; GO:0006559 24382 IPR005923

Formiminoglutamase (EC: 3.5.3.8), the fourth enzyme of histidine degradation, is similar to arginases and agmatinases. It is often encoded near other enzymes of the histidine degredation pathway: histidine ammonia-lyase, urocanate hydratase, and imidazolonepropionase.

 N-formimidoyl-L-glutamate + H2O = L-glutamate + formamide.

\ \ \ hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amidines ; GO:0016813 \N histidine catabolism ; GO:0006548 24383 IPR005924

L-Arginine is converted to nitric oxide and citrulline by the enzyme nitric oxide synthase and by the enzyme arginase as a part of the hepatic urea cycle. Arginase is a manganese metalloenzymes containing a metal-activated hydroxide ion, a critical nucleophile in metalloenzymes that catalyze hydrolysis or hydration reactions. A hydrogen bond formed by the metal-bound hydroxide holds the enzyme in the proper orientation for catalysis however nonmetal substrate-binding sites are also implicated in the enzyme mechanism. Regeneration of metal-bound hydroxide ion from a metal-bound water\ molecule requires proton transfer to bulk solvent mediated by a histidine proton shuttle residue.

\ \ arginase activity ; GO:0004053 \N arginine catabolism ; GO:0006527 24376 IPR005916

Phosphomevalonate kinase (EC: 2.7.4.2) catalyzes the phosphorylation of 5-phosphomevalonate into 5-diphosphomevalonate, an essential step in isoprenoid biosynthesis via the mevalonate pathway. In an example of nonorthologous gene displacement, two different types of phosphomevalonate kinase are found - the higher eukaryotic form and this ERG8 type [MEDLINE:21140494]. This model represents plant and fungal forms of the ERG8 type of phosphomevalonate kinase.

\ \ \ phosphomevalonate kinase activity ; GO:0004631 cytoplasm ; GO:0005737 isoprenoid biosynthesis ; GO:0008299 24377 IPR005917

Phosphomevalonate kinase (EC: 2.7.4.2) catalyzes the phosphorylation of 5-phosphomevalonate into 5-diphosphomevalonate, an essential step in isoprenoid biosynthesis via the mevalonate pathway. In an example of nonorthologous gene displacement, two different types of phosphomevalonate kinase are found - the higher eukaryotic form and this ERG8 type. This model represents the low GC Gram-positive organism forms of the ERG8 type of phosphomevalonate kinase.

\ \ \ \N \N \N 24378 IPR005919

Phosphomevalonate kinase (EC: 2.7.4.2) catalyzes the phosphorylation of 5-phosphomevalonate into 5-diphosphomevalonate, an essential step in isoprenoid biosynthesis via the mevalonate pathway. In an example of nonorthologous gene displacement, two different types of phosphomevalonate kinase are found - the higher eukaryotic form and the ERG8 type. This model represents the form of the enzyme found in animals.

\ \ \ phosphomevalonate kinase activity ; GO:0004631 cytoplasm ; GO:0005737 cholesterol biosynthesis ; GO:0006695 24371 IPR005911

This uncharacterized protein family shows significant similarity to IPR005910, a longer protein that is a histone acetyltransferase at its C-terminus and is a subunit of RNA polymerase II (in yeast). This family lacks the GNAT acetyltransferase domain.

\ \N \N \N 24372 IPR005912

The members of this family of conserved hypothetical proteins show a low level of similarity to several predicted RNA pseudouridine synthases. All trusted members of this family are archaeal. Several eukaryotic homologs lack N-terminal homology including two CXXC motifs.

\ \ \N \N \N 24373 IPR005913

dTDP-4-dehydrorhamnose reductase (EC: 1.1.1.133) catalyzes the last of 4 steps in making dTDP-rhamnose, a precursor of LPS molecules such as core antigen and O-antigen.

 dTDP-6-deoxy-L-mannose + NADP+ = dTDP-4-dehydro-6-deoxy-L-mannose + NADPH

\ \ \ dTDP-4-dehydrorhamnose reductase activity ; GO:0008831 \N extracellular polysaccharide biosynthesis ; GO:0045226 24374 IPR005914

Acetoacetyl-CoA synthase (EC: 6.2.1.16) catalyzes the first step of the mevalonate pathway of isoprenoid biosynthesis via isopentenyl diphosphate. Most bacteria do not use this pathway, but rather the deoxyxylulose pathway.

 ATP + acetoacetate + CoA = AMP + diphosphate + acetoacetyl-CoA

\ \ \ CoA-ligase activity ; GO:0016405 \N isoprenoid biosynthesis ; GO:0008299 24375 IPR005915

The members of this family share 50 % or greater sequence identity. They are found as eleven tandem genes, arranged head-to-tail, in Staphylococcus aureus strain COL. Distant full-length homologs are found in a Staphylococcus haemolyticus plasmid and in Bacillus halodurans. The function of these proteins is unknown.

\ \N \N \N 24369 IPR005909

This family of exclusively archaeal proteins has no characterized close homologs. An apparent similarity between the central region of this family and the central regions of the oxygen-independent coproporphyrinogen III dehydrogenase HemN has been observed.

\ \N \N \N 24370 IPR005910

The Saccharomyces cerevisiae member YPL086C has been characterized in vitro as an N-terminal acetyltransferase (EC: 2.3.1.48) for all four core histones. It is a component of the RNA polymerase II holoenzyme, designated Elp3p for Elongator Protein 3. Members of this family are found in eukaryotes and archaea. These proteins are part of the larger set of GNAT acetyltransferases. In vivo, ELP3 gene deletion confers typical ELP phenotypes such as slow growth adaptation, slow gene activation, and temperature sensitivity. This suggests a role for the proteins as novel, tightly RNAPII-associated histone acetyltransferases in transcription of DNA packaged in chromatin [MEDLINE:99374060] ].

\ \N \N \N 24366 IPR005906

This very small, poorly characterized protein in Thermus thermophilus has been shown to be essential for an unusual pathway of Lys biosynthesis from aspartate by way of -aminoadipate (AAA) rather than diaminopimelate. It is also found in Deinococcus radiodurans and Pyrococcus horikoshii, which appear to share the AAA pathway.

\ \N \N lysine biosynthesis, aminoadipic pathway ; GO:0019878 24367 IPR005907

Synonym: dTDP-D-glucose synthase

This group of proteins comprises a tightly conserved but broadly distributed subfamily (here designated as short form) of known and putative bacterial glucose-1-phosphate thymidylyltransferases (EC: 2.7.7.24). It is\ well characterized in several species as the first of four enzymes involved in the biosynthesis of dTDP-L-rhamnose, a cell wall constituent and a feedback inhibitor of the enzyme. The enzyme is active as a homotetramer.\

 dTTP + -D-glucose 1-phosphate = diphosphate + dTDP-glucose

\ \

The family of known and putative glucose-1-phosphate thymidyltransferases shows a deep split into a short form (see IPR005908) and a long form described by this model. The homotetrameric short form is found in numerous bacterial species that incorporate dTDP-L-rhamnose, which it helps synthesize, into the cell wall. It is subject to feedback inhibition. The long form, in contrast, is found in many species for which it serves as a sugar-activating enzyme for antibiotic biosynthesis and or other, unknown pathways, and in which dTDP-L-rhamnose is not necessarily produced.

\ \ \ glucose-1-phosphate thymidylyltransferase activity ; GO:0008879 \N extracellular polysaccharide biosynthesis ; GO:0045226 24368 IPR005908

Synonym: dTDP-D-glucose synthase

This group of proteins comprises a tightly conserved but broadly distributed subfamily of known and putative bacterial glucose-1-phosphate thymidylyltransferases (EC: 2.7.7.24). It is\ well characterized in several species as the first of four enzymes involved in the biosynthesis of dTDP-L-rhamnose, a cell wall constituent and a feedback inhibitor of the enzyme.

 dTTP + -D-glucose 1-phosphate = diphosphate + dTDP-glucose

\ \

The family of known and putative glucose-1-phosphate thymidyltransferases shows a deep split into a short form (see IPR005907) and a long form described by this model. The homotetrameric short form is found in numerous bacterial species that incorporate dTDP-L-rhamnose, which it helps synthesize, into the cell wall. It is subject to feedback inhibition. The long form, in contrast, is found in many species for which it\ serves as a sugar-activating enzyme for antibiotic biosynthesis and or other, unknown\ pathways, and in which dTDP-L-rhamnose is not necessarily produced.

\ \ \ glucose-1-phosphate thymidylyltransferase activity ; GO:0008879 \N antibiotic biosynthesis ; GO:0017000 24364 IPR005904

This entry presents hypoxanthine phosphoribosyltransferase (EC: 2.4.2.8), which belongs to phosphoribosyltransferase family and is involved in purine salvage.

\ \ hypoxanthine phosphoribosyltransferase activity ; GO:0004422 cytoplasm ; GO:0005737 purine salvage ; GO:0006166 24365 IPR005905

D-alanine--D-alanine ligase (EC: 6.3.2.4) is a bacterial enzyme involved in cell-wall biosynthesis. It participates in forming UDP-N-acetylmuramyl pentapeptide, the peptidoglycan precursor. These enzymes are proteins of 300 to 360 amino acids containing many conserved regions. The N-terminal Gly-rich region could be involved in ATP-binding.

This family of enzymes represent chromosomal versions of species not specifically resistant to glycopeptide antibiotics such as vancomycin. The mechanism of glyopeptide antibiotic resistance involves the production of D-alanine-D-lactate (VanA and VanB families) or D-alanine-D-serine (VanC). This model attempts to exclude the VanA/VanB and VanC subfamilies while capturing most other D-Ala-D-Ala ligases above the trusted cutoff. However, changes in small numbers of amino acids, as demonstrated crystallographically, can alter specificity. \ In Chlamydial species, this enzyme is found as a fusion protein with UDP-N-acetylmuramate--alanine ligase.

\ \ \ D-alanine-D-alanine ligase activity ; GO:0008716 cytoplasm ; GO:0005737 peptidoglycan biosynthesis ; GO:0009252 24360 IPR005899

This family comprises distantly related, low complexity, hydrophobic small subunits of several related sodium ion-pumping decarboxylases. These include\ oxaloacetate decarboxylase gamma subunit and methylmalonyl-CoA decarboxylase delta subunit.

\ \ \ sodium ion transporter activity ; GO:0015081 membrane ; GO:0016020 sodium ion transport ; GO:0006814 24361 IPR005900

6-phosphogluconolactonase (EC: 3.1.1.31) is the enzyme responsible for the hydrolysis of 6-phosphogluconolactone to 6-phosphogluconate, the second step in the pentose phosphate pathway.

 6-phospho-D-glucono-1,5-lactone + H2O = 6-phospho-D-gluconate.

\ \ \ \ 6-phosphogluconolactonase activity ; GO:0017057\ \N \N pentose-phosphate shunt ; GO:0006098 24362 IPR005902

This family of proteins is related to, but longer than, DNA-binding protein HU.It contains a distinctive domain architecture when compared to HU and related histone-like DNA-binding. Members include, so far, a protein from Bacteroides fragilis and ten from Porphyromonas gingivalis. Both species are oral\ pathogens.

\ \ \ \N \N \N 24363 IPR005903

2-desacetyl-2-hydroxyethyl bacteriochlorophyllide is a dehydrogenase and a subunit of bacteriochlorophyll synthase which catalyzes the penultimate step in bacteriochlorophyl A biosynthesis.

\ oxidoreductase activity ; GO:0016491 \N bacteriochlorophyll biosynthesis ; GO:0030494 24356 IPR005895

This family contains the cytochrome c biogenesis protein encoded by ccmA in bacteria and one arabidopsis protein, possibly encoded by an organelle. Bacterial c-type cytochromes are located on the periplasmic side of the cytoplasmic membrane.\ Several gene products encoded in a locus designated as 'ccm' are implicated in the\ transport and assembly of the functional cytochrome C. This cluster includes genes:\ ccmA;B;C;D;E;F;G and H. The post-translational pathway includes the transport of a heme moiety, the secretion of the apoprotein and the covalent attachment of the heme with the apoprotein. The proteins ccmA and B represent an ABC transporter; ccmC and D participate in heme transfer to ccmE, which functions as a periplasmic heme chaperone. The presence of ccmF, G and H is suggested to be obligatory for the final functional assembly of cytochrome c.

\ \ \ transporter activity ; GO:0005215 periplasmic space (sensu Gram-negative Bacteria) ; GO:0030288 cytochrome biogenesis ; GO:0017004 24357 IPR005896

This family contains glucan exporter ATP binding protein in bacteria. It belongs to the larger ABC transporter superfamily with the characteristic ATP binding motif. In general, this protein is in some ways implicated in osmo-regulation and is suggested to participate in the export of glucan from the cytoplasm to periplasm. The cyclic -1,2-glucan in the bacterial periplasmic space is suggested to confer the property of high osmolority. It has also been demonstrated that mutants in this loci have lost functions of virulence and motility. It is unclear as to how virulence and osmo-adaptaion are related.

\ \ \ transporter activity ; GO:0005215 \N transport ; GO:0006810 24358 IPR005897

This family contains ABC-type bacteriocin transporter. In general, bacteriocins are agents which are responsible for killing or inhibiting the closely related species or even different strains of the same species. Bacteriocins are encoded by bacterial plasmids. Bacteriocins are named after the species and hence in literature one encounters various names e.g., leucocin from Leuconostic geldium; pedicocin from Pedicoccus acidilactici; sakacin from Lactobacillus sake etc.

\ \ toxin transporter activity ; GO:0019534 membrane ; GO:0016020 transport ; GO:0006810 24359 IPR005898

Bacteria have elaborate pathways for the production of toxins and secondary metabolites. Many such compounds, including syringomycin and pyoverdine are synthesized on non-ribosomal templates consisting of a multienzyme complex. On several occasions the proteins of the complex and transporter protein are present on the same operon. Often times these compounds cross the biological membrane by specific transporters. This model describes a family of cyclic peptide transporters in bacteria. Syringomycin is an amphipathic, cyclic lipodepsipeptide when inserted into host causes formation of channels, permeable to a variety of cations. On the other hand, pyoverdine is a cyclic octa-peptidyl dihydroxyquinoline, which is efficient in sequestering iron for uptake.

\ \ peptide transporter activity ; GO:0015197 integral to membrane ; GO:0016021 peptide transport ; GO:0015833 24352 IPR005891

This family contains a predicted membrane subunit, DevC, of an ABC transporter known so far from two species of cyanobacteria. Some experimental data from mutational analysis {[MEDLINE:98230330] suggest that this protein, along with DevA and DevB encoded in the same operon, may be involved in the transport/export of glycolipids.

\ transporter activity ; GO:0005215 membrane ; GO:0016020 transport ; GO:0006810 24353 IPR005892

This family comprises the glycine betaine/L-proline ATP binding subunit in bacteria and its equivalents in archaea. This transport system belong to the larger ATP-Binding Cassette (ABC) transporter superfamily. The characteristic feature of these transporters is the obligatory coupling of ATP hydrolysis to substrate translocation.

Functionally, this transport system is involved in osmoregulation. Under conditions of stress, the organism recruits this transport system to accumulate glycine betaine and other solutes which offer osmo-protection. It has been demonstrated that glycine betaine uptake is accompanied by symport with sodium ions. The locus has been named variously as proU or opuA. A gene library from L. lactis functionally complements an Escherichia coli proU mutant. The complementing locus is similar to a opuA locus in Bacillus subtlis. This clarifies the differences in nomenclature.

\ \ amino acid transporter activity ; GO:0015171 membrane ; GO:0016020 amino acid transport ; GO:0006865 24354 IPR005893

This family comprises the spermidine/putrescine ABC transporter, ATP binding subunit in bacteria and its equivalents in archaea. This transport system belongs to the larger ATP-Binding Cassette (ABC) transporter superfamily. Polyamines like spermidine and putrescine play a vital role in cell proliferation, differentiation, and ion homeostasis. The concentration of polyamines within the cell are regulated by biosynthesis, degradation and transport (uptake and efflux included).

\ \ polyamine-transporting ATPase activity ; GO:0015417 membrane ; GO:0016020 polyamine transport ; GO:0015846 24355 IPR005894

This family contains the daunorubicin resistance ABC transporter, ATP binding subunit in bacteria and archaea. This model is restricted in its scope to preferentially recognize the ATP binding subunit associated with effux of the drug, daunorubicin. In other words it functions as an ATP dependent antiporter.

\ \ drug transporter activity ; GO:0015238 \N drug transport ; GO:0015893 24344 IPR005883

The opportunistic pathogen Pseudomonas aeruginosa produces type 4 fimbriae which promote adhesion to epithelial cells and are associated with a form of surface translocation called twitching motility. Four genes, pilM-P, encode the necessary proteins with predicted sizes of 37.9, 22.2, 22.8 and 19.0 kDa, respectively and appear to form an operon. This protein is required for the assembly of the type IV fimbria in Pseudomonas aeruginosa and for a similar pilus-like structure in Synechocystis. It isalso found in species such as Deinococcus described as having natural transformation (for which a type IV pilus-like structure is proposed) but not fimbria.

\ \ \ \N \N protein complex assembly ; GO:0006461 24345 IPR005884

In bacteria two distinct, membrane-bound, enzyme complexes are responsible for the interconversion of fumarate and succinate (EC: 1.3.99.1): fumaratereductase (Frd) is used in anaerobic growth, and succinate dehydrogenase (Sdh)is used in aerobic growth. Both complexes consist of two main components: a\ membrane-extrinsic component composed of a FAD-binding flavoprotein and an\ iron-sulfur protein; and an hydrophobic component composed of a membrane\ anchor protein and/or a cytochrome B.

In eukaryotes mitochondrial succinate dehydrogenase (ubiquinone) (EC: 1.3.5.1)\ is an enzyme composed of two subunits: a FAD flavoprotein and and iron-sulfur\ protein.

The flavoprotein subunit is a protein of about 60 to 70 Kd to which FAD is\ covalently bound to a histidine residue which is located in the N-terminal\ section of the protein [MEDLINE:89340438]. The sequence around that histidine is well conserved in Frd and Sdh from various bacterial and eukaryotic species [MEDLINE:92283874].

The terms succinate dehydrogenase and fumarate reductase may be used interchangeably in certain systems. However, a number of species have distinct complexes, with the fumarate reductase active under anaerobic conditions. This model represents the fumarate reductase flavoprotein subunit from several such species in which a distinct succinate dehydrogenase is also found.

\ \ \ oxidoreductase activity ; GO:0016491 \N anaerobic respiration ; GO:0009061 24346 IPR005885

This family of largely hypothetical proteins is found exclusively in the Archaea and contain a putative RNA methylase domain.

\ \N \N \N 24347 IPR005886

Synonym: UDP-galactose 4-epimerase UDP-glucose 4-epimerase (EC: 5.1.3.2)\ interconverts UDP-glucose and UDP-galactose which are precursors of glucose- and\ galactose-containing exopolysaccharides (EPS). A set of related proteins, some\ of which are tentatively identified as UDP-glucose-4-epimerase in Thermotoga maritima, Bacillus halodurans, and several archaea, but deeply branched from this set and lacking experimental evidence, are excluded and described by a separate model.

\ \ \ UDP-glucose 4-epimerase activity ; GO:0003978 \N galactose metabolism ; GO:0006012 24348 IPR005887

The identification of members of this family as putative -1,2-mannosidases is based on an unpublished characterization of the aman2 gene in Bacillus sp. M-90 by Maruyama,Y., Nakajima,M. and Nakajima,T. (Genbank accession BAA76709, pidg4587313). Most members of this family appear to have signal sequences. Members from the dental pathogen Porphyromonas gingivalis have been described as immunoreactive with periodontitis patient serum.

\ \ \ \N \N \N 24349 IPR005888

The conversion of dTDP-glucose into dTDP-4-keto-6-deoxyglucose by Escherichia coli dTDP-glucose 4,6-dehydratase) (EC: 4.2.1.46) takes place in the active site in three steps: dehydrogenation to dTDP-4-ketoglucose, dehydration to dTDP-4-ketoglucose-5,6-ene, and rereduction of C6 to the methyl group. The 4,6-dehydratase makes use of tightly bound NAD⁺ as the coenzyme for transiently oxidizing the substrate, activating it for the dehydration step [MEDLINE:21840704]. This and other 4,6-dehydratases catalyze the first committed step in all 6-deoxysugar biosynthetic pathways described to date. Numerous\ 6-deoxysugars are used in bacterial lipopolysaccharide production as well as in the biosynthesis of a diverse array of secondary metabolites.

\ \ \ dTDP-glucose 4,6-dehydratase activity ; GO:0008460 \N nucleotide-sugar metabolism ; GO:0009225 24350 IPR005889

This family comprises the nitrate transport permease in bacteria, the gene product of ntrB. The nitrate transport permease is the integral membrane component of the nitrate transport system and belongs to the ATP-binding cassette (ABC) superfamily. At least in photosynthetic bacteria nitrate assimilation is aided by other proteins derived from the operon which among others include products of ntrA, ntrB, ntrC, ntrD, narB. Functionally ntrC and ntrD resemble the ATP binding components of the binding protein-dependent transport systems. Mutational studies have shown that ntrB and ntrC are mandatory for nitrate accumulation. Nitrate reductase is encoded by narB.

\ \ nitrate transporter activity ; GO:0015112 integral to membrane ; GO:0016021 nitrate transport ; GO:0015706 24351 IPR005890

This model describes the ATP binding subunits of nitrate transport in bacteria and archaea. This protein belongs to the ATP-binding cassette (ABC) superfamily. It is thought that the two subunits encoded by ntrC and ntrD form the binding surface for interaction with ATP. This model is restricted in identifying ATP binding subunit associated with the nitrate transport. Nitrate assimilation is aided by other proteins derived from the operon which among others include products of ntrA - a regulatory protein; ntrB - a hydropbobic transmembrane permease and narB - a reductase.

\ \ nitrate transporter activity ; GO:0015112 membrane ; GO:0016020 nitrate transport ; GO:0015706 24340 IPR005879

\ \ \

Ribosomal protein L1 is the largest protein from the large ribosomal subunit. In Escherichia coli, L1 is known to bind to the 23S rRNA. This model describes the mitochondrial L1 protein.

\ \ structural constituent of ribosome ; GO:0003735 large ribosomal subunit ; GO:0015934 protein biosynthesis ; GO:0006412 24341 IPR005880

\ \ \

The protein L2 is found in all ribosomes and is one of the best conserved proteins of this mega-dalton complex. L2 is elongated, exposing one end of the protein to the surface of the intersubunit interface of the\ 50 S subunit and is essential for the association of the ribosomal subunits and might participate in the binding and translocation of the tRNAs [MEDLINE:20566725].

\ \ transferase activity ; GO:0016740 large ribosomal subunit ; GO:0015934 protein biosynthesis ; GO:0006412 24342 IPR005881

The biosynthesis of L-cysteine is the predominant way by which inorganic sulfur is incorporated into organic compounds. In this process, the most abundantutilizable source of sulfur, inorganic sulfate, is taken up and reduced to sulfide. Sulfide is used to produce L-cysteine, which serves for protein synthesis or the\ production of other sulfur-containing organic compounds. Two routes for cysteine biosynthesis in nature have been documented.\ Serine transacetylase (EC: 2.3.1.30) catalyzes steps in pathway I, the activation of L-serine by acetyl-coenzyme A, yielding O-acetyl-L-serine.

\ \ \ serine O-acetyltransferase activity ; GO:0009001 cytoplasm ; GO:0005737 cysteine biosynthesis from serine ; GO:0006535 24343 IPR005882

N-Acetylglucosamine-1-PO(4) uridyltransferase (GlmU, EC: 2.7.7.23) is a trimeric bifunctional enzyme that catalyzes the last two sequential reactions in the de novo biosynthetic pathway for UDP-GlcNAc.

The X-ray crystal structure of Escherichia coli GlmU in complex with UDP-GlcNAc and CoA has been determined to 2.1 A resolution and reveals a two-domain architecture that is responsible for these two reactions [MEDLINE:21229108]. The C-terminal domain is responsible for the CoA-dependent acetylation of Glc-1-PO(4) to GlcNAc-1-PO(4) and displays the longest left-handed parallel -helix observed to date. The acetyltransferase active site defined by the binding site for CoA makes use of residues from all three subunits and is positioned beneath an open cavity large enough to accommodate the Glc-1-PO(4) acetyl acceptor. The N-terminal domain catalyzes uridyl transfer from UTP to GlcNAc-1-PO(4) to form the final products UDP-GlcNAc and pyrophosphate. This domain is composed of a central seven-stranded -sheet surrounded by six -helices in a Rossmann fold-like topology.

\ \ UDP-N-acetylglucosamine pyrophosphorylase activity ; GO:0003977 \N lipopolysaccharide biosynthesis ; GO:0009103 24333 IPR005872

This family of archaeal and bacterial proteins is homologous to the eukaryotic translation intiation factor SUI1 involved in directing the ribosome to the proper start site of translation by functioning in concert with eIF-2 and the initiator tRNA-Met.

\ translation initiation factor activity ; GO:0003743 \N protein biosynthesis ; GO:0006412 24334 IPR005873

This expression of members of this family of proteins is increased at high cell density but not growth arrest. The function of these proteins is unknown [MEDLINE:98290551].

\ \N \N cell growth and/or maintenance ; GO:0008151 24335 IPR005874

Cells have evolved elaborate mechanisms to rid themselves of aberrant proteins and transcripts. The nonsense-mediated mRNA decay pathway (NMD) is an example of a pathway that eliminates aberrant mRNAs. In addition to its role in recognition of the AUG codon during translation initiation and maintenance of the appropriate reading frame during translation elongation by directing the ribosome to the proper start site of translation by functioning in concert with eIF-2 and the initiator tRNA-Met, the SUI1 protein plays a role in the NMD pathway.

\ translation initiation factor activity ; GO:0003743 \N protein biosynthesis ; GO:0006412 24336 IPR005875

Phosphoribosylaminoimidazole carboxylase (EC: 4.1.1.21) is a fusion protein in plants and fungi, but consists of two non-interacting proteins in bacteria, PurK and PurE. This family represents PurK, N5-carboxyaminoimidazole ribonucleotide (N5_CAIR) synthetase, which catalyzes the conversion of 5-aminoimidazole ribonucleotide (AIR), ATP, and bicarbonate to N5-CAIR, ADP, and Pi. PurE converts N5-CAIR to CAIR. In the presence of high concentrations of bicarbonate, PurE is reported able to convert AIR to CAIR directly and without ATP.

PurK belongs to the ATP grasp superfamily of C-N ligase enzymes. Each subunit of PurK is composed of three domains (A, B, and C). The B domain contains a flexible, glycine-rich loop (B loop, T123-G130) that is disordered in the sulfate-PurK structure and becomes ordered in the MgADP-PurK structure. MgADP is wedged between the B and C domains, as with all members of the ATP grasp superfamily. Other enzymes in this superfamily contain a conserved Omega loop proposed to interact with the B loop, define the specificity of their nonnucleotide substrate, and protect the acyl phosphate intermediate formed from this substrate. PurK contains a minimal Omega loopwithout conserved residues. In the reaction catalyzed by PurK, carboxyphosphate is the putative acyl phosphate intermediate. The sulphate of the sulphate ion-liganded PurK interacts electrostatically with Arg 242 and the backbone amide group of Asn 245, components of the J loop of the C domain. This sulfate may reveal the location of the carboxyphosphate binding site. Conserved residues within the C-terminus of the C domain define a pocket that is proposed to bind AIR in collaboration with an N-terminal strand loop helix motif in the A domain (P loop, G8-L1). The P loop is proposed to bind the phosphate of AIR on the basis of similar binding sites observed in PurN and PurE and proposed in PurD and PurT, four other enzymes in the purine pathway [MEDLINE:20039871].

\ \ \ phosphoribosylaminoimidazole carboxylase activity ; GO:0004638 phosphoribosylaminoimidazole carboxylase complex ; GO:0009320 'de novo' IMP biosynthesis ; GO:0006189 24337 IPR005876

This entry represents the ATP binding subunit of the multisubunit cobalt transporter in bacteria and its equivalents in archaea. This superfamily includes two groups, one which catalyses the uptake of small molecules, including ions from the external milieu and the other group which is engaged in the efflux of small molecular weight compounds and ions from within the cell. Energy derived from the hydrolysis of ATP drives both the process of uptake and efflux.

\ \ cobalt porter activity ; GO:0015632 inner membrane ; GO:0019866 cobalt ion transport ; GO:0006824 24338 IPR005877

Many surface proteins found in Streptococcus, Staphylococcus, and related lineages share apparently homologous signal sequences. A motif resembling [YF]SIRKxxxGxxS[VIA] appears at the start of the transmembrane domain. The GxxS motif appears perfectly conserved, suggesting a specific function and not just homology.

\ \N membrane ; GO:0016020 \N 24339 IPR005878

\ \ \

Ribosomal protein L1 is the largest protein from the large ribosomal subunit. In Escherichia coli, L1 is known to bind to the 23S rRNA. This model describes bacterial (and chloroplast) ribosomal protein L1. The apparent mitochondrial L1 is sufficiently diverged to be the subject of a separate model.

\ \ structural constituent of ribosome ; GO:0003735 large ribosomal subunit ; GO:0015934 protein biosynthesis ; GO:0006412 24328 IPR005867

This model describes the Photosystem II, DI subunit (also called Q(B)) in bacterial and its equivalents in chloroplast of algae and higher plants. Photosystem II is many ways functionally equivalent to bacterial reaction center. At the core of Photosystem II are several light harvesting cofactors including plastoquinones, pheophytins, phyloquinones etc. These cofactors are intimately associated with the polypeptides, which principally including subunits DI, DII, Cyt.b, Cyt.f and iron-sulphur protein. Together they participate in the electron transfer reactions that lead to the net production of the reducting equivalents in the form of NADPH, which are used for reduction of carbon dioxide to carbohydrates(C₆H₁₂0₆). Phosystem II operates during oxygenic photosynthesis and principal electron donor is water.

\ electron transporter, transferring electrons within the cyclic electron transport pathway of photosynthesis activity ; GO:0045156 light-harvesting complex (sensu Proteobacteria) ; GO:0030077 photosynthesis, light reaction ; GO:0019684 24329 IPR005868

This model describes the Photosystem II, DII subunit (also called Q(A)) in bacterial and its equivalents in chloroplast of algae and higher plants. Photosystem II is many ways functionally equivalent to bacterial reaction center. At the core of Photosystem II are several light harvesting cofactors including plastoquinones, pheophytins, phyloquinones etc. These cofactors are intimately associated with the polypeptides, which principally including subunits DI, DII, Cyt.b, Cyt.f and iron-sulphur protein. Together they participate in the electron transfer reactions that lead to the net production of the reducting equivalents in the form of NADPH, which are used for reduction of carbon dioxide to carbohydrates (C₆H₁₂0₆). Photosystem II operates during oxygenic photosynthesis and principal electron donor is water.

This model describes the Photosystem II, 44kDa subunit (also called P6 protein, CP43) in bacterial and its equivalents in chloroplast of algae and higher plants. Photosystem II is in many ways functionally equivalent to bacterial reaction center. At the core of Photosystem II are several light harvesting cofactors including plastoquinones, pheophytins, phyloquinones etc. These cofactors are intimately associated with the polypeptides, which principally including subunits 44 kDa protein,DI, DII, Cyt.b, Cyt.f, iron-sulphur protein and others. Functinally 44 kDa subunit is imlicated in chlorophyll binding. Together they participate in the electron transfer reactions that lead to the net production of the reducting equivalents inthe form of NADPH, which are used for reduction of carbon dioxide to carbohydrates(C₆H₁₂0₆). Photosystem II operates during oxygenic photosynthesis and principal electron donor is water.

\ \ \ \ electron transporter, transferring electrons within the cyclic electron transport pathway of photosynthesis activity ; GO:0045156 light-harvesting complex (sensu Proteobacteria) ; GO:0030077 photosynthesis, light reaction ; GO:0019684 24331 IPR005870

This family describes the subunit IV of the cytochrome b6/f complex. The cyt b6/f complex is central to the functions of the oxygenic phosynthetic electron transport in cyanobacteria and its equivalents in algae and higher plants. Energetically, on the redox scale the cytb6/f complex is placed below the other components - Q(A); Q(B) of the photosystem II in the Z-scheme, along the pathway of the electron transport. The complex is made of the following subunits: cytochrome f; cytochrome b6; Rieske 2Fe-2S; and subunits IV; V; VI; VII. Subunit IV is one of the principal subunits for the binding of the redox prosthetic groups. Each monomer of the complex contains a molecule of chlorophyll a and -carotene.

\ electron transporter, transferring electrons within the cyclic electron transport pathway of photosynthesis activity ; GO:0045156 \N photosynthetic electron transport in cytochrome b6/f ; GO:0009775 24332 IPR005871

This family consists of the photosynthetic reaction centre L subunit in non-oxygenic photosynthetic bacteria. Reaction centre is an integral membrane pigment-protein that carries out light-driven electron transfer reactions. At the core of reaction centre is a collection light-harvesting cofactors and closely associated polypeptides. The core protein complex is made of L, M and H subunits. The common cofactors include bacterichlorophyll, bacteriopheophytins, ubiquinone and no-heme ferrous iron. The net result of electron tranfer reactions is the establishment of proton electrochemical gradient and production of reducing equivalents in form of NADH. Ultimately the process results in the reduction of carbon dioxide to carbohydrates (C₆H₁₂0₆). Photosystem II operates during oxygenic photosynthesis and principal electron donor is water.

\ \ electron transporter, transferring electrons within the cyclic electron transport pathway of photosynthesis activity ; GO:0045156 light-harvesting complex (sensu Proteobacteria) ; GO:0030077 photosynthesis, light reaction ; GO:0019684 24325 IPR005864

Synonym(s): ATP synthase, F(1)-ATPase

The H(+)-transporting two-sector ATPase (EC: 3.6.3.14) produce ATP from ADP in the presence of a proton gradient across the membrane. These ATPases have two components, CF(1) the catalytic core and CF(0) the membrane proton channel.\ CF(1) has five subunits, (3), (3), gamma (1), delta (1) and epsilon (1). CF(0) seems to have nine subunits, A, B, C, D, E, F, G, F6 and 8 ( or A6L).

\ \

The CF(0) B/B' subunits are thought to interact with the stalk of the CF(1) subunits. Family comprises the F1/F0 ATP synthase b subunit in bacteria only and resolves b from the related b' subunit. Within the family is an example from a sodium-translocating rather than proton-translocating ATP synthase.

\ \ \ hydrogen-transporting two-sector ATPase activity ; GO:0003936 proton-transporting ATP synthase complex, coupling factor F(o) (sensu Bacteria) ; GO:0045264 proton transport ; GO:0015992 24326 IPR005865

This model describes the N5-methyltetrahydromethanopterin: coenzyme M methyltransferase subunit C in methanogenic archaea. This methyltranferase is amembrane-associated enzyme complex that uses methyl-transfer reaction to drive a sodium-ion pump. Archaea have evolved energy-yielding pathways marked by one-carbon biochemistry featuring novel cofactors and enzymes. This transferase is involved in the transfer of a methyl group from N5-methyltetrahydromethanopterin to coenzyme M. In an accompanying reaction, methane is produced by two-electron reduction of the methyl moiety in methyl-coenzyme M by another enzyme methyl-coenzyme M reductase.

\ \ \ tetrahydromethanopterin S-methyltransferase activity ; GO:0030269 integral to membrane ; GO:0016021 methanogenesis ; GO:0015948 24327 IPR005866

\ \ \ tetrahydromethanopterin S-methyltransferase activity ; GO:0030269 integral to membrane ; GO:0016021 methanogenesis ; GO:0015948 24315 IPR005854

Purine nucleotides are synthesized both via the de novo pathway and via the salvage pathway and are vital for cell functions and cell proliferation through DNA and RNA syntheses and ATP energy supply. Amidophosphoribosyltransferase (EC: 2.4.2.14) is the rate-limiting enzyme in the de novo pathway of purine ribonucleotide synthesis and is regulated by feedback inhibition by AMP and GMP.

 5-phospho--D-ribosylamine + diphosphate + L-glutamate = L-glutamine + 5-phospho--D-ribose 1-diphosphate + H2O

\ \ \ amidophosphoribosyltransferase activity ; GO:0004044 \N purine base biosynthesis ; GO:0009113 24316 IPR005855

Glucosamine:fructose-6-phosphate aminotransferase (EC: 2.6.1.16) catalyses the formation of glucosamine 6-phosphate and is the first and rate-limiting enzyme of the hexosamine biosynthetic pathway. The final product of the hexosamine pathway, UDP-N-acetyl glucosamine, is an active precursor of numerous macromolecules containing amino sugars.

\ glucosamine-fructose-6-phosphate aminotransferase (isomerizing) activity ; GO:0004360 cytoplasm ; GO:0005737 carbohydrate biosynthesis ; GO:0016051 24317 IPR005856

This model discriminates cysteine synthases (both CysK and CysM) from cystathionine -synthase, a protein found primarily in eukaryotes and carrying a C-terminal CBS domain lacking from this protein. Bacterial proteins lacking the CBS domain but otherwise showing resemblance to cystathionine -synthases and considerable phylogenetic distance from known cysteine synthases were excluded.

Cysteine synthase (O-acetylserine (thiol)-lyase, EC: 4.2.99.8) is the enzyme responsible for the formation of cysteine from O-acetyl-serine and hydrogen sulfide with the concomitant release of acetic acid. In bacteria such two forms of the enzyme are known (genes cysK and cysM). CysM differs from CysK in that it can also use thiosulfate instead of sulfide, to produce cysteine thiosulfonate instead of cysteine.

\ cysteine synthase activity ; GO:0004124 \N cysteine biosynthesis from serine ; GO:0006535 24318 IPR005857

This model discriminates cystathionine -synthase, a protein found primarily in eukaryotes and carrying a C-terminal CBS domain from cysteine synthases. Cysteine synthase (O-acetylserine (thiol)-lyase , EC: 4.2.99.8) is the enzyme responsible for the formation of cysteine from O-acetyl-serine and hydrogen sulfide with the concomitant release of acetic acid - the function of many of these enzymes is unproven.

\ cystathione beta-synthase activity ; GO:0004122 cytoplasm ; GO:0005737 cysteine biosynthesis via cystathione ; GO:0019343 24319 IPR005858

Cysteine synthase (O-acetylserine (thiol)-lyase , EC: 4.2.99.8) is the enzyme responsible for the formation of cysteine from O-acetyl-serine and hydrogen sulfide with the concomitant release of acetic acid. In bacteria such two forms of the enzyme are known (genes cysK and cysM). CysM differs from CysK in that it can also use thiosulfate instead of sulfide, to produce cysteine thiosulfonate instead of cysteine.

\ cysteine synthase activity ; GO:0004124 \N cysteine biosynthesis from serine ; GO:0006535 24320 IPR005859

Cysteine synthase (O-acetylserine (thiol)-lyase , EC: 4.2.99.8) is the enzyme responsible for the formation of cysteine from O-acetyl-serine and hydrogen sulfide with the concomitant release of acetic acid. In bacteria such two forms of the enzyme are known (genes cysK and cysM). CysK differs from CysM in that it can also use sulphide instead of thiosulfate, to produce cysteine instead of cysteine thiosulfonate.

\ cysteine synthase activity ; GO:0004124 \N cysteine biosynthesis from serine ; GO:0006535 24321 IPR005860

L-threonine-O-3-phosphate decarboxylase (CobD) was shown to decarboxylate L-threonine O-3-phosphate to yield (R)-1-amino-2-propanol O-2-phosphate, which is the precursor for the linkage between the nucleotide loop and the corrin ring in the biosynthesis of cobalamin [MEDLINE:98112812]. The molecule is a dimer where each subunit consists of a large and small domain [MEDLINE:21937746]. This family contains pyridoxal phosphate-binding class II aminotransferases closely related to histidinol-phosphate aminotransferase (HisC).

\ \ enzyme activity ; GO:0003824 \N vitamin B12 biosynthesis ; GO:0009236 24322 IPR005861

The biosynthesis of histidine is a central metabolic process in organisms ranging from bacteria to yeast and plants. The seventh step in the synthesis of histidine within eubacteria is carried out by a pyridoxal-5'-phosphate (PLP)-dependent l-histidinol phosphate aminotransferase (HisC, EC: 2.6.1.9). HisC is a dimeric enzyme with a mass of approximately 80 kDa. Like most PLP-dependent enzymes, each HisC monomer consists of two domains, a larger PLP-binding domain having an // topology, and a smaller domain. An N-terminal arm contributes to the dimerization of the two monomers [MEDLINE:21410065].

\ histidinol-phosphate aminotransferase activity ; GO:0004400 \N histidine biosynthesis ; GO:0000105 24323 IPR005862

The formation of isosinate, a precursor of adenylate and guanylate, from 5-phosphoribosyl 1-pyrophosphate in the de novo purine biosynthesis pathway isbasically composed of 10 steps of reactions. Phosphoribosylglycinamide formyltransferase 2 (EC: 2.1.2.-) is an alternative enzyme to phosphoribosylglycinamide formyltransferase that catalyzes the third step in the de novo purine biosynthesis pathway.

\ \ \ hydroxymethyl-, formyl- and related transferase activity ; GO:0016742 \N purine base biosynthesis ; GO:0009113 24324 IPR005863

UDP-N-acetylmuramoylalanyl-D-glutamyl-2,6-diaminopimelate-D-alanyl-D-alanyl ligase (MurF, EC: 6.3.2.15) is required to catalyze the final step in the synthesis of the cytoplasmic precursor of the bacterial cell wall peptidoglycan.

  ATP + UDP-N-acetylmuramoyl-L-alanyl-D-glutamyl-meso-2,6-diaminoheptanedioate + D-alanyl-D-alanine = ADP + phosphate + UDP-N-acetylmuramoyl-L-alanyl-D-glutamyl-6-carboxy-L-lysyl-D-alanyl-D-alanine.

. The crystal structure of the MurF apo-enzyme has been determined and refined to 2.3 A resolution. It contains three consecutive open

-sheet domains. The topology of the N-terminal domain of MurF is unique, while its central and C-terminal domains exhibit similar mononucleotide and dinucleotide-binding folds to MurD. The apo-enzyme of MurF crystal structure reveals an open conformation with the three domains juxtaposed in a\ crescent-like arrangement creating a wide-open space where substrates are expected to bind. As such, catalysis is not feasible and significant domain closure is expected upon substrate binding [MEDLINE:20545602].\

\ \ UDP-N-acetylmuramoylalanyl-D-glutamyl-2,6-diaminopimelate-D-alanyl-D-alanine ligase activity ; GO:0008766 cytoplasm ; GO:0005737 \N 24310 IPR005848

Urease (EC: 3.5.1.5) is a nickel-binding enzyme that catalyzes the hydrolysis of urea to carbon dioxideand ammonia [MEDLINE:88296463]:\

\
Urea + H₂O = CO₂ + 2 NH₃ \

\ Historically, it was the first enzyme to be crystallized (in 1926). It is mainly\ found in plant seeds and microorganisms. In plants, urease is a hexamer of identical chains. In bacteria\ [MEDLINE:89218765], it consists of either two or three different subunits (

, described in this entry,

IPR002019). The structure of the\ urease complex is known [MEDLINE:95273988].

This is the catalytic subunit of urease. It binds two nickel ions per subunit; four histidine, an aspartate and a carbamated-lysine serve as ligands to these metals; an additional histidine is involved in the catalytic mechanism [MEDLINE:95273988].

\ \ nickel ion binding activity ; GO:0016151 \N nitrogen metabolism ; GO:0006807 24311 IPR005849

Galactose-1-phosphate uridyl transferase catalyses the conversion of UTP and -D-galactose1-phosphate to UDP-glucose and pyrophosphate during galactose metabolism. The enzyme is present \ in prokaryotes and eukaryotes. Defects in GalT in humans is the cause of galactosemia, an \ inherited disorder of galactose metabolism that leads to jaundice, cataracts and mental retardation.

This domain describes the C terminal of Galactose-1-phosphate uridyl transferase. SCOP reports fold duplication of the C-terminal with the N-terminal domain. Both are involved in Zn and Fe binding

\ \ UTP-hexose-1-phosphate uridylyltransferase activity ; GO:0003982 \N galactose metabolism ; GO:0006012 24312 IPR005850

This domain describes the C terminal of Galactose-1-phosphate uridyl transferase. SCOP reports fold duplication of the C-terminal with the N-terminal domain. Both are involved in Zn and Fe binding

\ \ UTP-hexose-1-phosphate uridylyltransferase activity ; GO:0003982 \N galactose metabolism ; GO:0006012 24313 IPR005851

\ \ UTP-hexose-1-phosphate uridylyltransferase activity ; GO:0003982 \N galactose metabolism ; GO:0006012 24314 IPR005852

Phosphoglucomutase, -D-glucose phosphate-specific (EC: 5.4.2.2) links the anaerobic or aerobic glycolysis of glucose-6-phosphate and glucose-1-phosphate produced by various glycan phosphorylases by catalysing the transfer of a phosphate group between C-1 and C-6 of glucose.

 Alpha-D-glucose 1-phosphate = -D-glucose 6-phosphate.

\ \ phosphoglucomutase activity ; GO:0004614 \N carbohydrate metabolism ; GO:0005975 24302 IPR005839

This family is defined only on sequence similarity. The size of proteins belonging to this family range from 47 to 61 kDa and contain six conserved cysteines, three of which are clustered.

\ molecular_function unknown ; GO:0005554 \N \N 24303 IPR005840

This is a family of mainly hypothetical proteins of unknown function.

\ molecular_function unknown ; GO:0005554 \N \N 24304 IPR005841

Phosphoglucomutase (EC: 5.4.2.2) (PGM) is responsible for the conversion of D-glucose 1-phosphate to D-glucose 6-phosphate. The enzyme participates in both the\ breakdown and synthesis of glucose [MEDLINE:92210613]. Phosphomannomutase (EC: 5.4.2.8) (PMM) is\ involved in the conversion of D-mannose 1-phosphate to D-mannose\ 6-phosphate [MEDLINE:91236754]. The enzyme is required for different biosynthetic pathways\ in bacteria.

\ \

The catalytic mechanism of both PGM and PMM involves the formation of a\ phosphoserine intermediate. Residues around the active site serine are\ well conserved and characterise a wider PGM/PMM family.

\ \ intramolecular transferase activity, phosphotransferases ; GO:0016868 \N carbohydrate metabolism ; GO:0005975 24305 IPR005843

Phosphoglucomutase (EC: 5.4.2.2, PGM) is an enzyme responsible for the conversion of D-glucose 1-phosphate into D-glucose 6-phosphate. PGM\ participates in both the breakdown and synthesis of glucose. Phosphomannomutase (EC: 5.4.2.8, PMM) is an enzyme responsible for\ the conversion of D-mannose 1-phosphate into D-mannose 6-phosphate. PMM is\ required for different biosynthetic pathways in bacteria.

This domain is contained in the C-terminal of both proteins.

\ \ intramolecular transferase activity, phosphotransferases ; GO:0016868 \N carbohydrate metabolism ; GO:0005975 24306 IPR005844

This domain is contained in both proteins.

\ \ intramolecular transferase activity, phosphotransferases ; GO:0016868 \N carbohydrate metabolism ; GO:0005975 24307 IPR005845

This domain is contained in both proteins.

\ \ intramolecular transferase activity, phosphotransferases ; GO:0016868 \N carbohydrate metabolism ; GO:0005975 24308 IPR005846

This domain is contained in both proteins.

\ \ intramolecular transferase activity, phosphotransferases ; GO:0016868 \N carbohydrate metabolism ; GO:0005975 24309 IPR005847

This entry represents both an approximate 560aa domain found in the catalytic subunit of urease and an approximate 90aa domain found in the dihydroorotase family.

Urease (EC: 3.5.1.5) is a nickel-binding enzyme that catalyzes the hydrolysis of urea to carbon dioxide\ and ammonia [MEDLINE:88296463]:\

\
Urea + H₂O = CO₂ + 2 NH₃ \

IPR005848). The structure of the\ urease complex is known [MEDLINE:95273988].

Dihydroorotase (EC: 3.5.2.3) (DHOase) catalyzes the third step in the de novo biosynthesis of pyrimidine, the conversion of ureidosuccinic acid (N-carbamoyl-L-aspartate) into dihydroorotate. Dihydroorotase binds a zinc ion which is required for its catalytic activity [MEDLINE:91107654].

In bacteria DHOase is a dimer of identical chains of about 400 amino-acid residues (gene pyrC). In higher eukaryotes DHOase is part of a large multi-functional protein known as 'rudimentary' in Drosophila and CAD in mammals and which catalyzes the first three steps of pyrimidine biosynthesis [MEDLINE:93256915]. The DHOase domain is located in the central part of this polyprotein. In yeasts, DHOase is encoded by a monofunctional protein (gene URA4). However, a defective DHOase domain [MEDLINE:89378778] is found in a multifunctional protein (gene URA2) that catalyzes the first two steps of pyrimidine biosynthesis.

\ \ \ \N \N \N 24296 IPR005833

Microorganisms that can utilise halogenated compounds as growth substrates produce enzymes that cleave carbon-halogen bonds and are commonly called\ dehalogenases. The hydrolytic dehalogenases catalyse a nucleophilic\ displacement reaction, with water as the sole co-substrate [MEDLINE:95126555]. They are\ divided into haloalkane dehalogenases and haloacid dehalogenases (HAD).\ HADs belong to a large superfamily of hydrolases with diverse substrate\ specificity, which also includes epoxide hydrolases, phosphoglycolate\ phosphatases, histidinol phosphate phosphatases, nitrophenyl phosphatases\ and numerous putative (not yet characterised) proteins [MEDLINE:95055742]. \ The epoxide hydrolases (EH) add water to epoxides, forming the corresponding\ diol.

The\ mammalian soluble EHs may contain two evolutionarily distinct domains [MEDLINE:95134356]. The\ N-terminal domain is similar to bacterial HADs; the C-terminal domain is \ similar to soluble plant EH, microsomal EH, and bacterial haloalkane \ dehalogenase.

\ \ hydrolase activity ; GO:0016787 \N metabolism ; GO:0008152 24297 IPR005834

This family of hydrolase enzymes is structurally different from the / hydrolase family (abhydrolase). This family includes L-2-haloacid dehalogenase, epoxide hydrolases and phosphatases. The structure of the family consists of two domains. One is an\ inserted four helix bundle, which is the least well conserved region of the alignment, between residues 16 and 96 of\ HAD1_PSESP. The rest of the fold is composed of the core / domain.

\ \ hydrolase activity ; GO:0016787 \N metabolism ; GO:0008152 24298 IPR005835

This domain is found in a wide range of enzymes which transfer nucleotides onto phosphosugars.

\ nucleotidyltransferase activity ; GO:0016779 \N biosynthesis ; GO:0009058 24299 IPR005836

ADP-glucose pyrophosphorylase (glucose-1-phosphate adenylyltransferase) [MEDLINE:92032769], PUB00005072 (EC: 2.7.7.27) catalyzes a very important step in the biosynthesis of 1,4-glucans (glycogen or starch) in bacteria and plants: synthesis of the activated glucosyl donor, ADP-glucose, from glucose-1-phosphate and ATP.

ADP-glucose pyrophosphorylase is a tetrameric allosterically regulated enzyme. It is a homotetramer in bacteria while in plant chloroplasts and amyloplasts, it is a heterotetramer of two different, yet evolutionary related, subunits.

There are a number of conserved regions in the sequence of bacterial and plant ADP-glucose pyrophosphorylase subunits.

\ \ glucose-1-phosphate adenylyltransferase activity ; GO:0008878 \N glycogen biosynthesis ; GO:0005978 24300 IPR005837

This model describes bacterial flagellar biogenesis protein fliP, which is one of the genes within the motility locus on the bacterial chromosome that is involved in structure and function of bacterial flagellum. It was demonstrated that mutants in fliP locus were non-flagellated and non-motile, while revertants were flagellated and motile. In Escherichia coli and related proteins the fliP protein probably [MEDLINE:94110225] plays a role in the transport of flagellar proteins. FliP is a protein of about 30 Kd which contains three or four transmembrane regions. Proteins evolutionary related to fliP have been found in a wide range of bacteria (mopC, hrcR, hrpW, spaP, yscR, etc.) and are involved in a variety of signal-peptide independent secretion systems.

\ \ \N membrane ; GO:0016020 protein secretion ; GO:0009306 24301 IPR005838

Secretion of virulence factors in Gram-negative bacteria involves transportation of the protein across two membranes to reach the cell exterior [MEDLINE:97125927]. There have been four secretion systems described in animal enteropathogens such as Salmonella and Yersinia, with further sequence similarities in plant pathogens like Ralstonia and Erwinia. The type III secretion system is of great interest as it is used to transport virulence factors from the pathogen directly into the host cell [MEDLINE:99269264] and is only triggered when the bacterium comes into close contact with the host. The protein subunits of the system are very similar to those of bacterial flagellar biosynthesis [MEDLINE:20032050]. However, while the latter forms a ring structure to allow secretion of flagellin and is an integral part of the flagellum itself [MEDLINE:20032050], type III subunits in the outer membrane translocate secreted proteins through a channel-like structure. It is believed that the family of type III inner membrane proteins are used as structural moieties in a complex with several other subunits [MEDLINE:98284147], including the ATPase necessary for driving the secretion system.

One such set of inner membrane proteins, termed "P" here for nomenclature purposes, includes the Salmonella and Shigella SpaP, the Yersinia YscR, the Erwinia HrcR, and the Xanthamonas Pro2 genes [MEDLINE:98284147], as well as several FliP flagellar biosynthesis genes [MEDLINE:20032050]. FliP is an ~30Kd protein containing three or four transmembrane (TM) regions.

\ \ \ \N membrane ; GO:0016020 protein secretion ; GO:0009306 24292 IPR005829

The sugar transporters belong to a superfamily of membrane proteins responsible for the binding and transport of various carbohydrates, organic alcohols, and acids in a wide range of prokaryotic and eukaryotic organisms [MEDLINE:85272595]. These integral membrane proteins are predicted to comprise twelve membrane spanning domains. It is likely that the transporters have evolved from an ancient protein present in living organisms before the divergence into prokaryotes and eukaryotes\ \ \ [MEDLINE:87115869]. In mammals, these proteins are expressed in a number of organs [MEDLINE:89008414].

\ \ \ \ \ transporter activity ; GO:0005215 membrane ; GO:0016020 transport ; GO:0006810 24293 IPR005830

This family represents the pore forming lobe of aerolysin, and the related toxins hemolysin and the leukocidin S subunit.

\ toxin activity ; GO:0015070 \N pathogenesis ; GO:0009405 24294 IPR005831

Aerolysin is a cytolytic toxin exported by the Gram-negative Aeromonas\ bacteria. The mature toxin binds to eukaryotic cells and aggregates to form\ holes (approximately 3 nm in diameter) leading to the destruction of the\ membrane permeability barrier and osmotic lysis. Staphylococcus aureus also\ exports a cytotoxin, -toxin, whose biological activity is similar to\ that of aerolysin. The sequences of both toxins are not similar except for a\ stretch of ten residues rather well conserved.\

\ \ toxin activity ; GO:0015070 \N pathogenesis ; GO:0009405 24295 IPR005832

Aerolysin [MEDLINE:87222221] is a cytolytic toxin exported by Aeromonas hydrophila, a Gram-negative bacterium associated with diarrhoeal diseases and deep wound infections [MEDLINE:94166885]. The mature toxin binds to eukaryotic cells and aggregates to form holes (approximately 3 nm in diameter) leading to the destruction of the membrane permeability barrier and osmotic lysis. The structure of proaerolysin has been determined to 2.8A resolution and shows the protoxin to adopt a novel fold [MEDLINE:94166885]. Images of an aerolysin oligomer derived from electron microscopy have helped to construct a model of the protein and to outline a mechanism by which it might insert into lipid bilayers to form ion channels [MEDLINE:94166885].

Staphylococcus aureus also exports a cytotoxin, -toxin [MEDLINE:85053471], whose biological activity is similar to that of aerolysin. The sequences of both toxins are not similar except for a stretch of ten residues rather well conserved.

Pseudomonas aeruginosa cytotoxin [MEDLINE:90014160] contain a region whose sequence is similar to that of the conserved domain of areolysin/- toxin, but the similarity is very weak.

\ \ toxin activity ; GO:0015070 \N pathogenesis ; GO:0009405 24291 IPR005828

Recent genome-sequencing data and a wealth of biochemical and molecular genetic investigations have revealed the occurrence of dozens of families of primary and secondary transporters. Two such families have been found to occur ubiquitously in all classifications of living organisms. These are the ATP-binding cassette (ABC) superfamily and the major facilitator superfamily (MFS), also called the uniporter-symporter-antiporter family. While ABC family permeases are in general multicomponent primary active transporters, capable of transporting both small molecules and macromolecules in response to ATP hydrolysis the MFS transporters are single-polypeptide secondary carriers capable only of transporting small solutes in response to chemiosmotic ion gradients. Although well over 100 families of transporters have now been recognized and classified, the ABC superfamily and MFS account for nearly half of the solute transporters encoded within the genomes of microorganisms. They are also prevalent in higher organisms. Theimportance of these two families of transport systems to living organisms can therefore not be overestimated [MEDLINE:98190790].

\ \

The MFS was originally believed to function primarily in the uptake of sugars but subsequent studies revealed that drug efflux systems, Krebs cycle metabolites, organophosphate:phosphate exchangers, oligosaccharide:H1 symport permeases, and bacterial aromatic acid permeases were all members of the MFS. These observations led to the probability that the MFS is far more widespread in nature and far more diverse in function than had been thought previously. 17 subgroups of the MFS have been identified [MEDLINE:98190790].

\ \

Evidence suggests that the MFS permeases arose by a tandem intragenic duplication event in the early prokaryotes. This event generated a 2-transmembrane-spanner (TMS) protein topology from a primordial 6-TMS unit. Surprisingly, all currently recognized MFS permeases retain the two six-TMS units within a single polypeptide chain, although in 3 of the 17 MFS families, an additional two TMSs are found [MEDLINE:97140959]. Moreover, the well-conserved MFS specific motif between TMS2 and TMS3 and the related but less well conserved motif between TMS8 and TMS9 [MEDLINE:90239116] prove to be a characteristic of virtually all of the more than 300 MFS proteins identified.

\ \ \ transporter activity ; GO:0005215 membrane ; GO:0016020 transport ; GO:0006810 24290 IPR005827

KCNQ channels differ from other voltage-gated 6 TM helix channels, chiefly in that they possess no tetramerisation domain. Consequently, they rely on interaction with accessory subunits, or form heterotetramers with other members of the family PUB00009384. Currently, 5 members of the KCNQ family are known. These have been found to be widely distributed within the body, having been shown to be expressed in the heart, brain, pancreas, lung, placenta and ear. They were initially cloned as a result of a search for proteins involved in cardiac arhythmia. Subsequently, mutations in other KCNQ family members have been shown to be responsible for some forms of hereditary deafness [MEDLINE:96122034] and benign familial neonatal epilepsy [MEDLINE:98092527].

KCNQ1 was the first member of the KCNQ channel family to be isolated, and has been found to be the most common cause of the disease 'long QT syndrome' a cardiac arhythmia resulting in a prolonged QT interval. In exceptional cases, this can lead to sudden death, triggered by extreme stress [MEDLINE:97055938]. KCNQ1 is expressed in the stria vascularis of the inner ear, and may be the cause of hereditary deafness [MEDLINE:97172978].

\ \ voltage-gated potassium channel activity ; GO:0005249 voltage-gated potassium channel complex ; GO:0008076 potassium ion transport ; GO:0006813 24289 IPR005826

The Kv (TC:1.A.1.2) family can be divided into 4 subfamilies on the basis of sequence\ similarity and function: Shaker (Kv1), Shab (Kv2, TC:1.A.1.2.1) and Shal \ (Kv4, TC:1.A.1.2.3). All consist of pore-forming subunits that associate with \ different types of subunit. Each subunit comprises six hydrophobic TM domains with a P-domain between the fifth and sixth, which partially resides in the membrane. The fourth TM domain has positively charged residues at every third residue and acts as a voltage sensor, which triggers the conformational change that opens the channel pore in response to a displacement in membrane potential PUB00009384.

The Shab voltage-gated delayed rectifier K⁺ channels (also known as Kv2 \ channels) are responsible for much of the delayed rectifier current in \ Drosophila melanogaster nervous system and muscle. However, in vertebrate, Kv2 channels\ have largely undetermined roles in the delayed rectifier currents of the \ heart and skeletal muscle. Kv2 channels can be further divided into 2\ subtypes, designated Kv2.1 and Kv2.2 PUB00009786.

\ \

The first Kv2.2 channel was cloned from rat and was originally referred to\ as the circumvillate papilla delayed rectifying K⁺ channel or cDRK. Several \ mammalian channels have subsequently been found and, together with the rat \ Kv2.2 channel, form a small subfamily. They are predominantly expressed in \ the interneurones; however, their roles are largely undetermined PUB00009786.

\ \ voltage-gated potassium channel activity ; GO:0005249 voltage-gated potassium channel complex ; GO:0008076 potassium ion transport ; GO:0006813 24287 IPR005824

\ \ \

The KOW (Kyprides, Ouzounis, Woese) motif is found in a variety of ribosomal proteins and the bacterial transcription antitermination proteins NusG [MEDLINE:97141024]. Ribosomal protein L24 is one of the proteins from the large ribosomal subunit. In their mature form, these proteins have 103 to 150 amino-acid residues. \

\ \ \N \N \N 24288 IPR005825

\ \ \

Ribosomal protein L24 is one of the proteins from the large ribosomal subunit.\ L24 belongs to a family of ribosomal proteins which, on the basis of sequence\ similarities, groups:

\ \

- Eubacterial L24.

- Plant chloroplast L24 (nuclear-encoded).

- Red algal L24.

- Vertebrate L26.

- Yeast L26 (YL33).

- Archaebacterial HmaL24 (HL15).

- A probable ribosomal protein from Sulfolobus acidocaldarius.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 24286 IPR005823

\ \ \

Ribosomal protein L24 is one of the proteins from the large ribosomal subunit.\

L24 belongs to a family of ribosomal proteins which, on the basis of sequence\ similarities, groups:

Eubacterial L24.
Plant chloroplast L24 (nuclear-encoded).
Red algal L24.
Vertebrate L26.
Yeast L26 (YL33).
Archaebacterial HmaL24 (HL15).
A probable ribosomal protein from Sulfolobus acidocaldarius.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 24282 IPR005819

Histone H5 is a nuclear protein involved in the condensation of nucleosomechains into higher order structures. In this respect, it performs the same\ function as histone H1, and replaces H1 in certain cells.\ \ The structure of GH5, the globular domain (residues 22-100) of the linker\ histone H5, has been solved. The fold is similar to the DNA-binding\ domain of the catabolite gene activator protein, CAP, thus providing a\ possible model for the binding of GH5 to DNA. The structure comprises 3 -helices and 2 short -strands.\

\ \ DNA binding activity ; GO:0003677 nucleus ; GO:0005634 nucleosome assembly ; GO:0006334 24283 IPR005820 Cation channels are transport proteins responsible for the movement of cations through the membrane. This family contains sodium, potassium and calcium ion channels (TC:1.A.1). These proteins contain 6 transmembrane helices in which the last two helices flank a loop which determines ion selectivity. In some sub-families (e.g. Na channels) the domain is repeated four times, whereas in others (e.g. K channels) the protein forms a tetramer in the membrane. A bacterial structure of the protein is known for the last two helices but is not included in the Pfam family due to it lacking the first four helices. Proteins containing this domain are members of the non-ligand gated cation channel proteins, and are found in eukaryotes.\ cation channel activity ; GO:0005261 membrane ; GO:0016020 cation transport ; GO:0006812 24284 IPR005821

This family contains sodium, potassium, and calcium ion channels (TC:1.A.1). The proteins have 6 transmembrane helices in which the last two helices flank a loop which determines ion selectivity. In some sub-families (e.g. Na channels) the domain is repeated four times, whereas in others (e.g. K channels) the protein forms a tetramer in the membrane. A bacterial structure of the protein is known for the last two helices but is not included in the Pfam family due to it lacking the first four helices

\ ion channel activity ; GO:0005216 membrane ; GO:0016020 ion transport ; GO:0006811 24285 IPR005822

\ \ \

Ribosomal protein L13 is one of the proteins from the large ribosomal subunit\ [MEDLINE:94164901]. In Escherichia coli, L13 is known to be one of the early assembly\ proteins of the 50S ribosomal subunit.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 24279 IPR005816

The Wnt genes encode a large family of secreted protein growth factors [MEDLINE:21666013] which bind to two distinct families of cell-surface receptors, Frizzled proteins and LDL-receptor related proteins, and through them to three signal transduction pathways - the Wnt/-catenin, the Wnt/Calcium and Wnt/polarity pathways. When secreted, the proteins bind to the cell surface and associate with proteins in the extracellular matrix. During development, Wnts have diverse roles in governing cell fate, proliferation, migration, polarity, and death. In adults, Wnts function in homeostasis, and\ inappropriate activation of the Wnt pathway is implicated in a variety of cancers.

In humans, 19 Wnt proteins have been identified that share 27% to 83% amino-acid sequence identity and a conserved pattern of 23 or 24 cysteine residues. Wnt genes are highly conserved between vertebrate species sharing overall sequence identity and gene structure, and are slightly less conserved between vertebrates and\ invertebrates.

\ \ \ signal transducer activity ; GO:0004871 extracellular ; GO:0005576 development ; GO:0007275 24280 IPR005817

Wnt-1 (previously known as int-1) is a proto-oncogene induced by the integration of the mouse mammary tumor virus. It is thought to play a role in intercellular communication and seems to be a signalling molecule important in the development of the central nervous system (CNS). The sequence of wnt-1 is highly conserved in mammals, fish, and amphibians. Wnt-1 is a member of a large family of related proteins that are all thought to be developmental regulators. These proteins are known as wnt-2 (also known as irp), wnt-3 up to wnt-15. At least four members of this family are present in Drosophila. One of them, wingless (wg), is implicated in segmentation polarity. All these proteins share the following features characteristics of secretory proteins, a signal peptide, several potential N-glycosylation sites and 22 conserved cysteines that are probably involved in disulfide bonds. The Wnt proteins seem to adhere to the plasma membrane of the secreting cells and are therefore likely to signal over only few cell diameters.

\ signal transducer activity ; GO:0004871 extracellular ; GO:0005576 development ; GO:0007275 24281 IPR005818 Linker histone H1 is an essential component of chromatin structure. H1 links nucleosomes into higher order structures.Histone H5 performs the same\ function as histone H1, and replaces H1 in certain cells. \ The structure of GH5, the globular domain of the linker\ histone H5 is known [MEDLINE:93211475], [MEDLINE:87017002]. The fold is similar to the DNA-binding\ domain of the catabolite gene activator protein, CAP, thus providing a\ possible model for the binding of GH5 to DNA.\ \ DNA binding activity ; GO:0003677 nucleus ; GO:0005634 nucleosome assembly ; GO:0006334 24278 IPR005815

All members of the seed alignment have been demonstrated experimentally to act as (EC: 2.6.1.62), an enzyme in the biotin biosynthetic pathway. Alternate names include 7,8-diaminopelargonic acid aminotransferase, DAPA aminotransferase, and adenosylmethionine-8-amino-7-oxononanoate aminotransferase. The gene symbol is bioA in E. coli and BIO3 in S. cerevisiae.

\ \ adenosylmethionine-8-amino-7-oxononanoate aminotransferase activity ; GO:0004015 \N biotin biosynthesis ; GO:0009102 24277 IPR005814 Aminotransferases share certain mechanistic features with other pyridoxalphosphate-dependent enzymes, such as the covalent binding of the pyridoxalphosphate group to a lysine residue. On the basis of sequence \ similarity, these various enzymes can be grouped [MEDLINE:92316928] into subfamilies. One of these, called \ class-III, includes acetylornithine aminotransferase (EC: 2.6.1.11), which catalyzes the transfer of an \ amino group from acetylornithine to

-ketoglutarate, yielding N-acetyl-glutamic-5-semi-aldehyde and \ glutamic acid; ornithine aminotransferase (EC: 2.6.1.13), which catalyzes the transfer of an amino group \ from ornithine to

-ketoglutarate, yielding glutamic-5-semi-aldehyde and glutamic acid; omega-amino \ acid--pyruvate aminotransferase (EC: 2.6.1.18), which catalyzes transamination between a variety of \ omega-amino acids, mono- and diamines, and pyruvate; 4-aminobutyrate aminotransferase (EC: 2.6.1.19) (GABA \ transaminase), which catalyzes the transfer of an amino group from GABA to

-ketoglutarate, yielding \ succinate semialdehyde and glutamic acid; DAPA aminotransferase (EC: 2.6.1.62), a bacterial enzyme (bioA), \ which catalyzes an intermediate step in the biosynthesis of biotin, the transamination of \ 7-keto-8-aminopelargonic acid to form 7,8-diaminopelargonic acid; 2,2-dialkylglycine decarboxylase \ (EC: 4.1.1.64), a Pseudomonas cepacia enzyme (dgdA) that catalyzes the decarboxylating amino transfer of\ 2,2-dialkylglycine and pyruvate to dialkyl ketone, alanine and carbon dioxide; glutamate-1-semialdehyde \ aminotransferase (EC: 5.4.3.8) (GSA); Bacillus subtilis aminotransferases yhxA and yodT; Haemophilus \ influenzae aminotransferase HI0949; and Caenorhabditis elegans aminotransferase T01B11.2.\ \ transaminase activity ; GO:0008483 \N \N 24275 IPR005812

\ \ \

This family covers bacterial ribosomal protein L20 and \ its chloroplast equivalent.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 24276 IPR005813

\ \ \

L20 is a protein from the large (50S) subunit; in E.coli it is known to\ bind directly to the 23S rRNA, and is required for ribosome assembly, but\ does not take part in protein synthesis. It belongs to a family of ribosomal\ proteins, including L20 from eubacteria, plant and alga chloroplasts and\ cyanelles PUB00005071.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 24274 IPR005811

This family includes the CoA ligases Succinyl-CoA synthetase and chains, malate CoA ligase and ATP-citrate lyase. Some members of the family utilise ATP others use GTP.

\ \ enzyme activity ; GO:0003824 \N metabolism ; GO:0008152 24273 IPR005810

There are four different enzymes that share a similar catalytic mechanism which involves the phosphorylation by ATP (or GTP) of a specific histidine residue in the active site. These enzymes are: ATP citrate-lyase (EC: 4.1.3.8) [MEDLINE:92174902], the primary enzyme responsible for the synthesis of cytosolic acetyl-CoA in many tissues, catalyzes the formation of acetyl-CoA and oxaloacetate from citrate and CoA with the concomitant hydrolysis of ATP to ADP and phosphate. ATP-citrate lyase is a tetramer of identical subunits; Succinyl-CoA ligase (GDP-forming) (EC: 6.2.1.4) [MEDLINE:94004462] is a mitochondrial enzyme that catalyzes the substrate level phosphorylation step of the tricarboxylic acid cycle: the formation of succinyl-CoA from succinate with a concomitant hydrolysis of GTP to GDP and phosphate. This enzyme is a dimer composed of an and a subunits; Succinyl-CoA ligase (ADP-forming) (EC: 6.2.1.5) [MEDLINE:86104124] is a bacterial enzyme that during aerobic metabolism functions in the citric acid cycle, coupling the hydrolysis of succinyl-CoA to the synthesis of ATP. It can also function in the other direction for anabolic purposes. This enzyme is a tetramer composed of two and two subunits; and Malate-CoA ligase (EC: 6.2.1.9) (malyl-CoA synthetase) [MEDLINE:95050329], is a bacterial enzyme that forms malyl-CoA from malate and CoA with the concomitant hydrolysis of ATP to ADP and phosphate. Malate-CoA ligase is composed of two different subunits.

This entry corresponds to two regions, a glycine-rich conserved region, located in the second half of ATP citrate\ lyase and in the subunits of succinyl-CoA ligases and malate-CoA ligase; and the active site phosphorylated histidine residue, which is located some 50 residues to the C-terminal of the first region.

\ \ \ enzyme activity ; GO:0003824 \N metabolism ; GO:0008152 24272 IPR005809

This entry corresponds to a conserved region located in the first half of ATP citrate lyase and in the subunits of succinyl-CoA ligases and malate-CoA ligase.

\ \ \ enzyme activity ; GO:0003824 \N metabolism ; GO:0008152 24271 IPR005808

Secretion across the inner membrane in some Gram-negative bacteria occurs via the preprotein translocase pathway. Proteins are produced in the cytoplasm as precursors, and require a chaperone subunit to direct them to\ the translocase component. [MEDLINE:90361702]. From there, the mature proteins are either targeted to the outer\ membrane, or remain as periplasmic proteins. The translocase protein subunits are encoded on the bacterial\ chromosome.\

The translocase itself comprises 7 proteins, including a chaperone protein (SecB), an ATPase (SecA), an integral\ membrane complex (SecCY, SecE and SecG), and two additional membrane proteins that promote the release of\ the mature peptide into the periplasm (SecD and SecF) [MEDLINE:90361702]. The chaperone protein SecB [MEDLINE:21235707] is a highly acidic homotetrameric protein that exists as a "dimer of dimers" in the bacterial cytoplasm.\ SecB maintains preproteins in an unfolded state after translation, and targets these to the peripheral membrane\ protein ATPase SecA for secretion [MEDLINE:99346703]. SecE, part of the main \ SecYEG translocase complex, is ~106 residues in length, and spans the \ inner membrane of the Gram-negative bacterial envelope. Together with\ SecY and SecG, SecE forms a multimeric channel through which preproteins\ are translocated, using both proton motive forces and ATP-driven secretion. The latter is mediated by SecA. The structure of the\ Escherichia coli SecYEG assembly revealed a sandwich of two membranes interacting through the extensive cytoplasmic\ domains [MEDLINE:22157987] ]. Each membrane is composed of dimers of SecYEG. The monomeric complex contains 15\ transmembrane helices.

\ This entry is a subfamily of SecE proteins.

\ \ \ protein translocase activity ; GO:0015450 integral to membrane ; GO:0016021 protein secretion ; GO:0009306 24269 IPR005806

Ubiquinol-cytochrome c reductase (bc1 complex or complex III) is an enzyme complex of bacterial and mitochondrial oxidative phosphorylation systems It catalyses the oxidoreduction of the mobile redox components ubiquinol and cytochrome c, generating an \ electrochemical potential, which is linked to ATP synthesis [MEDLINE:85203899], [MEDLINE:86136096]. \ The complex consists of three subunits in most bacteria, and nine in mitochondria: both \ bacterial and mitochondrial complexes contain cytochrome b and cytochrome c1 subunits, \ and an iron-sulphur 'Rieske' subunit, which contains a high potential 2Fe-2S cluster [MEDLINE:88007612].The mitochondrial form also includes six other subunits that do not \ possess redox centres. Plastoquinone-plastocyanin reductase (b6f complex), present in \ cyanobacteria and the chloroplasts of plants, catalyses the oxidoreduction of plastoquinol\ and cytochrome f. This complex, which is functionally similar to ubiquinol-cytochrome c \ reductase, comprises cytochrome b6, cytochrome f and Rieske subunits [MEDLINE:93004481].

The Rieske subunit acts by binding either a ubiquinol or plastoquinol anion, transferring \ an electron to the 2Fe-2S cluster, then releasing the electron to the cytochrome c or \ cytochrome f haem iron [MEDLINE:85203899], [MEDLINE:93004481]. The rieske domain has a [2Fe-2S] centre. Two conserved cysteines that one Fe ion while the other Fe ion is coordinated by two conserved histidines. The 2Fe-2S cluster is bound in the \ highly conserved C-terminal region of the Rieske subunit.

\ \ oxidoreductase activity ; GO:0016491 \N electron transport ; GO:0006118 24270 IPR005807

\ \ \ protein translocase activity ; GO:0015450 integral to membrane ; GO:0016021 protein secretion ; GO:0009306 24268 IPR005805

\ \ ubiquinol-cytochrome c reductase activity ; GO:0008121 ubiquinol-cytochrome c reductase complex ; GO:0045285 electron transport ; GO:0006118 24267 IPR005804

Fatty acid desaturases (EC 1.14.99.-) are enzymes that catalyze the insertionof a double bond at the delta position of fatty acids. There seem to be two distinct families of fatty acid desaturases which do not\ seem to be evolutionary related. This entry is family 2 of the desaturases and\ includes, plant stearoyl-acyl-carrier-protein desaturase (EC:1.14.99.6) that catalyses\ the introduction of a double bond at the delta position of steraoyl-ACP to produce \ oleoyl-ACP [MEDLINE:91172837] and is responsible for the conversion of saturated fatty acids to unsaturated \ fatty acids in the synthesis of vegetable oils, and Cyanobacteria desA [MEDLINE:90370121] an enzyme that can introduce a second cis double bond at the delta position of fatty acid bound to membranes glycerolipids. \ DesA is involved in chilling tolerance; the phase transition temperature of lipids of \ cellular membranes being dependent on the degree of unsaturation of fatty acids of \ the membrane lipids.

\ \ oxidoreductase activity ; GO:0016491 \N \N 24262 IPR005797

In the mitochondrion of eukaryotes and in aerobic prokaryotes, cytochrome b is a component of respiratory chain complex III (EC: 1.10.2.2) - also known as the bc1 complex or ubiquinol-cytochrome c reductase. In plant chloroplasts and cyanobacteria, there is a analogous protein, cytochrome b6, a component of the plastoquinone-plastocyanin reductase (EC: 1.10.99.1), also known as the b6f complex.

Cytochrome b/b6 [MEDLINE:90040745], [MEDLINE:93320094] is an integral membrane protein of approximately 400 amino acid residues that probably has 8 transmembrane segments. In plants and cyanobacteria, cytochrome b6 consists of two subunits encoded by the petB and petD genes. The sequence of petB is colinear with the N-terminal part of mitochondrial cytochrome b, while petD corresponds to the C-terminal part.\ Cytochrome b/b6 non-covalently binds two heme groups, known as b562 and b566. Four conserved histidine residues are postulated to be the ligands of the iron atoms of these two heme groups.

Apart from regions around some of the histidine heme ligands, there are a few conserved regions in the sequence of b/b6. The best conserved of these regions includes an invariant P-E-W triplet which lies in the loop that separates the fifth and sixth transmembrane segments. It seems to be important for electron transfer at the ubiquinone redox site - called Qz or Qo (where o stands for outside) - located on the outer side of the membrane. This entry is the N-terminal of these proteins.

\ \ oxidoreductase activity ; GO:0016491 membrane ; GO:0016020 electron transport ; GO:0006118 24266 IPR005803

\ \ oxidoreductase activity ; GO:0016491 \N fatty acid biosynthesis ; GO:0006633 24265 IPR005802

Para-aminobenzoate synthase component I (pabB) is closely related to anthranilate synthase component I (trpE). The apparent orthologs of pabB in Aquifex aeolicus and Helicobacter pylori score well below most TrpE proteins because of a different architecture, in which the less strongly conserved N-terminal domain is absent. The noise cutoff is set to exclude most examples of TrpE. However, slr1979 from Synechocystis PCC6803, annotated as one of two TrpE sequences, clusters in a UPGMA difference tree among the pabB sequences and scores above the noise cutoff.

\ \N \N folic acid and derivative biosynthesis ; GO:0009396 24264 IPR005801 Anthranilate synthase catalyses the reaction:

\
chorismate + l-glutamine =  anthranilate + pyruvate + l-glutamate.\

\ The enzyme is a tetramer comprising 2 I and 2 II components: this family is component I that \ catalyses the formation of anthranilate using ammonia rather than glutamine, while component II\ provides glutamine amidotransferase activity IPR006220.\ \ \N \N biosynthesis ; GO:0009058 24261 IPR005795

Grass pollens are a major cause of type I allergy. Lol pI, the major rye grass (Lolium perenne) allergen, is a 240-amino acid protein [MEDLINE:90375479] ]. Analysis of the amino acid sequence has revealed a determinant within the Lol pI molecule that is recognised by human leukocyte antigen class II-restricted T cells obtained from patients allergic to rye grass pollen [MEDLINE:90375479] ].

Sequence analysis of a pollen-specific cDNA from maize has revealed a homologue (Zea mI) of the Lol pI gene [MEDLINE:94010312] ]. The protein is ~70% similar to the reported amino acid sequence of Lol pIA. Southern analysis indicates Zea mI to be a member of a small multigene family in maize. Northern analysis indicates expression only in pollen, not in vegetative or female floral tissues. The timing of expression is developmentally regulated,\ occurring at a low level prior to the first pollen mitosis, and at a high level after post-meiotic division [MEDLINE:94010312] ].

\ \ \N extracellular ; GO:0005576 sexual reproduction ; GO:0019953 24263 IPR005798

\ \ oxidoreductase activity ; GO:0016491 membrane ; GO:0016020 electron transport ; GO:0006118 24259 IPR005793

\ hydroxymethyl-, formyl- and related transferase activity ; GO:0016742 \N biosynthesis ; GO:0009058 24260 IPR005794

Methionyl-tRNA formyltransferase (EC: 2.1.2.9) transfers a formyl group onto the amino terminus of the acyl moiety of the methionyl aminoacyl-tRNA. The formyl group appears to play a dual role in the initiator identity of N-formylmethionyl-tRNA by promoting its recognition by IF2 and by impairing its binding to EFTU-GTP. The top-scoring characterized proteins other than methionyl-tRNA formyltransferase (fmt) itself are formyltetrahydrofolate dehydrogenases. The mitochondrial methionyl-tRNA formyltransferases are so divergent that, in a multiple alignment of bacterial fmt, mitochondrial fmt, and formyltetrahydrofolate dehydrogenases, the mitochondrial fmt appears the most different. However, because both bacterial and mitochondrial fmt are included in the seed alignment, all credible fmt sequences score higher than any non-fmt sequence.

\ methionyl-tRNA formyltransferase activity ; GO:0004479 \N protein biosynthesis ; GO:0006412 24258 IPR005792

This family represents eukaryotic protein disulphide isomerases retained in the endoplasmic reticulum (ER) and other closely related forms. Some members have been assigned alternative or additional functions such as prolyl 4-hydroxylase anddolichyl-diphosphooligosaccharide-protein glycotransferase. Members of this family have at least two protein-disulfide domains, each similar to thioredoxin but with the redox-active disulfide in the motif PWCGHCK, and an ER retention signal at the extreme C-terminus (KDEL, HDEL, and similar motifs).

\ \ \ isomerase activity ; GO:0016853 endoplasmic reticulum ; GO:0005783 \N 24257 IPR005791

Secretion across the inner membrane in some Gram-negative bacteria occurs via the preprotein translocase pathway. Proteins are produced in the cytoplasm as precursors, and require a chaperone subunit to direct them to the translocase component. [MEDLINE:90361702]. From there, the mature proteins are either targeted to the outer membrane, or remain as periplasmic proteins. The translocase protein subunits are encoded on the bacterial chromosome.

The translocase itself comprises 7 proteins, including a chaperone protein (SecB), an ATPase (SecA), an integral membrane complex (SecCY, SecE and SecG), and two additional membrane proteins that promote the release of the mature peptide into the periplasm (SecD and SecF) [MEDLINE:90361702]. The chaperone protein SecB [MEDLINE:21235707] is a highly acidic homotetrameric protein that exists as a "dimer of dimers" in the bacterial cytoplasm. SecB maintains preproteins in an unfolded state after translation, and targets these to the peripheral membrane\ protein ATPase SecA for secretion [MEDLINE:99346703]. Together with SecY and SecG, SecE forms a multimeric channel through which preproteins are translocated, using both proton motive forces and ATP-driven secretion. The latter is mediated by SecA. The structure of the Escherichia coli SecYEG assembly revealed a sandwich of two membranes\ interacting through the extensive cytoplasmic domains [MEDLINE:22157987] ]. Each membrane is composed of dimers of SecYEG. The\ monomeric complex contains 15 transmembrane helices.

\ \

This entry describes the SecD family of transport proteins. Members of this family are highly variable in length immediately after the well-conserved motif LGLGLXGG at the amino-terminal end of this model. Archaeal homologs are not included in the seed. SecD from Mycobacterium tuberculosis has a long Pro-rich insert.

\ \ \ protein translocase activity ; GO:0015450 inner membrane ; GO:0019866 intracellular protein transport ; GO:0006886 24255 IPR005789

Serine and threonine dehydratases [MEDLINE:89380167], [MEDLINE:87092415] are functionally and structurally relatedpyridoxal-phosphate dependent enzymes. L-serine dehydratase (EC: 4.3.1.17) and D-serine dehydratase (EC: 4.3.1.18) catalyze the dehydratation of L-serine (respectively D-serine) into ammonia and pyruvate. Threonine dehydratase (EC: 4.3.1.19) (TDH) catalyzes the dehydratation of threonine into -ketobutarate and ammonia. In Escherichia coli and other microorganisms, two classes of TDH are known to exist. One is involved\ in the biosynthesis of isoleucine, the other in hydroxamino acid catabolism. Threonine synthase (EC: 4.2.3.1) is also a pyridoxal-phosphate enzyme, it catalyzes the transformation of homoserine-phosphate into threonine.\ It has been shown [MEDLINE:87080286] that threonine synthase is distantly related to the serine/threonine dehydratases. In all these enzymes, the pyridoxal-phosphate group is attached to a lysine residue.

A form of threonine dehydratase with two copies of the C-terminal domain IPR001721 domain. Many members of this model are found in species with other isoleucine biosynthetic enzymes.

\ \ \ threonine dehydratase activity ; GO:0004794 \N \N 24256 IPR005790

DNA polymerase III delta (holA, EC: 2.7.7.7) and delta prime (holB) subunits are distinct proteins encoded by separate genes. The delta prime subunit (holB) exhibits sequence homology to the tau and gamma subunits (dnaX), but the delta subunit (holA) does not demonstrate this same homology with dnaX. The delta, delta prime, gamma, chi and psi subunits form the gamma complex sub-assembly of DNA polymerase III holoenzyme, which couples ATP to assemble the ring-shaped subunit around DNA forming a DNA sliding clamp. Both delta and delta prime are monomeric in their native state, and they bind each other tightly to form a 1:1 complex. Neither delta nor delta prime alone binds tightly to the gamma subunit [MEDLINE:93280137].

\ delta DNA polymerase activity ; GO:0003891 chromosome ; GO:0005694 DNA replication ; GO:0006260 24254 IPR005788

This is a domain of eukaryotic protein disulphide isomerases, generally foundin two copies. The domain is similar to thioredoxin but the redox-active disulfide region motif is APWCGHCK.

\ \ \ isomerase activity ; GO:0016853 \N \N 24252 IPR005786

One of these, called class-IV, currently consists of proteins of about 270 to 415 amino-acid residues that share a few regions of sequence similarity. Surprisingly, the best conserved region does not include the lysine residue to which the pyridoxal-phosphate group is known to be attached, in ilvE, but is located some 40 residues at the C-terminus side of the PlP-lysine.

Among the class IV aminotransferases are two phylogenetically separable groups of branched-chain amino acid aminotransferase (IlvE) (EC: 2.6.1.42). The last common ancestor of the two lineages appears also to have given rise to a family of D-amino acid aminotransferases (DAAT). This model represents the IlvE family less similar to the DAAT family.

\ \ \ branched-chain amino acid aminotransferase activity ; GO:0004084 \N branched chain family amino acid metabolism ; GO:0009081 24253 IPR005787

Serine and threonine dehydratases [MEDLINE:89380167], [MEDLINE:87092415] are functionally and structurally relatedpyridoxal-phosphate dependent enzymes. L-serine dehydratase (EC: 4.3.1.17) and D-serine dehydratase\ (EC: 4.3.1.18) catalyze the dehydratation of L-serine (respectively D-serine) into ammonia and pyruvate.\ Threonine dehydratase (EC: 4.2.1.16) (TDH) catalyzes the dehydratation of threonine into -ketobutarate\ and ammonia. In Escherichia coli and other microorganisms, two classes of TDH are known to exist. One is involved\ in the biosynthesis of isoleucine, the other in hydroxamino acid catabolism. Threonine synthase (EC: 4.2.3.1)\ is also a pyridoxal-phosphate enzyme, it catalyzes the transformation of homoserine-phosphate into threonine.\ It has been shown [MEDLINE:87080286] that threonine synthase is distantly related to the serine/threonine\ dehydratases. In all these enzymes, the pyridoxal-phosphate group is attached to a lysine residue.

This model describes a form of threonine dehydratase (EC: 4.3.1.19), with two copies of the threonine dehydratase C-terminal domain IPR001721. Members with known function participate in isoleucine biosynthesis and are inhibited by\ isoleucine.

\ \ \ threonine dehydratase activity ; GO:0004794 \N isoleucine biosynthesis ; GO:0009097 24251 IPR005785

\ \ \ branched-chain amino acid aminotransferase activity ; GO:0004084 \N branched chain family amino acid metabolism ; GO:0009081 24249 IPR005783

This family describes methymalonyl-CoA decarboxylase subunit in archaea and bacteria. Metylmalonyl-CoA decarboxylase Na+ pump (EC: 4.1.1.41) is a representative of a class of Na+ transport decarboxylases that couples the energy derived by decarboxylation of carboxylic acid substrates to drive the extrusion of Na+ ion across the membrane.

\ methylmalonyl-CoA decarboxylase activity ; GO:0004492 \N sodium ion transport ; GO:0006814 24250 IPR005784

D-amino acid aminotransferase (EC: 2.6.1.21) catalyzes transamination between various D-amino acids and -keto acids, This enzyme is a homodimer. The pyridoxal phosphate attachment site is a Lys in the motif Cys-Asp-Ile-Lys-Ser-Leu-Asn. Specificity is broad for various D-amino acids, and differs among members of the family [MEDLINE:89123327].

\ transaminase activity ; GO:0008483 \N metabolism ; GO:0008152 24248 IPR005782

This model describes Ca2+ ATPases (EC: 3.6.3.8) from eukaryotes and includes significantrepresentatives from plants. Plasma membrane Ca2+ ATPases are primarily responsible for extrusion of calcium from cytoplasmic milieu to outside, coupled to the hydrolyis of ATP. Besides Ca2+ ATPases, Na+/Ca2+ exchangers are also involved in the maintenance of Ca2+ homestasis in the cell.

\ \ \ calcium-transporting ATPase activity ; GO:0005388 integral to membrane ; GO:0016021 calcium ion transport ; GO:0006816 24247 IPR005781

This model describes the photosynthetic reaction centre M subunit in non-oxygenic photosynthetic bacteria. Reaction centre is an integral membrane pigment-protein that carries out light-driven electron transfer reactions. At the core of reaction centre is a collection of light-harvesting cofactors and closely associated polypeptides. The core protein complex is made of L, M and H subunits. The common cofactors include bacterichlorophyll, bacteriopheophytins, ubiquinone and no-heme ferrous iron. The net result of electron transfer reactions is the establishment of proton electrochemical gradient and production of reducing equivalents in form of NADH. Ultimately the process results in the reduction of C02 to carbohydrates(C6H12O6) In non-oxygenic organisms, the electron donor is some organic acid and not water. Much of our current functional understanding of photosynthesis comes from the structural determination, spectroscopic studies and mutational analysis on the reaction centre of Rhodobacter sphaeroides.

This model describes N5-methyltetrahydromethanopterin: coenzyme M methyltransferase subunit D in methanogenic archaea. This methyltranferase is amembrane-associated enzyme complex that uses methyl-transfer reaction to drive sodium-ion pump. \

 5-methyl-5,6,7,8-tetrahydromethanopterin + 2-mercaptoethanesulfonate = 5,6,7,8-tetrahydromethanopterin + 2-(methylthio)ethanesulfonate.

\ Archaea have evolved energy-yielding pathways marked by one-carbon biochemistry featuring novel cofactors and enzymes. This transferase (encoded by subunit A) is involved in the transfer of 'methyl' group from N5-methyltetrahydromethanopterin to coenzyme M. In an accompanying reaction, methane is produced by two-electron reduction of methyl-coenzyme M by another enzyme, methyl-coenzyme M reductase.

\ \ \ tetrahydromethanopterin S-methyltransferase activity ; GO:0030269 vesicle membrane ; GO:0012506 sodium ion transport ; GO:0006814 24246 IPR005780

This model describes N5-methyltetrahydromethanopterin: coenzyme M methyltransferase subunit E in methanogenic archaea. This methyltranferase is amembrane-associated enzyme complex that uses methyl-transfer reaction to drive sodium-ion pump. \

 5-methyl-5,6,7,8-tetrahydromethanopterin + 2-mercaptoethanesulfonate = 5,6,7,8-tetrahydromethanopterin + 2-(methylthio)ethanesulfonate.

\ \ \ tetrahydromethanopterin S-methyltransferase activity ; GO:0030269 vesicle membrane ; GO:0012506 sodium ion transport ; GO:0006814 24242 IPR005776

This family describes the bacterial oxaloacetate decarboxylase subunit and its equivalents in archaea [MEDLINE:21145115]. The oxaloacetate decarboxylase Na+ pump is the paradigm of the family of Na+ transport decarboxylases that present in bacteria and archaea. It a multi subunit enzyme consisting of a peripheral -subunit and integral membrane subunits and gamma. The energy released by the decarboxylation reaction of oxaloacetate is coupled to Na+ ion pumping across the membrane.

\ oxaloacetate decarboxylase activity ; GO:0008948 \N sodium ion transport ; GO:0006814 24244 IPR005778

This model describes N5-methyltetrahydromethanopterin: coenzyme M methyltransferase subunit A in methanogenic archaea. This methyltranferase is amembrane-associated enzyme complex that uses methyl-transfer reaction to drive sodium-ion pump. \

 5-methyl-5,6,7,8-tetrahydromethanopterin + 2-mercaptoethanesulfonate = 5,6,7,8-tetrahydromethanopterin + 2-(methylthio)ethanesulfonate.

\ \ \ tetrahydromethanopterin S-methyltransferase activity ; GO:0030269 vesicle membrane ; GO:0012506 sodium ion transport ; GO:0006814 24243 IPR005777

This model describes malonate decarboxylase subunit. Malonate decarboxylase Na+ pump is the paradigm of the family of Na+ transport decarboxylases. Essentially, it couples the energy derived from decarboxylation of a carboxylic acid substrate to move Na+ ion across the bilayer. Functional malonate decarboylase is a multi subunit protein. The subunit enzymatically performs the transfer of malonate (substrate) to an acyl carrier protein subunit for subsequent decarboxylation, hence the name: acetyl-S-acyl carrier protein:malonate carrier protein-SH transferase.

\ carboxy-lyase activity ; GO:0016831 \N sodium ion transport ; GO:0006814 24241 IPR005775

The chains of sodium/potassium-transporting ATPases (H+/K+ and Na+/K+-ATPase) catalyze the hydrolysis of ATP, coupled with the exchange of sodium and potassium ions across the plasma membrane. The proteins are located in the cell membrane [MEDLINE:90033318], the ion transport they mediate creating the electro-chemical gradient that provides the energy for the active transport of various nutrients. H+/K+-transporting ATPases are also responsible for production of acid in the stomach [MEDLINE:87057383].H+/K+ and Na+/K+-ATPase are members of the P-type (or E1-E2-type) cation-transporting ATPase superfamily, which has evolved from a common ancestral gene [MEDLINE:94202222]. The sequences contain 10 transmembrane (TM) helices, some of which are well\ conserved throughout the superfamily. They may thus all operate via a similar mechanism, with an aspartylphosphoryl enzyme intermediate [MEDLINE:87033715] being formed during the catalytic cycle.

\ \

This model describes the Na+/K+ ATPase subunit in eukaryotes. Na+/K+ ATPase (also called Sodium-Potassium pump) is intimately associated with the plasma membrane. It couples the energy released by the hydrolysis of ATP to extrude 3 Na+ ions, with the concomitant uptake of 2K+ ions, against their ionic gradients.

\ \ \ monovalent inorganic cation transporter activity ; GO:0015077 integral to membrane ; GO:0016021 monovalent inorganic cation transport ; GO:0015672 24240 IPR005774

This family of proteins, GalF, represents a non-catalytic subunit of the UTP-glucose pyrophosphorylase modulating the enzyme activity to increase the formation of UDP-glucose [MEDLINE:97126811].

\ \ \ enzyme regulator activity ; GO:0030234 \N UDP-glucose metabolism ; GO:0006011 24239 IPR005773

This model identifies the generic virulence translocation proteins in bacteria. It derives its name:'Yop' from Yersinia enterocolitica species, where this virulence protein was identified. In bacterial pathogenesis, Yop effector proteins are translocated into the eukaryotic cells.

\ type III protein (virulence-related) secretor activity ; GO:0015448 integral to membrane ; GO:0016021 protein transport ; GO:0015031 24237 IPR005771

Uridine 5'-triphosphate:glucose-1-phosphate uridylyltransferase (uridine diphosphoglucose pyrophosphorylase, EC: 2.7.7.9) is responsible for the synthesis of UDP-glucose, a key compound in the biosynthesis of polysaccharides. Glucose is fermented through the glycolysis step to pyruvate, which in turn is converted to lactate. The glycolytic intermediate glucose 6-phosphate is converted to glucose 1-phosphate by phosphoglucomutase activity, and this metabolite is subsequently converted to UDP-glucose by UDP-glucose pyrophosphorylase (GalU) activity.

\ \ \ UTP-glucose-1-phosphate uridylyltransferase activity ; GO:0003983 \N UDP-glucose metabolism ; GO:0006011 24238 IPR005772

\ \

\ \ \ \ \ \ \

This model describes the vacuolar ATP synthase F subunit (14 kDa subunit) in eukaryotes.

\ \ \ hydrogen-translocating F-type ATPase activity ; GO:0016467 \N ATP synthesis coupled proton transport ; GO:0015986 24236 IPR005770

Bacterial binding protein-dependent transport systems [MEDLINE:86294332], [MEDLINE:91035372] are multicomponent systems typically composed of a periplasmic substrate-binding protein, one or two reciprocally homologous integral inner-membrane proteins and one or two peripheral membrane ATP-binding proteins that couple energy to the active transport system. The integral inner-membrane proteins translocate the substrate across the membrane. It has been shown [MEDLINE:86081738], [MEDLINE:95020621] that most of these proteins contain a conserved region located about 80 to 100 residues from their C-terminal extremity. This region seems [MEDLINE:92149312] to be located in a cytoplasmic loop between two transmembrane domains. Apart from the conserved region, the sequence of these proteins is quite divergent, and they have a variable number of transmembrane helices.

This is a family of periplasmic proteins which are part of the transport system for \ alkylphosphonate uptake.

\ \ \ phosphonate transporter activity ; GO:0015604 periplasmic space (sensu Gram-negative Bacteria) ; GO:0030288 phosphonate transport ; GO:0015716 24230 IPR005763

L-fucose isomerase (EC: 5.3.1.25) catalyzes the first step in fucose metabolism, and has been characterized in Escherichia coli and Bacteroides thetaiotaomicron.

\ L-fucose isomerase activity ; GO:0008736 cytoplasm ; GO:0005737 fucose catabolism ; GO:0019317 24231 IPR005764

Adenine phosphoribosyltransferase (APRTase, EC: 2.4.2.7) is a widely distributed enzyme, and its deficiency in humans causes the accumulation of 2,8-dihydroxyadenine. It is the sole catalyst for adenine recycling in most eukaryotes.\

 AMP + diphosphate = adenine + 5-phospho--D-ribose 1-diphosphate

\ \ \ adenine phosphoribosyltransferase activity ; GO:0003999 \N adenine salvage pathway ; GO:0006168 24232 IPR005765

The enzyme uracil phosphoribosyltransferase (UPRT, EC: 2.4.2.9) catalyzes conversion of uracil to uridine 5'-monophosphate utilizing 5'-phosphoribosyl--1-pyrophosphate (PRPP).

 UMP + diphosphate = uracil + 5-phospho--D-ribose 1-diphosphate

\ \ \ uracil phosphoribosyltransferase activity ; GO:0004845 \N uracil salvage ; GO:0006223 24233 IPR005766

delta l-pyrroline-5-carboxylate synthetase contains a glutamate 5-kinase (ProB, EC: 2.7.2.11) region followed by a gamma-glutamyl phosphate reductase (ProA, EC: 1.2.1.41) region and catalyses the first and second steps in proline biosynthesis.

\ enzyme activity ; GO:0003824 \N proline biosynthesis ; GO:0006561 24234 IPR005768

In gram-positive bacteria which are surrounded by a single membrane and have therefore no periplasmic region the equivalent proteins are bound to the membrane via an N-terminal lipid anchor. These homolog proteins do not play an integral role in the transport process per se, but probably serve as receptors to trigger or initiate translocation of the solute through the membrane by binding to external sites of the integral membrane proteins of the efflux system. In addition at least some solute-binding proteins function in the initiation of sensory transduction pathways.

On the basis of sequence similarities, the vast majority of these solute-binding proteins can be grouped into eight families of clusters, which generally correlate with the nature of the solute bound. Family 3 groups together specific amino acids and opine-binding periplasmic proteins and a periplasmic homolog with catalytic activity.

\ \ \ transporter activity ; GO:0005215 periplasmic space (sensu Gram-negative Bacteria) ; GO:0030288 transport ; GO:0006810 24235 IPR005769

These proteins represent a family of phosphonate uptake transporters., probably responsible for the transport of phosphonate across the inner membrane.

\ \ \ phosphonate transporter activity ; GO:0015604 integral to plasma membrane ; GO:0005887 phosphonate transport ; GO:0015716 24228 IPR005761

Most members of this family are UDP-N-acetylmuramoylalanyl-D-glutamate--2,6-diaminopimelate ligases (EC: 6.3.2.13). An exception isStaphylococcus aureus, in which diaminopimelate is replaced by lysine in the\ peptidoglycan and MurE is (EC: 6.3.2.7). The Mycobacteria, part of the closest neighboring branch outside of the low-GC Gram-positive bacteria, use diaminopimelate.

\ \ \ acid-D-amino acid ligase activity ; GO:0016881 cytoplasm ; GO:0005737 cell wall biosynthesis (sensu Bacteria) ; GO:0009273 24229 IPR005762

In the complex process of biosynthesis of bacterial peptidoglycan, the assembly of the peptide moiety of its monomer unit has recently been the topic of numerousinvestigations. It is performed by a series of enzymes designated as the Mur synthetases (MurC,1 MurD, MurE, and MurF), which are responsible for the successive additions of L-alanine, D-glutamate, meso-diaminopimelate or L-lysine, and D-alanyl-D-alanine to UDP-N-acetylmuramic acid . MurD (UDP-N-acetylmuramoyl-L-alanine:D-glutamate ligase) ligase catalyses the addition of d-glutamate to the nucleotide precursor UDP-N-acetylmuramoyl-l-alanine.

\ \ \ UDP-N-acetylmuramoylalanine-D-glutamate ligase activity ; GO:0008764 cytoplasm ; GO:0005737 cell wall biosynthesis (sensu Bacteria) ; GO:0009273 24226 IPR005759

The spectrum of DNA damage caused by reactive oxygen species includes a wide variety of modifications of purine and pyrimidine bases. Among these modified bases, 7,8-dihydro-8-oxoguanine (8-oxoG) is an important mutagenic lesion. Base excision repair is a critical mechanism for preventing mutations by removing the oxidative lesion from the DNA. E.coli Nth protein (endonuclease III) has an 8-oxoG DNA glycosylase/AP lyase activity which removes 8-oxoG preferentially from 8-oxoG/G mispairs. Human hNTH1 protein, a homolog of E.coli Nth protein, has similar DNA glycosylase/AP lyase activity that removes 8-oxoG from 8-oxoG/G mispairs [MEDLINE:22272390].

\ DNA-(apurinic or apyrimidinic site) lyase activity ; GO:0003906 intracellular ; GO:0005622 base-excision repair ; GO:0006284 24227 IPR005760

The DNA repair enzyme MutY plays an important role in the prevention of DNA mutations resulting from the presence of the oxidatively damaged lesion 7,8-dihydro-8-oxo-2'-deoxyguanosine (OG). MutY is a base excision repair (BER) glycosylase that removes misincorporated adenine residues from OG:A mispairs, as well as G:A and C:A mispairs.

\ DNA N-glycosylase activity ; GO:0019104 intracellular ; GO:0005622 base-excision repair ; GO:0006284 24224 IPR005757

The tripeptide L-ananyl-gamma-D-glutamyl-meso-diaminopimelic acid is efficiently re-cycled during the formation of bacterial cell wall murein. UDP-N-acetylmuramate:L-alanyl-gamma-D-glutamyl-meso-diaminopimelate ligase is an essential enzyme in this process which links the tripeptide to UDP-N-acetylmuramate.

\ ligase activity ; GO:0016874 \N cell wall organization and biogenesis ; GO:0007047 24225 IPR005758

The bacterial UDP-N-acetylmuramyl-L-alanine ligase (MurC) an essential, cytoplasmic peptidoglycan biosynthetic enzyme, catalyzes the ATP-dependent ligation of L-alanine (Ala) and UDP-N-acetylmuramic acid (UNAM) to formUDP-N-acetylmuramyl-L-alanine (UNAM-Ala). The enzyme is a nonribosomal peptide ligase which utilizes ATP to form an amide bond between L-alanine and UNAM.1 Mechanistic studies on the Escherichia coli MurC enzyme using oxygen isotope analyses demonstrated that the enzyme-catalyzed reaction proceeds through an acyl phosphate UNAM intermediate prior to L-alanine addition.

\ \ \ UDP-N-acetylmuramate-alanine ligase activity ; GO:0008763 cytoplasm ; GO:0005737 cell wall biosynthesis (sensu Bacteria) ; GO:0009273 24222 IPR005755

\ \ \

Ribosomal protein L13 is one of the proteins from the large ribosomal subunit\ [MEDLINE:94164901]. In Escherichia coli, L13 is known to be one of the early assembly proteins of the 50S ribosomal subunit. This model represents ribosomal protein of L13 from the Archaea and from the eukaryotic cytosol.

\ \ \ structural constituent of ribosome ; GO:0003735 large ribosomal subunit ; GO:0015934 protein biosynthesis ; GO:0006412 24223 IPR005756

\ \ \

Ribosomal protein L24 is one of the proteins from the large ribosomal\ subunit. In their mature form, these proteins have 103 to 150 amino-acid residues. This model recognizes bacterial and organellar forms of ribosomal protein L24.

\ \ \ structural constituent of ribosome ; GO:0003735 large ribosomal subunit ; GO:0015934 protein biosynthesis ; GO:0006412 24219 IPR005752

RepA hexameric DNA helicase contain ATP-binding domains similar tothose seen in monomeric helicases but which are arranged in a ring. There is compelling evidence to suggest that a single ssDNA molecule passes through the centre\ of the hexameric ring. Activity of the enzyme is based upon two separate but coupled activities, ssDNA translocation and duplex\ destabilization, and is driven by energy derived from the continuous ATP-binding and hydrolysis events that take place in the active-site cleft. The resulting\ conformational changes that accompany these events underpin the coupling process and allow the helicase to translocate along the DNA, destabilizing the duplex and\ separating the two strands in an active process [MEDLINE:21108742]\

\ \ \ ATP dependent DNA helicase activity ; GO:0004003 cytoplasm ; GO:0005737 DNA unwinding ; GO:0006268 24220 IPR005753

The SOS response is required for efficient nucleotide excision repair (NER) of the major ultraviolet light (UV) induced DNA lesions. The expression of three NER genes, uvrA, uvrB, and uvrD, is upregulated as part of the SOS response. UvrD differs from the others in that it is not involved in lesion recognition but rather in promoting the post-incision steps of NER, including turnover of the UvrBC incision complex [MEDLINE:21469111]. The form of the UvrD helicase with optimal helicase activity is oligomeric with at least two sites for binding the DNA substrate, where one site contacts regions of the 3'-ssDNA tail that are distal from the single-stranded/double-stranded DNA junction.

\ ATP dependent DNA helicase activity ; GO:0004003 cytoplasm ; GO:0005737 DNA unwinding ; GO:0006268 24221 IPR005754

Surface proteins not only promote interaction between the invading pathogen and animal tissues, but also provide ingenious strategies for bacterial escape from the host's immune response. In the case of Staphylococcus aureus protein A, immunoglobulins are captured on the microbial surface and camouflage bacteria during the invasion of host tissues. Protein A is cleaved by a transpeptidase, sortase, between the threonine and the glycine of a conserved LPXTG motif. The carboxyl group of threonine is amide-linked to the amino group of the pentaglycine cross-bridge, thereby tethering the COOH-terminal end of protein A to the bacterial cell wall. This reaction, called cell wall sorting, is strikingly similar to the penicillin-sensitive transpeptidation reaction, and is likely to occur in most Gram-positive bacteria. Sortase, is the transpeptidase that anchors surface proteins to the bacterial cell wall [MEDLINE:99357874]

This family includes Staphylococcus aureus sortase, a transpeptidase that attaches surface proteins by the Thr of an LPXTG motif to the cell wall. It also includes a protein required for correct assembly of an LPXTG-containing fimbrial protein, a set of homologous proteins from Streptococcus pneumoniae, in which LPXTG proteins are common. However, related proteins are found in Bacillus subtilis and Methanobacterium thermoautotrophicum, in which LPXTG-mediated cell wall attachment is not known.

\ \ \ transferase activity ; GO:0016740 \N biosynthesis ; GO:0009058 24217 IPR005750

The bacterial enzyme UDP-N-acetylglucosamine (UDP-GlcNAc) enolpyruvyltransferase (MurA) catalyzes the transfer of enolpyruvate from phosphoenolpyruvate to uridine diphospho-N-acetylglucosamine, which is the first committed step of bacterial cell wall biosynthesis. Experimental evidence suggests that binding of substrates to the enzyme does not exclusively follow an ordered mechanism with\ UDP-GlcNAc binding first, although binding of UDP-GlcNAc to free enzyme is preferred and possibly influenced by pyruvate-P. The\ reaction thus appears to follow an induced-fit mechanism, in which the binding site for fosfomycin, and presumably also for pyruvate-P,\ is created by the interaction of free enzyme with the sugar nucleotide.

\ \ \ transferase activity ; GO:0016740 \N UDP-N-acetylgalactosamine biosynthesis ; GO:0019277 24218 IPR005751

The DNA helicase PcrA is found in gram-positive bacteria and belongs to a superfamily of helicases, together with Rep and UvrD helicases from Escherichia coli. The action of the 3'5' bacterial DNA helicase is based upon two separate but coupled activities, ssDNA translocation and duplexdestabilization, and is driven by energy derived from the continuous ATP-binding and hydrolysis events that take place in the active-site cleft. The resulting\ conformational changes that accompany these events underpin the coupling process and allow the helicase to translocate along the DNA, destabilizing the duplex and\ separating the two strands in an active process [MEDLINE:21108742].

\ \ \ ATP dependent DNA helicase activity ; GO:0004003 cytoplasm ; GO:0005737 DNA unwinding ; GO:0006268 24214 IPR005747

The MutS protein of Escherichia coli plays a key role in the recognition and repair of errors made during the replication of DNA. Homologs of MutS have been found in many species including eukaryotes, archaea and bacteria, and together these proteins have been grouped into the MutS family. Although many of these proteins have similar activities to the E.coli MutS, there is significant diversity of function among the MutS family members. This diversity is even seen within species; many species encode multiple MutS homologs with distinct functions [MEDLINE:98391755].

\ DNA binding activity ; GO:0003677 cytoplasm ; GO:0005737 maintenance of fidelity during DNA dependent DNA replication ; GO:0045005 24216 IPR005749

\ \ \ .\ \ structural constituent of ribosome ; GO:0003735 large ribosomal subunit ; GO:0015934 protein biosynthesis ; GO:0006412 24215 IPR005748

\ ATP binding activity ; GO:0005524 cytoplasm ; GO:0005737 mismatch repair ; GO:0006298 24213 IPR005746 Thioredoxins [MEDLINE:85277988], [MEDLINE:89340492], [MEDLINE:95308039], [MEDLINE:95308040] are small disulphide-containing redox proteins that have been found in all the kingdoms of living organisms. Thioredoxin serves as a general protein disulphide oxidoreductase. It interacts with a broad range of proteins by a redox mechanism based on reversible oxidation of 2 cysteine thiol groups to a disulphide, accompanied by the transfer of 2 electrons and 2 protons. The net result is the covalent interconversion of a disulphide and a dithiol.

TR-S₂ + NADPH + H⁺ -> TR-(SH)₂ + NADP⁺ (1)

\ \ \ \

trx-S₂ + TR-(SH)₂ -> trx-(SH)₂ + TR-S₂ (2)

\ \ \ \

Protein-S₂ + trx-(SH)₂ -> Protein-(SH)₂ + trx-S₂ (3)

fold, consisting of a 5-stranded parallel

-sheet core, enclosed by 4

\ \ electron transporter activity ; GO:0005489 \N electron transport ; GO:0006118 24212 IPR005745

\ \ \ \

Ribosomal protein L14 is one of the proteins from the large ribosomal subunit.\ In bacteria, L14 is known to bind directly to the 23S rRNA. It belongs to a\ family of ribosomal proteins which have been grouped on the basis of sequence\ similarities PUB00005071.\ L14 is a protein of 119 to 137 amino-acid residues. This family distinguishes bacterial and most organellar examples of ribosomal protein L14 from all archaeal and eukaryotic forms.

\ \ \ \ structural constituent of ribosome ; GO:0003735 large ribosomal subunit ; GO:0015934 protein biosynthesis ; GO:0006412 24211 IPR005744

This family includes proteins from pathogenic and non-pathogenic bacteria, Homo sapiens and Drosophila. In Bacillus cereus, a pathogen, it has been show to function as a channel-forming cytolysin. The human protein is expressed preferentially in mature macrophages, consistent with a cytolytic role.

\ lysin activity ; GO:0015465 integral to membrane ; GO:0016021 cytolysis ; GO:0019835 24210 IPR005743

Topoisomerases catalyse the interconversion of topological isomers of DNA and play a key role in DNA metabolism. Topoisomerase I catalyses an ATP-independent reaction, while topoisomerase II catalyses an ATP-dependent reaction, resulting in the formation of DNA supercoils [MEDLINE:91339166], [MEDLINE:91270367], [MEDLINE:89017161]. Eukaryotic enzymes can form both positive and negative supercoils, while prokaryotic enzymes form only negative supercoils.

Eukaryotic topoisomerase II exists as a homodimer; in bacteriophage T4 it \ consists of three heterologous subunits; in prokaryotes it exists as a tetramer\ of two subunits (two each of gyrA and gyrB); and in Escherichia coli, a second type II topoisomerase, involved in chromosome segregation (topoisomerase IV), consists of two subunits (parC and parE).

\ \ \

Not every bacterium has both a topo II and a topo IV. The topo IV families of the Gram-positive bacteria and the Gram-negative bacteria appear not to represent a single clade among the type II topoisomerases, and are represented by separate entries for this reason.

\ \ \ DNA topoisomerase type II activity ; GO:0003918 chromosome ; GO:0005694 DNA unwinding ; GO:0006268 24209 IPR005742

Eukaryotic topoisomerase II exists as a homodimer; in bacteriophage T4 it \ consists of three heterologous subunits; in prokaryotes it exists as a tetramer\ of two subunits (two each of gyrA and gyrB); and in Escherichia coli, a second type II\ topoisomerase, involved in chromosome segregation (topoisomerase IV),\ consists of two subunits (parC and parE). GyrB, parE, and the product of \ bacteriophage T4 gene 39, are all similar to the eukaryotic proteins.

Investigations have shown that full-length ParC and ParE are required to\ reconstitute Topo IV activity, while truncated ParC and ParE are inactive. Topo IV activity is inhibited by quinolone and coumarin antibiotics, but the concentrations required for 50% inhibition of activity are 3-30-fold higher than those required to inhibit DNA gyrase [MEDLINE:94043292]. Norfloxacin-induced DNA cleavage patterns of Topo IV and DNA gyrase are distinct, but over-lapping. The native forms of ParC and ParE are respectively a dimer and a monomer, while the active form of Topo IV is a heterotetramer, ParC2ParE2. It is thought that the inactivity of truncated forms of ParC and ParE might be attributed to their failure to form the heterotetramer [MEDLINE:94043292].

\ \

\ \ \ DNA topoisomerase type II activity ; GO:0003918 chromosome ; GO:0005694 DNA unwinding ; GO:0006268 24208 IPR005741

DNA gyrase is the target of two classes of inhibitor: coumarins and\ quinolones. Coumarins bind to gyrB and are competitive inhibitors with\ respect to ATP. Quinolones bind DNA gyrase when the enzyme is complexed\ with DNA, and trap the enzyme in an abortive ternary complex.

\ \

The crystal structure of an N-terminal fragment of the Escherichia coli DNA gyrase B in complex with a non-hydrolysable ATP analogue, has been\ determined to 2.5A resolution [MEDLINE:91270367]. The fold comprises two domains, both of which exhibit novel topologies. The fragment forms a dimer, whose N-terminal domains are responsible for ATP binding and hydrolysis. The C-terminal\ domains form the sides of a 20A hole through the protein dimer, which may play a role in DNA strand passage during the supercoiling reaction [MEDLINE:91270367].

\ \ \ DNA topoisomerase type II activity ; GO:0003918 chromosome ; GO:0005694 DNA unwinding ; GO:0006268 24207 IPR005740

Eukaryotic topoisomerase II exists as a homodimer; in bacteriophage T4 it \ consists of three heterologous subunits; in prokaryotes it exists as a tetramer\ of two subunits (two each of gyrA and gyrB); and in Escherichia coli, a second type II\ topoisomerase, involved in chromosome segregation (topoisomerase IV),\ consists of two subunits (parC and parE). GyrB, parE, and the product of \ bacteriophage T4 gene 39, are all similar to the eukaryotic proteins.

Investigations have shown that full-length ParC and ParE are required to\ reconstitute Topo IV activity, while truncated ParC and ParE are inactive. Topo IV activity is inhibited by quinolone and coumarin antibiotics, but the concentrations required for 50% inhibition of activity are 3-30-fold higher than those required to inhibit DNA gyrase [MEDLINE:94043292]. Norfloxacin-induced DNA cleavage patterns of Topo IV and DNA gyrase are distinct, but overlapping. The native forms of ParC and ParE are respectively a dimer and a monomer, while the active form of Topo IV is a heterotetramer, ParC2ParE2. It is thought that the inactivity of truncated forms of ParC and ParE might be attributed to their failure to form the heterotetramer [MEDLINE:94043292].

\ \

\ \ \ DNA topoisomerase type II activity ; GO:0003918 chromosome ; GO:0005694 DNA unwinding ; GO:0006268 24206 IPR005739

Prokaryotic topoisomerase I (EC: 5.99.1.2) [MEDLINE:95292060], PUB00001074, PUB00001074, otherwise known as relaxing enzyme, untwisting enzyme or swivelase, catalyses the ATP-independent breakage of single-stranded DNA, followed by passage and rejoining of another single-stranded DNA region [MEDLINE:94159070]. This reaction brings about the conversion of one topological isomer of DNA into another: e.g., relaxation of superhelical turns; interconversion of simple and knotted rings of single-stranded DNA; and intertwisting of single-stranded rings of complementary sequences [MEDLINE:94159070], [MEDLINE:90036864].Prokaryotic topoisomerase I folds in an unusual way to give 4 distinct\ domains, enclosing a hole large enough to accommodate a double-stranded DNA\ segment [MEDLINE:94159070]. A tyrosine at the active site, which lies at the interface of 2 domains, is involved in transient breakage of a DNA strand, and formation of a covalent protein-DNA intermediate [MEDLINE:94159070]. The structure reveals a plausible mechanism by which this and related enzymes could catalyse the passage of one DNA strand through a transient break in another strand [MEDLINE:94159070].\ E.coli contains 2 type I topoisomerases: topoisomerases I and III [MEDLINE:90036864].

\ \

This family describes topoisomerase I from archaea. These enzymes are involved in the control of DNA topology. DNA topoisomerase I belongs to the type I topoisomerases, which are ATP-independent.

\ \ \ DNA topoisomerase activity ; GO:0003916 chromosome ; GO:0005694 DNA unwinding ; GO:0006268 24205 IPR005738

Prokaryotic topoisomerase I (EC: 5.99.1.2) [MEDLINE:95292060], PUB00001074, PUB00001074, otherwise known as relaxing enzyme, untwisting enzyme or swivelase, catalyses the ATP-independent breakage of single-stranded DNA, followed by passage and rejoining of another single-stranded DNA region [MEDLINE:94159070]. This reaction brings about the conversion of one topological isomer of DNA into another: e.g., relaxation of superhelical turns; interconversion of simple and knotted rings of single-stranded DNA; and intertwisting of single-stranded rings of complementary sequences [MEDLINE:94159070], [MEDLINE:90036864].Prokaryotic topoisomerase I folds in an unusual way to give 4 distinct\ domains, enclosing a hole large enough to accommodate a double-stranded DNA\ segment [MEDLINE:94159070]. A tyrosine at the active site, which lies at the interface of 2 domains, is involved in transient breakage of a DNA strand, and formation of a covalent protein-DNA intermediate [MEDLINE:94159070]. The structure reveals a plausible mechanism by which this and related enzymes could catalyse the passage of one DNA strand through a transient break in another strand [MEDLINE:94159070].\ Escherichia coli contains 2 type I topoisomerases: topoisomerases I and III [MEDLINE:90036864].

This model describes topoisomerase III from bacteria and its equivalents encoded on\ plasmids. The gene is designated topB if found in the bacterial chromosome, traE on\ conjugative plasmid RP4, etc. These enzymes are involved in the control of DNA topology.\ DNA topoisomerase III belongs to the type I topoisomerases, which are ATP-independent.

\ \ \ DNA topoisomerase activity ; GO:0003916 chromosome ; GO:0005694 DNA unwinding ; GO:0006268 24204 IPR005737

Eukaryotic topoisomerase II exists as a homodimer; in bacteriophage T4 it \ consists of three heterologous subunits; in prokaryotes it exists as a tetramer\ of two subunits (two each of gyrA and gyrB); and in Escherichia coli, a second type II\ topoisomerase, involved in chromosome segregation (topoisomerase IV),\ consists of two subunits (parC and parE). GyrB, parE, and the product of \ bacteriophage T4 gene 39, are all similar to the eukaryotic proteins.

\ \ \ DNA topoisomerase type II activity ; GO:0003918 chromosome ; GO:0005694 DNA unwinding ; GO:0006268 24201 IPR005734

In all organisms, type II DNA topoisomerases are essential for untangling chromosomal DNA. The structure of the DNA-binding core of the Methanococcus jannaschii DNA topoisomerase VI A subunit has been determined to 2.0A resolution. The overall structure of the subunit is unique, demonstrating that archaeal type II enzymes are distinct from other type II topoisomerases. Nevertheless, the core structure contains a pair of domains that are also found in type IA and classic type II topoisomerases. Such regions may form the basis of a DNA cleavage mechanism shared among these enzymes [MEDLINE:20012926] ].

\ \

Archaeal topisomerase VI has no similarity with other type II topoisomerases, except for three motifs in the B subunit probably involved in ATP binding and hydrolysis.

\ \ \ DNA topoisomerase type II activity ; GO:0003918 chromosome ; GO:0005694 DNA unwinding ; GO:0006268 24202 IPR005735

This model describes a putative zinc finger domain found in three closely spaced copies in Arabidopsis protein LSD1 and in two copies in other proteins from the same species. The motif resembles CxxCRxxLMYxxGASxVxCxxC [MEDLINE:97207015]. This domain may play a role in the regulation of transcription, via either repression of a prodeath pathway or activation of an antideath pathway, in response to signals emanating from cells undergoingpathogen-induced hypersensitive cell death.

\ \ \ \N \N \N 24203 IPR005736

This model describes reverse gyrase, found in both archaeal and bacterial thermophiles. This enzyme, a fusion of a type I topoisomerase domain and a helicase domain, introduces positive supercoiling to increase the melting temperature of DNA double strands. Generally, these gyrases are encoded as a single polypeptide. An exception was found in Methanopyrus kandleri, where the enzyme is split within the topoisomerase domain, yielding a heterodimer of gene products designated RgyB and RgyA.

\ DNA topoisomerase activity ; GO:0003916 chromosome ; GO:0005694 DNA unwinding ; GO:0006268 24200 IPR005733

Prokaryotic topoisomerase I (EC: 5.99.1.2) [MEDLINE:95292060], PUB00001074, PUB00001074, otherwise known as relaxing enzyme, untwisting enzyme or swivelase, catalyses the ATP-independent breakage of single-\ stranded DNA, followed by passage and rejoining of another single-stranded \ DNA region [MEDLINE:94159070]. This reaction brings about the conversion of one topological\ isomer of DNA into another: e.g., relaxation of superhelical turns; \ interconversion of simple and knotted rings of single-stranded DNA; and\ intertwisting of single-stranded rings of complementary sequences [MEDLINE:94159070], [MEDLINE:90036864].\ Prokaryotic topoisomerase I folds in an unusual way to give 4 distinct\ domains, enclosing a hole large enough to accommodate a double-stranded DNA\ segment [MEDLINE:94159070]. A tyrosine at the active site, which lies at the interface of\ 2 domains, is involved in transient breakage of a DNA strand, and formation\ of a covalent protein-DNA intermediate [MEDLINE:94159070]. The structure reveals a\ plausible mechanism by which this and related enzymes could catalyse the \ passage of one DNA strand through a transient break in another strand [MEDLINE:94159070].\ Escherichia coli contains 2 type I topoisomerases: topoisomerases I and III [MEDLINE:90036864].\ Topoisomerase III can be purified as a potent concatenase, but its role in\ DNA metabolism is still unclear [MEDLINE:90036864].

\ \ DNA topoisomerase type I activity ; GO:0003917 chromosome ; GO:0005694 DNA unwinding ; GO:0006268 24199 IPR005732

\ \ \

The small ribosomal subunit protein S19 contains 88-144 amino acid residues.\ In Escherichia coli, S19 is known to form a complex with S13 that binds strongly to 16S ribosomal RNA. Experimental evidence [MEDLINE:98058740] has revealed that \ S19 is moderately exposed on the ribosomal surface.

\ \ \ structural constituent of ribosome ; GO:0003735 small ribosomal subunit ; GO:0015935 protein biosynthesis ; GO:0006412 24195 IPR005728

This domain describes protein translations of the Rickettsia palindromic elements (RPE). In Rickettsia conorii, 19 copies are found within protein coding regions, where they encode an insert relative to homologs from other species but do not disrupt the reading frame. Insertion is always in the same reading frame. This model finds RPE-encoded regions in several Rickettsial species.

\ \N \N \N 24196 IPR005729

\ \ \

This model describes the archaeal ribosomal protein and its equivalents in eukaryotes.

\ \ structural constituent of ribosome ; GO:0003735 small ribosomal subunit ; GO:0015935 protein biosynthesis ; GO:0006412 24197 IPR005730

Carboxynorspermidine synthase, mediates the nicotinamide-nucleotide-linked reduction of the Schiff base H2N(CH2)3N = CHCH2CH(NH2)COOH. This is formed from L-aspartic -semialdehyde (ASA) and 1,3-diaminopropane (DAP) and is reduced to carboxynorspermidine [H2N(CH2)3NH(CH2)2CH(NH2)COOH], an intermediate in the novel pathway for norspermidine biosynthesis shown in Vibrio alginolyticus.

\ carbon-carbon lyase activity ; GO:0016830 \N nor-spermidine biosynthesis ; GO:0045312 24198 IPR005731

\ \ \

Included in the family are one member each from Saccharomyces cerevisiae and\ Schizosaccharomyces pombe. These proteins lack an N-terminal mitochondrial transit\ peptide but contain additional sequence C-terminal to the ribosomal S10 protein region.

\ \ \ structural constituent of ribosome ; GO:0003735 small ribosomal subunit ; GO:0015935 protein biosynthesis ; GO:0006412 24194 IPR005727

\ \ \

This model decribes bacterial and chloroplast ribosomal protein L22

\ \ structural constituent of ribosome ; GO:0003735 large ribosomal subunit ; GO:0015934 protein biosynthesis ; GO:0006412 24193 IPR005726

Adenosine 5'-triphosphate (ATP) synthesis by oxidative phosphorylation or photophosphorylation is a multi-step,membrane-located process that provides the bulk of cellular energy in eukaryotes and many prokaryotes. The archaeal A1Ao-ATP synthase (A-ATPase)\ has ten subunits (A3:B3:C:D:E:F:G:H:I:Kx), the actual subunit stoichiometry being unknown [MEDLINE:21424133]. The term ATPase reflects the fact\ that the A-enzymes are reversible and can act as proton (or Na+)-pumping complexes. The A-ATPases transform energy from a gradient of ions\ across the membrane to synthesize ATP.

Based on their subunit composition and primary sequences, the A-type (archaeal) enzymes are more closely related through evolution to V-type ( IPR005723)\ ATPases.

\ \ \ hydrogen-translocating A-type ATPase activity ; GO:0016466 integral to membrane ; GO:0016021 ATP synthesis coupled proton transport ; GO:0015986 24192 IPR005725

The pH of intracellular compartments in eukaryotic cells is a carefully controlled parameter that affects many cellular processes, including\ intracellular membrane transport, prohormone processing and\ transport of neurotransmitters, as well as the entry of many viruses\ into cells. The transporters responsible for controlling this crucial\ parameter in many intracellular compartments are the vacuolar\ (H+)-ATPases (V-ATPases) [MEDLINE:21826800]. The V-ATPases are composed of two functional domains [MEDLINE:21424133]. The V1 domain is a 570-kDa peripheral complex responsible for hydrolysis of ATP. V1 is composed of eight different\ subunits of molecular mass 70-14 kDa (subunits A-H), with three copies each of the A and B subunits and single copies of the remaining subunits. The A and B subunits both participate in nucleotide binding, with the catalytic site located on the A subunit. The V0 domain is a 260-kDa integral complex that is responsible for proton translocation across the membrane. V0 contains five different subunits of molecular mass 100-17 kDa (subunits a, d, c, c', and c"), with six copies of the c/c' subunits and single copies of the other subunits . Electron microscopy has shown the\ existence of multiple stalks that connect V1 and V0.

The V-ATPases resemble the F-ATPases: IPR005723, which normally function in ATP synthesis, and are also believed to operate through a rotary mechanism. This family represents members of the B subunit of this protein.

\ \ \ hydrogen-translocating V-type ATPase activity ; GO:0000260 cytoplasm ; GO:0005737 energy coupled proton transport, against the electrochemical gradient ; GO:0015988 24191 IPR005724

Based on their subunit composition and primary sequences, the A-type (archaeal) enzymes are more closely related through evolution to V-type (IPR005723)\ ATPases.

\ \ \ hydrogen-translocating A-type ATPase activity ; GO:0016466 integral to membrane ; GO:0016021 ATP synthesis coupled proton transport ; GO:0015986 24189 IPR005722

ATP synthase is a ubiquitous, highly conserved enzyme that catalyses the formation of ATP from ADP and Pi using a unique rotary motor\ mechanism [MEDLINE:21424808]. The enzyme is located in the inner membrane of mitochondria, in the\ thylakoid membrane of chloroplasts, and in the plasma membrane of\ bacteria. ATP synthase (TC:3.A.2.1.1) is a large (500 kDa) multisubunit protein, consisting of an\ intrinsic membrane domain, Fo, linked through central and side stalks to a\ globular catalytic domain, F1. The F1 portion consists of three - and three -subunits and a single gamma, delta, epsilon-subunit, whereas Fo comprises one a-subunit, two b-subunits and 1012 c-subunits.

The synthesis of ATP is brought about by the rotary motion of the FoF1\ complex: when a large electrochemical potential (proton gradient) flows\ through the Fo subunit, this causes rotation of the Fo subunit and,\ subsequently, F1, leading to ATP synthesis. \ ATP hydrolysis by ATPase the reverse reaction induces rotation of\ the Fo rotor in the opposite direction. So, ATP synthase can be viewed as\ a complex of two motors: an ATP-driven F1 motor and the proton-driven\ Fo motor.

\ \

The sequences of ATP synthase F1 and subunits are related and both contain a nucleotide-binding site for ATP and ADP. They have a common amino terminal domain but vary at the C-terminus. The chain has catalytic activity, while the chain is a regulatory subunit. Proton translocating ATP synthase, F1 subunit is homologous to proton translocating ATP synthase archaeal/vacuolar(V1), A subunit.

\ \ \ hydrogen-translocating F-type ATPase activity ; GO:0016467 hydrogen-translocating F-type ATPase complex ; GO:0045255 ATP synthesis coupled proton transport ; GO:0015986 24190 IPR005723

The V-ATPases resemble the F-ATPases: IPR005722, which normally function in ATP synthesis, and are also believed to operate through a rotary mechanism.

The eukaryotic vacuolar (H+)-ATPase shares extensive sequence similarity with archaeal ATP synthase. This family represents members of the B subunit of this protein.

\ \ \ hydrogen-translocating V-type ATPase activity ; GO:0000260 cytoplasm ; GO:0005737 energy coupled proton transport, against the electrochemical gradient ; GO:0015988 24187 IPR005720

Dihydroorotate dehydrogenase (EC: 1.3.3.1) (DHOdehase) catalyzes the fourth step in the de novo biosynthesis of pyrimidine, the conversion of dihydroorotate into orotate. DHOdehase is a ubiquitous FAD flavoprotein. In bacteria (gene pyrD), DHOdease is \ located on the inner side of the cytosolic membrane. In some yeasts, such as in \ Saccharomyces cerevisiae (gene URA1), it is a cytosolic protein while in other eukaryotes it is found in the mitochondria [MEDLINE:93028386].

\ \

This family includes subfamily 1 dihydroorotate dehydrogenases, a number of uncharacterized proteins and a domain of dihydropyrimidine dehydrogenase.

\ \ \ dihydroorotate oxidase activity ; GO:0004158 cytoplasm ; GO:0005737 'de novo' pyrimidine base biosynthesis ; GO:0006207 24188 IPR005721

\ \ \

This family describes the ribosomal protein of the eukaryotic cytosol and of the Archaea, variously designated as L17, L22, and L23.

\ \ structural constituent of ribosome ; GO:0003735 large ribosomal subunit ; GO:0015934 protein biosynthesis ; GO:0006412 24185 IPR005718

\ \ \

This protein describes bacterial ribosomal protein L32 and the equivalent protein from mitochondria and chloroplasts.

\ \ structural constituent of ribosome ; GO:0003735 large ribosomal subunit ; GO:0015934 protein biosynthesis ; GO:0006412 24186 IPR005719

This model describes dihydroorotate dehydrogenase subfamily 2 and includes members from bacteria, yeast and plants . The subfamilies 1 and 2 share extensive homology, particularly toward the C-terminus, however subfamily 2 has a longer N-terminal region.

\ \ \ dihydroorotate oxidase activity ; GO:0004158 membrane ; GO:0016020 'de novo' pyrimidine base biosynthesis ; GO:0006207 24184 IPR005717

\ \ \

This model describes the bacterial and organellar branch of the ribosomal protein S7 family (includes prokaroytic S7 and eukaryotic S5).

\ \ structural constituent of ribosome ; GO:0003735 small ribosomal subunit ; GO:0015935 protein biosynthesis ; GO:0006412 24180 IPR005713

\ \ \ \

This family represents eukaryotic ribosomal protein S15 and its archaeal equivalent. It excludes bacterial and organellar ribosomal protein S19. The nomenclature for the archaeal members is unresolved and given variously as S19 (after the more distant bacterial homologs) or S15.

\ \ \ structural constituent of ribosome ; GO:0003735 small ribosomal subunit ; GO:0015935 protein biosynthesis ; GO:0006412 24183 IPR005716

\ \ \

This family describes the members from the eukaryotic cytosol and the Archaea of the family that includes ribosomal protein S7 of bacteria and S5 of eukaryotes.

\ \ structural constituent of ribosome ; GO:0003735 small ribosomal subunit ; GO:0015935 protein biosynthesis ; GO:0006412 24182 IPR005715

L-glutamate 5-phosphotransferase, (gamma-glutamyl kinase , proB, EC: 2.7.2.11), catalyzes the first step in proline biosynthesis

 ATP + L-glutamate = ADP + L-glutamate 5-phosphate.

\ the product of which rapidly cyclizes to 5-oxoproline and phosphate.

\ \

Bacterial ProB proteins hits the full length of this model, but the ProB-like domain of delta 1-pyrroline-5-carboxylate synthetase does not hit the C-terminal 100 residues.

\ \ \ glutamate 5-kinase activity ; GO:0004349 cytoplasm ; GO:0005737 proline biosynthesis ; GO:0006561 24181 IPR005714

This family of ATPases demonstrates extensive homology with ATP synthase F1, subunit. It is a mixture of members with two different protein functions. The first group is exemplified by Salmonella typhimurium FliI protein. It is needed for flagellar assembly, its ATPase activity is required for flagellation, and it may be involved in a specialized protein export pathway that proceeds without signal peptide cleavage. The second group of proteins function in the export of virulence proteins; exemplified by Yersinia sp. YscN protein an ATPase involved in the type III secretory pathway for the antihost Yops proteins.

\ ATPase activity ; GO:0016887 cytoplasm ; GO:0005737 protein transport ; GO:0015031 24179 IPR005712

\ \ \

This family includes chloroplast ribosomal protein S5 as well as bacterial ribosomal protein S5. A candidate mitochondrial form (Saccharomyces cerevisiae YBR251W and its homolog) differs substantially and is not included in this model.

\ \ structural constituent of ribosome ; GO:0003735 small ribosomal subunit ; GO:0015935 protein biosynthesis ; GO:0006412 24178 IPR005711

\ \ \

This model finds eukaryotic ribosomal protein S2 as well as archaeal ribosomal protein S5.

\ \ structural constituent of ribosome ; GO:0003735 small ribosomal subunit ; GO:0015935 protein biosynthesis ; GO:0006412 24177 IPR005710

\ \ \

The S4 domain is a small domain consisting of 60-65 amino acid residues that probably mediates binding to RNA. This model finds eukaryotic ribosomal protein S9 as well as eukaryotic and archaeal ribosomal protein S4.

\ \ structural constituent of ribosome ; GO:0003735 small ribosomal subunit ; GO:0015935 protein biosynthesis ; GO:0006412 24176 IPR005709

\ \ \

The S4 domain is a small domain consisting of 60-65 amino acid residues that probably mediates binding to RNA. This family consists of organelle (chloroplast and mitochondrial) ribosomal protein S4 as well as bacterial ribosomal protein S4.

\ \ structural constituent of ribosome ; GO:0003735 small ribosomal subunit ; GO:0015935 protein biosynthesis ; GO:0006412 24174 IPR005707

\ \ \

This family describes the ribosomal protein of the eukaryotic cytosol and of Archaea, homologous to S2 of bacteria. It is designated typically as Sa in eukaryotes and Sa or S2 in the archaea.

\ \ structural constituent of ribosome ; GO:0003735 small ribosomal subunit ; GO:0015935 protein biosynthesis ; GO:0006412 24175 IPR005708

Alkaptonuria (AKU), a rare hereditary disorder, was the first disease to be interpreted as an inborn error of metabolism. Thedeficiency causes homogentisic aciduria, ochronosis, and arthritis. AKU patients are deficient for homogentisate 1,2 dioxygenase (EC: 1.13.11.5), the enzyme that mediates the conversion of homogentisate to maleylacetoacetate; a step in the catabolism of both tyrosine and phenylalanine. \

 Homogentisate + O(2) = 4-maleylacetoacetate.

\ \ \ homogentisate 1,2-dioxygenase activity ; GO:0004411 \N tyrosine metabolism ; GO:0006570 24172 IPR005705

This family contains gamma proteobacterial proteins involved in ATP-dependent capsule polysaccharide export [MEDLINE:91310565], [MEDLINE:91186821].

\ sugar efflux transporter activity ; GO:0015542 inner membrane ; GO:0019866 extracellular carbohydrate transport ; GO:0006859 24173 IPR005706

\ \ \

This family describes the bacterial, mitochondrial and chloroplast forms of ribosomal protein S2.

\ \ structural constituent of ribosome ; GO:0003735 small ribosomal subunit ; GO:0015935 protein biosynthesis ; GO:0006412 24171 IPR005704

\ \ \

Ribosomal protein S3 is one of the proteins from the small ribosomal subunit.\ This family describes the bacterial type of ribosomal protein S3 and also and many chloroplast forms.. Chloroplast and mitochondrial forms have large, variable inserts between conserved N-terminal and C-terminal domains.

\ \ \ structural constituent of ribosome ; GO:0003735 small ribosomal subunit ; GO:0015935 protein biosynthesis ; GO:0006412 24169 IPR005702

This family describes the capsular exopolysaccharide proteins in bacteria. Theexopolysaccharide gene cluster consists of several genes which encode a number of\ proteins which regulate the exoploysaccharide biosynthesis (EPS). At least 13 genes EpsA to EpsM in streptococcus species seem to direct the EPS proteins and share high homology.

\ \ \ enzyme regulator activity ; GO:0030234 \N capsule polysaccharide biosynthesis ; GO:0045227 24170 IPR005703

\ \ \

Ribosomal protein S3 is one of the proteins from the small ribosomal subunit. This family describes ribosomal protein S3 of the eukaryotic cytosol and of the archaea.

\ \ structural constituent of ribosome ; GO:0003735 small ribosomal subunit ; GO:0015935 protein biosynthesis ; GO:0006412 24166 IPR005699

This family comprises lipoproteins from four gamma proteobacterial species: PulS protein of Klebsiella pneumoniae (P20440) and Pectobacterium chrysanthemi, and the functionally uncharacterized E. coli protein EtpO. PulS and OutS have been shown to interact with and facilitate insertion of secretins into the outer membrane, suggesting a chaperone-like, or piloting function for members of this family.

\ protein transporter activity ; GO:0008565 \N intracellular protein transport ; GO:0006886 24167 IPR005700

The bacterial exopolysaccharide transport protein is part of a large genetic locus which is associated with exopolysaccharide (EPS) biosynthesis. Detailed molecular characterization and gene fusion analysis revealed at least seven gene products are involved in the overall regulation, which among other things, include exopolysaccharide biosynthesis, property of conferring virulence and exopolysaccharide export.

\ sugar efflux transporter activity ; GO:0015542 \N extracellular carbohydrate transport ; GO:0006859 24168 IPR005701

The MPA1 proteins function in capsule polysaccharide and exopolysaccharide polymerization and/or export. They possess a characteristic carboxy-terminal ATP-binding domain and one or more regions which can form coiled-coils and are located in the periplasmic domain between the two transmembrane regions of the protein [MEDLINE:20121732].

\ sugar efflux transporter activity ; GO:0015542 integral to membrane ; GO:0016021 extracellular carbohydrate transport ; GO:0006859 24163 IPR005696

Bacteriocins are antibacterial proteinaceous compounds produced by bacteria. In Gram-positive bacteria, they are divided into four classes. Within the class II, constituted by non-modified peptides produced mainly by lactic acid bacteria, bacteriocins of the subclass IIa, such as mesentericin Y105, are of particular interest.\ They are active against the foodborne pathogen Listeria monocytogenes and share a similar primary structure, with a conserved N-terminal motif (YGNGV). Subclass IIa bacteriocins induce membrane permeabilization of sensitive strains, but\ their target specificity and their molecular mode of action remain elusive. This family of proteins is involved in the secretion of such bacteriocins although the mechanism of this process is not well understood.

\ \ \ transporter activity ; GO:0005215 \N transport ; GO:0006810 24164 IPR005697

This family of enzymes (EC: 2.3.1.46) catalyses the first step in the biosynthesis of methionine.

 Succinyl-CoA + L-homoserine = CoA + O-succinyl-L-homoserine.

\ acyltransferase activity ; GO:0008415 cytoplasm ; GO:0005737 methionine biosynthesis from homoserine via O-succinyl-L-homoserine and cystathione ; GO:0019281 24165 IPR005698

Phosphocarrier HPr protein, a small cytoplasmic protein, is a component of the phosphoenolpyruvate-dependent sugar phosphotransferasesystem (PTS) major carbohydrate transport system in bacteria [MEDLINE:94066914], [MEDLINE:90328751]. The phosphoryl group from phosphoenolpyruvate (PEP) is transferred to HPr, the phosphoryl carrier protein, by enzyme I. Phospho-HPr then transfers it to the permease. In some bacteria HPr is a domain in a larger protein that includes a EIII(Fru)\ (IIA) domain and in some cases also a EI domain.

The phosphoenolpyruvate-dependent sugar phosphotransferase system (PTS)\ is a major carbohydrate transport system in bacteria. The PTS catalyses the phosphorylation of sugar substrates during their translocation across the cell membrane. The mechanism involves the transfer of a phosphoryl group from phosphoenolpyruvate (PEP) via enzyme I (EI) to enzyme II (EII) of the PTS system, which in turn transfers it to a phosphocarrier protein (HPr) [MEDLINE:95156481], [MEDLINE:95219382].

There is a conserved histidine in the N-terminus of HPr IPR001020, which serves as an acceptor for\ the phosphoryl group of EI. In the central part of HPr there is a conserved serine IPR001020/> which, in Gram-positive bacteria only, is phosphorylated by an\ ATP-dependent protein kinase; a process which probably play a regulatory role in sugar transport.

\ \ \ sugar porter activity ; GO:0005351 \N phosphoenolpyruvate-dependent sugar phosphotransferase system ; GO:0009401 24157 IPR005690

Two integral outer envelope GTPases, Toc34 and Toc86, are proposed to regulate the recognition and translocation of nuclear-encoded preproteins during the early stages of protein import into chloroplasts. The long precursor of the 86K protein is proposed to have three domains. The N-terminal A-domain is acidic, repetitive, weakly conserved, readily removed by proteolysis during chloroplast isolation, and not required for protein translocation [MEDLINE:20177862]. The other domains are designated G (GTPase) and M (membrane anchor); this family includes most of the G domain and all of M.

\ protein translocase activity ; GO:0015450 chloroplast outer membrane ; GO:0009707 intracellular protein transport ; GO:0006886 24158 IPR005691

Two families of proteins are involved in the chloroplast envelope import apparatus. They are the three proteins of the outer membrane (TOC) and four proteins in the inner membrane (TIC). This family is specific for the TIC20 protein.

\ protein translocase activity ; GO:0015450 chloroplast inner membrane ; GO:0009706 intracellular protein transport ; GO:0006886 24159 IPR005692

\ protein translocase activity ; GO:0015450 chloroplast inner membrane ; GO:0009706 intracellular protein transport ; GO:0006886 24160 IPR005693

The ability to gain entry and resist the antimicrobial intracellular environment of mammalian cells is an essential virulence property of Mycobacterium tuberculosis. The protein mce (mycobacterial cell entry), a virulence protein required for invasion of non-phagocytic cells. N-terminus deletion constructs of Mce1 identified a domain located between amino acid positions 106 and 163 that was needed for this cell uptake activity. Although the exact function of Mce1is still unknown, it appears to serve as an effector molecule expressed on the surface of M. tuberculosis that is capable of eliciting plasma membrane perturbations in non-phagocytic mammalian cells.

\ \N \N pathogenesis ; GO:0009405 24161 IPR005694

emrA and emrB confer resistance to carbonylcyanide m-chlorophenylhydrazone, nalidixic acid, and a number of other toxic compounds. EmrB encodes a highly hydrophobic 56.2-kDa peptide, with 14 potential -helices to span the inner membrane. EmrA encodes a putative 42.7-kDa peptide containing a single hydrophobic domain and a large C-terminal hydrophilic domain.

\ drug transporter activity ; GO:0015238 inner membrane ; GO:0019866 multidrug transport ; GO:0006855 24162 IPR005695

Gram-negative bacteria have evolved transport complexes that export macromolecules and toxic substances such as heavy metals across the two membranes of the cell envelope in a single energy coupled step. The process requires (1) a cytoplasmic membrane export system, (2) a membrane fusion protein (MFP), and (3) an outer membrane factor. Phylogenetic analyses reveal that the MFPs cluster in accordance with the type of cytoplasmic membrane transport systems with which they function - proteins in this family are associated with reisistance to heavy metal poisoning.

\ heavy metal ion transporter activity ; GO:0015076 \N heavy metal ion transport ; GO:0006823 24149 IPR005682

The mitochondrial protein translocase (MPT) family, which brings nuclearly encoded preproteins into mitochondria, is very complex with 19 currently identified protein constituents. These proteins include several chaperone proteins, four proteins of the outer membrane translocase (Tom) import receptor, five proteins of the Tom channel complex, five proteins of the inner membrane translocase (Tim) and three "motor" proteins.The inner membrane translocase is formed of a complex with a number of proteins, including the Tim17, Tim23 and Tim44 subunits. Tim17 and Tim23 are thought to form the translocation channel of the inner membrane.

\ protein translocase activity ; GO:0015450 mitochondrial inner membrane translocase complex ; GO:0005744 intracellular protein transport ; GO:0006886 24150 IPR005683

\ protein translocase activity ; GO:0015450 mitochondrial outer membrane ; GO:0005741 intracellular protein transport ; GO:0006886 24151 IPR005684

This protein is one of the two subunits of integration host factor, a specific DNA-binding protein that functions in genetic recombination as well as in transcriptional and translational control.

\ DNA binding activity ; GO:0003677 chromosome ; GO:0005694 regulation of protein biosynthesis ; GO:0006417 24152 IPR005685

This protein is one of the two subunits of integration host factor, a specific DNA-binding protein that functions in genetic recombination as well as in transcriptional and translational control.

\ DNA binding activity ; GO:0003677 chromosome ; GO:0005694 regulation of protein biosynthesis ; GO:0006417 24153 IPR005686

\ protein translocase activity ; GO:0015450 mitochondrial outer membrane ; GO:0005741 intracellular protein transport ; GO:0006886 24154 IPR005687

\ protein translocase activity ; GO:0015450 mitochondrial outer membrane ; GO:0005741 intracellular protein transport ; GO:0006886 24155 IPR005688

Two integral outer envelope GTPases, Toc34 and Toc86, are proposed to regulate the recognition and translocation of nuclear-encoded preproteins during the early stages of protein import into chloroplasts.. The cytosolic region of Toc34 reveals 34% -helical and 26% -strand structure and is stabilized by intramolecular electrostatic interaction. Toc34 binds both chloroplast preproteins and isolated transit peptides in a guanosine triphosphate- (GTP-) dependent mechanism [MEDLINE:21685750].

\ protein translocase activity ; GO:0015450 chloroplast outer membrane ; GO:0009707 intracellular protein transport ; GO:0006886 24156 IPR005689

\ protein translocase activity ; GO:0015450 chloroplast outer membrane ; GO:0009707 intracellular protein transport ; GO:0006886 24148 IPR005681

\ protein translocase activity ; GO:0015450 mitochondrial inner membrane translocase complex ; GO:0005744 intracellular protein transport ; GO:0006886 24147 IPR005680

\ \ \

Ribosomal protein S12 is one of the proteins from the small ribosomal subunit. In Escherichia coli, S12 is known to be involved in the translation initiation step. It is a very basic protein of 120 to 150 amino-acid residues. S12 belongs to a family\ of ribosomal proteins which are grouped on the basis of sequence similarities. This family represents the eukaryotic and archaeal homologs of bacterial ribosomal protein S12. This protein is known typically as S23 in eukaryotes and as either S12 or S23 in the Archaea.

\ \ \ structural constituent of ribosome ; GO:0003735 small ribosomal subunit ; GO:0015935 protein biosynthesis ; GO:0006412 24141 IPR005674

This family includes the cocaine esterase CocE, several glutaryl-7-ACA acylases, and the putative diester hydrolase NonD of Streptomyces griseus (all hydrolases). This family shows extensive, low-level similarity to a family of xaa-pro dipeptidyl-peptidases, and to many other hydrolases.

\ hydrolase activity ; GO:0016787 \N metabolism ; GO:0008152 24142 IPR005675

This model represents largely uncharacterized proteins related to 2-isopropylmalate synthases and homocitrate synthases but phylogenetically distinct.

\ lyase activity ; GO:0016829 \N metabolism ; GO:0008152 24143 IPR005676

Aspartate-semialdehyde dehydrogenase (EC: 1.2.1.11) catalyzes the second step in the common metabolic pathway to synthesize threonine and methionine from aspartic acid. Two closely related families of aspartate-semialdehyde dehydrogenase are found. They differ by a deep split in phylogenetic and percent identity trees and in gap patterns. Members of this type are found primarily in organisms that lack peptidoglycan.

\ aspartate-semialdehyde dehydrogenase activity ; GO:0004073 \N threonine biosynthesis ; GO:0009088 24144 IPR005677

Fumarase C (EC: 4.2.1.2) catalyzes the stereospecific interconversion of fumarate to L-malate as part of the metabolic citric acid or Kreb's cycle. The recent three-dimensional structure of fumarase C from Escherichia coli has identified a binding site for anions which is generated by side chains from three of the four subunits within the tetramer. These same side chains are found in the three most highly conserved regions within the class II fumarate hydratase family. Putative fumarases from several species (Mycobacterium tuberculosis, Streptomyces coelicolor, Pseudomonas aeruginosa) branch deeply, although within the same branch of a phylogenetic tree rooted by aspartate ammonia-lyase sequences.

\ fumarate hydratase activity ; GO:0004333 TCA cycle enzyme complex ; GO:0045239 fumarate metabolism ; GO:0006106 24145 IPR005678

The mitochondrial protein translocase (MPT) family, which brings nuclearly encoded preproteins into mitochondria, is very complex with 19 currently identified protein constituents. These proteins include several chaperone proteins, four proteins of the outer membrane translocase (Tom) import receptor, five proteins of the Tom channel complex, five proteins of the inner membrane translocase (Tim) and three "motor" proteins. The inner membrane translocase is formed of a complex with a number of proteins, including the Tim17, Tim23 and Tim44 subunits. Tim17 and Tim23 are thought to form the translocation channel of the inner membrane.

\ protein translocase activity ; GO:0015450 mitochondrial inner membrane translocase complex ; GO:0005744 intracellular protein transport ; GO:0006886 24135 IPR005668

Alpha-isopropylmalate synthase (EC: 4.1.3.12) catalyses the first step in the biosynthesis of leucine, the condensation of acetyl-CoA and - ketoisovalerate to form 2-isopropylmalate synthase. This model describes a family of 2-isopropylmalate synthases as found in yeasts and in a minority of studied bacteria.

\ oxo-acid-lyase activity ; GO:0016833 \N leucine biosynthesis ; GO:0009098 24146 IPR005679

\ \ \

Ribosomal protein S12 is one of the proteins from the small ribosomal subunit. In Escherichia coli, S12 is known to be involved in the translation initiation step. It is a very basic protein of 120 to 150 amino-acid residues. S12 belongs to a family\ of ribosomal proteins which are grouped on the basis of sequence similarities. This family consists of ribosomal protein S12 of Bacteria, mitochondria, and chloroplasts.

\ \ \ structural constituent of ribosome ; GO:0003735 small ribosomal subunit ; GO:0015935 protein biosynthesis ; GO:0006412 24136 IPR005669

Thiosulphate-binding proteins (gene cysP) specifically binds thiosulphate and are involved in the transport systems for this nutrients [MEDLINE:90264335], [MEDLINE:91210162]. There are \ two conserved regions in the protein, one located in the N-terminal region and the other in the central part of these proteins. The second pattern includes two adjacent amino acids (Ser-Gly) that, in sbp, are known to be essential for sulfate binding [MEDLINE:88245181].

\ \ \ sulfate/thiosulfate porter activity ; GO:0015419 periplasmic space (sensu Gram-negative Bacteria) ; GO:0030288 sulfate transport ; GO:0008272 24137 IPR005670

This is a family of phosphate transport system permease proteins.

\ phosphate transporter activity ; GO:0015114 inner membrane ; GO:0019866 phosphate transport ; GO:0006817 24140 IPR005673

This family represents a sub-group of the phosphate-binding periplasmic proteins, one of the bacterial proteins required for binding-protein-mediatedphosphate transport. The accumulation of protein is enhanced under phosphate starvation.

\ \ \ phosphate transporter activity ; GO:0015114 \N phosphate transport ; GO:0006817 24138 IPR005671

Alpha-isopropylmalate synthase (EC: 4.1.3.12) catalyses the first step in the biosynthesis of leucine, the condensation ofacetyl-CoA and - ketoisovalerate to form 2-isopropylmalate synthase. This model describes a family of 2-isopropylmalate synthases found primarily in Bacteria. The homologous families in the Archaea may represent isozymes and/or related enzymes.

\ oxo-acid-lyase activity ; GO:0016833 \N leucine biosynthesis ; GO:0009098 24139 IPR005672

\ phosphate transporter activity ; GO:0015114 inner membrane ; GO:0019866 phosphate transport ; GO:0006817 24134 IPR005667

\ uptake permease activity ; GO:0015563 inner membrane ; GO:0019866 transport ; GO:0006810 24133 IPR005666

These proteins are involved in the transmembrane transport of sulphate and thiosulphate.

\ \ ABC-type uptake permease activity ; GO:0015406 inner membrane ; GO:0019866 transport ; GO:0006810 24131 IPR005664

This enzyme is part of the diaminopimelate pathway of lysine biosynthesis and is also known by the alternate name of tetrahydrodipicolinate N-succinyltransferase. The closely related TabB protein of Pseudomonas syringae (pv. tabaci),\ P31852 appears to act in the biosynthesis of tabtoxin rather than lysine.

\ \ \ transferase activity, transferring glycosyl groups ; GO:0016757 \N lysine biosynthesis via diaminopimelate ; GO:0009089 24132 IPR005665

Secretion across the inner membrane in some Gram-negative bacteria occurs via the preprotein translocase pathway. Proteins are produced in the cytoplasm as precursors, and require a chaperone subunit to direct them to the translocase component. [MEDLINE:90361702]. From there, the mature proteins are either targeted to the outer membrane, or remain as periplasmic proteins. The translocase protein subunits are encoded on the bacterial chromosome.

The translocase itself comprises 7 proteins, including a chaperone protein (SecB), an ATPase (SecA), an integral membrane complex (SecCY, SecE and SecG), and two additional membrane proteins that promote the release of the mature peptide into the periplasm (SecD and SecF) [MEDLINE:90361702]. The chaperone protein SecB [MEDLINE:21235707] is a highly acidic homotetrameric protein that exists as a "dimer of dimers" in the bacterial cytoplasm. SecB maintains preproteins in an unfolded state after translation, and targets these to the peripheral membrane\ protein ATPase SecA for secretion [MEDLINE:99346703]. Together with SecY and SecG, SecE forms a multimeric channel through which preproteins are translocated, using both proton motive forces and ATP-driven secretion. The latter is mediated by SecA. The structure of the\ Escherichia coli SecYEG assembly revealed a sandwich of two membranes interacting through the extensive cytoplasmic\ domains [MEDLINE:22157987] ]. Each membrane is composed of dimers of SecYEG. The monomeric complex contains 15\ transmembrane helices. \

This family consists of various prokaryotic SecF protein export membrane proteins. The SecD and SecF equivalents of the Gram-positive bacterium Bacillus subtilis are jointly present in one polypeptide, denoted SecDF, that is required to maintain a high capacity for protein secretion. Unlike the SecD subunit of the pre-protein translocase of Escherichia coli, SecDF of B. subtilis was not required for the release of a mature secretory protein from\ the membrane, indicating that SecDF is involved in earlier translocation steps [MEDLINE:98362000]. Comparison with SecD and SecF proteins from other organisms revealed the presence of 10 conserved regions in SecDF, some of which appear to be important for SecDF function. Interestingly, the SecDF protein of B. subtilis has 12 putative transmembrane domains. Thus, SecDF does not only show sequence similarity but also structural similarity to secondary solute transporters [MEDLINE:98362000].

\ \ \ protein translocase activity ; GO:0015450 inner membrane ; GO:0019866 intracellular protein transport ; GO:0006886 24130 IPR005663

This family of proteins consists of bacterial multicomponent K+:H+ and Na+:H+ antiporters. The best characterized systems are the PhaABCDEFG system of Rhizobium meliloti which functions in pH adaptation and as a K+ efflux system and the MnhABCDEFG system of Staphylococcus aureus which functions as a Na+:H+ antiporter.

\ monovalent inorganic cation transporter activity ; GO:0015077 \N monovalent inorganic cation homeostasis ; GO:0030004 24124 IPR005657

Triabin is a serine-protease inhibitor. It forms a non-covalent complex with thrombin at a molecular ratio of 1:1, and inhibits thrombin-induced platelet aggregation.

\ \N \N \N 24125 IPR005658

Ecotin is a broad range serine protease inhibitor, which forms homodimers. The C-terminal region contains the dimerisation motif [MEDLINE:95276656].

\ \N \N \N 24126 IPR005659

This chemotaxis protein stimulates methylation of MCP proteins.

\ \N \N \N 24127 IPR005660

This presumed domain is found in one or two copies per protein. The domain is about 230 amino acids in length and has many conserved motifs that are probably functionally important.

\ \N \N \N 24128 IPR005661

Members of this family are integral membrane proteins. The decarboxylation reactions they catalyse are coupled to the vectorial transport of Na⁺ across the cytoplasmic membrane, thereby creating a sodium ion motive force that is used for ATP synthesis [MEDLINE:98088990].

\ \N \N \N 24129 IPR005662

Era is an essential G-protein in Escherichia coli identified originally as a homologue protein to Ras (E. coli Ras-like protein). It binds to GTP/GDP and contains a low intrinsic GTPase activity. Its function remains elusive, although it may be associated with cell division, energy metabolism, and cell-cycle check point. The protein has recently been shown to specifically bind to 16S rRNA and the 30S ribosomal subunit [MEDLINE:99458620]. Involvement of Era in protein synthesis is suggested by the fact that Era depletionresults in the translation defect both in vitro and in vivo. A Type 2 KH domain is found near the C-terminus.

\ \ \ \N \N cell growth and/or maintenance ; GO:0008151 24116 IPR005649 The chorion genes of Drosophila are amplified in response to developmental signals in the follicle cells of the ovary [MEDLINE:91337030].\ \N \N \N 24117 IPR005650 The penicillinase repressor negatively regulates expression of the penicillinase gene. The N-terminal region of this protein is involved in operator recognition, while the C-terminal is responsible for dimerisation of the protein [MEDLINE:94042914].\ \N \N \N 24118 IPR005651

This family of short proteins have no known function. The bacterial members are about 60-70 amino acids in length and the eukaryotic examples are about 120 amino acids in length. The C-terminus contains the strongest conservation.

\ \N \N \N 24119 IPR005652

The family corresponds to the cytoplasmic part of the photosynthetic reaction centre H-chain.

\ \N \N \N 24120 IPR005653

This family of proteins are mostly uncharacterised. However the family does include Escherichia coli OstA P31554.

\ \N \N \N 24121 IPR005654

This family of proteins contains a P-loop motif and are predicted to be ATPases.

\ \N \N \N 24122 IPR005655

UL37 interacts with UL36, which is thought to be an important early step in tegumentation during virion morphogenesis in the cytoplasm [MEDLINE:21851120].

\ \N \N viral assembly ; GO:0019068 24123 IPR005656

This family includes 2-methylcitrate dehydratase EC: 4.2.1.79 (PrpD) that is required for propionate catabolism. It catalyses the third step of the 2-methylcitric acid cycle.

\ \N \N \N 24110 IPR005643

The c-Jun NH(2)-terminal kinase (JNK) is a member of an evolutionarily conserved sub-family of mitogen-activated protein (MAP) kinases [MEDLINE:21295470], [MEDLINE:21650405].

\ \N \N \N 24111 IPR005644

This is a group of NolW-like proteins, which are closely related to bacterial type II and III secretion system protein (IPR004846).

\ \N \N \N 24112 IPR005645

The function of the proteins from this family is unknown.

\ \N \N \N 24113 IPR005646 This family of bacterial proteins has no known function. The proteins are in the region of 500-600 amino acid residues in length.\ \N \N \N 24114 IPR005647 This family of proteins includes MND1 from S. cerevisiae. The mnd1 protein forms a complex with hop2 to promote homologous chromosome pairing and meiotic double-strand break repair [MEDLINE:21938533].\ \N \N \N 24115 IPR005648 FlgD is known to be absolutely required for hook assembly, yet it has not been detected in the mature flagellum [MEDLINE:94209227]. It appears to act as a hook-capping protein to enable assembly of hook protein subunits [MEDLINE:94209227].\ \N \N \N 24106 IPR005639

This family contains insecticidal toxins produced by Bacillus species of bacteria. During spore formation the bacteria produce crystals of this protein. When an insect ingests these proteins they are activated by proteolytic cleavage. The N-terminus is cleaved in all of the proteins and a C-terminal extension is cleaved in some members. Once activated the endotoxin binds to the gut epithelium and causes cell lysis leading to death. This activated region of the delta endotoxin is composed of three structural domains. The N-terminal helical domain is involved in membrane insertion and pore formation. The second and third domains are involved in receptor binding.

\ \N \N \N 24107 IPR005640

Animal lectins display a wide variety of architectures.They are classified according to the carbohydrate-recognition\ domain (CRD) of which there are two main types, S-type and C-type.

C-type lectins display a wide range of specificities.\ They require Ca²⁺ for their activity\ They are found predominantly but not exclusively in vertebrates.

This entry presents N-terminal domain, which is found in C-type lectins.

\ \ \N \N \N 24108 IPR005641

Hexon (IPR000736) is the major coat protein from adenovirus type 2. Hexon forms a homo-trimer. The 240 copies of the hexon trimer are organised so that 12 lie on each of the 20 facets. The central 9 hexons in a facet are cemented together by 12 copies of polypeptide IX.

\ \N \N \N 24109 IPR005642

Members of this family contain a conserved core of four predicted transmembrane segments. Some members have an additional pair of N-terminal transmembrane helices. The functions of the proteins in this family are unknown.

\ \N \N \N 24098 IPR005631

This is a family of uncharacterised small proteins.

\ \N \N \N 24099 IPR005632 This family includes outer membrane proteins such as OmpH among others.\ \N \N \N 24100 IPR005633

The N-terminal domain appears to be specific to the eukaryotic ribosomal proteins L25, L23, and L23a.

\ \N \N \N 24101 IPR005634

This is a family of Drosophila proteins, that are typified by the repetitive motif C-G-P.

\ \N \N \N 24105 IPR005638

\ \N \N \N 24104 IPR005637 The vertebrate Tap protein is a member of the NXF family of shuttling transport receptors for nuclear export of mRNA. Tap has a modular structure, and its most C-terminal domain is important for binding to FG repeat-containing nuclear pore proteins (FG-nucleoporins) and is sufficient to mediate nuclear shuttling [MEDLINE:21912422]. The structure of the C-terminal domain is composed of four helices [MEDLINE:21912422]. The structure is related to the UBA domain.\ \N \N \N 24103 IPR005636

This presumed domain is found in bacterial and eukaryotic proteins. Its function is unknown. The domain contains multiple conserved motifs including a DTXW motif that this domain has been named after.

\ \N \N \N 24102 IPR005635

This region of the inner centromere protein has been found to be necessary and sufficient for binding to aurora-related kinase. This interaction has been implicated in the coordination of chromosome segregation with cell division in yeast.

\ \N \N \N 24088 IPR005622 This family of uncharacterised proteins may be zinc metallopeptidases.\ \N \N \N 24089 IPR005623 This is an uncharacterized protein involved in formation of periplasmic nitrate reductase.\ \N \N \N 24090 IPR005624 This family contains uncharacterised proteins, including GlcG P45504. The alignment contains many conserved motifs that are suggestive of cofactor binding and enzymatic activity.\ \N \N \N 24091 IPR005625

This is a family of uncharacterized iron-regulated membrane proteins.

\ \N \N \N 24092 IPR005626

This is a family of FLP proteins that catalyse recombination between large inverted repetitions of the plasmid.

\ \ \ \N \N \N 24093 IPR005626

This is a family of FLP proteins that catalyse recombination between large inverted repetitions of the plasmid.

\ \ \ \N \N \N 24094 IPR005627 Copper transport in Escherichia coli is mediated by the products of at least six genes, cutA, cutB, cutC, cutD, cutE, and cutF. A mutation in one or more of these genes results in an increased copper sensitivity. Members of this family are between 200 and 300 amino acids in length and are found in both eukaryotes and bacteria.\ \N \N \N 24097 IPR005630

Sequences containing this domain belong to the terpene synthase family. It has been suggested that this gene family be designated tps (for terpene synthase). Sequence comparisons reveal similarities between the monoterpene (C₁₀) synthases, sesquiterpene (C₁₅) synthases and the diterpene (C₂₀) synthases. It has been split into six subgroups on the basis of phylogeny, called Tpsa-Tpsf [MEDLINE:97413772].\ \

Tpsa includes vetispiridiene synthase Q39979
Tpsb includes (-)-limonene synthase, Q39979/>.
Tpsc includes copalyl diphosphate synthase (kaurene synthase A), O04408.
Tpsd includes taxadiene synthase, O04408/>, pinene synthase, O24475.
Tpse includes ent-kaurene synthase B O24475/>.
Tpsf includes linalool synthase Q9ZPN5.

\ \

In the fungus Phaeosphaeria sp.L487 the synthesis of ent-kaurene from geranylgeranyl dophosphate is promoted by a single bifunctional protein [MEDLINE:97413762].

\ \ \N \N \N 24095 IPR005628 Members of this family are involved in the general secretion pathway. The family includes proteins such as ExeK, PulK, OutX and XcpX.\ \N \N \N 24096 IPR005629

All these fungal proteins are involved in cell wall synthesis or sporulation survival. However, the precise function is poorly characterised.

\ \N \N \N 24081 IPR005614

NrfD is an integral transmembrane protein with loops in both the periplasm and the cytoplasm. NrfD is thought to participate in the transfer of electrons, from the quinone pool into the terminal components of the Nrf pathway [MEDLINE:94335626].

\ \N \N \N 24082 IPR005615

This homodimeric enzyme catalyses the second step in glutathione bisynthesis,

 ATP + Gamma-L-Glutamyl-L-Cysteine + Glycine = ADP +\
                                                     Phosphate + Glutathione.

\ \ \N \N \N 24083 IPR005616 Members of this family include NrfF, CcmH, CycL, Ccl2.\ \N \N \N 24084 IPR005617

The N-terminal domain of the Grouch/TLE co-repressor proteins are involved in oligomerisation.

\ \N \N \N 24085 IPR005618 This family includes outer membrane protein W (OmpW) proteins from a variety of bacterial species. This protein may form the receptor for S4 colicins in E. coli [MEDLINE:99287842].\ \N \N \N 24075 IPR005608

Adenovirus infection inhibits synthesis and processing of rRNA and redistributes nucleolar antigens. Adenovirus protein V associates with nucleoli in infected cells.

\ \ \N \N \N 24076 IPR005609

This family consists of homologues of Sec61beta - a component of the Sec61/SecYEG protein secretory system. The domain is found in eukaryotes and archaea and is possibly homologous to the bacterial SecG.

\ \N \N \N 24077 IPR005610

PsbW is directly assembled in dimeric PSII supercomplexes. The negatively charged N-terminal region is essential for this process [MEDLINE:21901086].

\ \N \N \N 24078 IPR005611

Amb V is an Ambrosia sp (ragweed) pollen allergen. Amb t V has been shown to contain a C-terminal helix as the major T cellepitope. Free sulfhydryl groups also play a major\ role in the T cell recognition of cross-reactivity T cell epitopes within these related allergens [MEDLINE:96062331].

\ \ \N \N \N 24079 IPR005612

The L-A dsRNA1 virus has a single segment of 4.6 kilobases which replicates inside yeast cells, where it is maintained at a copy numberof 1,000 or more without a substantial adverse effect on cell growth. The icosahedral L-A virus particles are composed of\ 120 copies of the major coat protein (Gag) and about 2 copies of a Gag-Pol fusion protein. The L-A (+) strand serves as the\ mRNA, encoding Gag and Gag-Pol, the latter formed by a 1 ribosomal frameshift event. These proteins also support the\ propagation of a satellite RNA, called M1 dsRNA, which encodes the secreted polypeptide "killer toxin" and immunity to this toxin.\ Propagation of M1 is particularly sensitive to the efficiency of expression of the L-A mRNA, suggesting that only excess Gag and Gag-Pol, above the needs of L-A itself, are available to support M1.

Mutations in genes resulting in an inability to propagate M1 dsRNA are called mak mutations. Mak21p is\ homologous to a human and mouse CAATT-binding protein and is essential for growth and necessary for\ 60S ribosomal subunit biogenesis.

\ \ \N \N \N 24080 IPR005613

Aip3p/Bud6p is a regulator of cell and cytoskeletal polarity in Saccharomyces cerevisiae that was previously identified as an actin-interacting protein. Actin-interacting protein 3 (Aip3p) localizes at the cell cortex where cytoskeleton assembly must be achieved\ to execute polarized cell growth, and deletion of AIP3 causes gross defects in cell and cytoskeletal polarity. Aip3p localization is mediated by the secretory pathway, mutations in early- or late-acting components of the secretory apparatus lead\ to Aip3p mislocalization [MEDLINE:20143585].

\ \ \N \N \N 24087 IPR005621 The binding of SeqA protein to hemimethylated GATC sequences is important in the negative modulation of chromosomal initiation at oriC, and in the formation of SeqA foci necessary for Escherichia coli chromosome segregation [MEDLINE:21433959]. SeqA tetramers are able to aggregate or multimerize in a reversible, concentration-dependent manner [MEDLINE:21433959]. Apart from its function in the control of DNA replication, SeqA may also be a specific transcription factor [MEDLINE:21337010].\ \N \N \N 24086 IPR005619 The function of this presumed lipoprotein is unknown. The family includes Escherichia coli YajG P36671.\ \N \N \N 24064 IPR005597

The monomer of the Satellite tobacco necrosis virus coat protein contains a "jelly-roll" motif. The narrow end of the jelly roll forms fivefold contacts about a Ca2+ ion. Electron density maps suggest that double-helical RNA segments are associated with each coat protein dimer [MEDLINE:96130197].

\ \N viral capsid ; GO:0019028 \N 24065 IPR005598

Membrane-bound ATP synthases (F1F0) catalyze the synthesis of ATP via a rotary catalytic mechanism utilizing the energy of an electrochemical ion gradient. The transmembrane potential is supposed to propel rotation of a subunit c ring of F0 together with\ subunits gamma and epsilon of F1, thereby forming the rotor part of the enzyme, whereas the remainder of the F1F0 complex\ functions as a stator for compensation of the torque generated during rotation.

A possible function for this protein is to guide the assembly of the membrane sector of the ATPase enzyme complex.

\ \ \N \N \N 24066 IPR005599 The SMP protein has been implemented in plasmid stability [MEDLINE:91172125].\ \N \N \N 24067 IPR005600

The DNA binding domain (residues 1 to 147) of the yeast transcriptional activator GAL4 exists in solution in dimeric form, with the region responsible for dimerisation somewhere between residues 74 and 147. Experimental studies confirmed that the\ 'hydrophobic region' of the protein (residues 54-97, which contains a larger proportion of -helix), is essential for dimerisation [MEDLINE:96331038].

\ \ \N \N \N 24068 IPR005601

Irreversible binding of T-even bacteriophages to Escherichia coli is mediated by the short tail fibres, which serve as inextensible stays during DNA injection. Short tail fibres are exceptionally stable elongated trimers of gene product 12 (gp12), a 56 kDa protein. The\ N-terminal region of gp12 is important for phage attachment, the central region forms a long shaft, while a C-terminal globular region is\ implicated in binding to the bacterial lipopolysaccharide core. The distal half-fiber contains two molecules each of gp36\ and gp37 and one molecule of gp35.\

\ \ \N \N \N 24069 IPR005602

This is a family of proteins found in Staphylococcus aureus plasmid with no characterised function.

\ \N \N \N 24070 IPR005603

This non-structural protein does not appear to be essential for viral growth in tissue culture and its physiological role is unknown.

\ \N \N \N 24071 IPR005604

The bacteriophage T7 tail complex consists of a conical tail-tube surrounded by six kinked tail-fibers, which are oligomers of the viral protein gp17.

\ \N \N \N 24072 IPR005605

Saccharomyces cerevisiae Spo7 P18410.

\ \N \N \N 24073 IPR005606

Sec20 is a membrane glycoprotein associated with secretory pathway.

\ \N \N \N 24074 IPR005607 This domain contains a distinctive -FW- motif. It is found in a family of eukaryotic transcription factors as well as a set of proteins of unknown function.\ \N \N \N 24045 IPR005578 This family includes a number of eukaryotic proteins. It is an integral membrane protein, conserved in at least 1 copy in all sequenced eukaryotes. The gene name in Schizosaccharomyces pombe is hrf1+ for Heavy metal Resistance Factor 1 (unpublished).\ \N \N \N 24046 IPR005579

Members of this family are coiled-coil proteins that are involved in pre-rRNA processing [MEDLINE:21930290].

\ \N \N \N 24047 IPR005580

This RNA binding domain is found at the C-terminus of a number of DEAD helicase proteins [MEDLINE:99412424].

\ \N \N \N 24048 IPR005581

This family includes eukaryotic fructosamine-3-kinase enzymes [MEDLINE:20468660] which may initiate a process leading to the deglycation of fructoselysine and of glycated proteins and in the phosphorylation of 1-deoxy-1-morpholinofructose, fructoselysine, fructoseglycine, fructose and glycated lysozyme. The family also includes bacterial members that have not been characterised but probably have a similar or identical function.

\ \ \N \N \N 24049 IPR005582

The kicA and kicB genes are found upstream of mukB. It has been suggested that the kicB gene encodes a killing factor and the kicA gene codes for a protein that suppresses the killing function of the kicB gene product [MEDLINE:94232180]. It was also demonstrated that KicA and KicB can function as a post-segregational killing system, when the genes are transferred from the E. coli chromosome onto a plasmid [MEDLINE:94232180].

\ \N \N \N 24050 IPR005583

The members of this family are functionally uncharacterised. They are about 250 amino acids in length.

\ \N \N \N 24051 IPR005584 The function of this short domain is unknown it contains four conserved cysteines and may therefore be involved in zinc binding.\ \N \N \N 24052 IPR005585

The proteins in this family are around 140-170 residues in length. The proteins contain many conserved residues, with the most conserved motifs found in the central and C-terminal region. The function of these proteins is unknown.

\ \N \N \N 24053 IPR005586

The proteins in this family are uncharacterised. The proteins are 170-190 amino residues in length.

\ \N \N \N 24054 IPR005587

This presumed domain is about 160 residues long. It is found in archaebacteria and eubacteria. In Q9EUM2 it is associated with a helix-turn-helix domain. This suggests that this may be a ligand-binding domain.

\ \N \N \N 24055 IPR005588

The members of this family are regulators of the anti-sigma E protein RseD.

\ \N \N \N 24056 IPR005589

Proteins containing this domain are uncharacterised proteins from a number of bacterial species. The proteins range in size from 50-70 residues.

\ \N \N \N 24057 IPR005590

This small domain of about 70 residues is found in a number of bacterial proteins. It is found at the N-terminus the of O28332 protein. The proteins containing this domain are uncharacterised.

\ \N \N \N 24058 IPR005591

The napB gene encodes a dihaem cytochrome c, the small subunit of a heterodimeric periplasmic nitrate reductase [MEDLINE:21285728].

\ \N \N \N 24059 IPR005592

The N-terminal region of IPR002921, is found on a subset of Lipase 3 containing proteins.

\ \N \N \N 24060 IPR005593

This bacterial enzyme splits fructose-6-P and/or xylulose-5-P with the aid of inorganic phosphate into either acetyl-P and erythrose-4-P and/or acetyl-P and glyeraldehyde-3-P EC: 4.1.2.9, EC: 4.1.2.22\ \ \ [MEDLINE:21189320]. This family is distantly related to transketolases e.g. IPR005477.

\ \ \N \N \N 24061 IPR005594 This region represents the C-terminal 120 amino acids of a family of surface-exposed bacterial proteins. YadA, an adhesin from Yersinia, was the first member of this family to be characterized. UspA2 from Moraxella was second. The Eib immunoglobulin-binding proteins from E. coli were third, followed by the DsrA proteins of Haemophilus ducreyi and others. These proteins are homologous at their C-terminal and have predicted signal sequences, but they diverge elsewhere. The C-terminal 9 amino acids, consisting of alternating hydrophobic amino acids ending in F or W, comprise a targeting motif for the outer membrane of the Gram negative cell envelope. This region is important for oligomerisation [MEDLINE:21562582].\ \N \N \N 24062 IPR005595

The -subunit of the TRAP complex (TRAP ) is a single-spanning membrane protein of the endoplasmic reticulum (ER) which is found in proximity of nascent polypeptide chains translocating across the membrane [MEDLINE:94326944].

\ \N \N \N 24063 IPR005596 Beta-carotene hydroxylase is involved in zeaxanthin synthesis by hydroxylating

-carotene, exploiting iron activated oxygen to break the C-H bond with concomitant formation of double bond or oxygen insertion. The enzyme may also be involved in other pathways [MEDLINE:99358763].\ \ \N \N \N 24044 IPR005576

The eukaryotic RNA polymerase subunits RPB4 and RPB7 form a heterodimer that reversibly associates with the RNA polymerase II core. Archaeal cells contain a single RNAP made up of about 12 subunits, displaying considerable homology to the eukaryotic RNAPII subunits. The RPB4 and RPB7 homologs are called subunits F and E, respectively, and\ have been shown to form a stable heterodimer. While the RPB7 homolog is\ reasonably well conserved, the similarity between the eukaryotic RPB4 and the archaeal F subunit is barely detectable [MEDLINE:21617599].

\ \ \N \N \N 24038 IPR005570 Rpb8 is a subunit common to the three yeast RNA polymerases, pol I, II and III. Rpb8 interacts with the largest subunit Rpb1, and with Rpb3 and Rpb11, two smaller subunits.\ \N \N \N 24039 IPR005571 Rpb5 has a bipartite structure which includes a eukaryote-specific N-terminal domain and a C-terminal domain resembling the archaeal RNAP subunit H [MEDLINE:20300896], [MEDLINE:20300897]. The N-terminal domain is involved in DNA binding and is part of the jaw module in the RNA pol II structure [MEDLINE:20247428]. This module is important for positioning the downstream DNA.\ \N \N \N 24043 IPR005575

Statherin functions biologically to inhibit the nucleation and growth of calcium phosphate minerals. The N-terminus of statherin is highly charged, the glutamic acids of which have been shown to be important in the recognition hydroxyapatite [MEDLINE:92210564].

\ \N \N \N 24042 IPR005574

\ \ \N \N \N 24041 IPR005573

Sigma-E is important for the induction of proteins involved in heat shock response. RseA binds sigma-E via its N-terminal domain, sequestering sigma-E and preventing transcription from heat-shock promoters [MEDLINE:97303092]. The C-terminal domain is located in the periplasm, and may interact with other protein that signal periplasmic stress.

\ \N \N \N 24040 IPR005572

\ \N \N \N 24037 IPR005569 Arc repressor act by the cooperative binding of two Arc repressor dimers to a 21-base-pair operator site. Each Arc dimer uses an antiparallel

-sheet to recognize bases in the major groove [MEDLINE:94150708].\ \N \N \N 24029 IPR005561

ANTAR (AmiR and NasR transcription antitermination regulators) is an RNA-binding domain found in bacterial transcription antitermination regulatory proteins. The majority of the domain consists of a coiled-coil.

\ \N \N \N 24030 IPR005562

Members of this family are all transcribed from the spoVA operon. These proteins are poorly characterised, but are thought to be involved in dipicolinic acid transport into the developing forespore during sporulation [MEDLINE:21623564].

\ \N \N \N 24031 IPR005563

The single-stranded RNA genome of bacteriophage MS2 is 3,569 nt long and contains 4 genes. Their products are necessary for phagematuration, encapsidation, lysis of the host, and phage RNA replication, respectively. The maturation protein is required for the typical attachment of the phage to the side of the bacterial pili. It accompanies the viral DNA into the cell.

\ \ \ \N \N \N 24032 IPR005564

Major capsid protein E plays a role in the stabilization of the condensed form of the DNA molecule in phage heads [MEDLINE:89178657].

\ \N \N \N 24033 IPR005565

Haemolysin (HlyA) and related toxins are secreted across both the cytoplasmic and outer membranes of Gram-negative bacteria in a process which proceeds without a periplasmic intermediate. HlyA is directed by an uncleaved C-terminal targeting signal and the HlyD and HlyB translocator proteins [MEDLINE:93040381].

\ \N \N \N 24034 IPR005566

Expression of Hydrophobic Abundant protein is thought to be developmentally regulated and possibly involved in spherule cell wall formation [MEDLINE:89008099].

\ \N \N \N 24035 IPR005567

This region contains the important motif (LXXLL) necessary for the interaction of FTZ with the nuclear receptor FTZ-F1. FTZ is thought to represent a category of LXXLL motif-dependent co-activators for nuclear receptors.

\ \N \N \N 24036 IPR005568

\ \ \

L6 is a protein from the large (50S) subunit. In Escerichia coli, it is located in the aminoacyl-tRNA binding\ site of the peptidyltransferase centre, and is known to bind directly to 23S rRNA. It belongs\ to a family of ribosomal proteins, including L6 from bacteria, cyanelles (structures that\ perform similar functions to chloroplasts, but have structural and biochemical characteristics\ of Cyanobacteria) and mitochondria; and L9 from mammals, Drosophila , plants and yeast. L6\ comprises 2 almost identical folds, suggesting that is was derived by the duplication of an\ ancient RNA-binding protein gene. Analysis reveals several sites on the protein surface where\ interactions with other ribosome components may occur, the N-terminus being involved in \ protein-protein interactions and the C-terminus containing possible RNA-binding sites [MEDLINE:94085364].

\ \ \N \N \N 24021 IPR005553

Clag (cytoadherence linked asexual gene) is a malaria surface protein which has been shown to be involved in the binding of Plasmodium falciparum infected erythrocytes to host endothelial cells, a process termed cytoadherence. The cytoadherence phenomenon is associated with the sequestration of infected erythrocytes in the blood vessels of the brain, cerebral malaria. Clag is a multi-gene family in Plasmodium falciparum with at least 9 members identified to date. Orthologous proteins in the rodent malaria species Plasmodium chabaudi (Lawson D Unpubl. obs.) suggest that the gene family is found in other malaria species and may play a more generic role in cytoadherence.

\ \N \N \N 24022 IPR005554 Members of this family are nucleolar RNA-associated proteins (Nrap) which are highly conserved from yeast (Saccharomyces cerevisiae) to human. In the mouse, Nrap is ubiquitously expressed and is specifically localized in the nucleolus [MEDLINE:21893048]. Nrap is a large nucleolar protein (of more than 1000 amino acids). Nrap appears to be associated with ribosome biogenesis by interacting with pre-rRNA primary transcript [MEDLINE:21893048].\ \N \N \N 24023 IPR005555 The M-factor is a pheromone produced upon nitrogen starvation. The production of M-factor is increased by the pheromone signal. The protein undergoes post-translational modification to remove the C-terminal signal peptide, the carboxy-terminal cysteine residue is carboxy-methylated and S-alkylated with a farnesyl residue [MEDLINE:97033086].\ \N \N \N 24024 IPR005556

Members of this family include Nca3, Sun4 and Sim1. This is a family of proteins from Saccharomyces cerevisiae, involved in a diverse set of functions (DNA replication, aging, mitochondrial biogenesis and cell septation) [MEDLINE:20330540].

\ \N \N \N 24025 IPR005557

Colicin immunity proteins are plasmid encoded proteins necessary for protecting the cell against colicins. Colicins are toxins released by bacteria during times of stress [MEDLINE:21474782].

\ \N \N \N 24016 IPR005548

FtsQ is one of several cell division proteins. FtsQ interacts with other Fts proteins, reviewed in [MEDLINE:99084933]. The precise function of FtsQ is unknown.

\ \N \N \N 24017 IPR005549

Members of this family are components of the mitotic spindle. It has been shown that Nuf2 from yeast is part of a complex called the Ndc80p complex [MEDLINE:21167904]. This complex is thought to bind to the microtubules of the spindle. An arabidopsis protein has been included in this family that has previously not been identified as a member of this family, Q9C953. The match is not strong, but in common with other members of this family contains coiled-coil to the C-terminus of this region.

\ \N \N \N 24018 IPR005550

Members of this family are components of the mitotic spindle. It has been shown that Ndc80/HEC from yeast is part of a complex called the Ndc80p complex [MEDLINE:21167904]. This complex is thought to bind to the microtubules of the spindle.

\ \N \N \N 24019 IPR005551

Citrate lyase phosphoribosyl-dephospho-CoA transferase (EC: 4.2.-.-"/) catalyzes the formation of 2-(5''-triphosphoribosyl)-3'- dephosphocoenzyme-A, the precursor of the prosthetic group of the holo-acyl carrier protein (gamma chain) of citrate lyase, from ATP and dephospho-CoA.

 Dephospho-CoA + ATP = 2-(5''-\
                                                               triphosphoribosyl)-3'-Dephospho-CoA  + adenine

\ \ \N \N \N 24028 IPR005560 This entry is a small cysteine-rich repeat. The cysteines mostly follow a C-X(2)-C-X(3)-C-X(2)-C-X(3) pattern, though they often appear at other positions in the repeat as well.\ \N \N \N 24026 IPR005558

Crustacean neurohormone H proteins are referred to as precursor-related peptides as they are typically co-transcribed and translated with the CHH neurohormone (IPR001166.

\ \N \N \N 24027 IPR005559

CG-1 domains are highly conserved domains of about 130 amino-acid residues containing a predicted bipartite NLS and named after a partial cDNA clone isolated from parsley encoding a sequence-specific DNA-binding protein [MEDLINE:94355665]. CG-1 domains are associated with CAMTA proteins (for CAlModulin -binding Transcription Activator) that are transcription factors containing a calmodulin-binding domain and ankyrins (ANK) motifs (Bouche et al. 2002, J. Biol. Chem., in press).

\ \N \N \N 24020 IPR005552 Scramblase is palmitoylated and contains a potential protein kinase C phosphorylation site. Scramblase exhibits Ca²⁺-activated phospholipid scrambling activity in vitro. There are also possible SH3 and WW binding motifs. Scramblase is involved in the redistribution of phospholipids after cell activation or injury [MEDLINE:21379143].\ \N \N \N 24015 IPR005547

Members of this family are involved in determining life span [MEDLINE:99091901]. The molecular mechanisms by which LAG1 determines longevity are unclear, although some evidence suggest a participation in ceramide synthesis [MEDLINE:92375360].

\ \N \N \N 24011 IPR005543

The PASTA domain is found at the C-termini of several Penicillin-binding proteins (PBP) and bacterial serine/threonine kinases. It binds the -lactam stem, which implicates it in sensing D-alanyl-D-alanine - the PBP transpeptidase substrate. In PknB of Mycobacterium tuberculosis (P71584), all of the extracellular portion is predicted to be made up of four PASTA domains, which strongly suggests that it is a signal-binding sensordomain. The domain has also been found in proteins involved in cell wall biosynthesis, where it is implicated in localizing the\ biosynthesis complex to unlinked peptidoglycan.

PASTA is a small globular fold consisting of 3 -sheets and an -helix, with a loop region of variable length between the first and\ second -strands. The name PASTA is derived from PBP and Serine/Threonine kinase Associated domain [MEDLINE:22207943].

\ \ penicillin binding activity ; GO:0008658 \N \N 24014 IPR005546

Secretion of protein products occurs by a number of different pathways in bacteria. One of these pathways known as the type V pathway was first described for the IgA1 protease [MEDLINE:87115823]. The protein component that mediates secretion through the outer membrane is contained within the secreted protein itself, hence the proteins secreted in this way are called autotransporters. This family corresponds to the presumed integral membrane -barrel domain that transports the protein. This domain is found at the C-terminus of the proteins it occurs in. The N-terminus contains the variable passenger domain that is translocated across the membrane. Once the passenger domain is exported it is cleaved auto-catalytically in some proteins, in others a different protease is used and in some cases no cleavage occurs [MEDLINE:98451753].

\ \N \N \N 24012 IPR005544

This domain normally occurs as tandem repeats and is found in bacteria, yeast and plants. It contains two fully conserved histidines and one glutamate residue. Members of the family include DnrN, NorA and ScdA, which have been implicated in NO response and cell wall physiology.

\ \N \N \N 24013 IPR005545

The majority of proteins in this group contain a single copy of this domain, though it is also found as a repeat (Q9AJZ7). A strongly conserved histidine and a aspartate suggest that the domain has an enzymatic function.

\ \N \N \N 24005 IPR005537

The members of this family have no known function. They are around 300 amino acids in length and have two conserved motifs. At the N-terminus is a PXXIG motif and a more strongly conserved motif in the central region YXPGXXXKGXXR where X can be any amino acid.

\ molecular_function unknown ; GO:0005554 \N \N 24006 IPR005538

This family is uncharacterised. It contains the protein LrgA that has been hypothesised to export murein hydrolases [MEDLINE:96422016].

\ molecular_function unknown ; GO:0005554 integral to membrane ; GO:0016021 \N 24007 IPR005539

This domain is required for the nuclear localisation of these proteins [MEDLINE:21249801]. All of these proteins are members of the Tale/Knox homeodomain family, a subfamily, containing homeobox IPR001356.

\ DNA binding activity ; GO:0003677 nucleus ; GO:0005634 \N 24008 IPR005540

The MEINOX region is comprised of two domains, KNOX1 and KNOX2. KNOX1 plays a role in suppressing target gene expression. KNOX2, essential for function, is thought to be necessary for homo-dimerization [MEDLINE:21434421].

\ DNA binding activity ; GO:0003677 nucleus ; GO:0005634 \N 24009 IPR005541

\ DNA binding activity ; GO:0003677 nucleus ; GO:0005634 \N 24010 IPR005542

Pbx proteins are members of the TALE (three-amino-acid loop extension) family of atypical homeodomain proteins, whose membersare characterized by a three-residue insertion in the first helix of the homeodomain involved in their interaction with Hox proteins. Examination\ of Pbx1 has shown that, in addition to the homeodomain, a short 16-residue C-terminal tail is essential for maximal cooperative interactions with\ Hox partners as well as for maximal monomeric binding of Pbx1 to DNA.

The PBX domain is a bipartite acidic domain [MEDLINE:93251016].

\ \ transcription factor activity ; GO:0003700 nucleus ; GO:0005634 \N 23996 IPR005528

This is a small domain found in a family of secreted streptomyces proteins. It occurs singly or as a pair. Many of the domains have two cysteines that may form a disulphide bridge.

\ \N \N \N 23997 IPR005529 This family may be related to the FARP (FMRFamide) family, IPR002544. Currently this repeat was only detectable in Arabidopsis thaliana.\ \N \N \N 23998 IPR005530

A short repeat found in a small family of membrane-bound proteins. This repeat contains a conserved SPW motif in the first of two transmembrane helices.

\ \N \N \N 23999 IPR005531

This is a family of small proteins. It includes a protein identified as an alkaline shock protein [MEDLINE:95169160] so may be involved in stress response.

\ \N \N \N 24001 IPR005533

This domain may have a role in cell adhesion. It is called the AMOP domain after Adhesion associated domain in MUC4 and Other Proteins. This domain is extracellular and contains a number of cysteines that probably form disulphide bridges.

\ molecular_function unknown ; GO:0005554 \N \N 24002 IPR005534

CsgG is an outer membrane-located lipoprotein that is highly resistant to protease digestion. During curli assembly, an adhesive surface fibre, CsgG is required to maintain the stability of CsgA and CsgB [MEDLINE:98043534].

\ \N \N \N 24003 IPR005535

This family contains a set of cyclic peptides with a variety of activities. The structure consists of a distorted triple-stranded -sheet and a cysteine-knot arrangement of the disulfide bonds [MEDLINE:20069951].

\ defense/immunity protein activity ; GO:0003793 \N defense response ; GO:0006952 24004 IPR005536

This domain is found in almost all members of peptidase family C25. Peptidase family C25 is a protein family found in the bacteria Porphyromonas gingivalis (Bacteroides gingivalis) a gram-negative anaerobic bacterial species strongly associated with adult periodontitis. One of its distinguishing characteristics and putative virulence properties is the ability to agglutinate erythrocytes [MEDLINE:97047672]. It is a highly proteolytic organism which metabolizes small peptides and amino acids. Indirect evidence suggests that the proteases produced by this microorganism constitute an important virulence factor [MEDLINE:92347990]. Protease-encoding genes have been shown to contain multiple copies of repeated nucleotide sequences. These conserved sequences have also been found in hemagglutinin genes [MEDLINE:98298016].

\ peptidase activity ; GO:0008233 \N proteolysis and peptidolysis ; GO:0006508 24000 IPR005532

This presumed domain is found in bacterial proteins. In some cases these proteins also contain a protein kinase domain. The function of this domain is unknown.

\ molecular_function unknown ; GO:0005554 \N \N 23993 IPR005525

The members of this protein family are uncharacterised.

\ molecular_function unknown ; GO:0005554 \N \N 23994 IPR005526 In Escherichia coli P06138. The C-terminal half of MinC is the most conserved and interacts with MinD. The N-terminal half is thought to interact with FtsZ.\ \N \N regulation of cell cycle ; GO:0000074 23995 IPR005527

Cytokinesis needs to be regulated spatially in order to ensure that it occurs between the daughter genomes. In prokaryotes such as Escherichia coli, cytokinesis isinitiated by FtsZ, a tubulin-like protein that assembles into a ring structure at the cell center called the Z ring. A fundamental problem in prokaryotic cell biology is to\ understand how the midcell division site is identified. Two major negative regulatory systems are known to be involved in preventing Z-ring assembly at all sites\ except the midcell. One of these systems, called nucleoid occlusion, blocks Z-ring assembly in the area occupied by an unsegregated nucleoid until a critical stage in\ chromosome replication or segregation is reached. The other system consists of three proteins, MinC, MinD and MinE, which prevent assembly of Z rings in regions\ of the cell not covered by the nucleoid, such as the cell poles. MinC is an inhibitor of FtsZ polymerization, resulting in the inhibition of Z ring assembly in the cell; MinD greatly enhances the inhibitory effects of MinC in vivo; and MinE antagonizes the effects of MinC and MinD [MEDLINE:21272221].

MinE is a small bifunctional protein. The amino terminus of MinE is required to interact with MinD, while the carboxyl terminus is required for 'topological specificity' - that is, the ability of MinE to antagonize MinCD inhibition of Z rings at the midcell position but not at the poles.

\ \ \ \N \N \N 23990 IPR005522

ArgRIII has been demonstrated to be an inositol polyphosphate kinase [MEDLINE:20045030] which catalyses the reaction

ATP + 1D-myo-inositol 1,4,5-trisphosphate = ADP + 1D-myo-inositol 1,3,4,5-tetrakisphosphate

\ .

\ \ \ 1D-myo-inositol-trisphosphate 3-kinase activity ; GO:0008440\ \N \N \N 23991 IPR005523

This domain is currently found in streptomyces bacteria, in a set of bacterial proteins with no known function. Most proteins contain two copies of this domain.

\ \N \N \N 23992 IPR005524

This family of integral membrane proteins is predicted to be a group of permeases of unknown specificity.

\ \N \N \N 23984 IPR005516

Remorin binds both simple and complex galaturonides. The N-terminal region of remorin is proline rich, while the C-terminal region has been predicted to form a coiled-coil, that is expected to interact with other macromolecules, most likely DNA. Functional similarities between the behavior of the proteins and viral proteins involved in intercellular communication have been noted [MEDLINE:97143876].

\ \N \N \N 23985 IPR005517 This domain is found in elongation factor G, elongation factor 2 and some tetracycline resistance proteins and adopts a ribosomal protein S5 domain 2-like fold.\ GTP binding activity ; GO:0005525 \N \N 23986 IPR005518

\ \N \N \N 23987 IPR005519 This family of class B acid phosphatases also contains a number of vegetative storage proteins (VPS25). The acid phosphatase activity of VPS has been experimentally demonstrated [MEDLINE:92348466].\ \N \N \N 23989 IPR005521

This domain is found in attacin, sarcotoxin and diptericin. All members of these proteins are insect antibacterial proteins which are induced by the fat body and subsequently secreted into the hemolymph where they act synergistically to kill the invading microorganism [MEDLINE:95290121].

\ antibacterial peptide activity ; GO:0003797 \N antibacterial humoral response (sensu Invertebrata) ; GO:0006961 23988 IPR005520

This domain is found in attacin and sarcotoxin, but not diptericin (which shares similarity to the C-terminal region of attacin). All these proteins are insect antibacterial proteins which are induced by the fat body and subsequently secreted into the hemolymph where they act synergistically to kill the invading microorganism [MEDLINE:95290121].

\ antibacterial peptide activity ; GO:0003797 \N antibacterial humoral response (sensu Invertebrata) ; GO:0006961 23981 IPR005513

LEA proteins are late embryonic proteins abundant in higher plant seed embryos. They may play an essential role in seed survival and control of water exchanges during seed desiccation and imbibition. Family members are conserved along the entire coding region, especially within the hydrophobic internal 20 amino acid motif. This motif may be repeated.

\ \N \N embryonic development ; GO:0009790 23982 IPR005514

This is a family of uncharacterised proteins from Caenorhabditis elegans.

\ \N \N \N 23983 IPR005515

VOMI binds tightly to ovomucin fibrils of the egg yolk membrane. The structure [MEDLINE:94178242] consists of three -sheets forming Greek key motifs, which are related by an internal pseudo three-fold symmetry. Furthermore, the structure of VOMI has strong similarity to the structure of the delta-endotoxin, as well as a carbohydrate-binding site in the top region of the common fold [MEDLINE:96402607].

\ \N \N \N 23976 IPR005508 This domain is found in family of proteins from Arabidopsis thaliana with uncharacterised function.\ \N \N \N 23977 IPR005509 The AfsA family are key enzymes in A-factor biosynthesis, which is essential for streptomycin production and resistance.\ \N \N \N 23978 IPR005510 This family contains a number of proteins which are completely uncharacterised.\ molecular_function unknown ; GO:0005554 \N \N 23979 IPR005511 SMP-30, also known as regucalcin, seems to play a critical role in the highly differentiated functions of the liver and kidney and to exert a major impact on Ca²⁺ homeostasis [MEDLINE:99121179].\ \N \N \N 23980 IPR005512 This domain is found in a family of plant hypothetical proteins.\ \N \N \N 23973 IPR005505 This uncharacterised membrane protein is believed to play some role in the sporulation process, as mutants of the spmB gene in B. subtilis have reduced heat resistance.\ \N \N \N 23974 IPR005506 This set of repeats is found in a small family of secreted proteins of no known function, which may be involved in signal transduction.\ \N \N \N 23975 IPR005507 The proteins in this family are poorly characterised, but an investigation [MEDLINE:21479647] has indicated that the immediate early protein is required for the down-regulation of MHC class I expression in dendritic cells. Human herpesvirus 6 immediate early protein is also referred to as U90.\ \N \N \N 23968 IPR005500 This domain is found in eubacterial and archaebacterial proteins of unknown function. The proteins contain a motif HXXXEXX(W/Y) where X can be any amino acid. This motif is likely to be functionally important and may be involved in metal binding.\ molecular_function unknown ; GO:0005554 \N \N 23969 IPR005501 This family includes LamB. The lam locus of Aspergillus nidulans consists of two divergently transcribed genes, lamA and lamB, involved in the utilization of lactams such as 2-pyrrolidinone. Both genes are under the control of the positive regulatory gene amdR and are subject to carbon and nitrogen metabolite repression [MEDLINE:92107186]. The exact molecular function of the proteins in this family is unknown.\ \N \N \N 23970 IPR005502 This family includes enzymes that perform ADP-ribosylations, such as ADP-ribosylarginine hydrolase EC: 3.2.2.19 which cleaves ADP-ribose-L-arginine [MEDLINE:93352593]. The family also includes dinitrogenase reductase activating glycohydrolase [MEDLINE:89384461], and most surprisingly jellyfish crystallins [MEDLINE:89384461], although these proteins appear to have lost the presumed active site residues.\ \N \N \N 23971 IPR005503 This FliL protein controls the rotational direction of the flagella during chemotaxis [MEDLINE:86223759]. FliL is a cytoplasmic membrane protein associated with the basal body [MEDLINE:99368271].\ \N flagellar basal body (sensu Bacteria) ; GO:0009425 chemotaxis ; GO:0006935 23972 IPR005504 This family contains a number of archaeal proteins that are completely uncharacterised. The proteins are between 130 and 160 amino acids long. Their C-terminus contains several conserved residues.\ molecular_function unknown ; GO:0005554 \N \N 23965 IPR005497 PetN is a small hydrophobic protein, crucial for cytochrome b6-f complex assembly and/or stability.\ electron transporter, transferring electrons within cytochrome b6/f complex of photosystem II activity ; GO:0045158 cytochrome b6f complex ; GO:0009512 cytochrome biogenesis ; GO:0017004 23966 IPR005498 Although not essential for conjugation, the TrbI protein greatly increases conjugational efficiency [MEDLINE:96312368].\ \N \N unidirectional conjugation ; GO:0009291 23967 IPR005499 This family contains the enzyme 6-carboxyhexanoate--CoA ligase EC: 6.2.1.14. This enzyme is involved in the first step of biotin synthesis, where it converts pimelate into pimeloyl-CoA [MEDLINE:93075017]. The enzyme requires magnesium as a cofactor and forms a homodimer [MEDLINE:93075017].\ \N \N biotin biosynthesis ; GO:0009102 23964 IPR005496 This family contains a number of integral membrane proteins including the TerC protein. TerC has been implicated in resistance to tellurium, and may be involved in efflux of tellurium ions.The tellurite-resistant Escherichia coli strain KL53 was found during testing of a group of clinical isolates for antibiotic and heavy metal ion resistance [MEDLINE:99168161]. The determinant of the strain's tellurite resistance was located on a large conjugative plasmid, and analyses showed the genes terB, terC, terD and terE were essential for conservation of this resistance.\ Members of this family contain a number of conserved aspartates which may be involved in metal ion binding.\ \ \N integral to membrane ; GO:0016021 \N 23962 IPR005494 This region contains the Glutathionylspermidine synthase enzymatic activity EC: 6.3.1.8. This is the C-terminal region in bienzymes such as P43675.\ \N \N \N 23963 IPR005495 Members of this family are predicted integral membrane proteins of unknown function. They are about 350 amino acids long, contain about 6 transmembrane regions and may be permeases, although there is no verification of this.\ molecular_function unknown ; GO:0005554 integral to membrane ; GO:0016021 \N 23961 IPR005493 Demethylmenaquinone methyltransferases convert dimethylmenaquinone (DMK) to menaquinone (MK) in the final step of menaquinone biosynthesis. This region is also found at the C-terminus of the DlpA protein Q48806.\ \N \N \N 23955 IPR005487 The glucokinase regulatory protein (GCKR) [MEDLINE:95010134] is a vertebrate protein that inhibits glucokinase by forming an inactive complex with the enzyme. It is a protein of about 70 Kd which seems to be evolutionary related to a number of uncharacterized bacterial proteins which are about half the size of GCKR.\ enzyme regulator activity ; GO:0030234 \N \N 23956 IPR005488 The glucokinase regulatory protein (GCKR) [MEDLINE:95010134] is a vertebrate protein that inhibits glucokinase by forming an inactive complex with the enzyme. It is a protein of about 70 Kd which seems to be evolutionary related to a number of uncharacterized bacterial proteins which are about half the size of GCKR.\ \N \N \N 23957 IPR005489

This family of proteins is of unknown function.

\ \N \N \N 23958 IPR005490 This family of proteins are found in a range of bacteria. The conserved region contains a histidine and cysteine suggesting that these proteins have an enzymatic activity. Several members of this family contain peptidoglycan binding domains and therefore may use peptidoglycan or a precursor as their substrate.\ \N \N \N 23959 IPR005491 Emsy protein is amplified in breast cancer and interacts with BRCA2. The Emsy N terminal (ENT) domain is found in other vertebrate and plant proteins of unknown function, and has a completely conserved histidine residue that may be functionally important.\ \N \N \N 23960 IPR005492

Mutations in the LGI/Epitempin gene can result in a special form of epilepsy, autosomal dominant lateral temporal epilepsy. The Epitempin protein was seen to contain a 130 amino acid repeat in its C-terminal section, although a sub-domain of 50 amino acids has now been further defined within this. The domain is often repeated and each repeat forms a -sheet, suggesting the formation of a -sheet structure. This presumed domain has no known function, but might form an Ig like fold such as a propeller.

This domain has now been found in a number of proteins associated with neurological disorders suggesting that it may play a role in the development of epilepsy and other related conditions [MEDLINE:22207944].

\ \ \N \N \N 23952 IPR005484

This family includes L18 from bacteria and L5 from eukaryotes. The ribosomal 5S RNA isthe only known rRNA species to bind a ribosomal protein before its assembly into the\ ribosomal subunits \ [MEDLINE:93233645]. \ In eukaryotes, the 5S rRNA molecule binds one protein species, a 34-kDa protein which has been implicated in the intracellular\ transport of 5 S rRNA, while in bacteria it binds\ two or three different protein species \ [MEDLINE:94033319].

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 23953 IPR005485

This family consists of ribosomal protein L5 from eukaryotes. The ribosomal 5S RNA isthe only known rRNA species to bind a ribosomal protein before its assembly into the\ ribosomal subunits \ [MEDLINE:93233645]. \ In eukaryotes, the 5S rRNA molecule binds one protein species, a 34-kDa protein which has been implicated in the intracellular\ transport of 5 S rRNA.[MEDLINE:94033319].

\ \ \ 5S RNA binding activity ; GO:0008097\ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 23950 IPR005482

Acetyl-CoA carboxylase is found in all animals, plants, and bacteria and catalyzes the first committed step in fatty acid synthesis. It is a multicomponent enzyme containing a biotin carboxylase activity, a biotin carboxyl carrier protein, and a carboxyltransferase\ functionality. The\ "B-domain" extends from the main body of the subunit where it folds into two -helical regions and three strands of -sheet.\ Following the excursion into the B-domain, the polypeptide chain folds back into the body of the protein where it forms an\ eight-stranded antiparallel -sheet. In addition to this major secondary structural element, the C-terminal domain also contains a\ smaller three-stranded antiparallel -sheet and seven -helices [MEDLINE:94347758].

\ \ ligase activity ; GO:0016874 \N \N 23951 IPR005483

Two main CPSases have been identified in mammals, CPSase I is mitochondrial, is found in \ high levels in the liver and is involved in arginine biosynthesis; while CPSase II is cytosolic, is \ associated with aspartate carbamoyltransferase (ATCase) and dihydroorotase (DHOase) and is involved in \ pyrimidine biosynthesis. In the pyrimidine pathway in most eukaryotes, CPSase is found as a domain in a \ multi-functional protein, which also has GATase, ACTase and DHOase activity. Ammonia-dependent CPSase \ (CPSase I) is involved in the urea cycle in ureolytic vertebrates and is a monofunctional protein located \ in the mitochondrial matrix. The CPSase domain is typically 120 kD in size and has arisen from the \ duplication of an ancestral subdomain of about 500 amino acids. Each subdomain independently binds to ATP \ and it is suggested that the two homologous halves act separately, one to catalyze the phosphorylation of \ bicarbonate to carboxyphosphate and the other that of carbamate to carbamyl phosphate. The CPSase subdomain \ is also present in a single copy in the biotin-dependent enzymes acetyl-CoA carboxylase (EC: 6.4.1.2) (ACC), \ propionyl-CoA carboxylase (EC: 6.4.1.3) (PCCase), pyruvate carboxylase (EC: 6.4.1.1) (PC) and urea carboxylase\ (EC: 6.3.4.6).

\ \ carbamoyl-phosphate synthase activity ; GO:0004086 \N \N 23954 IPR005486 The glucokinase regulatory protein (GCKR) [MEDLINE:95010134] is a vertebrate protein that inhibits glucokinase by forming an inactive complex with the enzyme. It is a protein of about 70 Kd which seems to be evolutionary related to a number of uncharacterized bacterial proteins which are about half the size of GCKR.\ \N \N \N 23949 IPR005481

In bacteria such as E. coli, a \ single enzyme is involved in both biosynthetic pathways while other bacteria have separate enzymes. The \ bacterial enzymes are formed of two subunits. A small chain (carA) that provides glutamine amidotransferase \ activity (GATase) necessary for removal of the ammonia group from glutamine, and a large chain (carB)\ that provides CPSase activity. The large subunit consists of four structural units: the carboxyphosphate synthetic component, the\ oligomerization domain, the carbamoyl phosphate synthetic component and the allosteric domain [MEDLINE:99190825]. Such a\ structure is also present in fungi for arginine biosynthesis (CPA1 and CPA2). Such a structure is also present in fungi for arginine biosynthesis (CPA1 \ and CPA2).

\ \ ligase activity ; GO:0016874 \N metabolism ; GO:0008152 23948 IPR005480

In bacteria such as E. coli, a \ single enzyme is involved in both biosynthetic pathways while other bacteria have separate enzymes. The \ bacterial enzymes are formed of two subunits. A small chain (carA) that provides glutamine amidotransferase \ activity (GATase) necessary for removal of the ammonia group from glutamine, and a large chain (carB)\ that provides CPSase activity. The large subunit consists of\ four structural units: the carboxyphosphate synthetic component, the oligomerization domain, the carbamoyl phosphate synthetic\ component and the allosteric domain [MEDLINE:99190825]. Such a structure is also present in fungi for arginine biosynthesis (CPA1 \ and CPA2).

\ \ carbamoyl-phosphate synthase activity ; GO:0004086 cytoplasm ; GO:0005737 pyrimidine base biosynthesis ; GO:0019856 23947 IPR005479

Carbamoyl-phosphate synthase (CPSase) catalyzes the ATP-dependent synthesis of carbamyl-phosphate from glutamine (EC: 6.3.5.5) or ammonia (EC: 6.3.4.16) and bicarbonate [MEDLINE:90285162]. This important enzyme \ initiates both the urea cycle and the biosynthesis of arginine and pyrimidines. Glutamine-dependent CPSase \ (CPSase II) is involved in the biosynthesis of pyrimidines and purines. In bacteria such as E. coli, a \ single enzyme is involved in both biosynthetic pathways while other bacteria have separate enzymes. The \ bacterial enzymes are formed of two subunits. A small chain (carA) that provides glutamine amidotransferase \ activity (GATase) necessary for removal of the ammonia group from glutamine, and a large chain (carB)\ that provides CPSase activity. Such a structure is also present in fungi for arginine biosynthesis (CPA1 \ and CPA2).

\ \ ATP binding activity ; GO:0005524 \N \N 23946 IPR005478

Transketolase (EC 2.2.1.1) (TK) catalyzes the reversible transfer of a two-carbon ketol unit from xylulose 5-phosphate to an aldose receptor, such as ribose 5-phosphate, to form sedoheptulose 7-phosphate and glyceraldehyde 3- phosphate. This\ enzyme, together with transaldolase, provides a link between the glycolytic and pentose-phosphate pathways. TK requires\ thiamine pyrophosphate as a cofactor.

\ This group includes\ two proteins from the yeast Saccharomyces cerevisiae but excludes dihydroxyactetone synthases\ (formaldehyde transketolases) from various yeasts and the even more distant mammalian\ transketolases. Among the family of thiamine diphosphate-dependent enzymes that includes\ transketolases, dihydroxyacetone synthases, pyruvate dehydrogenase E1- subunits, and\ deoxyxylulose-5-phosphate synthases, mammalian and bacterial transketolases seem not to\ be orthologous.

\ \ transketolase activity ; GO:0004802 \N \N 23945 IPR005477

DXP synthase is a thiamine diphosphate-dependent enzyme related to transketolase and the pyruvate dehydrogenase E1- subunit. DXP synthase is found in bacteria (gene dxs)\ and plants (gene CLA1) which catalyzes the thiamine pyrophosphoate-dependent acyloin condensation reaction between\ carbon atoms 2 and 3 of pyruvate and glyceraldehyde 3-phosphate to yield 1-deoxy-D- xylulose-5-phosphate (dxp), a\ precursor in the biosynthetic pathway to isoprenoids, thiamine (vitamin B1), and pyridoxol (vitamin B6). DXP synthase is\ evolutionary related to TK. The N-terminal section, contains a histidine residue which appears to function in proton transfer\ during catalysis [MEDLINE:92331588]. In the central section there are conserved acidic residues that are part of the active cleft\ and may participate in substrate-binding [MEDLINE:92331588]. This family includes transketolase enzymes EC: 2.2.1.1. and also\ partially matches to 2-oxoisovalerate dehydrogenase subunit P37941 EC: 1.2.4.4. Both these enzymes utilise thiamine\ pyrophosphate as a cofactor, suggesting there may be common aspects in their mechanism of catalysis.

\ \ \ 1-deoxyxylulose-5-phosphate synthase activity ; GO:0008661\ \N \N terpenoid biosynthesis ; GO:0016114 23944 IPR005476

Transketolase (EC: 2.2.1.1) (TK) catalyzes the reversible transfer of atwo-carbon ketol unit from xylulose 5-phosphate to an aldose receptor, such as\ ribose 5-phosphate, to form sedoheptulose 7-phosphate and glyceraldehyde 3-\ phosphate. This enzyme, together with transaldolase, provides a link between\ the glycolytic and pentose-phosphate pathways.\ TK requires thiamine pyrophosphate as a cofactor. In most sources where TK has\ been purified, it is a homodimer of approximately 70 Kd subunits. TK sequences\ from a variety of eukaryotic and prokaryotic sources [MEDLINE:92231878], [MEDLINE:92144611] show that the\ enzyme has been evolutionarily conserved.\ In the peroxisomes of methylotrophic yeast Hansenula polymorpha, there is a\ highly related enzyme, dihydroxy-acetone synthase (DHAS) (EC: 2.2.1.3) (also\ known as formaldehyde transketolase), which exhibits a very unusual\ specificity by including formaldehyde amongst its substrates.

\ 1-deoxyxylulose-5-phosphate synthase (DXP synthase) [MEDLINE:98058734] is an enzyme so far\ found in bacteria (gene dxs) and plants (gene CLA1) which catalyzes the\ thiamine pyrophosphoate-dependent acyloin condensation reaction between carbon\ atoms 2 and 3 of pyruvate and glyceraldehyde 3-phosphate to yield 1-deoxy-D-\ xylulose-5-phosphate (dxp), a precursor in the biosynthetic pathway to\ isoprenoids, thiamine (vitamin B1), and pyridoxol (vitamin B6). DXP synthase\ is evolutionary related to TK.\ The N-terminal section, contains a histidine residue which appears to function in\ proton transfer during catalysis [MEDLINE:92331588]. In the central\ section there are conserved acidic residues that are part of the active cleft\ and may participate in substrate-binding [MEDLINE:92331588].\ This family includes transketolase enzymes EC: 2.2.1.1\ and also partially matches to 2-oxoisovalerate dehydrogenase subunit P37941\ \ \ \ EC: 1.2.4.4. Both these enzymes\ utilise thiamine pyrophosphate as a cofactor, suggesting\ there may be common aspects in their mechanism of catalysis.

\ \ \N \N \N 23943 IPR005475

\ 1-deoxyxylulose-5-phosphate synthase (DXP synthase) [MEDLINE:98058734] is an enzyme so far\ found in bacteria (gene dxs) and plants (gene CLA1) which catalyzes the\ thiamine pyrophosphoate-dependent acyloin condensation reaction between carbon\ atoms 2 and 3 of pyruvate and glyceraldehyde 3-phosphate to yield 1-deoxy-D-\ xylulose-5-phosphate (dxp), a precursor in the biosynthetic pathway to\ isoprenoids, thiamine (vitamin B1), and pyridoxol (vitamin B6). DXP synthase\ is evolutionary related to TK. \ The N-terminal section, contains a histidine residue which appears to function in\ proton transfer during catalysis [MEDLINE:92331588]. In the central\ section there are conserved acidic residues that are part of the active cleft\ and may participate in substrate-binding [MEDLINE:92331588].\ This family includes transketolase enzymes EC: 2.2.1.1\ and also partially matches to 2-oxoisovalerate dehydrogenase subunit P37941\ \ \ \ EC: 1.2.4.4. Both these enzymes\ utilise thiamine pyrophosphate as a cofactor, suggesting\ there may be common aspects in their mechanism of catalysis.

\ \ \N \N \N 23940 IPR005472

The pathway for glycerol catabolism in Streptomyces coelicolor is determined by the gylABX operon. The gylABX operon contains two major promoters, gylP1 and gylP2, separated by 50 bp. Both promoters are glycerol-inducible and glucose-repressible. A 900-base transcription unit, gylR, is situated immediately upstream of the gylABX\ promoter region and contains an open reading frame for a 27,600 Mr protein, a members of the iclR family [MEDLINE:92114799], [MEDLINE:94316500]. These proteins have\ a Helix-Turn-Helix motif at the N-terminus. The C-terminal region may bind to the regulatory\ substrate.

\ \ DNA binding activity ; GO:0003677 \N regulation of transcription, DNA-dependent ; GO:0006355 23941 IPR005473

This family of bacterial transcriptional regulators includes theacetate operon repressor\ both of which are members of the iclR family [MEDLINE:92114799], [MEDLINE:94316500]. These proteins have\ a Helix-Turn-Helix motif at the N-terminus. The C-terminal region may bind to the regulatory\ substrate (unpublished observation, Bateman A.).

\ \ DNA binding activity ; GO:0003677 \N regulation of transcription, DNA-dependent ; GO:0006355 23942 IPR005474

\ 1-deoxyxylulose-5-phosphate synthase (DXP synthase) [MEDLINE:98058734] is an enzyme so far\ found in bacteria (gene dxs) and plants (gene CLA1) which catalyzes the\ thiamine pyrophosphoate-dependent acyloin condensation reaction between carbon\ atoms 2 and 3 of pyruvate and glyceraldehyde 3-phosphate to yield 1-deoxy-D-\ xylulose-5-phosphate (dxp), a precursor in the biosynthetic pathway to\ isoprenoids, thiamine (vitamin B1), and pyridoxol (vitamin B6). DXP synthase\ is evolutionary related to TK. The N-terminal section, contains a histidine residue which appears to function in\ proton transfer during catalysis [MEDLINE:92331588]. In the central\ section there are conserved acidic residues that are part of the active cleft\ and may participate in substrate-binding [MEDLINE:92331588].\ This family includes transketolase enzymes EC: 2.2.1.1\ and also partially matches to 2-oxoisovalerate dehydrogenase subunit P37941\ \ \ \ EC: 1.2.4.4. Both these enzymes\ utilise thiamine pyrophosphate as a cofactor, suggesting\ there may be common aspects in their mechanism of catalysis.

\ \ \N \N \N 23938 IPR005469 Avidin [MEDLINE:90355908] is a minor constituent of egg white in several groups of oviparousvertebrates. Avidin, which was discovered in the 1920's, takes its name from\ the avidity with which it binds biotin. These two molecules bind so strongly\ that is extremely difficult to separate them. Streptavidin is a protein produced\ by Streptomyces avidinii which also binds biotin and whose sequence is\ evolutionary related to that of avidin.\

Avidin and streptavidin both form homotetrameric complexes of noncovalently\ associated chains. Each chain forms a very strong and specific non-covalent\ complex with one molecule of biotin.

\ \

The three-dimensional structures of both streptavidin [MEDLINE:89184594], [MEDLINE:93294833] and avidin [MEDLINE:89196806]\ have been determined and revealed them to share a common fold: an eight\ stranded anti-parallel -barrel with a repeated +1 topology enclosing an\ internal ligand binding site.

Fibropellins I and III [MEDLINE:93273088] are proteins that form the apical lamina of the sea\ urchin embryo, a component of the extracellular matrix. These two proteins\ have a modular structure composed of a CUB domain (seePDOC00908), followed\ by a variable number of EGF repeats and a C-terminal avidin-like domain.

\ \ \N \N \N 23939 IPR005471

The many bacterial transcription regulation proteins which bind DNA through a 'helix-turn-helix' motif can be classified into subfamilies on the basis of\ sequence similarities. One of these subfamilies, called 'iclR', groups several proteins including:\ \

gylR, a possible activator protein for the gylABX glycerol operon in\ Streptomyces.

iclR, the repressor of the acetate operon (also known as glyoxylate bypass\ operon) in Escherichia coli and Salmonella typhimurium.

\ \

These proteins have\ a Helix-Turn-Helix motif at the N-terminus that is similar to that of other DNA-binding proteins [MEDLINE:92114799].

\ \ DNA binding activity ; GO:0003677 \N regulation of transcription, DNA-dependent ; GO:0006355 23937 IPR005468 Avidin [MEDLINE:90355908] is a minor constituent of egg white in several groups of oviparousvertebrates. Avidin, which was discovered in the 1920's, takes its name from\ the avidity with which it binds biotin. These two molecules bind so strongly\ that is extremely difficult to separate them. Streptavidin is a protein produced\ by Streptomyces avidinii which also binds biotin and whose sequence is\ evolutionary related to that of avidin.\

Avidin and streptavidin both form homotetrameric complexes of noncovalently\ associated chains. Each chain forms a very strong and specific non-covalent\ complex with one molecule of biotin.

\ \

\ \ \N \N \N 23936 IPR005467

Phosphotransfer-mediated signaling pathways allow cells to sense and respond to environmental stimuli. Autophosphorylating histidine protein kinases (HPKs) provide phosphoryl groups\ for response regulator proteins which, in turn, function as molecular switches that control\ diverse effector activities. Structural studies of proteins involved in two-component signaling\ systems have revealed a modular architecture with versatile conserved domains that are readily\ adapted to the specific needs of individual systems [MEDLINE:21300007], [MEDLINE:21262405].

\ \

All HPKs have a conserved ATP-binding catalytic domain that is required for kinase activity PUB00010651. Activity depends on homodimer formation, with the dimerisation domains, which have two-stranded coiled-coils, coming together to form a four-helix bundle. In most family members, the dimerisation domain includes a motif, known as the H-box, which contains the site of autophosphorylation. The catalytic domain consists of several -helices packed over one face of a large anti-parallel sheet forming a loop which closes over the bound ATP. Hydrolysis of ATP is coupled to Mg ²⁺ release and conformational changes in the ATP-binding cavity.

The typical HPK is a transmembrane sensor with an uncleaved signal sequence, which serves as the first transmembrane helix, an extracellular sensing domain and a second transmembrane helix. Inside the cytoplasm, a HAMP domain (IPR003660) is located between the second transmembrane domain and the dimerization domain.

\ \ kinase activity ; GO:0016301 \N signal transduction ; GO:0007165 23935 IPR005466

In addition to its well established role in the enzymatic biosynthesis of\ carbohydrates, UDP-glucose also acts as an extracellular signalling molecule\ through binding to cell-surface receptors [MEDLINE:20219108]. An orphan G protein-coupled receptor, previously known as KIAA0001 or GPR105, has been identified as a\ receptor for UDP-glucose. The receptor is expressed widely, with highest\ levels in the placenta, adipose tissue, stomach and intestine, and moderate\ levels in various regions of the brain, spleen, lung and heart. Signal\ transduction from the receptor is through pertussis toxin-sensitive G\ proteins, probably of the Gi class [MEDLINE:20219108].\ \

\ \ \ rhodopsin-like receptor activity ; GO:0001584 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 23934 IPR005465

Thyrotropin-releasing hormone (thyroliberin) (TRH) stimulates synthesis and\ release of thyroid-stimulating hormone in the anterior pituitary PUB00011121. It\ also stimulates synthesis and release of prolactin. In the CNS, TRH\ stimulates a number of behavioural and pharmacological actions, including\ increased turnover of catecholamines in the nucleus accumbens.

\ \

A second receptor for thyrotropin-releasing hormone has been identified PUB00011121.\ TRHR2 is expressed in the brain and spinal cord, with highest levels in the\ pontine nucleus, thalamus and cerebellar cortex. Moderate expression was\ also found in the anterior olfactory nucleus, neocortex, superior and\ inferior colliculi, central grey and in several other brainstem nuclei. In\ contrast to TRHR1, no expression was found in the pituitary. In the spinal\ cord, TRHR2 expression was detected only in the dorsal horn [MEDLINE:99042002]. The\ distribution of TRHR2 suggests a role for the receptor in somatosensory,\ antinociceptive and motor functions. Binding of TRH to the receptor leads to\ activation of phospholipase C through coupling to Gq proteins [MEDLINE:99042002].

\ \ thyrotropin-releasing hormone receptor activity ; GO:0004997 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 23933 IPR005464

Psychosine is a glycosphingolipid implicated in the pathology of globoid\ cell leukodystrophy (GLD), a hereditary metabolic disorder that results from\ the absence of the enzyme galactosyl ceramide. This deficiency results in\ the accumulation of psychosine in the brain, leading to apoptosis of\ oligodendrocytes, progressive demyelination and the existence of large,\ multinuclear cells (globoid cells) derived from microglia [MEDLINE:21206025].

\ The molecular mechanism by which these toxic effects might be mediated has\ recently been elucidated by the identification of TDAG8, an orphan G\ protein-coupled receptor, as a receptor for psychosine [MEDLINE:21206025]. TDAG8 is\ expressed at high levels in the spleen, peripheral blood leukocytes, lymph\ nodes and lung. Activation of the receptor in RH7777 hepatoma cells by\ psychosine and related lysoglycolipids results in a pertussis toxin-\ insensitive inhibition of forskolin-induced cAMP accummulation, possibly \ through coupling to Gz proteins [MEDLINE:21206025].\

\ \ rhodopsin-like receptor activity ; GO:0001584 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 23931 IPR005462

Transient receptor potential (Trp) and related proteins are thought to be Ca2+ ion channel subunits that mediate capacitative Ca2+ entry in response \ to a range of external and internal cell stimuli. Such Ca2+ entry is thought \ to be an essential component of cellular responses to many hormones and\ growth factors, and acts to replenish intracellular Ca2+ stores that have\ been emptied through the action of inositol triphosphate (IP3) and other \ agents. In non-excitable cells, i.e. those that lack voltage-gated Ca2+\ channels, such as hepatocytes, this mode of Ca2+ entry is thought to be an\ important step in generating the oscillations of intracellular Ca2+\ concentration that characterise their response to stimulatory agents [MEDLINE:96234226].\ \ Studies on the visual transduction system in Drosophila led to the molecular\ cloning of Trp and the cDNA of a related protein, Trp-like, which show\ similarity to voltage gated Ca2+ channels in the regions known as S3 through\ S6, including the S5-S6 linker that forms the ion-selective channel pore [MEDLINE:98037793].\ This provided evidence that Trp and/or related proteins might form mammalian\ capacitative Ca2+ entry channels.

\ \

A number of Trp and Trp-like channel gene isoforms have now been cloned, \ including several mammalian homologues. The Trp family is thought to encode\ at least 20 Ca2+-permeable channel proteins. Hydropathy analysis suggests \ that they share a common transmembrane (TM) topology. Each family member is \ predicted to possess 6 TM domains with intracellular N- and C-termini, which\ is similar to the core structure of the pore-forming subunits of the voltage-gated Na+ and Ca2+ channels. By analogy with these proteins, which have \ 4 linked domains of 6 TM segments, it is likely that Trp channels are\ homo- or heterotetramers of 4 single subunits [MEDLINE:21283259].\ The Trp family can be divided on the basis of sequence similarity into 3\ subfamilies: short (S), long (L) and osm-like (O) Trp channels. The \ STrp subfamily includes Drosophila Trp and Trpl-like, and the mammalian \ homologues TrpC1-7. Channels of the STrpC subfamily are activated following\ receptor-mediated stimulation of different isoforms of phospholipase C [MEDLINE:20184001].

TrpC6 was originally cloned from mouse tissue [MEDLINE:98037793]; human, rat and guinea pig\ isoforms have also been identified. Expression studies have demonstrated\ that TrpC6 displays low selectivity for Ca2+ over Na+, and, like TrpC3 and \ TrpC7, is activated by diacylglycerol in a protein kinase C-independent\ manner [MEDLINE:99127891]. TrpC6 has recently been shown to be an essential component of the alpha1-adrenoceptor-activated cation channel [MEDLINE:21113398].\

\ \ calcium channel activity ; GO:0005262 integral to membrane ; GO:0016021 calcium ion transport ; GO:0006816 23932 IPR005463

\ \

TrpC7 was originally cloned from mouse tissue [MEDLINE:99419008]; a human isoform has also\ been identified. Expression studies have shown that TrpC7 displays low \ selectivity for Ca2+ over Na+, and, like TrpC3 and TrpC6, is activated by \ diacylglycerol in a protein kinase C-independent manner [MEDLINE:99419008].\

\ \ calcium channel activity ; GO:0005262 integral to membrane ; GO:0016021 calcium ion transport ; GO:0006816 23930 IPR005461

\ \

TrpC5 was originally cloned from rabbit and mouse tissues [MEDLINE:98353453]; a human\ isoform has also been identified. Expression studies have demonstrated that\ TrpC5 is able to form homomeric cation channels that are activated following\ stimulation of Gq-coupled receptors and by receptor tyrosine kinases [MEDLINE:20298822]. In mammalian brain, TrpC5 has been reported to form heteromers with TrpC1,\ which appear to be activated by Gq-linked receptors, but not by store \ depletion [MEDLINE:21197839]. This has led to the proposal that different TrpC heteromers\ may form diverse receptor-regulated channels.\

\ \ calcium channel activity ; GO:0005262 integral to membrane ; GO:0016021 calcium ion transport ; GO:0006816 23929 IPR005460

\ \

TrpC4 was originally cloned from bovine tissue [MEDLINE:98353453]; rat, mouse and human\ isoforms have also been identified. Expression studies have demonstrated \ that TrpC4 is able to form homomeric cation channels that are activated \ following stimulation of Gq-coupled receptors and by receptor tyrosine \ kinases [MEDLINE:20298822].\

\ \ calcium channel activity ; GO:0005262 integral to membrane ; GO:0016021 calcium ion transport ; GO:0006816 23928 IPR005459

\ \

TrpC3 was originally cloned from human tissue [MEDLINE:96234226]; mouse and rat isoforms\ have also been identified. Expression studies have shown that TrpC3 displays\ low selectivity for Ca2+ over Na+, and, like TrpC6 and TrpC7, is activated\ by diacylglycerol in a protein kinase C-independent manner [MEDLINE:99127891]. \

\ \ calcium channel activity ; GO:0005262 integral to membrane ; GO:0016021 calcium ion transport ; GO:0006816 23927 IPR005458

\ \

TrpC2 was originally cloned from mouse tissue [MEDLINE:99162557]. Rat and bovine isoforms\ have also been identified, but the human form appears to be a pseudogene.\ Expression studies have demonstrated that TrpC2 may be activated by receptor-\ mediated stimulation of PLC, and also by intracellular Ca2+ store depletion. TrpC2 has been implicated in sperm-egg interactions, having recently\ been shown to be essential for the activation of sustained Ca2+ influx into\ sperm during fertilisation [MEDLINE:21231376].\

\ \ calcium channel activity ; GO:0005262 integral to membrane ; GO:0016021 calcium ion transport ; GO:0006816 23926 IPR005457

\ \

TrpChannel 1 was the first mammalian STrpC subfamily member to be cloned [MEDLINE:96003837]. It has been shown to function as a store-operated Ca2+-permeable cation channel\ in a number of expression systems [MEDLINE:96258271]. In mammalian brain, TrpC1 has been reported to form heteromers with TrpC3 and TrpC5 [MEDLINE:21197839]. The TrpC1/TrpC5 \ heteromers appear to be activated by Gq-linked receptors, but, by contrast\ with expression study findings, not by store depletion. This has led to the \ proposal that different TrpC heteromers may form diverse receptor-regulated\ channels in the mammalian brain [MEDLINE:21197839].\

\ \ calcium channel activity ; GO:0005262 integral to membrane ; GO:0016021 calcium ion transport ; GO:0006816 23924 IPR005455

Profilin is a small eukaryotic protein that binds to monomeric actin (G-actin) in a 1:1 ratio thus preventing the polymerization of actin into filaments (F-actin). It can also \ in certain circumstance promote actin polymerization. Profilin also binds to polyphosphoinositides\ such as PIP2. Overall sequence similarity among profilin from organisms which belong to \ different phyla (ranging from fungi to mammals) is low, but the N-terminal region is relatively\ well conserved. That region is thought to be involved in the binding to actin. \ This group of proteins are profilins found in plants.\

\ \ actin binding activity ; GO:0003779 \N actin cytoskeleton organization and biogenesis ; GO:0030036 23925 IPR005456

Melanin-concentrating hormone (MCH) is a cyclic peptide originally identified in teleost fish [MEDLINE:99347735],[MEDLINE:99347736]. In fish, MCH is released from the\ pituitary and causes lightening of skin pigment cells through pigment\ aggregation [MEDLINE:21120504]. In mammals, MCH is predominantly expressed in the\ hypothalamus, and functions as a neurotransmitter in the control of a range\ of functions. A major role of MCH is thought to be in the regulation of\ feeding: injection of MCH into rat brains stimulates feeding; expression of\ MCH is upregulated in the hypothalamus of obese and fasting mice; and mice\ lacking MCH are lean and eat less [MEDLINE:99347735]. MCH and melanocyte-stimulating\ hormone (-MSH) have antagonistic effects on a number of physiological\ functions. Alpha-MSH darkens pigmentation in fish and reduces feeding in\ mammals, whereas MCH increases feeding [MEDLINE:21120504] ].

\ MCH is derived from a pre-pro-hormone (pre-pro-MCH), which contains 1-2\ hormones other than MCH, depending on the species. In all species, the 17-19\ C-terminal amino acids are cleaved to release MCH. In mammals, amino acids\ 132-144 encode the hormone neuropeptide EI (NEI), whilst in salmonids, the\ analagous region encodes neuropeptide EV (NEV), and in other fish, the region\ determines MCH gene-related peptide (Mgrp) [MEDLINE:96141203]. A further peptide, known as\ neuropeptide GE (NGE), is thought to be found in mammalian pre-pro-MCH\ upstream of NEI, encoded by amino acids 110-129. NEI has been shown to\ enhance oxytocin and reduce arginine vasopressin secretion from rat\ pituitary [MEDLINE:97318956]. Two paralogues of MCH, known as pro-MCH-like 1 and 2 genes\ (PMCHL1 and PMCHL2), which arose recently in primate evolution, also\ exist. At present, it is unclear whether the PMCHL genes are functional \ genes or inactive pseudogenes.\

\ \ melanin-concentrating hormone activity ; GO:0030354 \N synaptic transmission ; GO:0007268 23923 IPR005454

\ \ actin binding activity ; GO:0003779 \N actin cytoskeleton organization and biogenesis ; GO:0030036 23922 IPR005453

Grass pollen allergy is a major human health problem throughout the world, perennial ryegrass (Lolium perenne) being one of the more important species \ causing such allergy. Several proteins from this grass pollen have been \ characterised and used to study specific serum antibody responses in\ individuals allergic to pollen proteins. Such individuals often show \ concordant presence of serum antibodies to all three Lol p allergens. Most\ (~95%) possess serum IgE and/or IgG antibodies to Lol p I, and ~45% have\ antibodies to Lol p II and III. Both Lol p II and III are highly cross-\ reactive with human, goat and rabbit antibodies. However, antibodies to \ Lol p I are unique and do not cross-react with Lol p II and III [MEDLINE:92218832].

The amino acid sequences of Lol p II and Lol p III are highly similar,\ sharing 59% identity. Both have a region of amphipathicity (residues \ 61-67, Lol p III numbering) that might contain sites for binding to Ia\ molecules or T cell receptors. This region is identical between Lol p II \ and III, except for an Arg-Lys substitution, and could account for the DR3 \ association with responsiveness to both molecules [MEDLINE:89233902] ,[MEDLINE:88305749]. However, although\ Lol p II and III show significant structural similarities and antibody \ cross reactivity, it is intriguing that only Lol p III is able to induce\ significant T cell responses [MEDLINE:92218832]. Also interesting is that immune response\ to Lol p III is associated with DR5 (in addition to DR3), whereas no DR5\ association is found in Lol p II. One possibility is that Lol p III has an\ additional site that binds to the DR5 Ia molecule. Indeed, Lol p III \ has a second highly amphipathic peptide (residues 24-30, RPGDTLA), which is \ different and not amphipathic in Lol II [MEDLINE:89212951]. Moreover, comparison of the\ sequences of DRB gene products has shown that the first hypervariable \ region (residues 9-13) of DR3 and DR5, and no other region, contains the\ sequence EYSTSTS. It is thought that this sequence in the DR 1 \ polypeptide chain is associated with the immune responsiveness to the\ allergen Lol p III. In addition, both allergens share similar structure\ with an antibody-binding fragment for Lol p I. However, Lol p II appears to\ contain unique Ia recognition sites not shared with Lol p II and III. This\ could explain why Ab responses to the three allergens are associated with\ DR3 and why most Lol p II and III responders are also Lol p I responders,\ but Lol p I responders are not necessarily Lol p II and III responders.

\ The structure of allergen Phl p 2 from Timothy grass (P43214) has been determined to\ 1.9A by X-ray crystallography [MEDLINE:97276803], and more recently by NMR [MEDLINE:99404940] ]. The protein\ contains mainly structures typical of the immunoglobulin-like fold.

\ \ \N extracellular ; GO:0005576 \N 23921 IPR005452

\ \

Generally, the channel proteins are composed of 4 tightly-coupled subunits\ (-1, -2, and gamma), the -1 subunit from each creating\ the pore for the import of extracellular calcium ions. The -1 subunit\ shares sequence characteristics with all voltage-dependent cation channels,\ and exploits the same 6-helix bundle structural motif - in both sodium and\ calcium channels, this motif is repeated 4 times within the sequence to give\ a 24-helix bundle. Within each of these repeats, 5 of the transmembrane (TM)\ segments (S1, S2, S3, S5, S6) are hydrophobic and one is positively charged\ (S4) - the latter is characterised by charged amino acids at very third\ position, and probably represents the voltage-sensor.

\ Several genes encoding -1 subunits have been identified, each forming\ a distinct electrophysiological channel. L-type calcium channels are\ formed from -1S, -1C and -1D subunits. Alpha-1D subunits allow cells to slowly inactivate voltage-gated Ca2+ influx to weak depolarisations PUB00010557. This\ property allows them to participate in important physiological functions,\ such as tonic neurotransmitter release in cochlear inner hair cells [MEDLINE:20105567]. \ In addition, these properties make them ideally suited to contribute to\ subthreshold Ca2+ signalling, for example in hippocampal pyramidal cells [MEDLINE:97083942].\

\ \ voltage-gated calcium channel activity ; GO:0005245 integral to membrane ; GO:0016021 calcium ion transport ; GO:0006816 23920 IPR005451

\ \

\ Several genes encoding -1 subunits have been identified, each forming\ a distinct electrophysiological channel. L-type calcium channels are\ formed from -1S, -1C and -1D subunits. The variability in the C-terminal region of the -1C subunit generated by alternative splicing influences the kinetics,\ calcium- and voltage-dependence of L-type channels PUB00010557. The N-terminus\ is also a site of significant structural diversity [MEDLINE:97218532].\

\ \ voltage-gated calcium channel activity ; GO:0005245 integral to membrane ; GO:0016021 calcium ion transport ; GO:0006816 23919 IPR005450

\ \

\ The -1S subunit is present in skeletal muscle and has also been detected in kidney\ and brain PUB00010557. In the skeletal muscle, it is present in two size variants,\ a full-length, minor (~5%) form of ~212kDa, and a major (~95%) species of\ ~190kDa, derived from the longer protein by post-translational cleavage.\

\ \ voltage-gated calcium channel activity ; GO:0005245 integral to membrane ; GO:0016021 calcium ion transport ; GO:0006816 23918 IPR005449

\ \

\ Several genes encoding -1 subunits have been identified, each forming\ a distinct electrophysiological channel. R-type calcium channels are\ composed of -1E subunits and are found in a variety of neuronal\ populations, such as cerebellar granule neurons and dendrites of hippocampal\ pyrimidal neurons PUB00010557. They are believed to play an important role in the\ body's natural communication network, where they contribute to the \ regulation of brain function by synaptic integration [MEDLINE:20521867]. Their hypolarised\ inactivation range and rapid kinetics of inactivation make R-type channels\ more suited to providing a transient surge of Ca2+ influx [MEDLINE:21555332].\

\ \ voltage-gated calcium channel activity ; GO:0005245 integral to membrane ; GO:0016021 calcium ion transport ; GO:0006816 23917 IPR005448

\ \

\ Several genes encoding -1 subunits have been identified, each forming\ a distinct electrophysiological channel. P- and Q-type channels are \ formed from -1A subunits and function in transmitter release PUB00010557.\ P-type channels are prevalent in cerebellar Purkinje cells, but are also \ expressed in many central and peripheral neurons, such as the spinal cord \ and visual cortex. By contrast, Q-type channels are found in cerebellar \ granule neurones and the hippocampus. Different mutations in the -1A\ subunit produce 3 human diseases:

(1) episodic ataxia type-2; (2) familial\ hemiplegic migraine; and (3) spinocerebellar ataxia type-6.

All 3 diseases\ result in cerebellar atrophy, but they differ in the extent and rate of \ progression of neuronal degeneration\

\ \ voltage-gated calcium channel activity ; GO:0005245 integral to membrane ; GO:0016021 calcium ion transport ; GO:0006816 23916 IPR005447

\ \

\ Several genes encoding -1 subunits have been identified, each forming\ a distinct electrophysiological channel. L-type calcium channels are\ formed from -1S, -1C and -1D subunits.\

\ \ voltage-gated calcium channel activity ; GO:0005245 integral to membrane ; GO:0016021 calcium ion transport ; GO:0006816 23915 IPR005446

\ \

\ Several genes encoding -1 subunits have been identified, each forming\ a distinct electrophysiological channel. T-type calcium channels are \ composed of -1G and -1H subunits. They exhibit unique voltage-\ dependent kinetics, small single channel conductance, rapid inactivation,\ slow deactivation and a relatively high permeability to calcium PUB00010557. They\ are primarily responsible for rebound burst firing in central neurons and\ are implicated in normal brain functions, such as slow wave sleep, and in\ diseased states, such as epilepsy [MEDLINE:96254681]. They also play an important role in\ hormone secretion [MEDLINE:94049802] and smooth muscle excitability [MEDLINE:90095909].\

\ \ voltage-gated calcium channel activity ; GO:0005245 integral to membrane ; GO:0016021 calcium ion transport ; GO:0006816 23914 IPR005445

\ \

\ \ voltage-gated calcium channel activity ; GO:0005245 integral to membrane ; GO:0016021 calcium ion transport ; GO:0006816 23913 IPR005444

\ \

L-type calcium channnels are formed from different -1 subunit isoforms that determine the pharmacological properties of the channel, since they form the drug binding domain. Other properties, such as gating voltage- dependence, G protein modulation and kinase susceptibility, are influenced \ by -2, delta and subunits PUB00010557.

\ Co-expression of subunit mRNA with -1 subunit mRNA in xenopus\ oocytes produces increased calcium currents, which are accompanied by a\ shift in the voltage-dependence of activation to more negative membrane\ potentials. Conversely, microinjection of antisense oligonucleotides to subunit mRNA produces decreased calcium currents and shifts voltage-\ dependent activation to more positive membrane potentials. There are\ four distinct subunits: -1, -2, -3 and -4; and the\ magnitude of these effects varies with the particular subtype. \ \ There are 3 splice variants of the -1 subunit: -1a, -1b and 1c. Beta-1a is the most extensively studied of these and is known to be \ expressed in skeletal muscle and brain, but not in smooth muscle or heart.\ Beta-1a appears to be important for the functional expression of the -1\ subunit in skeletal muscle. It is a 524-residue peripheral membrane protein \ that associates with a conserved 9-residue motif between repeats I and II \ of the -1 subunit [MEDLINE:98226759]. Beta-1b was identified by cloning in rat brain, \ heart and hippocampus, and differs from -1a by having a deletion of ~50\ amino acids at residue 209, and having a 120-residue C-terminal elongation.\ Beta-1c was cloned from human heart and hippocampus and has the same\ deletion as -1b, but lacks the C-terminal extension.\

\ \ voltage-gated calcium channel activity ; GO:0005245 \N calcium ion transport ; GO:0006816 23912 IPR005443

\ \

\ \ voltage-gated calcium channel activity ; GO:0005245 \N calcium ion transport ; GO:0006816 23910 IPR005441

Growth hormone (GH) is a pituitary hormone involved in cell and overall body growth, carbohydrate-protein-lipid metabolism and osmotic homeostasis.\ Control of GH release was initially ascribed to 2 pathways: stimulation by\ hypothalamic GH-releasing hormone (GHRH) and inhibition by somatostatin.\ More recently, synthetic compounds, termed GH secretagogues (GHS), were \ shown to stimulate GH release strongly. This effect is elicited by an orphan\ G protein-coupled receptor (GPCR), subsequently named the GHS receptor\ (GHS-R). The endogenous ligand for this receptor was purified from rat and\ human stomach and named ghrelin [MEDLINE:21203998].

\ The purified cDNA for ghrelin encodes a 117 amino acid prepropeptide. The\ first 23 amino acid residues form a signal peptide that is cleaved to leave\ proghrelin. Residues 24-51 are cleaved to yield active ghrelin, discarding\ the C-terminal fragment [MEDLINE:20067959]. The 28-residue ghrelin peptide that is left is biologically inactive. Esterification with n-octanoic acid at Ser3 is \ required for biological activity. Ghrelin mRNA is expressed mainly in the\ stomach in a distinct endocrine cell type in the submucosal layer, known as\ X/A-like cells. The active peptide is secreted into the bloodstream rather\ than the stomach. Ghrelin responsive cells are found in abundance in a \ limited area of the hypothalamic arcuate nucleus (ARC), a region involved in\ control of food intake. As well as releasing GH indirectly via its action \ on the ARC region of the hypothalamus, ghrelin also appears to be able to\ stimulate GH release via direct action on the pituitary [MEDLINE:21376543].

\ A further variant of the ghrelin peptide exists in rat stomach, des-Gln14-\ ghrelin. This is produced by alternative splicing and does not require the\ esterification by n-octanoic acid for biological activity. However, its \ presence in only small quantities in the stomach suggests ghrelin is the\ major active form. The ghrelin active peptide and the GHS receptor share\ sequence similarity with motilin and the motilin receptor, respectively, \ suggesting an evolutionary relationship.\

\ \ growth hormone-releasing hormone activity ; GO:0016608 extracellular ; GO:0005576 \N 23911 IPR005442

Glutathione S-transferases (GSTs) are soluble proteins with typical molecular masses of around 50 kDa, each composed of two polypeptide subunits. GSTs catalyze the transfer of the tripeptide glutathione (gamma-glutamyl-cysteinyl-glycine; GSH) to a cosubstrate (R-X) containing a reactive electrophilic centre to form a polar S-glutathionylated reaction product (R-SG). Each soluble GST is a dimer of approximately 26 kDa subunits, typically forming a hydrophobic 50 kDa protein with an isoelectric point in the pH range 4-5. The ability to form heterodimers greatly increases the diversity of the GSTs, but the functional significance of this mixing and matching of subunits has yet to be determined. Each GST subunit of the protein dimer contains an independent catalytic site composed of two components. The first is a binding site specific for GSH or a closely related homolog (the G site) formed from a conserved group of amino-acid residues in the amino-terminal domain of the polypeptide. The second component is a site that binds the hydrophobic substrate (the H site), which is much more structurally variable and is formed from residues in the carboxy-terminal domain. Between the two domains is a short variable linker region of 5-10 residues.

The GST proteins have evolved by gene duplication to perform a range of functional roles. GSTs also have non-catalytic roles, binding flavonoid natural products in the cytosol prior to their deposition in the vacuole. Recent studies have also implicated GSTs as components of ultraviolet-inducible cell signalling pathways and as potential regulators of apoptosis [MEDLINE:21895521].

The mammalian GSTs active in drug metabolism are now classified into the , mu and pi classes. Additional classes of GSTs have been identified in animals that do not have major roles in drug metabolism; these include the sigma GSTs, which function as prostaglandin synthases. In cephalopods, however, sigma GSTs are lens S-crystallins, giving an indication of the functional diversity of these proteins. The soluble glutathione transferases can be divided into the phi, tau, theta, zeta and lambda classes. The theta and zeta GSTs have counterparts in animals, whereas the other classes are plant-specific. In the case of phi and tau GSTs, only subunits from the same class will dimerize. Within a class, however, the subunits can dimerize even if they are quite different in amino-acid sequence. An insect-specific delta class has also been described, and bacteria contain a prokaryote-specific class of GST. \

\ \

Recombinant human omega-class GST shows glutathione-dependent thiol transferase and dehydroascorbate reduction activity. This sort of activity has not been observed in any other\ class of GSTs, but is associated with the glutaredoxins (thioltransferases).\ Members of this class of GST have a novel unique N-terminal extension, and a\ cysteine residue in the active site, which is different from the tyrosine\ and serine residues found at the active sites of other eukaryotic GSTs [MEDLINE:20387379].\

\ \ glutathione transferase activity ; GO:0004364 cytoplasm ; GO:0005737 glutathione conjugation reaction ; GO:0006803 23908 IPR005439

Gamma-aminobutyric acid type A (GABAA) receptors are members of the neurotransmitter ligand-gated ion channels: they mediate neuronal inhibition on binding GABA. The effects of GABA on GABAA receptors are modulated by a range\ of therapeutically important drugs, including barbiturates, anaesthetics and\ benzodiazepines (BZs) [MEDLINE:96122225]. The BZs are a diverse range of compounds,\ including widely prescribed drugs, such as librium and valium, and their\ interaction with GABAA receptors provides the most potent pharmacological\ means of distinguishing different GABAA receptor subtypes.

Most GABAA receptors contain one type of and subunit, and a single gamma polypeptide in a ratio of 2:2:1. Whilst the critical residue involved in benzodiazepine (BZ) binding is believed to\ be located within the subunit [MEDLINE:21568956], the BZ binding site is considered\ to be located at the interface between adjacent and gamma subunits:\ replacement of gamma subunits with delta and epsilon renders the receptor\ insensitive to BZs due to disruption of the binding site [MEDLINE:98317658]. Three\ mammalian gamma subunits have been identified (gamma 1 to 3), each encoded\ by a separate gene, plus an avian gamma 4 subunit.

\ The presence of a gamma 2 subunit, together with 1, confers \ 'classical' BZ-binding activity to GABAA receptors; substitution for \ gamma 1 or 3 leads to an altered binding profile for BZs [MEDLINE:98317658]. The gamma 2 gene undergoes alternative exon splicing leading to the generation of two isoforms that differ by an additional 24-bp exon in the large putative\ cytoplasmic domain [MEDLINE:21179859]. The isoforms are termed gamma 2L (long) and gamma 2S (short), and are ubiquitously expressed. The gamma 2L splice variant has\ been implicated in potentiation of GABAA receptors by ethanol.\

\ \ GABA-A receptor activity ; GO:0004890 integral to membrane ; GO:0016021 gamma-aminobutyric acid signaling pathway ; GO:0007214 23909 IPR005440

\ The presence of a gamma 2 subunit, together with 1, confers \ 'classical' BZ-binding activity to GABAA receptors; substitution for \ gamma 1 or 3 leads to an altered binding profile for BZs [MEDLINE:98317658]. The gamma 3 subunit confers a slightly reduced binding affinity for BZs when compared \ to gamma 2-containing receptors [MEDLINE:96122225], although the difference is not as\ great as that observed for gamma 1-containing receptor subtypes.\

\ \ GABA-A receptor activity ; GO:0004890 integral to membrane ; GO:0016021 gamma-aminobutyric acid signaling pathway ; GO:0007214 23907 IPR005438

\ The presence of a gamma 2 subunit, together with 1, confers \ 'classical' BZ-binding activity to GABAA receptors; substitution for \ gamma 1 or 3 leads to an altered binding profile for BZs [MEDLINE:98317658]. The presence of a gamma 2 subunit, together with 1, confers 'classical' BZ-binding activity to GABAA receptors; substitution for\ gamma 1 or 3 leads to an altered binding profile for BZs [MEDLINE:98317658]. GABAA\ receptors containing the gamma 1 subunit generally show a decreased\ affinity for BZs, although some BZ site inverse agonists behave as \ agonists at gamma 1-containing receptors [MEDLINE:96122225].\

\ \ GABA-A receptor activity ; GO:0004890 integral to membrane ; GO:0016021 gamma-aminobutyric acid signaling pathway ; GO:0007214 23906 IPR005437

\ \

\ \ \ GABA-A receptor activity ; GO:0004890 integral to membrane ; GO:0016021 gamma-aminobutyric acid signaling pathway ; GO:0007214 23905 IPR005436

Most GABAA receptors contain one\ type of and subunit, and a single gamma polypeptide in a ratio of\ 2:2:1 [MEDLINE:21568956]. The BZ binding site is located at the interface of adjacent and gamma subunits; therefore, the type of subunit present is\ instrumental in determining BZ selectivity and sensitivity. Receptors can be\ categorised into 3 groups based on their subunit content and, hence,\ sensitivity to BZs: 1-containing receptors have greatest sensitivity \ towards BZs (type I); 2, 3 and 5-containing receptors have similar but\ distinguishable properties (type II); and 4- and 6-containing\ assemblies have very low BZ affinity [MEDLINE:21568956]. A conserved histidine residue in the subunit of type I and II receptors is believed to be responsible for BZ affinity [MEDLINE:21568956].

\ Alpha 4- and 6-containing receptors are often referred to as 'diazepam-\ insensitive' receptors, since inclusion of such subunits in place of type I\ and II polypeptides virtually eliminates sensitivity to BZs. The 6\ subunit is found exclusively in the cerebellar granule cells. It also\ undergoes alternative splicing, generating a non-functional isoform that\ lacks 10 residues from the N-terminal domain [Ashcroft, F.M.\ GABA(A) Receptors. In Ion Channels and Disease. Academic Press 2000, PP.325-336.].\

\ \ GABA-A receptor activity ; GO:0004890 integral to membrane ; GO:0016021 gamma-aminobutyric acid signaling pathway ; GO:0007214 23904 IPR005435

Most GABAA receptors contain one\ type of and subunit, and a single gamma polypeptide in a ratio of\ 2:2:1 [MEDLINE:21568956]. The BZ binding site is located at the interface of adjacent and gamma subunits; therefore, the type of subunit present is\ instrumental in determining BZ selectivity and sensitivity. Receptors can be\ categorised into 3 groups based on their subunit content and, hence,\ sensitivity to BZs: 1-containing receptors have greatest sensitivity \ towards BZs (type I); 2, 3 and 5-containing receptors have similar but\ distinguishable properties (type II); and 4- and 6-containing assemblies have very low BZ affinity [MEDLINE:21568956]. A conserved histidine residue in the subunit of type I and II receptors is believed to be responsible for BZ affinity [MEDLINE:21568956].

\ Amongst type II members, 5-containing receptors exhibit an altered BZ\ selectivity. Affinity towards the compound zolpidem distinguishes 5\ from 2- and 3-containing receptor subtypes [MEDLINE:96122225]. The 5\ subunit is expressed primarily in the hippocampus.\

\ \ GABA-A receptor activity ; GO:0004890 integral to membrane ; GO:0016021 gamma-aminobutyric acid signaling pathway ; GO:0007214 23903 IPR005434

Most GABAA receptors contain one\ type of and subunit, and a single gamma polypeptide in a ratio of\ 2:2:1 [MEDLINE:21568956]. The BZ binding site is located at the interface of adjacent and gamma subunits; therefore, the type of subunit present is\ instrumental in determining BZ selectivity and sensitivity. Receptors can be\ categorised into 3 groups based on their subunit content and, hence,\ sensitivity to BZs: 1-containing receptors have greatest sensitivity \ towards BZs (type I); 2, 3 and 5-containing receptors have similar but\ distinguishable properties (type II); and 4- and 6-containing assemblies have very low BZ affinity [MEDLINE:21568956]. A conserved histidine residue in the subunit of type I and II receptors is believed to be responsible for BZ affinity [MEDLINE:21568956].

\ Alpha 4- and 6-containing receptors are often referred to as 'diazepam- insensitive' receptors, since inclusion of such subunits in place of type I and II polypeptides virtually eliminates sensitivity to BZs. The 4 receptor subtype is localised primarily in the thalamus [MEDLINE:96122225].\

\ \ GABA-A receptor activity ; GO:0004890 integral to membrane ; GO:0016021 gamma-aminobutyric acid signaling pathway ; GO:0007214 23902 IPR005433

Most GABAA receptors contain one\ type of and subunit, and a single gamma polypeptide in a ratio of\ 2:2:1 [MEDLINE:21568956]. The BZ binding site is located at the interface of adjacent and gamma subunits; therefore, the type of subunit present is\ instrumental in determining BZ selectivity and sensitivity. Receptors can be\ categorised into 3 groups based on their subunit content and, hence,\ sensitivity to BZs: 1-containing receptors have greatest sensitivity \ towards BZs (type I); 2, 3 and 5-containing receptors have similar but\ distinguishable properties (type II); and 4- and 6-containing assemblies have very low BZ affinity [MEDLINE:21568956]. A conserved histidine residue in the subunit of type I and II receptors is believed to be responsible for BZ affinity [MEDLINE:21568956].

\ Amongst type II members, 2-containing receptors have a very similar BZ\ affinity profile to those containing the 3 subunit. Differences in\ efficacy can be exploited to differentiate such subtypes: for example, the\ compound flunitrazepam has a greater efficacy on the 2 subtype. Alpha\ 3-containing receptors are less widely distributed and are found primarily\ in the cerebellum granule layer [MEDLINE:96122225].\

\ \ GABA-A receptor activity ; GO:0004890 integral to membrane ; GO:0016021 gamma-aminobutyric acid signaling pathway ; GO:0007214 23901 IPR005432

Most GABAA receptors contain one\ type of and subunit, and a single gamma polypeptide in a ratio of\ 2:2:1 [MEDLINE:21568956]. The BZ binding site is located at the interface of adjacent and gamma subunits; therefore, the type of subunit present is\ instrumental in determining BZ selectivity and sensitivity. Receptors can be\ categorised into 3 groups based on their subunit content and, hence,\ sensitivity to BZs: 1-containing receptors have greatest sensitivity \ towards BZs (type I); 2, 3 and 5-containing receptors have similar but\ distinguishable properties (type II); and 4- and 6-containing assemblies have very low BZ affinity [MEDLINE:21568956]. A conserved histidine residue in the subunit of type I and II receptors is believed to be responsible for BZ affinity [MEDLINE:21568956].

\ Amongst type II members, 2-containing receptors have a very similar BZ\ affinity profile to those containing the 3 subunit. Differences in\ efficacy can be exploited to differentiate such subtypes: for example, the\ compound flunitrazepam has a greater efficacy on the 2 subtype. Alpha\ 2-containing receptors are widely distributed throughout the CNS and are\ also found in some motor neurones and the pancreas [MEDLINE:96122225].\

\ \ GABA-A receptor activity ; GO:0004890 integral to membrane ; GO:0016021 gamma-aminobutyric acid signaling pathway ; GO:0007214 23900 IPR005431

Most GABAA receptors contain one\ type of and subunit, and a single gamma polypeptide in a ratio of\ 2:2:1 [MEDLINE:21568956]. The BZ binding site is located at the interface of adjacent and gamma subunits; therefore, the type of subunit present is\ instrumental in determining BZ selectivity and sensitivity. Receptors can be\ categorised into 3 groups based on their subunit content and, hence,\ sensitivity to BZs: 1-containing receptors have greatest sensitivity \ towards BZs (type I); 2, 3 and 5-containing receptors have similar but\ distinguishable properties (type II); and 4- and 6-containing assemblies have very low BZ affinity [MEDLINE:21568956]. A conserved histidine residue in the subunit of type I and II receptors is believed to be responsible for BZ affinity [MEDLINE:21568956].

\ The 1 subunit is the most widely expressed of the family members\ and most commonly found in receptors comprising a gamma 2 and subunits.\ Such subtypes display 'classical' BZ affinity and efficacy.\

\ \ GABA-A receptor activity ; GO:0004890 integral to membrane ; GO:0016021 gamma-aminobutyric acid signaling pathway ; GO:0007214 23899 IPR005430

The Gram-negative pathogen Escherichia coli causes several common bacterial illnesses in humans, including diarrhoea, neonatal meningitidis and urinary tract infections. Attachment to host tissues is essential for successful invasion, and requires interaction between a bacterial adhesive protein and its target receptor. This protein is usually supported on a larger structure made up of heteropolymeric fibres [MEDLINE:92204235]. Pyelonephritogenic E.coli specifically invade the uroepithelium by expressing between 100 and 300 pili on their cell surface. Pili are macromolecular structures that allow binding to a digalactoside receptor in the urinary tract.\

P pili, or fimbriae, are ~68A in diameter and 1 micron in length, the bulk of which is a fibre composed of the main structural protein PapA [MEDLINE:92204235]. At its tip, the pilus is terminated by a fibrillum consisting of repeating units of the PapE protein. This, in turn, is topped by the adhesins, PapF and PapG, both of which are needed for receptor binding. The tip fibrillum is anchored to the main PapA fibre by the PapK pilus-adaptor protein. PapH, an outer membrane protein, then anchors the entire rod in the bacterial envelope [MEDLINE:95115757]. A cytoplasmic chaperone (PapD) assists in assembling the monomers of the macromolecule in the membrane.

\ PapF, in addition to aiding in the virulence and binding of uropathogenic E.coli, also functions as an adapter protein that joins the distal end of the tip fibrillum to the main PapG adherence factor. By providing a complementary binding surface for PapE and PapG, pilus assembly is rapidly completed [MEDLINE:93209230].\

\ \ \N fimbrin ; GO:0009417 pathogenesis ; GO:0009405 23897 IPR005428

CD36 is a transmembrane, highly glycosylated, 88kDa glycoprotein expressed by monocytes, macrophages, platelets, microvascular endothelial cells and adipose tissue. It is a scavenger receptor for oxidized LDL and shed photoreceptor outer segments and in recognition and\ phagocytosis of apoptotic cells . CD36 is the cell adhesion molecule in platelet adhesion and aggregation,\ platelet-monocyte and platelet-tumor cell interaction. This family consists of the CD36 adhesion molecules.

\ \ \ cell adhesion molecule activity ; GO:0005194 \N cell adhesion ; GO:0007155 23898 IPR005429

Lysosome membrane protein II (LIMP II) is a 478-residue glycoprotein expressed in the membrane of lysosomes and secretory granules with lysosomal\ properties [MEDLINE:91358482]. The N-terminal segment (residues ~4-26) constitutes an \ uncleavable signal peptide [MEDLINE:91358482]. LIMP II possesses an additional C-terminal\ hydrophobic region that, together with the signal peptide, may anchor the\ protein to the membrane [MEDLINE:91358482]. The major portion of the protein resides on the\ luminal side and contains 11 potential N-glycosylation sites and 5 cysteine\ residues. The N- and C-terminal ends of the protein constitute short \ cytoplasmic tails. LIMP II is a subgroup of a larger family of the cell surface \ protein CD36 involved in cell adhesion.

\ \ receptor activity ; GO:0004872 lysosome ; GO:0005764 \N 23896 IPR005427

Some Gram-negative animal enteropathogens express a specialised secretion system to directly "inject" exotoxins into the cytoplasm of host cells. The system is composed of structural proteins and \ exotoxin effectors; these are often encoded on large virulence plasmids\ or on the bacterial chromosome itself [MEDLINE:20471859].

\ The Shigella flexneri invasion plasmid antigen (ipa) genes are found on such \ a plasmid, and are highly regulated [MEDLINE:89057927]. Homologues of the ipa genes \ (SipC/SspC) have been found in Salmonella typhimurium [MEDLINE:95332200], and both \ pathogens utilise their type III system to translocate their invasive \ effectors. These are responsible for interacting directly with the host \ eukaryotic cell. IpaC can activate cellular kinase activity once in the \ host cytoplasm, and thus promotes cellular uptake of Shigella flexneri [MEDLINE:99003141]. \ In addition, it has been found that SipC interacts with another Salmonella \ protein, SipA, to enhance its reorganisation of the host cell actin \ cytoskeleton, thereby facilitating cellular uptake of the Salmonella \ bacterium by the eukaryotic cell [MEDLINE:99003141].\

\ \ \N \N pathogenesis ; GO:0009405 23895 IPR005426

The KCNE family of K+ channel subunits are membrane glycoproteins that \ possess a single transmembrane (TM) domain. They share no structural \ relationship with the subunit proteins, which possess pore forming \ domains. The subunits appear to have a regulatory function, modulating the \ kinetics and voltage dependence of the subunits of voltage-dependent\ K+ channels [Conley, E.C. and Brammar, W.J. MinK. in The Ion Channel Factsbook, Vol. IV, Academic Press, 1999, PP.703-767.]. KCNE subunits are formed from short polypeptides of ~130 amino acids, and are divided into five subfamilies: KCNE1 (MinK/IsK),\ KCNE2 (MiRP1), KCNE3 (MiRP2), KCNE4 (MiRP3) and KCNE1L (AMMECR2).

\ KCNE3 is known to associate with the pore forming subunits KCNQ1, KCNQ4,\ HERG and Kv3.4. KCNE3 forms complexes with Kv3.4 in skeletal muscle -\ KCNE3 mutations have been identified in families with skeletal muscle\ disorders PUB00009384. In the intestine, KCNE3 associates with KCNQ1 to form\ channels that are stimulated by cAMP and are thought to be involved in\ secretory diarrhoea and cystic fibrosis [MEDLINE:20110524].\

\ \ voltage-gated potassium channel activity ; GO:0005249 membrane ; GO:0016020 potassium ion transport ; GO:0006813 23894 IPR005425

\ KCNE2 subunits associate with the eag-like HERG subunits, which are\ the pore-forming subunits of cardiac IKr channels. Channels formed solely\ from HERG subunits display similar properties to native IKr channels;\ however, they differ in their gating and single channel conductance. \ Channels formed from both KCNE2 and HERG exhibit properties that are \ identical to those seen in native IKr channels. Three mutations in the KCNE2\ gene are associated with long QT syndrome and ventricular fibrillation. \ These mutations result in channels that open slower and close more rapidly,\ the net effect being a reduced K+ current PUB00009384.\

\ \ voltage-gated potassium channel activity ; GO:0005249 membrane ; GO:0016020 potassium ion transport ; GO:0006813 23893 IPR005424

\ KCNE1 subunits associate with KCNQ1 subunits to form channels that\ are responsible for the IkS currents that determine the duration of the\ action potential in cardiac muscle. Mutations in both of the genes encoding\ these subunits cause an inherited disorder that increases the risk of death\ from cardiac arrhythmia (long QT syndrome type 1) and Jervell and\ Lange-Nielsen syndrome, associated with congenital deafness PUB00009384.\

\ \ voltage-gated potassium channel activity ; GO:0005249 membrane ; GO:0016020 potassium ion transport ; GO:0006813 23891 IPR005422

\ \

The voltage-dependent calcium channel gamma (VDCCG) subunit family consists \ of at least 8 members, which share a number of common structural features \ PUB00010557. Each member is predicted to possess four TM domains, with intracellular N- and C- termini. The first extracellular loop contains a highly conserved\ N-glycosylation site and a pair of conserved cysteine residues. The \ C-terminal seven residues of VDCCG-2, -3, -4 and -8 are also conserved and \ contain a consensus site for phosphorylation by cAMP and cGMP-dependent\ protein kinases, and a target site for binding by PDZ domain proteins.

\ The VDCCG-2 subunit (also known as stargazin) was isolated by identifying \ the locus of the genetic disruption in the epileptic mouse mutant line\ known as stargazer [MEDLINE:98361159]. VDCCG-2 subunits are brain specific and enriched in synaptic plasma membranes. In vitro studies using recombinant P/Q-type \ calcium channels show that VDCCG-2 subunit expression increases steady-state\ channel inactivation, leading to the suggestion that, in stargazer mutants, \ inappropriate calcium entry may contribute to the seizure phenotype.\

\ \ voltage-gated calcium channel activity ; GO:0005245 integral to membrane ; GO:0016021 calcium ion transport ; GO:0006816 23892 IPR005423

\ \

The VDCCG-4 subunit is predominantly expressed in neuronal tissue, although\ there is some evidence for expression in lung and prostate [MEDLINE:21100909], [MEDLINE:20200313]. The\ modulatory properties of the subunit have been investigated using\ heterologous expression systems. Coexpression of the VDCGG-4 subunit with \ P/Q-type channels shifts the steady-state inactivation curve of these \ channels to more hyperpolarised potentials [MEDLINE:20200313], [MEDLINE:21214272].\

\ \ voltage-gated calcium channel activity ; GO:0005245 integral to membrane ; GO:0016021 calcium ion transport ; GO:0006816 23890 IPR005421

\ \

\ The VDCCG-1 subunit is a 25kDa protein expressed exclusively in skeletal \ muscle cells, where it functions as a dihydropyridine-sensitive, L-type \ calcium channel subunit [MEDLINE:90232362]. The modulatory properties of VDCCG-1 subunits have been investigated using heterologous expression systems. Coexpression\ of VDCCG-1 subunits with L-type or P/Q-type channels induces moderate \ changes in activation and inactivation properties, and modification of the\ peak current amplitude of these channels [MEDLINE:92042108], [MEDLINE:91376664].\

\ \ voltage-gated calcium channel activity ; GO:0005245 integral to membrane ; GO:0016021 calcium ion transport ; GO:0006816 23888 IPR005419

The zona occuldens proteins (ZO-1, ZO-2 and ZO-3) are a family of TJ- associated proteins that function as cross-linkers, anchoring the TJ strand \ proteins to the actin-based cytoskeleton [MEDLINE:97362070]. Each protein contains three \ PDZ (postsynaptic density, disc-large, ZO-1) domains, a single SH3 (Src \ Homology-3) domain and a GK (guanylate kinase) domain, the presence of which\ identifies them as members of the membrane-associated guanylate kinase \ (MAGUK) protein family. They also share an acidic domain at the C-terminal \ region of the molecules not found in other MAGUK proteins. It has been \ demonstrated that the first PDZ domain is involved in binding the C-terminal\ -Y-V motif of claudins [MEDLINE:20069797]. By contrast, the occludin-binding domain of\ ZO-1 has been shown to lie in the GK and acidic domains [MEDLINE:99009089]. Although the precise location of the actin-binding motif has not been elucidated, it \ appears to be within the C-terminal half of the molecules, since \ transfection of this region into fibroblasts induces co-localisation \ of ZO-1 and ZO-2 with actin fibres.

\ ZO-2 was first identified as a 160kDa protein that co-immunoprecipitates\ with ZO-1 [MEDLINE:91195371]. It shares ~65% overall similarity with ZO-1 and ZO-3\ proteins, with highest levels of similarity in the MAGUK and acid domains. \ In vitro binding studies indicate that ZO-2 may interact directly with ZO-1\ through its second PDZ domain, although it does not appear to bind directly\ to ZO-3.\

\ \ \N tight junction ; GO:0005923 \N 23889 IPR005420

\ ZO-3 was first identified as a 130kDa protein that co-immunoprecipitates\ with ZO-1 [MEDLINE:94012976]. It shares ~65% overall similarity with ZO-1 and ZO-2 \ proteins, with highest levels of similarity in the MAGUK and acid domains.\ In vitro binding studies indicate that ZO-3 may interact directly with ZO-1\ through its second PDZ domain, although it does not appear to bind directly\ to ZO-2 [MEDLINE:98198478].\

\ \ \N tight junction ; GO:0005923 \N 23886 IPR005417

\ \ \ \N tight junction ; GO:0005923 \N 23887 IPR005418

\ ZO-1 was first identified as a 220kDa antigen for a monoclonal antibody\ raised to junction-enriched cell fractions [MEDLINE:86304554]. The protein shares ~65% \ overall similarity with ZO-2 and ZO-3 proteins, with highest levels of \ similarity in the MAGUK and acid domains. The structure of ZO-1 is distinct\ from the other ZO protein family members in that it contains a ZU5 domain \ at the C-terminal end of the molecule, although the function of this domain\ is unknown. Binding and tranfection studies indicate that ZO-1 is capable \ of associating with ZO-2 and ZO-3 through binding of the second PDZ domains\ [MEDLINE:98198478].\

\ \ \N tight junction ; GO:0005923 \N 23885 IPR005416

The type III secretion system of Gram-negative bacteria is used to transport virulence factors from the pathogen directly into the host cell [MEDLINE:98284147] and is only triggered when the bacterium comes into close contact with the host. Effector proteins secreted by the type III system do not possess a secretion signal, and are considered unique because of this. Yersinia spp. secrete an effector protein called YopE through the type III needle [MEDLINE:90279509]. This acts as a Rho GTPase-activating protein that disrupts the host cell actin cytoskeleton, and is regulated by a chaperone protein called SycE/YerA [MEDLINE:95024141]. In the absence of the SycE chaperone, YopE is not transported through the needle and remains in the bacterial cytoplasm, so suggesting a crucial role for this moiety [MEDLINE:99348356].

\ \

Both the YopE regulator and SycE/YerA proteins share similarity with the\ exoenzyme S (ExoS) gene product of Pseudomonas aeruginosa [MEDLINE:95104980]. ExoS has both ADP-ribosylating and GTPase activity, and is implicated as a virulence \ factor. As type III secretion in Pseudomonas is often associated with\ systemic and even fatal infections in susceptible patients [MEDLINE:21265118], the proteins involved are of interest as vaccine and drug targets.\

\ \ \N \N \N 23884 IPR005415

The type III secretion system of Gram-negative bacteria is used to transport virulence factors from the pathogen directly into the host cell [MEDLINE:98284147] and is only triggered when the bacterium comes into close contact with the host. Effector proteins secreted by the type III system do not possess a secretion signal, and are considered unique because of this. Yersinia spp. secrete effector proteins called YopB and YopD that facilitate the spread of other translocated proteins through the type III needle and the host cell \ cytoplasm [MEDLINE:98101474]. Both are believed to act as pore translocases, forming apertures in the host cell \ membrane and allowing the bacterium easy access to its cytoplasm. YopD\ also acts as a negative regulator of the Yersinia low-calcium response, and \ in turn is controlled by a chaperone, SycD [MEDLINE:95024141]. This protein also regulates YopB secretion. SycD is located on the Yop pathogenicity island of Yersinia \ spp., and is speculated to prevent a premature interaction between YopB, \ YopD and the calcium-response LcrV protein [MEDLINE:99406904].

\ \

It has been speculated that a type III secretion mechanism also exists in\ Chlamydial species. With the sequencing of the Chlamydia trachomatis genome,\ several proteins similar to characterised type III proteins have emerged, \ including a SycD homologue [MEDLINE:20572077]. The Pseudomonas aeruginosa gene PcrH is also similar to the Yersinia chaperone, suggesting a comparable function.

\ \ \ \N \N response to stress ; GO:0006950 23883 IPR005414

The type III secretion system of Gram-negative bacteria is used to transport virulence factors from the pathogen directly into the host cell [MEDLINE:98284147] and is only triggered when the bacterium comes into close contact with the host. Effector proteins secreted by the type III system do not possess a secretion signal, and are considered unique because of this. Salmonella spp. secrete an effector protein called SopE that is responsible for stimulating \ the reorganisation of the host cell actin cytoskeleton, and ruffling of the \ cellular membrane [MEDLINE:98151555]. It acts as a guanyl-nucleotide-exchange factor on Rho-GTPase proteins such as Cdc42 and Rac. As it is imperative for the bacterium \ to revert the cell back to its "normal" state as quickly as possible, \ another tyrosine phosphatase effector called SptP reverses the actions \ brought about by SopE [MEDLINE:21316518].

\ \

Recently, it has been found that SopE and its protein homologue SopE2 can\ activate different sets of Rho-GTPases in the host cell [MEDLINE:21316518]. Far from being a redundant set of two similar type III effectors, they both act in unison \ to specifically activate different Rho-GTPase signalling cascades in the\ host cell during infection.\

\ \ \N \N \N 23882 IPR005413

The type III secretion system of Gram-negative bacteria is used to transport virulence factors from the pathogen directly into the host cell [MEDLINE:98284147] and is only triggered when the bacterium comes into close contact with the host. Effector proteins secreted by the type III system do not possess a secretion signal, and are considered unique because of this. Yersinia spp. secrete effector proteins called YopB and YopD that facilitate the spread of other translocated proteins through the type III needle and the host cell cytoplasm [MEDLINE:98101474]. In turn, the transcription of these moieties is thought to be\ regulated by another gene, lcrV, found on the Yops virulon that encodes the \ entire type III system [MEDLINE:98155148]. The product of this gene, LcrV protein, also \ regulates the secretion of YopD through the type III translocon [MEDLINE:21336514], and \ itself acts as a protective "V" antigen for Yersinia pestis, the causative \ agent of plague [MEDLINE:21382180].

\ \

Recently, a homologue of the Yersinia LcrV protein (PcrV) was found in\ Pseudomonas aeruginosa, an opportunistic pathogen. In vivo studies using\ mice found that immunisation with the protein protected burned animals from \ infection by Pseudomonas aeruginosa, and enhanced survival. In addition, it\ is speculated that PcrV determines the size of the needle pore for type III\ secreted effectors. [MEDLINE:21391858].\

\ \ \N extracellular ; GO:0005576 pathogenesis ; GO:0009405 23881 IPR005412

The Factor for Inversion Stimulation (FIS) protein is a regulator of bacterial functions, and binds specifically to weakly related DNA sequences \ [MEDLINE:95238273]. It activates ribosomal RNA transcription, and is involved in upstream\ activation of rRNA promoters. Found in gamma proteobacterial microbes, the\ protein has been shown to play a part in the regulation of virulence factors\ in both Salmonella typhimurium and Esherichia coli [MEDLINE:20572089]. Some of its\ functions include inhibition of the initiation of DNA replication from the\ OriC site, and promotion of Hin-mediated DNA inversion [MEDLINE:21424668].

\ In its C-terminal extremity, FIS encodes a helix-turn-helix (HTH) DNA-\ binding motif, which shares a high degree of similarity with other HTH\ motifs of more primitive bacterial transcriptional regulators, such as the\ nitrogen assimilation regulatory proteins (NtrC) from species like Azobacter,\ Rhodobacter and Rhizobium. This has led to speculation that both evolved\ from a single common ancestor [MEDLINE:98409323].

\ \

Recently, the crystal structure of wild-type Escherichia coli FIS was \ resolved, together with six mutants [MEDLINE:20500109] - the first crystal structure was\ solved in 1991. From the most recent 2.0A structure [MEDLINE:92052131] of wild-type\ FIS, the protein was observed to exist as a homodimer in the bacterial\ cytoplasm. By comparison with the structures of FIS mutants, it was deduced\ that arginine-71 is critical for the binding of FIS to RNA polymerase, while\ glycine-72 stabilises the tertiary structure.\

\ \ DNA binding activity ; GO:0003677 \N regulation of transcription, DNA-dependent ; GO:0006355 23880 IPR005411

\ \ \

\ \

Claudin-2 was initially isolated as a peptide fragment from TJ-enriched \ junctional cell fractions. Following sequencing and similarity searching \ it was cloned and expressed in cells, where it was shown to concentrate at \ TJs [MEDLINE:98311639]. Human and mouse isoforms have been identified. Claudin-2 shares ~22-46% overall similarity with other claudin family members at the amino\ acid level, displaying highest similarity to claudin-14.

\ \ \ structural molecule activity ; GO:0005198 tight junction ; GO:0005923 \N 23879 IPR005410

The THIK (Tandem pore-domain Halothane Inhibited K+ channel) family\ contains two members: THIK-1 and THIK-2. Both proteins were first isolated\ from rat and have subsequently been found in human. THIK-1 is expressed\ ubiquitously and is activated by arachidonic acid and inhibited by the\ volatile anaesthetic halothane. The second member, THIK-2, shares 58% amino\ acid identity with THIK-1, but is not functionally expressed. THIK-2 is \ strongly expressed in several tissues, and is particularly abundant in the\ brain PUB00009384.

\ \ \ potassium channel activity ; GO:0005267 integral to membrane ; GO:0016021 potassium ion transport ; GO:0006813 23878 IPR005409

Shaker-type and\ Kir K+ channel subunits both contain a single P-domain, and four such\ subunits are thought to associate to form a multimer, together with \ associated auxillary (regulatory) subunits. Recently, a new class of K+ \ channel subunits was cloned, which is clearly distinct from the Shaker and\ Kir families; the new class contains not one but two P-domains in each \ subunit, and evidence suggests a complete channel may be formed by the \ dimerisation of two such subunits.

\ \ The THIK (Tandem pore-domain Halothane Inhibited K+ channel) family\ contains two members: THIK-1 and THIK-2. Both proteins were first isolated\ from rat and have subsequently been found in human. THIK-1 is expressed\ ubiquitously and is activated by arachidonic acid and inhibited by the\ volatile anaesthetic halothane. The second member, THIK-2, shares 58% amino\ acid identity with THIK-1, but is not functionally expressed. THIK-2 is \ strongly expressed in several tissues, and is particularly abundant in the\ brain PUB00009384.

\ \ \ potassium channel activity ; GO:0005267 integral to membrane ; GO:0016021 potassium ion transport ; GO:0006813 23877 IPR005408

2P-domain channels influence the resting membrane potential and as a result can control cell excitability. In addition, they pass K+in response to changes in membrane potential, and are also tightly regulated by molecular oxygen, GABA (gamma-aminobutyric acid), noradrenaline and serotonin.

The first member of this family (TOK1), cloned from Saccharomyces cerevisiae\ \ \ \ [MEDLINE:95379951], is\ predicted to have eight potential transmembrane (TM) helices. However,\ subsequently-cloned two P-domain family members from Drosophila and\ mammalian species are predicted to have only four TM segments. They are\ usually referred to as TWIK-related channels (Tandem of P-domains in a \ Weakly Inward rectifying K+ channel) [MEDLINE:97075152], [MEDLINE:97157476], [MEDLINE:96183184], [MEDLINE:97459932]. Functional characterisation of these channels has revealed a diversity of properties in that they may show inward or outward rectification, their activity may be modulated in different directions by protein phosphorylation, and their sensitivity to changes in intracellular or extracellular pH varies. Despite these disparate properties, they are all thought to share the same topology of\ four TM segments, including two P-domains. That TWIK-related K+ channels\ all produce instantaneous and non-inactivating K+ currents, which do not\ display a voltage-dependent activation threshold, suggests that they are\ background (leak) K+ channels involved in the generation and modulation of the resting membrane potential in various cell types. Further studies have revealed that they may be found in many species, including: plants, invertebrates and mammals.

TWIK family members (TWIK-1 and TWIK-2) produce constitutive K+ currents of\ weak amplitude PUB00009384. They are present in a variety of tissues, including\ brain and cells of the immune system. Together with their functional \ properties, their wide distribution suggests that these channels may be\ involved in the control of background K+ conductances in many cell types.\

\ \ potassium channel activity ; GO:0005267 integral to membrane ; GO:0016021 potassium ion transport ; GO:0006813 23876 IPR005407

\ \

TASK-3 was first cloned from rat and has been subsequently cloned from human\ and guinea pig. It is expressed in many tissues, especially the brain. It\ is involved in setting the membrane potential as well as action potential \ duration in certain neurons. It is closed at pH6.6: the histidine residue\ at position 98 located near a 'GYG' motif in the first P-domain is thought\ to confer the extracellular pH sensitivity [MEDLINE:20200422].\

\ \ potassium channel activity ; GO:0005267 integral to membrane ; GO:0016021 potassium ion transport ; GO:0006813 23875 IPR005406

\ TASK-1 was the first member of the TASK family to be cloned. It is widely\ distributed, being particularly abundant in the pancreas and placenta, but\ is also found in the brain, heart, lung and kidney. In addition to the \ maintenance of the resting membrane potential, it is also involved in K+\ transport associated with recycling/secretion and the modulation of\ electrical activity of excitable cells [MEDLINE:20508366].

\ \ potassium channel activity ; GO:0005267 integral to membrane ; GO:0016021 potassium ion transport ; GO:0006813 23874 IPR005405

The Shaw gene was first isolated from Drosophila melanogaster. Several vertebrate, K⁺ channels with similar amino acid sequences were subsequently found and, together with the Drosophila melanogaster Shaw channel, now constitute the Shaw (Kv3) family. These channels are thought to play a role in shortening of action potential durations and modulating pre-synaptic neurotransmitter release. In mammals, the family consists of 4 genes (Kv3.1, Kv3.2, Kv3.3 and Kv3.4). Each gene product has its own subcellular location and function PUB00009872.

\ Kv3.4 channels are expressed in cells that surround the cerebellar Purkinje\ cells. In the presence of protein kinase C, rapid inactivation is eliminated,\ resulting in a non-inactivating delayed rectifying current. The implications\ of this are seen for signal encoding in the central nervous system.\

\ \ voltage-gated potassium channel activity ; GO:0005249 integral to membrane ; GO:0016021 potassium ion transport ; GO:0006813 23873 IPR005404

\ Kv3.3 channels are evenly distributed over the soma and proximal apical\ dendrites. They have also been found in the lens epithelium, corneal\ endothelium, cerebellar cells and the deep cerebellar nuclei. When\ co-expressed with NADPH oxidase, they function as an oxygen sensor complex\ in airway chemoreceptors.\

\ \ voltage-gated potassium channel activity ; GO:0005249 integral to membrane ; GO:0016021 potassium ion transport ; GO:0006813 23872 IPR005403

\ Kv3.1 channels have slow-rising delayed rectifier-type outward currents that\ inactivate slowly. They have a tentative role in the fast action potential\ repolarisation abundant in rapidly firing neurons, such as the auditory\ brainstem, and hippocampal and cortical interneurons . There are two \ forms, -a and -b, which differ in expression during development. Kv3.1a\ appears to be found in the neurons of the adult brain, whereas Kv3.1b is\ expressed in embryonic and perinatal neurons. In addition, Kv3.1 channels\ can also be found in T-lymphocytes.\

\ \ voltage-gated potassium channel activity ; GO:0005249 integral to membrane ; GO:0016021 potassium ion transport ; GO:0006813 23871 IPR005402

Some types of K+ channel are closed at the resting potential of the cell,\ but open on membrane depolarisation, and are thus known as voltage-gated \ channels. Each of these types of channel typically comprises 4 pore-forming subunits that may associate with one of a number of different types of subunit. Two types of subunit (KCNE and KCNAB) are presently known\ to associate with voltage-gated subunits (Kv, KCNQ and eag-like).\ However, not all combinations of and subunits are possible.\ \ The KCNAB family of K+ channel subunits form tetramers arranged in\ a similar manner to the pore forming subunits. KCNAB subunits are\ oxidoreductase enzymes, complete with nicotinamide (NADPH)-cofactors in \ their active sites. Changes in the oxidoreductase activity appear to \ markedly influence the gating mode of Kv channels, since mutations to the\ catalytic residues in the active site lessen the inactivating activity of\ KCNAB PUB00009384. The KCNAB family is further divided into 3 subfamilies: KCNAB1 (Kvbeta3), KCNAB2 (Kvbeta2) and KCNAB3.

\ KCNAB3 associates with Kv1.5 subunits, resulting in a much faster\ inactivation than is observed in kv1.5 channels formed from subunits\ alone [MEDLINE:99074289]. KCNAB3 channels are expressed specifically in the brain, with most prominent expression in the cerebellum. Weaker expression is observed\ in the cortex, occipital lobe, frontal lobe and temporal lobe\

\ \ voltage-gated potassium channel activity ; GO:0005249 integral to membrane ; GO:0016021 potassium ion transport ; GO:0006813 23870 IPR005401

\ KCNAB2 associates with Kv1.4 subunits; however, association has only\ very modest effects on the gating of this channel PUB00009384. Two isoforms of KCNAB2\ exist, which are produced by alternative splicing of amino acids 26-39.

\ \ \ \ voltage-gated potassium channel activity ; GO:0005249 integral to membrane ; GO:0016021 potassium ion transport ; GO:0006813 23869 IPR005400

\ \ KCNAB1 associates with Kv1.4 and Kv1.5 subunits and appears to have \ an N-terminal sequence that is similar to the Kv1 channel inactivation gate.\ Thus, when KCNAB1 subunits associate, their N-termini appear to be able to \ substitute for subunit inactivation gates PUB00009384. Three isoforms of \ KCNAB1 exist, which are produced by alternative splicing of the N-terminal\ 90 amino acids. KCNAB1 channels are expressed in brain (caudate nucleus,\ hippocampus, amygdala, subthalamic nucleus and thalamus) and heart.

\ \ \ voltage-gated potassium channel activity ; GO:0005249 integral to membrane ; GO:0016021 potassium ion transport ; GO:0006813 23867 IPR005398

A mutation in the mouse tub gene causes maturity-onset obesity, insulin resistance and sensory deficits [MEDLINE:96200779], [MEDLINE:96195061]. By contrast with the rapid juvenile-onset weight gain seen in diabetes (db) and obese (ob) mice, obesity in\ tubby mice develops gradually, and strongly resembles the late-onset obesity\ observed in the human population [MEDLINE:96195061]. Excessive deposition of adipose tissue culminates in a two-fold increase of body weight. Tubby mice also suffer\ retinal degeneration and neurosensory hearing loss. The tripartite\ character of the tubby phenotype is highly similar to human obesity\ syndromes, such as Alstrom and Bardet-Biedl. Although these phenotypes\ indicate a vital role for tubby proteins, no biochemical function has yet\ been ascribed to any family member [MEDLINE:20059926], although it has been suggested that the phenotypic features of tubby mice may be the result of cellular \ apoptosis triggered by expression of the mutuated tub gene.

\ \ Mammalian tub is a hydrophilic protein of ~500 residues. The N-terminal\ portion of the protein is conserved neither in length nor sequence, but the \ C-terminal 250 residues are highly conserved. The C-terminal extremity\ contains a cysteine residue that might play an important role in the normal\ functioning of these proteins. The C-terminal is represented by IPR000007.

\ \ \ \N \N \N 23868 IPR005399

\ \ voltage-gated potassium channel activity ; GO:0005249 integral to membrane ; GO:0016021 potassium ion transport ; GO:0006813 23866 IPR005397

Neuropeptide FF (and neuropeptide AF, which is also derived from the same\ precursor) belong to a family of neuropeptides containing an RF-amide motif\ at their C-terminus. Neuropeptide FF (NPFF) is found at high\ concentrations in the posterior pituitary, spinal cord, hypothalamus and\ medulla and is believed to be involved in pain modulation, opioid tolerance,\ cardiovascular regulation, memory and neuroendocrine regulation [MEDLINE:96397012]. Two G protein-coupled receptors for NPFF have been identified; both are expressed\ in the central nervous system and couple to Gi proteins to inhibit adenylyl\ cyclase [MEDLINE:21225177], [MEDLINE:20564301].

\ \ The type 2 neuropeptide FF receptor is expressed at high levels in the\ thymus and placenta, with moderate levels in the pituitary, spleen, testis\ and brain. Low levels were detected in the spinal cord, pancreas, small\ intestine, uterus, stomach, lung, heart and skeletal muscle. No expression\ was detected in liver or kidney [MEDLINE:21225177].\

\ \ \ neuropeptide receptor activity ; GO:0008188 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 23865 IPR005396

\ \ The type 1 neuropeptide FF receptor is expressed at highest levels in the\ hypothalamus, with moderate expression in the thalamus, midbrain, medulla\ oblongata, testis and eye [MEDLINE:20482175].\

\ \ neuropeptide receptor activity ; GO:0008188 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 23864 IPR005395

\ \ neuropeptide receptor activity ; GO:0008188 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 23863 IPR005394

Receptors for adenine nucleotides are collectively termed P2 purinoceptors. They can be further subdivided into two structural classes: P2X receptors \ are ligand-gated ion channels, while P2Y receptors are G protein-coupled \ receptors. P2Y receptors have also been identified that are selective for \ uridine (rather than adenine) nucleotides [MEDLINE:20349362]. \ \ cDNA encoding a platelet ADP receptor, designated P2Y12, has been isolated \ and functionally characterised [MEDLINE:21269433]. The receptor is coupled to the \ inhibition of adenylyl cyclase through Gi. In conjunction with P2Y1, P2Y12 \ receptors mediate ADP-induced platelet aggregation. The receptor is a \ target of the thienopyridine antithrombotic drugs clopidogrel and\ ticlopidine, which have been demonstrated to be effective in treating a \ variety of thrombotic diseases [MEDLINE:21037966].\

\ \ purinergic nucleotide receptor activity, G-protein coupled ; GO:0045028 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 23862 IPR005393

\ \

Lymphotactin is the only known member of the C\ chemokine family. It has closest similarity to the C-C chemokines but\ contains only the second and fourth of the conserved cysteine residues. The\ chemokine is produced by certain subsets of T cells and natural killer cells\ and is also chemotactic for these cell types [MEDLINE:95064019].

\ \

An orphan receptor (GPR5) has been identified as a receptor for lymphotactin\ and has been renamed XCR1 [MEDLINE:98298178]. XCR1 is strongly expressed in placenta and at lower levels in the spleen and thymus. It is detected only at very low\ levels in peripheral blood leukocytes. Within these tissues, expression\ of XCR1 appears to be restricted to CD8+ T cells and natural killer cells. Binding of lymphotactin to XCR1 stimulates calcium mobilisation and\ migration in a pertussis toxin-sensitive manner, indicating coupling of the\ receptor to Gi type proteins. The matching expression patterns of both\ lymphotactin and its receptor suggest a role for the chemokine in self- \ recruitment of leukocytes [MEDLINE:99448374].\

\ \ chemokine receptor activity ; GO:0004950 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 23861 IPR005392

Neuromedin U is a neuropeptide, first isolated from porcine spinal cord and\ expressed widely in the gastrointestinal, genitourinary and central nervous\ systems [MEDLINE:20490668]. Neuromedin U has potent contractile activity on smooth muscle and this activity is believed to reside within the C-terminal portion of \ the peptide, which is highly conserved between species. Other roles \ for the peptide include: regulation of blood flow and ion transport in \ the intestine, regulation of adrenocortical function and increased blood\ pressure [MEDLINE:20351041]. The roles of neuromedin U in the central nervous system\ are poorly understood, but may include: regulation of food intake,\ neuroendocrine control, modulation of dopamine actions and involvement in\ neuropsychiatric disorders. Two G protein-coupled receptor subtypes,\ with differing expression patterns, have been identified and shown to bind\ neuromedin U.

\ The neuromedin U type 2 receptor (NMU2) is expressed most abundantly in the\ central nervous system, particularly in the medulla oblongata, pontine\ reticular formation, substantia nigra, spinal cord and thalamus [MEDLINE:20490668]. High levels of expression have also been found in the thymus, thyroid and testes\ [MEDLINE:20351041]. NMU2 has been detected at much lower levels in some peripheral tissues, including the kidney, lung, trachea and gastrointestinal tract.\

\ \ neuromedin U receptor activity ; GO:0001607 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 23860 IPR005391

\ The neuromedin U type 1 receptor (NMU1) is expressed predominantly in the\ periphery, with highest levels in the gastrointestinal and urogenital\ systems, particularly in the testes [MEDLINE:20490668]. The receptor is also found in the\ kidney, pancreas, lung, trachea, adrenal cortex, liver and mammary glands\ [MEDLINE:20351041]. Within the small intestine and ileum, NMU1 is specifically expressed in goblet cells. In the central nervous system, the receptor is\ expressed only at much lower levels and has been detected most abundantly\ in the cerebellum, dorsal root ganglia, hippocampus and spinal cord.\ Binding of neuromedin U to the receptor results in phospholipase C\ activation and increased intracellular calcium concentrations through\ coupling to Gq proteins.\

\ \ neuromedin U receptor activity ; GO:0001607 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 23859 IPR005390

\ \ neuromedin U receptor activity ; GO:0001607 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 23857 IPR005388

An orphan receptor, G2A, has recently been identified that acts as a high \ affinity receptor for lysophosphatidylcholine (LPC) and a lower affinity receptor for the related lysophospholipid, SPC [MEDLINE:21368243]. G2A is expressed mainly in lymphocytes and its expression is up-regulated by stress and prolonged mitogenic signals. Mice\ lacking the receptor have been found to develop a late-onset autoimmune\ disease [MEDLINE:21264343]. It has therefore been suggested that G2A may function as a sensor of LPC levels at sites of inflammation and act as a negative\ regulator of lymphocyte growth to limit expansion of tissue-infiltrating\ cells and overt autoimmune disease. Activation of G2A by LPC results in\ an increase in intracellular calcium levels (through coupling to Gi\ proteins) and activation of MAP kinases. The receptor has also been shown \ to couple to G13 proteins, causing RhoA activation and formation of actin\ stress fibres.\

\ \ rhodopsin-like receptor activity ; GO:0001584 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 23858 IPR005389

Sphingosylphosphorylcholine (SPC) is produced from degradation of sphingomyelin and regulates many diverse cellular functions, such as: proliferation, growth inhibition, smooth muscle\ contraction and wound healing. It is also thought to play a role in\ the cardiovascular system and potently activates inwardly rectifying K+\ channels, suggesting a possible role in regulation of heart rate.

\ \ The orphan receptor OGR1 has been identified as a high affinity receptor for\ SPC [MEDLINE:20268195]. OGR1 is expressed in ovarian cancer cell lines and also in spleen, testis, small intestine, peripheral blood leukocytes, brain, heart, lung,\ placenta and kidney. Expression has not been found in thymus, prostate,\ ovary, colon, liver, skeletal muscle or pancreas [MEDLINE:96299795]. Upon activation by\ SPC, OGR1 couples to both Gi proteins, causing increases in intracellular \ calcium, and Gq proteins, to activate MAP kinases, inhibiting proliferation.\ SPC also causes regulation of ion channel activity, binding of activator\ protein-1 to DNA, and expression of cell adhesion molecule-1 and \ interleukin-6 [MEDLINE:20268195].\

\ \ rhodopsin-like receptor activity ; GO:0001584 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 23856 IPR005387

\ \

The only C-x3-C chemokine identified to date is\ fractalkine, a TM molecule containing a chemokine domain on an extended\ mucin-like stalk [MEDLINE:98050927]. The membrane-bound form of fractalkine can be \ induced on endothelial cells in response to inflammation, and promotes\ adhesion of monocytes and T lymphocytes. The chemokine can also be released\ in a soluble form, which causes chemotaxis of monocytes and T cells.

\ \ Both the adhesive and chemotactic effects of fractalkine are mediated \ through a G protein-coupled receptor - CX3CR1. CX3CR1 is expressed \ specifically on T cells, natural killer cells and monocytes and has closest \ similarity to the C-C chemokine receptors. Coupling of the receptor to \ pertussis toxin-sensitive Gi proteins leads to calcium mobilisation and \ chemotaxis. In contrast, adhesion mediated by the receptor is insensitive to\ pertussis toxin and does not appear to involve calcium mobilisation. \ CX3CR1 has also been found to act as a weak fusion cofactor for some HIV-1 \ strains, an interaction that can be potently and specifically blocked by \ fractalkine [MEDLINE:98395093].

\ \ \ chemokine receptor activity ; GO:0004950 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 23855 IPR005386

Sphingosine 1-phosphate (S1P) is released from activated platelets and is also produced by a number of other cell types in response to growth factors and cytokines [MEDLINE:20583949]. It is\ proposed to act both as an extracellular mediator and as an intracellular\ second messenger. Recently, 5\ G protein-coupled receptors have been identified that act as high affinity\ receptors for S1P and also as low affinity receptors for the related\ lysophospholipid, SPC [MEDLINE:21164675]. EDG-1, EDG-3, EDG-5 and EDG-8 share a high degree of similarity and are also referred to as lpB1, lpB3, lpB2 and lpB4,\ respectively. EDG-6 is referred to as lpC1, reflecting its more distant\ relationship to the other S1P receptors.\

EDG-8 is expressed predominantly in the white matter tracts of the brain and\ in the pancreas [MEDLINE:20583949]. Upon binding of S1P, EDG-8 appears to couple to Gi and G12 proteins but not Gq family members. Unlike other EDG receptors, which \ activate MAP kinases and stimulate proliferation, EDG-8 causes inhibition \ of ERK MAP kinases and proliferation, and also inhibition of adenylyl cyclase [MEDLINE:76091647].

\ \ \ lysosphingolipid and lysophosphatidic acid receptor activity ; GO:0001619 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 23854 IPR005385

The G protein-coupled receptors EDG-2, EDG-4 and EDG-7 have now been identified\ as high affinity receptors for lysophosphatidic acid (LPA). EDG-7 is expressed at high levels in the testis, prostate, heart, pancreas and frontal cerebral cortex in humans and at lower levels in the intestine, lung and ovary. Binding of LPA to the receptor leads to increased cyclic AMP and calcium levels and activation of MAP kinases. It is believed that these effects are mediated by Gq and possibly Gi class proteins [MEDLINE:20545693]. EDG-7 does not appear to be able to couple to G1.\

\ \ lysosphingolipid and lysophosphatidic acid receptor activity ; GO:0001619 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 23853 IPR005384

\ \

The Duffy antigen/chemokine receptor was originally identified as a blood\ group antigen on the surface of red blood cells (RBCs). It has been found \ to act as a multispecific receptor for chemokines of both the C-C and C-X-C\ families, including: Il-8, MGSA, RANTES and MCP-1 [MEDLINE:97275115]. While the receptor is predicted to have 7 TM domains, it shares only very low levels of \ sequence similarity with the other chemokine receptors (indeed, the \ characteristic rhodopsin-like signature is virtually absent) - it is\ considered to be most similar to the interleukin-8B receptors.

\ \

Duffy is expressed on RBCs (in Duffy-positive individuals), endothelial\ cells of postcapillary venules and Purkinje cells of the cerebellum. On \ RBCs, the Duffy antigen acts as a receptor for invasion by the malarial\ parasite, Plasmodium vivax; Duffy-negative individuals, whose RBCs do not\ express the receptor are resistant to such infection. The normal\ physiological function of Duffy remains unclear. It is believed to play a \ more important role on endothelial cells, since expression on these cell\ types is highly conserved, whereas the function on RBCs appears to be \ dispensable in order to confer resistance to malaria. The signalling\ pathways activated by Duffy are also unknown and the receptor has not \ been shown to act through a G protein.

\ \ \ rhodopsin-like receptor activity ; GO:0001584 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 23849 IPR005380

The XS (rice gene X and SGS3) domain is found in a family of plant proteins including gene X Q9SBW2 The XS domain containing proteins contain coiled-coils, which suggests that they will oligomerise. Most coiled-coil proteins form either a dimeric or a trimeric structure. It is possible that different members\ of the XS domain family could oligomerise via their coiled-coils forming a variety of complexes PUB00007755 .

\ \ \N \N \N 23850 IPR005381

This domain is a putative nucleic acid binding zinc finger and is found in proteins that also contain an XS domain IPR005380.

\ \N \N \N 23851 IPR005382

\ \

An orphan receptor, G protein-coupled receptor 2 (GPR2), was recently \ identified to be the target of the skin-associated chemokine CCL27. This \ receptor was designated CC chemokine receptor 10 [MEDLINE:20191997], 10725697]. Human and murine forms of the receptor have been cloned and found to be expressed at \ high levels in the testis, small intestine, foetal lung and kidney, with \ lower expression in the spleen, thymus, lymph node, colon and heart. \ Application of CCL27 chemokine to murine cells expressing CC CKR10 results \ in intracellular calcium mobilisation and transfectant cell migration.

\ \ \ C-C chemokine receptor activity ; GO:0016493 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 23847 IPR005378

The movement of lipid and protein components between intracellular organelles requires the regulated interactions of manymolecules. Vacuolar protein sorting-associated protein (Vps)5 is a yeast protein that is a subunit of a large multimeric\ complex, termed the retromer complex, involved in retrograde transport of proteins from endosomes to the trans-Golgi network. Sorting nexin (SNX) 1 and SNX2 are its mammalian orthologs [MEDLINE:20556005].

\ \

To carry out its biological functions, Vps5 forms the retromer complex\ with at least four other proteins: Vps17, Vps26, Vps29, and Vps35.Vps35 contains a central region of weaker sequence similarity, thought to indicate the presence of at least three domains [MEDLINE:20556005].

\ \ \N \N \N 23852 IPR005383

\ \

C-C chemokine receptor type 11 (CC CKR11), formerly designated C-C chemokine\ receptor like 1 (CCRL1), is expressed at high levels in the heart, small\ intestine and lung. Lower levels of expression have been detected in the \ kidney, liver and colon [MEDLINE:20231748], 11134065]. The receptor binds the monocyte chemo- attractant protein (MCP) family of chemokines with high affinity. In \ common with other C-C chemokine receptor family members, agonist binding \ elicits intracellular calcium mobilisation and subsequent transfectant \ cell migration.

\ \ \ C-C chemokine receptor activity ; GO:0016493 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 23848 IPR005379

The XH (rice gene X Homology) domain is found in a family of plant proteins including Oryza sativa Q9SBW2) that is also found in the PTGS protein SGS3. As the XS and XH domains are fused in most of these proteins, these two domains may interact. The XH domain is between 124 and 145 residues in\ length and contains a conserved glutamate residue that may be functionally important PUB00007755.

\ \ \N \N \N 23842 IPR005373

Members of this family are proteins of unknown function.

\ molecular_function unknown ; GO:0005554 \N \N 23843 IPR005374

This is a small family of mainly hypothetical proteins of unknown function.

\ molecular_function unknown ; GO:0005554 \N \N 23844 IPR005375

This family contains a number of small uncharacterised proteins including BM-002 Q9NZF2.

\ molecular_function unknown ; GO:0005554 \N \N 23845 IPR005376

The adenovirus single-stranded DNA binding protein (Ad DBP) is a multifunctional protein required, amongst other things, for DNA replication and transcription control. It binds to single- and double-stranded DNA, as well as to RNA, in a sequence-independent\ manner. This signature represents the zinc binding domain of the viral DNA- binding protein, which is active in DNA replication. The zinc atoms appear to be required for the stability of the protein fold rather than being involved in\ direct contacts with the DNA, the protein contains two zinc atoms in\ different, novel coordinations. Two copies of this domain are found at the C-terminus of many members of the family [MEDLINE:94313980].

\ \ zinc ion binding activity ; GO:0008270 \N DNA replication ; GO:0006260 23846 IPR005377

The movement of lipid and protein components between intracellular organelles requires the regulated interactions of many molecules. Vacuolar protein sorting-associated protein (Vps)5 is a yeast protein that is a subunit of a large multimeric complex, termed the retromer complex, involved in retrograde transport of proteins from endosomes to the trans-Golgi network. Sorting nexin (SNX) 1 and SNX2 are its mammalian orthologs [MEDLINE:20556005].

To carry out its biological functions, Vps5 forms the retromer complex\ with at least four other proteins: Vps17, Vps26, Vps29, and Vps35 [MEDLINE:20556005]. This family of Vps26-proteins also contains Down syndrome critical region 3/A.

\ \ \N \N intracellular protein transport ; GO:0006886 23831 IPR005361

This is a small family of hypothetical bacterial proteins of unknown function.

\ molecular_function unknown ; GO:0005554 \N \N 23832 IPR005362

This family of uncharacterised proteins are only found in Treponema pallidum. They contain a putative signal peptide so may be secreted proteins.

\ molecular_function unknown ; GO:0005554 \N \N 23833 IPR005363

The proteins in this family are about 200 amino acids long and each contain 3 CXXC motifs.

\ molecular_function unknown ; GO:0005554 \N \N 23834 IPR005365

This is a small family of proteins of unknown function.

\ molecular_function unknown ; GO:0005554 \N \N 23835 IPR005366

This is a small family of proteins of unknown function.

\ molecular_function unknown ; GO:0005554 \N \N 23836 IPR005367

This is a small family of mainly hypothetical bacterial proteins of unknown function.

\ molecular_function unknown ; GO:0005554 \N \N 23837 IPR005368

This family contains small proteins of unknown function.

\ molecular_function unknown ; GO:0005554 \N \N 23838 IPR005369

The function of this family is unknown, however the proteins contain two cysteine clusters that may be iron sulphur redox centres.

\ molecular_function unknown ; GO:0005554 \N \N 23839 IPR005370

The members of this family are small uncharacterised proteins.

\ molecular_function unknown ; GO:0005554 \N \N 23840 IPR005371

This family contains small proteins of about 50 amino acids of unknown function. The family includes YoaH P76260.

\ molecular_function unknown ; GO:0005554 \N \N 23841 IPR005372

This family contains uncharacterised integral membrane proteins.

\ molecular_function unknown ; GO:0005554 integral to membrane ; GO:0016021 \N 23820 IPR005350

This family of bacterial proteins includes a number of plasmid-encoded virulence proteins.

\ molecular_function unknown ; GO:0005554 \N \N 23821 IPR005351

This is a small family of proteins of unknown function which appear to be related to the hypothetical protein CG10674 from Drosophila melanogaster (Q9VRJ8).

\ molecular_function unknown ; GO:0005554 \N \N 23822 IPR005352

This family of uncharacterised proteins are integral membrane proteins. They may contain 4 transmembrane helices. The family contains a conserved arginine and histidine that may be functionally important.

\ molecular_function unknown ; GO:0005554 integral to membrane ; GO:0016021 \N 23823 IPR005353

The function of this family of proteins is unknown.

\ molecular_function unknown ; GO:0005554 \N \N 23824 IPR005354

This family of small proteins has no known function.

\ molecular_function unknown ; GO:0005554 \N \N 23825 IPR005355

This small family of uncharacterised proteins contains a potential zinc binding motif.

\ molecular_function unknown ; GO:0005554 \N \N 23826 IPR005356

The protein in this family are about 190 amino acids long. The function of these proteins is unknown.

\ molecular_function unknown ; GO:0005554 \N \N 23827 IPR005357

This family of small proteins is uncharacterised. In Q9A3L8, which suggests that this is some kind of ligand binding domain.

\ molecular_function unknown ; GO:0005554 \N \N 23828 IPR005358

This family of proteins contain 8 conserved cysteines that may form a zinc binding site. The function of these proteins is unknown.

\ molecular_function unknown ; GO:0005554 \N \N 23829 IPR005359

This family contains a set of short bacterial proteins of unknown function.

\ molecular_function unknown ; GO:0005554 \N \N 23830 IPR005360

Members of this family of proteins are about 80 amino acids in length and their function is unknown. The proteins contain a conserved GRY motif.

\ molecular_function unknown ; GO:0005554 \N \N 23818 IPR005348

This is a family of small integral membrane proteins found in some archaebacteria.

\ molecular_function unknown ; GO:0005554 integral to membrane ; GO:0016021 \N 23819 IPR005349

This family of short membrane proteins is as yet uncharacterised.

\ molecular_function unknown ; GO:0005554 membrane ; GO:0016020 \N 23807 IPR005336

This is a family of proteins of unknown function.

\ molecular_function unknown ; GO:0005554 \N \N 23808 IPR005337

This is a family of putative P-loop ATPases. Many of the proteins in this family are hypothetical and kinase activity has been proposed for some family members.

\ \N \N \N 23809 IPR005338

The proteins is this family are about 370 amino acids long and have no known function.

\ molecular_function unknown ; GO:0005554 \N \N 23810 IPR005339

This is a small family of mainly hypothetical proteins of unknown function.

\ molecular_function unknown ; GO:0005554 \N \N 23811 IPR005340

This is a family of mainly hypothetical proteins of unknown function.

\ molecular_function unknown ; GO:0005554 \N \N 23812 IPR005341

This is a small family of proteins of unknown function.

\ molecular_function unknown ; GO:0005554 \N \N 23813 IPR005343

This is a small family of mainly hypothetical proteins of unknown function.

\ molecular_function unknown ; GO:0005554 \N \N 23814 IPR005344

Uncharacterised integral membrane protein family.

\ molecular_function unknown ; GO:0005554 integral to membrane ; GO:0016021 \N 23815 IPR005345

The proteins of this family are uncharacterised, they contain five CXXC motifs.

\ molecular_function unknown ; GO:0005554 \N \N 23816 IPR005346

This is a small family of proteins of unknown function.

\ \N \N \N 23817 IPR005347

This family of proteins are uncharacterised, however BtrG Q9F1Z7.

\ molecular_function unknown ; GO:0005554 \N \N 23805 IPR005334

Tctex-1 is a dynein light chain. Dynein translocates rhodopsin-bearing vesicles along microtubules and it has been shown that Tctex-1 can bind to the cytoplasmic tail of rhodopsin. An efficient vectorial transport system must be required to deliver large numbers of newly synthesized rhodopsin molecules (~10⁷ molecules per\ day per photoreceptor) to the base of the outer segment of the photoreceptor, Tctex-1 may well play a role in this process. C-terminal rhodopsin mutations responsible for retinitis pigmentosa inhibit the interaction between Tctex-1 and rhodopsin, which may be the molecular basis of\ retinitis pigmentosa.

In the mouse, the\ chromosomal location and pattern of expression of Tctex-1 make it a candidate for involvement in male sterility [MEDLINE:89376546].

\ \ \N \N \N 23806 IPR005335

Packaging of double-stranded viral DNA concatemers requires interaction of the prohead with virus DNA. This process is mediated by a phage-encoded DNA recognition and terminase protein. The terminase enzymes described so far, which are hetero-oligomers composed of a small and a large subunit, do not have a significant level of sequence homology. The small terminase subunit is thought to form a nucleoprotein structure that helps to position the terminase large subunit at the packaging initiation site [MEDLINE:90024953].

\ \N \N DNA packaging ; GO:0006323 23800 IPR005329

SNXs are hydrophilic molecules that are localized in the cytoplasm and have the potential for membrane association either through their lipid-binding\ PX domains (IPR001683) or through proteinprotein interactions with membrane-associated\ protein complexes [MEDLINE:22350170]. Indeed, several of the SNXs require several targeting motifs\ for their appropriate cellular localization. In almost every case studied,\ mammalian SNXs can be shown to have a role in protein sorting, with the\ most commonly used experimental model being plasma-membrane receptor\ endocytosis and sorting through the endosomal pathway. However, it is equally\ probable that SNXs sort vesicles that are not derived from the plasma\ membrane, and have a function in the accurate targeting of these vesicles and\ their cargo.

The N-terminal domain appears to be specific to sorting nexins 1 and 2. SNX1 is both membrane-associated and cytosolic, where it probably exists as a\ tetramer in large protein complexes and may hetero-oligomerize with SNX2.

\ \ protein transporter activity ; GO:0008565 \N intracellular protein transport ; GO:0006886 23804 IPR005333

The cycloidea (cyc) and teosinte branched 1 (tb1) genes code for structurally related proteins implicated in the evolution of key morphological traits. However, the biochemical function of CYC and TB1 proteins remains to be demonstrated. One of the conserved regions is predicted to form a non-canonical basic-Helix-Loop-Helix (bHLP) structure. This domain is also found in two rice DNA-binding proteins, PCF1 and PCF2, where it has been shown to be involved in DNA-binding and dimerization. This indicates a new family of transcription factors, which we have termed the TCP family after its first characterised members (TB1, CYC and PCFs) [MEDLINE:99291552].

\ \N \N \N 23802 IPR005331

Chondroitin 4-sulfotransferase catalyses the transfer of sulfate to the C-4 position of N-acetylgalactosamine in chondroitin and desulfated dermatan sulfate but did not form 4, 6-di-O-sulfated\ N-acetylgalactosamine when chondroitin sulfate C was used as an acceptor. This suggests that 4-O-sulfation at N-acetylgalactosamine may precede epimerization of glucuronic acid to iduronic acid during dermatan sulfate\ biosynthesis. HNK-1 and other Golgi-associated sulfotransferases share homologous sequences\ including the RDP motif.

\ \ \N \N \N 23803 IPR005332

Two small nested genes (p19 and p22) are located near the 3' end of the genome of tomato bushy stunt virus (TBSV) - the p19 gene encodes a soluble protein, whereas the p22 gene specifies a membrane-associated protein. p22 is required for cell-to-cell movement in all plants tested. [MEDLINE:96074518].

\ \ \N viral capsid ; GO:0019028 \N 23801 IPR005330

This pattern is found as an N-terminal triplet tandem repeat in bacterial signalling proteins. Proteins containing this repeat include CoxC (Q9KX27) from Pseudomonas carboxydovorans. Each repeat contains two transmembrane helices.

\ \N \N \N 23797 IPR005326

This presumed domain is found at the N terminus of some isoforms of the cytoskeletal muscle protein plectin as well as the ribosomal S10 protein. This domain may be involved in RNA binding.

\ \N \N \N 23798 IPR005327

The small hydrophobic integral membrane protein, SH (previously designated 1A) is found to have a variety of glycosylated forms [MEDLINE:93033134], [MEDLINE:90324943]. This protein is a component of the mature respiratory syncytial virion [MEDLINE:93033134] where it may form complexes and appears to play a structural role.

\ \N \N \N 23799 IPR005328

Serotype M1 group A Streptococcus strains cause epidemic waves of human infections. This family includes the sic protein, an extracellular protein (streptococcal inhibitor of complement) that inhibits human complement [MEDLINE:99353360]. The exact mechanism of inhibition has not been completely elucidated, but Sic is\ incorporated into the complement membrane-attack complex\ (C5bC9) responsible for target killing. Preliminary analysis of variation in the sic gene in\ M1 Group A streptococci strains identified a level of polymorphism far\ exceeding that of other genes in these organisms, selection of new\ Sic structural variants on mucosal surfaces generates a very\ large pool of subclones in the course of epidemic waves. This\ process may help to sustain and enlarge the epidemic waves

\ \ \N \N \N 23793 IPR005322

Five catalytic types of peptidase can now be identified in which serine, threonine, cysteine, aspartic or metallo groups play primary roles in catalysis. The serine, threonine and cysteine peptidases utilise the catalytic part of an amino acid as a nucleophile and form an acyl intermediate - these peptidases can also readily act as transferases. In the case of aspartic and metallopeptidases, the nucleophile is an activated water molecule.

The systemic nomenclature for peptidases is detailed in the Handbook of Proteolytic Enzymes ed Barret, Rawlings and Woessner ed. Academic Press or by accessing the MEROPs website [http://www.merops.co.uk/merops/merops.htm]

All peptidases classified as unknown, have an unidentified catalytic mechanism.

Proteins in this family appear to be mainly dipeptidases and belong to the U34 peptidase group.

\ \ dipeptidase activity ; GO:0016805 \N proteolysis and peptidolysis ; GO:0006508 23794 IPR005323

Domain is found in pullanase - carbohydrate de-branching - proteins. It is found both to the N or the C-terminii of of the -amylase active site region. This domain contains several conserved aromatic residues that are suggestive of a carbohydrate binding function.

\ carbohydrate binding activity ; GO:0030246 \N carbohydrate metabolism ; GO:0005975 23795 IPR005324

This is a family of proteins related to the 30S ribosomal protein S5P from Sulfolobus acidocaldarius (O05641). Ribosomal protein S5 is one of the proteins from the small ribosomal subunit. In Escherichia coli, S5 is known to be important in the assembly and function\ of the 30S ribosomal subunit. Mutations in S5 have been shown to increase\ translational error frequencies.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 23796 IPR005325

This represents a group of short repeats that occurs in a limited number of membrane proteins. It may divide further in short repeats of around 7-10 residues of the pattern G-#-X(2)-#(2)-X (#=hydrophobic).

\ \N \N \N 23792 IPR005321

Proteins in this family are all members of the T4 group of proteases. The family contains several examples of D-aminopeptides.

\ \ \N \N \N 23790 IPR005319

Proteins in this family are all members of the S48 group of serine proteases.

\ \ \N \N \N 23791 IPR005320

\ \

Proteins in this family are all members of the S51 group of serine proteases.

\ \ peptidase activity ; GO:0008233 \N proteolysis and peptidolysis ; GO:0006508 23783 IPR005311

This domain is found at the N-terminus of Class B High Molecular Weight Penicillin-Binding Proteins. Its function has not been precisely defined, but is strongly implicated in PBP polymerisation. The domain forms a largely disordered "sugar tongs" structure.

\ penicillin binding activity ; GO:0008658 \N \N 23784 IPR005312

This is a small family of peptidases of unknown function found exclusively in a nematodes.

\ \N \N \N 23785 IPR005313

Aspartate peptidases are so named because Asp residues are the ligands of the activated water molecule in all examples where the catalytic residues have been identifed, although at least one viral enzyme is believed to have as Asp and an Asn as its catalytic dyad. All or most aspartate peptidases are endopeptidases. These enzymes have been assigned into clans, and further sub-divided into families, largely on the basis of their tertiary structure.

This small family of peptidases is found as a capsid protein in some tetraviridae.

\ \ \N \N \N 23786 IPR005314

The proteolytic enzymes that depend upon a cysteine residue for activity have come from at least seven different evolutionary origins, each of which has produced a group of cysteine peptidases with distinctive structures and properties. Separin-like proteases (C50) are members of Clan CD which also contains the families of clostripain (C11), gingipain R (C25), legumain (C13) and caspase-1 (C14). These enzymes have specificities dominated by the interactions of the S1 subsite.

\ \N nucleus ; GO:0005634 \N 23787 IPR005315

\ Peptidases in which the nucleophile is the sulphydryl group of a cysteine residue are known as cysteine peptidases. The protein donor in all or most cysteine proteases is a His residue - a third residue to orientate the imidazolium ring of the histidine is not always required in this group of proteases. Cysteine proteases are divided into clans, and further sub-divided into families, on the basis of the architecture of their catalytic dyad or triad.

This family consists of a small group of peptidases of unknown function which are found in Cryphonectria hypovirus.

\ \ molecular_function unknown ; GO:0005554 \N \N 23788 IPR005317

This family mainly consists of dipeptidyl peptidase III aminopeptidases which cleave dipeptides from the N-terminal of peptides consisting of four or more amino acids and act with broad specificity.

\ dipeptidyl-peptidase III activity ; GO:0017039 cytoplasm ; GO:0005737 proteolysis and peptidolysis ; GO:0006508 23789 IPR005318

This is a family of probable porin proteins. One of them, porin D2 (OprD) of the outer membrane of Pseudomonas aeruginosa, was demonstrated to be a member of the serine protease family [MEDLINE:98300298]. Physiological role of the protein could be to bind ligands and to facilitate the diffusion through the channel. This family might be a family of proteins, bearing both porin and protease activities.

\ \ porin activity ; GO:0015288 integral to membrane ; GO:0016021 transport ; GO:0006810 23782 IPR005310

PapG, the adhesin of the P-pili, is situated at the tip and is only a minor component of the whole pilus structure. A two-domain structure has been postulated for PapG; a carbohydrate binding N-terminus (this domain) and chaperone binding C-terminus. The carbohydrate-binding domain interacts with the receptor glycan [MEDLINE:21356497], [MEDLINE:21334150].

\ carbohydrate binding activity ; GO:0030246 \N cell adhesion ; GO:0007155 23781 IPR005309

PapG, the adhesin of the P-pili, is situated at the tip and is only a minor component of the whole pilus structure. A two-domain structure has been postulated for PapG; a carbohydrate binding N-terminus and chaperone binding C-terminus (this domain). The chaperone-binding domain is highly conserved, and is essential for the correct assembly of the pili structure when aided by the chaperone molecule PapD [MEDLINE:21356497], [MEDLINE:21334150].

\ \N \N \N 23776 IPR005304

Originally isolated from Schizosaccharomyces pombe, Mra1 (Q10107 and lies downstream of Ras1 in a unique signal transduction pathway.

\ \N nucleus ; GO:0005634 ribosome biogenesis ; GO:0007046 23777 IPR005305

The members of this family are derived from nepoviruses. Together with comoviruses and picornaviruses, nepoviruses are classified in the picornavirus superfamily of plus strand single-stranded RNA viruses. This family aligns several nepovirus coat protein sequences. In several cases, this is found at the C-terminus of the RNA2-encoded viral polyprotein. The coat protein consists of three trapezoid-shaped -barrel domains, and forms a pseudo T = 3 icosahedral capsid structure [MEDLINE:98179933].

\ \N viral capsid ; GO:0019028 \N 23778 IPR005306

\ \N viral capsid ; GO:0019028 \N 23779 IPR005307

The nuclear movement protein or NudC, was first identified as a nuclear distribution (nud) gene that regulates nuclear movement in the filamentous fungus. The mammalian homologue of NudC interacts with Lis1, a neuronal migration protein important during neocorticogenesis. Nuclear movement and neuronal migration are thought to use a common mechanism [MEDLINE:21602212].

\ \N \N \N 23780 IPR005308

This domain has a flavodoxin-like fold, and is termed the "wing" domain because of its position in the overall 3D structure. Ornithine decarboxylase from Lactobacillus 30a (L30a OrnDC, P43099) is representative of the large, pyridoxal-5'-phosphate-dependent decarboxylases that act on lysine, arginine or ornithine. The crystal structure of the L30a OrnDC has been solved to 3.0 A resolution. Six dimers related by C6 symmetry compose the enzymatically active\ dodecamer (approximately 10⁶ Da). Each monomer of L30a OrnDC can be described in terms of five sequential folding domains.\ The amino-terminal domain, residues 1 to 107, consists of a five-stranded -sheet termed the "wing" domain. Two wing domains of\ each dimer project inward towards the center of the dodecamer and contribute to dodecamer stabilization [MEDLINE:96017733].

\ \ carboxy-lyase activity ; GO:0016831 \N \N 23774 IPR005302

The MOSC (MOCO sulfurase C-terminal) domain is a superfamily of -strand-rich domains identified in the molybdenum cofactor sulfurase and several other proteins from both prokaryotes and eukaryotes. These MOSC domains contain an absolutely conserved cysteine and occur either as stand-alone forms such as P32157, or fused to other domains such as NifS-like catalytic domain in Molybdenum cofactor sulfurase. The MOSC domain is predicted to be a sulfur-carrier domain that receives sulfur abstracted by the pyridoxal phosphate-dependent NifS-like enzymes, on its conserved cysteine, and delivers it for the formation of diverse sulfur-metal clusters.

\ \N \N \N 23775 IPR005303

This domain is found to the N-terminus of MOSC domain (IPR005302). The function of this domain is unknown, however it is predicted to adopt a barrel fold.

\ \N \N \N 23773 IPR005301

Mob1 is an essential Saccharomyces cerevisiae protein, identified from a two-hybrid screen, that binds Mps1p, a protein kinase essential for spindle pole body duplication and mitotic checkpoint regulation. Mob1 contains no known structural motifs; however MOB1 is a member of a conserved gene family and shares sequence similarity with a nonessential yeast gene, MOB2. Mob1 is a phosphoprotein in vivo and a substrate for the Mps1p kinase in vitro. Conditional alleles of MOB1 cause a late nuclear division arrest at restrictive temperature [MEDLINE:98099687]. This family also includes phocein Q9QYW3.

\ \N \N \N 23767 IPR005295

These proteins are the product of ORF 3B from Avian infectious bronchitis virus (IBV). Currently, the function of this protein remains unknown [MEDLINE:97311409].

\ \N \N \N 23768 IPR005296

These proteins are the product of ORF 3C from Avian infectious bronchitis virus (IBV). Currently, the function of this protein remains unknown.

\ \N \N \N 23769 IPR005297

This family occurs as tandem repeats in a set of lipoproteins. The alignment contains a Y-X4-D motif.

\ \N \N \N 23770 IPR005298

This presumed 110 amino acid residue domain is found in multiple copies in MAP (MHC class II analog protein) Q9Z4J2\ \ \ [MEDLINE:95394893]. Each of the repeated domains contain a subdomain of 31 residues that share striking sequence homology with a segment in the peptide binding groove of the chain of the major histocompatibility complex (MHC) class II proteins from different mammalian species. The domain has been found to a range of other extracellular matrix proteins [MEDLINE:95394893] and may play a role in protein recognition and binding.

\ \ \N \N \N 23771 IPR005299

This family of plant methyltransferases contains enzymes that act on a variety of substrates including salicylic acid, jasmonic acid and 7-Methylxanthine. Caffeine is synthesized through sequential three-step methylation of xanthine derivatives at positions 7-N, 3-N, and 1-N. The protein 7-methylxanthine methyltransferase (designated as CaMXMT) catalyses the second step to produce theobromine [MEDLINE:21269383].

\ \N \N \N 23765 IPR005293

Proteins of this family are involved in the transport of antigens from the cytoplasm to a membrane-bound compartment for association with MHC class I molecules.

\ \ \N \N \N 23766 IPR005294

The sequences of ATP synthase F1 (EC: 3.6.3.14) and subunits are related and both contain a nucleotide-binding site for ATP and ADP. They have a common amino terminal domain but vary at the C-terminus. The chain has catalytic activity, while the chain is a regulatory subunit. The -subunit contains a highly conserved adenine-specific noncatalytic nucleotide-binding domain. The conserved amino acid sequence is Gly-X-X-X-X-Gly-Lys. Proton translocating ATP synthase F1, subunit is homologous to proton translocating ATP synthase archaeal/vacuolar(V1), B subunit.

\ \N \N \N 23772 IPR005300

This family of proteins includes MltA; a membrane-bound, murein degrading transglycosylase enzyme which plays an important role in the controlled growth of the stress-bearing sacculus of E. coli. [MEDLINE:99156961],[MEDLINE:97431497].

\ \ hydrolase activity, hydrolyzing O-glycosyl compounds ; GO:0004553 \N \N 23764 IPR005292

This family consists of multi drug resistance-associated protein (MRP) in eukaryotes. The multidrug resistance-associated protein is an integral membrane protein that causes multidrug resistance when overexpressed in mammalian cells. It belongs to the ABC transporter superfamily. The protein topology and function was experimentally demonstrated by epitope tagging and immunofluorescence. Insertion of tags in the critical regions associated with drug efflux reduced its function. The C-terminal domain seems to be highly conserved.

\ \ \N \N \N 23763 IPR005291

These proteins are integral membrane proteins and they are involved in the transport of chloride ions. Many of these proteins are the cystis fibrosis transmembrane conductor regulators (CFTR) in\ eukaryotes. The principal role of this protein is chloride ion conductance. The protein is\ predicted to consist of 12 transmembrane domains. Mutations or lesions in the genetic loci\ have been linked to the aetiology of asthma, bronchiectasis, chronic obstructive pulmonary\ disease etc. Disease-causing mutations have been studied by 36Cl efflux assays in vitro\ cell cultures and electrophysiology, all of which point to the impairment of chloride channel\ stability and not the biosynthetic processing per se.

\ \ \N \N \N 23761 IPR005289

This is a GTP-binding domain, that was found in proteins from various families (Ras GTPase superfamily, HSR1-related GTP-binding protein), which perform different functions.

\ \N \N \N 23762 IPR005290

\ \ \

This family includes specifically bacterial, chloroplast, and mitochondrial ribosomal protein S15. The homologous proteins of Archaea and Eukarya are designated S13.

\ \

Escherichia coli ribosomal protein S15 has been shown to regulate the expression of its own mRNA by a feedback mechanism at the translational level. The translational\ operator overlaps the ribosome binding site and folds into two mutually exclusive structures, one consisting of two stem-loops (I and II) and the other one\ forming a pseudoknot. The two structures, which seem to be energetically equivalent are in dynamic equilibrium, and the\ pseudoknot is stabilized by binding of S15. However, binding of S15 does not prevent 30 S subunit binding but traps the subunit into an incompetent\ translation initiation complex. Repression can be alleviated by 16 S rRNA, which is able to displace the bound S15, thus allowing translation to\ proceed [MEDLINE:22125950].

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 23759 IPR005287

This family of conserved hypothetical proteins has no known function.

\ \N \N \N 23760 IPR005288

L-aspartate oxidase is the B protein, NadB, of the quinolinate synthetase complex. Quinolinate synthetase makes a precursor of the pyridine nucleotide portion of NAD. This model identifies proteins that cluster as L-aspartate oxidase (a flavoprotein difficult to separate from the set of closely related flavoprotein subunits of succinate dehydrogenase and fumarate reductase) by both UPGMA and neighbor-joining trees.

\ \N \N \N 23758 IPR005286

The proteins of this family are thought to belong to ABC transporter family. Their function is unknown.

\ \ \N \N \N 23756 IPR005284

This family includes different parts of a membrane-spanning permease system necessary for the transport of pigment precursor into pigment cells responsible for eye color. White protein dimerises with brown protein for the transport of guanine and with scarlet protein for the transport of tryptophan.

\ \ \N \N \N 23757 IPR005285

This family includes transporters, whose physiological function is not yet established. These proteins are thought to confer resistance to the chemicals cycloheximide and sulfomethuron methyl, BFA, azole antifungal agents, other antifungal agents: amorolfine and terbinafine. Some of them could serve as an efflux pump of various antibiotics.

\ \ \N \N \N 23754 IPR005282

Most of the members of this family are integral membrane lysosomal proteins and they are thought to transport cystines out of lysosomes.

\ \N \N \N 23755 IPR005283

The members of this family are integral membrane proteins and they are involved in the import of activated long-chain fatty acids from the cytosol to the peroxisomal matrix.

\ \ \N \N \N 23751 IPR005279

The transport of peptides into cells is a well-documented biological phenomenon which is accomplished by specific, energy-dependent transporters found in a number of organisms as diverse as bacteria and humans. The PTR family of proteins is distinct from the ABC-type peptide transporters and was uncovered by sequence analysis of a number of recently discovered peptide transport proteins [MEDLINE:96059630].

This family consists of bacterial proton-dependent oligopeptide transporters, although they are found in yeast, plants and animals. They function by proton symport in a 1:1 stoichiometry, which is variable in different species. All of them are predicted to contain 12 transmembrane domains, for which limited experimental evidence exists.

\ \ \N \N \N 23752 IPR005280

Homoserine kinase is required in the biosynthesis of threonine from aspartate.The member of this family from Pseudomonas aeruginosa was shown by direct assay and complementation to act specifically as a homoserine kinase.

\ \N \N \N 23753 IPR005281

\ \ \N \N \N 23750 IPR005277

The MFS is a very old, large and diverse superfamily that includes several hundred sequenced members. They catalyze uniport, solute:cation (H+ or Na+) symport and/or solute:H+ or solute:solute antiport. Most are of 400-600 amino acyl residues in length and possess either 12 or 14 putative transmembrane a-helical spanners. They exhibit specificity for sugars, polyols, drugs, neurotransmitters, Krebs cycle metabolites, phosphorylated glycolytic intermediates, amino acids, peptides, osmolites, nucleosides, organic anions, inorganic anions, etc. They are found ubiquitously in all three kingdoms of living organisms. The generalized transport reactions catalyzed by MFS porters are:

(1)Uniport: S (out) S (in).

\ \

(2)Symport: S (out) + [H+ or Na+] (out) ---> S (in) + [H+ or Na+] (in).

\ \

(3)Antiport: S1 (out) + S2 (in) S1 (in) + S2 (out), (S1 may be H+ or a solute)\

\ \

This family of proteins are uncharacterized proteins from archaea, which may be major facilitators. This family includes proteins from Archaeoglobus fulgidus and Aeropyrum pernix.

\ \ \N \N \N 23745 IPR005272

These small proteins are approximately 100 amino acids in length and appear to be found only in gamma proteobacteria. The function of this protein family is unknown.

\ \ \ \ \N \N \N 23746 IPR005273

This well-conserved family of proteins is about 200 residues in length and homologous to the N-terminus of the DNA polymerase of phage SPO1 of Bacillus subtilis. The function of these proteins is unknown.

\ \N \N \N 23747 IPR005274

Members of this family show similarity to ribonuclease BN, but their function is unknown.

\ \N \N \N 23748 IPR005275

This family describes the L-fucose permease in bacteria. L-fucose(6-deoxy-L-galactose) is a monosaccharide found in glycoproteins and cell wall polysaccharides. L-fucose is used in bacteria through an inducible pathway mediated by at least four enzymes: a permease, isomerase, kinase and an aldolase which are encoded by fucP, fucI, fucK, fucA respectively.

\ \N \N \N 23749 IPR005276

This family of proteins is involved in the uptake of 3-phenylpropionic acid. This uptake mechanism is for the metabolism of phenylpropanoid compounds and plays an important role in the natural degradative cycle of these aromatic molecules.

\ \N \N \N 23737 IPR005264

N-acetylneuraminate lyase catalyzes the cleavage of N-acetylneuraminic acid (sialic acid) to form pyruvate and N-acetyl-D-mannosamine. The enzyme plays an important role in the regulation of sialic acid metabolism in bacteria.

\ \N \N \N 23738 IPR005265

It appears the conserved hypothetical integral membrane proteins of this family are found only in gram negative bacteria and their function is unknown.

\ \N \N \N 23739 IPR005266

The function of this family is unknown. These proteins are from 222 to 233 residues in length, lack hydrophobic stretches, and are found so far only in thermophiles.

\ \N \N \N 23740 IPR005267

This family includes very hydrophobic proteins, predicted to span the membrane at least 8 times. The two members confirmed experimentally as glycerol-3-phosphate transporters, from E. coli and B. subtilis, share more than 50 % amino acid identity.

\ \N \N \N 23741 IPR005268

This family of conserved hypothetical proteins has no known function.

\ \N \N \N 23742 IPR005269

This family of conserved hypothetical proteins has no known function.

\ \N \N \N 23743 IPR005270

The function of this family is unknown, but it may include TIM-barrel proteins.

\ \N \N \N 23744 IPR005271

Methyl transfer from the ubiquitous S-adenosyl-L-methionine (AdoMet) to either nitrogen, oxygen or carbon atoms is frequently employed in diverse organisms ranging from bacteria to plants and mammals. The reaction is catalyzed by methyltransferases (Mtases) and modifies DNA, RNA, proteins and small molecules, such as catechol for regulatory purposes. The various aspects of the role of DNA methylation in prokaryotic restriction-modification systems and in a number of cellular processes in eukaryotes including gene regulation and differentiation is well documented.

Three classes of DNA Mtases transfer the methyl group from AdoMet to the target base to form either N-6-methyladenine, or N-4-methylcytosine, or C-5- methylcytosine. In C-5-cytosine Mtases, ten conserved motifs are arranged in the same order [MEDLINE:94173650]. Motif I (a glycine-rich or closely related consensus sequence; FAGxGG in M.HhaI [MEDLINE:93345018]), shared by other AdoMet-Mtases [MEDLINE:90062128], is part of the cofactor binding site and motif IV (PCQ) is part of the catalytic site. In contrast, sequence comparison among N-6-adenine and N-4-cytosine Mtases indicated two of the conserved segments [MEDLINE:90098846], although more conserved segments may be present. One of them corresponds to motif I in C-5-cytosine Mtases, and the other is named (D/N/S)PP(Y/F). Crystal structures are known for a number of Mtases [MEDLINE:95331548], [MEDLINE:93345018], [MEDLINE:94173650], [MEDLINE:95062184]. The cofactor binding sites are almost identical and the essential catalytic amino acids coincide. The comparable protein folding and the existence of equivalent amino acids in similar secondary and tertiary positions indicate that many (if not all) AdoMet-Mtases have a common catalytic domain structure. This permits tertiary structure prediction of other DNA, RNA, protein, and small-molecule AdoMet-Mtases from their amino acid sequences [MEDLINE:95205408].

\ \

The proteins of this family are restricted to the Proteobacteria, sharing consistent length, full-length homology, and on average better than 35 % identity. It is reasonable to predict equivalent function within this subfamily.

\ \ \N \N \N 23734 IPR005261

Members of this small but broadly distibuted (Gram-positive, Gram-negative, and Archaeal) family appear to have multiple transmembrane segments. The function is unknown.

\ \N \N \N 23735 IPR005262

The function of this domain is unknown. A small region (~50 amino acids) within the domain appears to be related to a family of sugar transferases.

\ \ \N \N \N 23736 IPR005263

Dihydropicolinate synthase (DHDPS, EC: 4.2.1.52) is the key enzyme in lysine biosynthesisvia the diaminopimelate pathway of prokaryotes, some phycomycetes and\ higher plants. The enzyme catalyses the condensation of L-aspartate--\ semialdehyde and pyruvate to dihydropicolinic acid via a ping-pong\ mechanism in which pyruvate binds to the enzyme by forming a Schiff-base\ with a lysine residue [MEDLINE:95156485]. Three other proteins are structurally related to DHDPS and probably also act\ via a similar catalytic mechanism. These are E. coli N-acetylneuraminate lyase (EC: 4.1.3.3, IPR005264) (gene nanA), which\ catalyzes the condensation of N-acetyl-D-mannosamine and pyruvate to form\ N-acetylneuraminate; Rhizobium meliloti protein mosA [MEDLINE:93352426], which is involved in the biosynthesis\ of the rhizopine 3-O-methyl-scyllo-inosamine; and E. coli hypothetical protein yjhH.\ The sequences of DHDPS from different sources are well-conserved. The\ structure takes the form of a homotetramer, in which 2 monomers are\ related by an approximate 2-fold symmetry [MEDLINE:95156485]. Each monomer comprises\ 2 domains: an 8-fold -/-barrel, and a C-terminal -helical\ domain. The fold resembles that of N-acetylneuraminate lyase. The active\ site lysine is located in the barrel domain, and has access via 2 channels\ on the C-terminal side of the barrel.

This family represents a subclass of dihydrodipicolinate synthase.

\ \ \N \N \N 23731 IPR005258

Cyclins are eukaryotic proteins which play an active role in controlling nuclear cell division cycles PUB00001013,PUB00001013, PUB00005504 , and regulate cyclin dependent kinases (CDKs). Cyclins, together with the p34 (cdc2) or\ cdk2 kinases, form the Maturation Promoting Factor (MPF). There are two main groups of cyclins, G1/S cyclins, which\ are essential for the control of the cell cycle at the G1/S (start) transition, and G2/M cyclins, which are essential\ for the control of the cell cycle at the G2/M (mitosis) transition. G2/M cyclins accumulate steadily during G2 and\ are abruptly destroyed as cells exit from mitosis (at the end of the M-phase). In most species, there are multiple\ forms of G1and G2 cyclins. For example, in vertebrates, there are two G2 cyclins, A and B, and at least three\ G1 cyclins, C, D, and E. A cyclin homolog has also been found in herpesvirus saimiri\ \ \ \ PUB00005504.

All proteins in this family for which functions are known are cyclins that are components of TFIIH, a complex that is involved in nucleotide excision repair and transcription initiation.

\ \ \N \N \N 23732 IPR005259

All proteins in this family for which functions are known are components of the primosome which is involved in replication, repair, and recombination.

\ \N \N \N 23733 IPR005260

This family is a subclass of aspartate kinases. These are mostly Lys-sensitive and not fused to homoserine dehydrogenase, unlike some Thr-sensitive and Met-sensitive forms. Homoserine dehydrogenase is part of Thr and Met but not Lys biosynthetic pathways.

Aspartate kinase catalyzes a first step in the biosynthesis from Asp to Lys (and its precursor diaminopimelate), Met, and Thr. In E. coli, a distinct isozyme is inhibited by each of the three amino acid products. The Met-sensitive (I) and Thr-sensitive (II) forms are bifunctional enzymes fused to homoserine dehydrogenases and form homotetramers, while the Lys-sensitive form (III) is a monofunctional homodimer.

The Lys-sensitive enzyme of Bacillus subtilis resembles the E. coli form but is an 2/ 2 heterotetramer, where the subunit is translated from an in-phase alternative initiator at Met-246. The protein slr0657 from Synechocystis PCC6803 is extended by a duplication of the C-terminal region corresponding to the chain. Incorporation of a second copy of the C-terminal domain may be quite common in this subgroup of aspartokinases.

\ \ \ \N \N \N 23724 IPR005251

The delineation of this family is based in part on a discussion and neighbor-joining phylogenetic study, by Kyrpides and Woese, of archaeal and other proteins homologous to the , , and delta subunits of eukaryotic initiation factor 2B (eIF-2B), a five-subunit molecule that catalyzes GTP recycling for eIF-2. They concluded that these proteins were related to the common ancestor of eIF-2B , , and delta rather then specifically to any one of them, and that designation of particular archaeal members as corresponding to eIF-2B or eIF-2B delta is imprecise. They suggest designating the archaeal set that includes MJ0454 as aIF-2BI and the set that includes MJ0122 as aIF-2BII, and viewing the role of these proteins in translation initiation as unproven. In an extension of their work, we find strong affinity between archaeal members of the aIF-2BI set and their closest eubacterial homologs, and so include all together as putative orthologs in this family, designated aIF-2BI_fam.

\ \N \N \N 23725 IPR005252

Two different ts mutants of this gene displayed auxotrophy for -alanine, while only one showed a defect in DNA synthesisat a higher non-permissive temperature. One pseudorevertant had increased levels of aspartate-1-decarboxylase (PanD), a pyruvoyl-dependent enzyme synthesized as an inactive proenzyme and responsible for the synthesis of -alanine. Homologs of dfp are found in species that lack a pathway for pantothenate biosynthesis but may have other pyruvoyl-dependent enzymes; this protein, a flavoprotein, might play a role in the maturation of\ panD and related proenzymes. Alternatively, it might degrade some toxic metabolite that otherwise inhibits panD.

\ \ \N \N \N 23726 IPR005253

This protein is predicted to have 10 transmembrane regions. Members of this family are found so far in the Archaea (Archaeoglobus fulgidus and Pyrococcus horikoshii) and in a bacterial thermophile, Thermotoga maritima. This family shows similarity (but not necessarily homology) to gluconate permease and other transport proteins.

\ \N \N \N 23727 IPR005254

This is a family of uncharacterized proteins encoded next to a heme-biosynthetic enzyme in two gamma division proteobacteria (Escherichia coli and Haemophilus influenzae). It is known in no other species. The gene symbol hemY is unfortunate in that an unrelated protein, protoporphyrinogen oxidase, is designated as HemG in E. coli but as HemY in Bacillus subtilis.

\ \ \ \N \N \N 23728 IPR005255

This is a family of 4-hydroxythreonine-4-phosphate dehydrogenase (EC: 1.1.1.262). PdxA protein takes part in vitamin B6 biosynthesis: it forms pyridoxine 5'-phosphate from 4-(phosphohydroxy)-L-threonine and 1-deoxy-D-xylulose-5-phosphate.

\ \ \N \N \N 23729 IPR005256

This enzyme resembles some other chorismate-binding enzymes, including para-aminobenzoate synthase (pabB) and isochorismate synthase. There is a fairly deep split between two sets, seen in the pattern of gaps as well as in amino acid sequence differences. This group includes eukaryotes, archaea, and many bacterial lineages; sequences from the second group may resemble pabB more closely than other trpE from the other group. The other group includes Gram-negative proteobacteria such as Escherichia coli and Helicobacter pylori but also the Gram-positive organism Corynebacterium glutamicum, and is described by IPR005257.

A sequence from Bacillus subtilis that scores above the trusted cutoff is annotated as PabB rather than TrpE. However, it is part of an operon that is required for Trp as well as folate biosynthesis, is Trp-repressible, and contains TrpG. It is likely that this sequence annotated as PabB functions both as PabB and as TrpE.

\ \ \ \N \N \N 23730 IPR005257

This enzyme resembles some other chorismate-binding enzymes, including para-aminobenzoate synthase (pabB) and isochorismate synthase. There is a fairly deep split between two sets, seen in the pattern of gaps as well as in amino acid sequence differences. This group includes proteobacteria such as Escherichia coli and Helicobacter pylori but also the gram-positive organism Corynebacterium glutamicum. The second group (IPR005256) includes eukaryotes, archaea, and most other bacterial lineages; sequences from the second group may resemble pabB more closely than other trpE from this group.

\ \ \N \N \N 23717 IPR005244

This entry describes a family of conserved hypothetical proteins with no known function.

\ \N \N \N 23718 IPR005245

This entry describes a family of conserved hypothetical proteins with no known function.

\ \N \N \N 23719 IPR005246

All known phenylalanyl-tRNA synthetases, excepting a monomeric mitochondrial form, have an 2 2 heterotetrameric structure. This family of archaeal proteins resembles known phenylalanyl-tRNA synthetase chains but is longer and of unknown function; more generally, it resembles class 2 aminoacyl tRNA ligases.

\ \N \N \N 23720 IPR005247

This entry describes a family of conserved hypothetical proteins with no known function.

\ \N \N \N 23721 IPR005248

This family of conserved hypothetical proteins has no known function. It may be a family of nicotinate-nucleotide adenylyltransferases (EC: 2.7.7.18).

\ \N \N \N 23722 IPR005249

This family of conserved hypothetical proteins has no known function.

\ \N \N \N 23723 IPR005250

The delineation of this family is based in part on a discussion and neighbor-joining phylogenetic study, by Kyrpides and Woese, of archaeal and other proteins homologous to the , , and delta subunits of eukaryotic initiation factor 2B (eIF-2B), a five-subunit molecule that catalyzes GTP recycling for eIF-2. They concluded that these proteins were related to the common ancestor of eIF-2B , , and delta rather then specifically to any one of them, and that designation of particular archaeal members as corresponding to eIF-2B or eIF-2B delta is imprecise. They suggest designating the archaeal set that includes MJ0454 as aIF-2BI and this set, which includes MJ0122, as aIF-2BII, and viewing the role of these proteins in translation initiation as unproven. So far, members of this family are found only in the Archaea, but not in all Archaea.

\ \N \N \N 23705 IPR005232

This family of conserved hypothetical proteins has no known function.

\ \N \N \N 23706 IPR005233

This domain is found in a family of archaeal proteins that includes AF0785 of Archaeoglobus fulgidus and in several eubacterial proteins, including the much longer protein sll1151 from Synechocystis PCC6803.

\ \ \N \N \N 23707 IPR005234

This family of conserved hypothetical proteins has no known function.

\ \N \N \N 23708 IPR005235

This family of conserved hypothetical proteins has no known function.

\ \N \N \N 23709 IPR005236

The proteins of this family have been found so far only in the four archaeal species. The central region of the proteins shows considerable homology to the amino-terminal half of dihydropteroate synthases.

\ \N \N \N 23710 IPR005237

This family of conserved hypothetical proteins has no known function.

\ \N \N \N 23711 IPR005238

Potentially this is a family of 2-phosphosulfolactate phosphatases (EC: 3.1.3.-).

\ \N \N \N 23712 IPR005239

This family of conserved hypothetical proteins has no known function.

\ \N \N \N 23713 IPR005240

This family of conserved hypothetical proteins has no known function. It includes potential integral membrane proteins.

\ \N \N \N 23714 IPR005241

This family of proteins is, so far, restricted to archaeal genomes. The family appears to be distantly related to the N-terminal region of the eukaryotic transcription initiation factor IIE chain.

\ \N \N \N 23715 IPR005242

This family of conserved hypothetical proteins has no known function. It includes potential integral membrane proteins.

\ \N \N \N 23716 IPR005243

This small protein is found in three archaeal species so far (Methanococcus jannaschii, Archeoglobus fulgidus, and Methanobacterium thermoautotrophicum) as well as in Anabaena PCC7120. It is homologous to thioredoxins, glutaredoxins, and protein disulfide isomerases, and shares with them a redox-active disulfide. The redox active disulfide region CXXC motif resembles neither thioredoxin nor glutaredoxin.

\ \N \N \N 23695 IPR005222

Proteins of this family are found in species that do (Bacillus subtilis, Haemophilus influenzae) or do not (Escherichia coli, Borrelia burgdorferi) have described systems for natural transformation with exogenous DNA. They are involved in competence for transformation in Bacillus subtilis.

\ \N \N \N 23696 IPR005223

MreC (murein formation C) is involved in the rod shape determination in Escherichia coli, and more generally in cell shape determination of bacteria whether or not they are rod-shaped. Cells defective in MreC are round. Species with MreC include many of the Proteobacteria, Gram-positives, and spirochetes.

\ \N \N \N 23697 IPR005224

The sugar fermentation stimulation protein is a probable regulatory factor involved in maltose metabolism. It contains a putativeDNA-binding domain, and was isolated as a gene which enabled Escherichia coli strain MK2001 to use maltose.

\ \ \N \N \N 23698 IPR005225

Proteins with a small GTP-binding domain include Ras, RhoA, Rab11, translation elongation factor G, translation initiation factor IF-2, tetratcycline resistance protein TetM, CDC42, Era, ADP-ribosylation factors, tdhF, and many others. In some proteins the domain occurs more than once.Among them there is a large number of small GTP-binding proteins and related domains in larger proteins. Note that the chains of heterotrimeric G proteins are larger proteins in which the NKXD motif is separated from the GxxxxGK[ST] motif (P-loop) by a long insert and are not easily detected by this model.

\ \ \ \N \N \N 23699 IPR005226

This family has no known function. It includes potential membrane proteins.

\ \N \N \N 23700 IPR005227

This family of conserved hypothetical proteins has no known function.

\ \N \N \N 23701 IPR005228

This family of conserved hypothetical proteins has no known function.

\ \N \N \N 23702 IPR005229

This family of conserved hypothetical proteins has no known function.

\ \N \N \N 23703 IPR005230

Proteins of this family take part in the shutdown of the peptide sex pheromone cPD1 which is produced by the plasmid free recipient cell prior to conjugative transfer in Enterococcus faecalis. Once the recipient acquires the plasmid, production of cPD1 is shut down.

\ \N \N \N 23704 IPR005231

This hypothetical protein is found so far only in the Archaea. Its C-terminal domain of about 40 amino acids is homologous to the C-termini of the nascent polypeptide-associated complex chain (-NAC) and its yeast ortholog Egd2p and to the huntingtin-interacting protein HYPK. It shows weaker similarity, possibly through shared structural constraints rather than through homology, with the amino-terminal domain of elongation factor Ts. Alpha-NAC plays a role in preventing nascent polypeptides from binding inappropriately to membrane-targeting apparatus during translation, but is also active as a transcription regulator.

\ \ \N \N \N 23684 IPR005211

This family groups together the viral proteins BLRF1, U46, 53, and UL73. The UL73-like envelope glycoproteins, which associates in a high molecular mass complex with its counterpart, gM, induce neutralizing antibody responses in the host. These glycoprotein are highly polymorphic, particularly in the N-terminal region [MEDLINE:21488529].

\ \N viral envelope ; GO:0019031 \N 23685 IPR005212

This family includes a range of proteins from antibiotic production pathways. The family includes gra-ORF27 Q9ZA32\ \ \ [MEDLINE:96236066] , eryBVI from the erythromycin cluster in S. erythraea and snoH from the nogalamycin cluster in S. nogalater. The proteins in this family are composed of two copies of a 200 amino acid long unit that may be a structural domain.

\ \ \N \N \N 23686 IPR005213

This short (30 amino acids) repeat is found in a number of plant proteins. It contains a conserved HGWP motif, hence its name. The function of these proteins is unknown.

\ \N \N \N 23687 IPR005214

The gene product of gene 3 from Avian infectious bronchitis virus. Currently, the function of this protein remains unknown.

\ \N \N \N 23688 IPR005215

The trigger factor is found in several prokaryotes, and is involved in protein export. It acts as a chaperone by maintaining the newly synthesised protein in an open conformation.

\ \N \N protein transport ; GO:0015031 23689 IPR005216

[Citrate (pro-3S)-lyase] ligase (EC: 6.2.1.22), also known as citrate lyase ligase, is responsible for acetylation of the prosthetic group (2-(5''-phosphoribosyl)-3'-dephosphocoenzyme-A) of the gamma subunit of citrate lyase converting the inactive thiol form of the enzyme to the active form.

\ \N \N \N 23690 IPR005217

This is a family of potential integral membrane proteins.

\ \N \N \N 23691 IPR005218

Although the proteins in this group all contain the diacylglycerol kinase catalytic domain IPR001206, their function is, as yet, unknown.

\ \N \N \N 23692 IPR005219

This family consists of uncharacterized predicted integral membrane proteins found, so far, only in the Proteobacteria. Of two members in Escherichia coli, one is induced by paraquat and is designated PqiA, paraquat-inducible protein A.

\ \N \N \N 23693 IPR005220

This family includes putative periplasmic proteins.

\ \N \N \N 23694 IPR005221

\ \N \N \N 23679 IPR005206

The immediate-early protein ICP4 (infected-cell polypeptide 4) is required for efficient transcription of early and late viral genes and is thus essential for productive infection. ICP4 is a large phosphoprotein that binds DNA in a sequence specific manner as a homodimer. ICP4 represses transcription from LAT, ICP4 and ORF-P that have high-affinity a ICP4 binding site that spans the transcription initiation site. ICP4 proteins have two highly conserved regions, this family contains the N-terminal region that contains sites for DNA binding and homodimerisation [MEDLINE:21602550].

\ transcriptional activator activity ; GO:0016563 host cell nucleus ; GO:0042025 positive regulation of transcription ; GO:0045941 23680 IPR005207

This is a family of Herpesvirus proteins including UL14. UL14 protein is a minor component of the virion tegument [MEDLINE:20057893] and is expressed late in infection. UL14 protein can influence the intracellular localization patterns of a number of proteins belonging to the capsid or the DNA encapsidation machinery [MEDLINE:21102966].

\ \N \N \N 23681 IPR005208

This is a family of Herpesvirus proteins including UL33 P10217. The proteins in this family are involved in packaging viral DNA.

\ \N \N viral DNA genome packaging ; GO:0019073 23678 IPR005205

The immediate-early protein ICP4 (infected-cell polypeptide 4) is required for efficient transcription of early and late viral genes and is thus essential for productive infection. ICP4 is a large phosphoprotein that binds DNA in a sequence specific manner as a homodimer. ICP4 represses transcription from LAT, ICP4 and ORF-P that have high-affinity a ICP4 binding site that spans the transcription initiation site. ICP4 proteins have two highly conserved regions, this family contains the C-terminal region that probably acts as an enhancer for the N-terminal region [MEDLINE:21602550].

\ transcriptional activator activity ; GO:0016563 host cell nucleus ; GO:0042025 positive regulation of transcription ; GO:0045941 23683 IPR005210

The UL36 open reading frame (ORF) encodes the largest herpes simplex virus type 1 (HSV-1) protein, a 270 kDa polypeptide designated VP1/2, which is also a component of the virion tegument. A null mutation in the UL36 gene of herpes simplex virus type 1 results in accumulation of unenveloped DNA-filled capsids in the cytoplasm of infected cells [MEDLINE:93059721]. The region which defines these sequences only covers a small central part of this large protein.

\ \N \N \N 23682 IPR005209

This family includes the UL34 protein from herpesviruses P10218\ \ \ [MEDLINE:21398568].

\ \ \N \N \N 23675 IPR005202

Sequence analysis of the products of the GRAS (GAI, RGA, SCR) gene family indicates that they share a variable N-terminus and a highly conserved C-terminus that contains five recognizable motifs [MEDLINE:99272994]. Proteins in the GRAS family are transcription factors that seem to be involved in development and other processes. Mutation of the SCARECROW (SCR) gene results in a radial pattern defect, loss of a ground tissue layer, in the root. The PAT1 protein is involved in phytochrome A signal transduction [MEDLINE:20278068].

\ \N \N \N 23676 IPR005203

Haemocyanins are copper-containing oxygen transport proteins found in the haemolymph of many invertebrates. They are divided into 2 main groups, arthropodan and molluscan. These have structurally \ similar oxygen-binding centres, which are similar to the oxygen-binding centre of tyrosinases \ PUB00004010, but their quaternary structures are arranged differently. The arthropodan proteins exist \ as hexamers comprising 3 heterogeneous subunits (a, b and c) and possess 1 oxygen-binding centre per \ subunit; and the molluscan proteins exist as cylindrical oligomers of 10 to 20 subunits and possess 7 \ or 8 oxygen-binding centres per subunit PUB00004010. Although the proteins have similar amino acid \ compositions, the only real similarity in their primary sequences is in the region corresponding to the\ second copper-binding domain, which also shows similarity to the copper-binding domain of tyrosinases \ PUB00004010.

Larval storage proteins (LSP) PUB00004010 are proteins from the hemolymph of insects,\ which may serve as a store of amino acids for synthesis of adult proteins. There are two classes of \ LSP's, arylphorins, which are rich in aromatic amino acids, and methionine-rich LSP's. LSP's forms \ hexameric complexes. LSP's are structurally related to arthropods hemocyanins.

\ \ \ \N \N \N 23673 IPR005200

This is a family of eukaryotic -1,3-glucanases belonging to glycoside hydrolase family 81 (CAZY:GH_81).

\ \ \N \N \N 23674 IPR005201

This is a family of endo--N-acetylglucosaminidases belonging to glycoside hydrolase family 85 (CAZY:GH_85). These enzymes work on a broad spectrum of substrates.

\ \ \N \N \N 23677 IPR005204

\ \ \N \N \N 23672 IPR005199

This is a family of endo--N-glucuronidase, or heparanase belonging to glycoside hydrolase family 79 (CAZY:GH_79.

\ \ \N \N \N 23669 IPR005196

The family of glycosyl hydrolases (CAZY:GH_65 although its precise function remains unknown.

\ \ \N \N \N 23670 IPR005197

This is a family of -1,3-glucanases belonging to glycoside hydrolase family 71 (CAZY:GH_71).

\ \ \N \N \N 23671 IPR005198

This is a family of -1,6-mannanases belonging to glycoside hydrolase family 76 (CAZY:GH_76).

\ \ \N \N \N 23667 IPR005194

This family of glycosyl hydrolases (CAZY:GH_65.

\ \ \N \N \N 23668 IPR005195

The family of glycosyl hydrolases (CAZY:GH_65. The catalytic domain also forms the majority of the dimerisation interface.

\ \ \N \N \N 23666 IPR005193

This is a family of -L-arabinofuranosidases (EC: 3.2.1.55) which are all members of glycoside\ hydrolase family 62 (CAZY:GH_62). This enzyme hydrolyzed aryl -L-arabinofuranosides and cleaves arabinosyl side chains from arabinoxylan and arabinan.

\ \ \N \N \N 23648 IPR005174

This family of proteins are found in plants. The function of the proteins is unknown.

\ \N \N \N 23649 IPR005175

This putative domain is found in proteins that contain AT-hook motifs IPR000637, which strongly suggests a DNA-binding function for the proteins as a whole, however the function of this domain is unknown.

\ \N \N \N 23650 IPR005176

Members of this family contain a basic helix-loop-helix leucine zipper motif [MEDLINE:20293053].

\ \N \N \N 23651 IPR005177

This is a family of bacterial proteins with no known function.

\ \N \N \N 23652 IPR005178

This is a family of mainly hypothetical proteins of no known function.

\ \N \N \N 23653 IPR005180

This domain is found in an undescribed set of proteins. It normally occurs uniquely within a sequence, but is found as a tandem repeat (Q9X8B8).

\ \N \N \N 23654 IPR005181

The distribution of this domain seems limited to prokaryotes and viruses.

\ \N \N \N 23655 IPR005182

A domain that is found in uncharacterised family of membrane proteins. 1-3 copies found in each protein, with each copy flanked by transmembrane helices.

\ \N \N \N 23656 IPR005183

A domain that is found in small family of bacterial secreted proteins with no known function. It ia also found in Paramecium bursaria chlorella virus 1. This domain is short and found in one or two copies. The domain has a conserved HH motif that may be functionally important.

\ \N \N \N 23657 IPR005184

A small domain family found in proteins of of unknown function. Some of these proteins are secreted (e.g. O25998).

\ \N \N \N 23658 IPR005185

A domain which occurs as one or more copies in a small family of putative membrane proteins.

\ \N \N \N 23659 IPR005186

Although these proteins are known to be important for flagellar their exact function is unknown.

\ \N \N \N 23660 IPR005187

The influenza C virus genome consists of seven single-stranded RNA segments. The shortest RNA segment encodes a 286 amino acid non-structural protein NS1 [MEDLINE:20381165]. This protein contains 6 conserved cysteines that may be functionally important, perhaps binding to a metal ion.

\ \N \N \N 23661 IPR005188

The influenza C virus genome consists of seven single-stranded RNA segments. The shortest RNA segment encodes a 286 amino acid non-structural protein NS1 IPR005187 as well as the NS2 protein. The NS2 protein is only about 60 amino acids in length and of unknown function.

\ \N \N \N 23662 IPR005189

Focal adhesion kinase (FAK) is a tyrosine kinase found in focal adhesions, intracellular signaling complexes that are formed following engagement of the extracellular matrix by integrins. The C-terminal "focal adhesion targeting" (FAT) region is necessary and sufficient for localizing FAK to focal adhesions. The crystal structure of FAT shows it forms a four-helix bundle that resembles those found in two other proteins involved in cell adhesion, -catenin and vinculin [MEDLINE:21671749]. The binding of FAT to the focal adhesion protein, paxillin, requires the integrity of the helical bundle, whereas binding to another focal adhesion protein, talin, does not.

\ \N \N \N 23645 IPR005171

Cytochrome c oxidase (COX) is a multi-subunit enzyme complex that catalyzes the final step of electron transfer through the respiratory chain on the mitochondrial inner membrane. This family is composed of cytochrome c oxidase subunit 4 from prokaryotes.

\ \N \N \N 23646 IPR005172

This family includes proteins that have two copies of a cysteine rich motif as follows: C-X-C-X4-C-X3-YC-X-C-X6-C-X3-C-X-C-X2-C. The family includes Tesmin Q9Y4I5\ \ \ [MEDLINE:99208669] and TSO1 Q9Y4I5/>\ \ \ \ [MEDLINE:20233842]. This family is called a CXC domain in [MEDLINE:20233842].

\ \ \N \N \N 23664 IPR005191

Glutaminyl cyclase catalyses the formation of the pyroglutamyl residue present at the N-terminus of numerous secretory peptides and proteins. Glutaminyl cyclase posses a zinc aminopeptidase domain in which the four functionally important histidines form the active site. It is hypothesised that mammalian glutaminyl cyclases may have structural and catalytic similarities bacterial zinc aminopeptidases[MEDLINE:21435678].

\ \N \N \N 23665 IPR005192

This is a family of dextranase (EC: 3.2.1.11) and isopullulanase (EC: 3.2.1.57) which are all members of glycoside hydrolase family 49 (CAZY:GH_49). Dextranase hydrolyses -1,6-glycosidic bonds in dextran polymers.

\ \ \N \N \N 23663 IPR005190

This is a conserved repeated domain found in GlnE proteins. These proteins adenylate and deadenylate glutamine synthases:

 ATP + {L-Glutamate:ammonia ligase (ADP-forming)} = Diphosphate + Adenylyl-{L-Glutamate:Ammonia ligase  (ADP-forming)}.

The domain is related to the nucleotidyltransferase domain IPR002934.

\ \N \N \N 23647 IPR005173

This region is found to the C terminus of the DM DNA-binding domain IPR001275\ \ \ \ [MEDLINE:20195628]. DM-domain proteins with this motif are known as DMRTA proteins. The function of this region is unknown.

\ \ \N \N \N 23635 IPR005161

The Ku heterodimer (composed of Ku70 P12956.

\ \N \N \N 23636 IPR005162

Transposable elements (TEs) promote various chromosomal rearrangements more efficiently, and often more specifically, than other cellular processes. Retrotransposons are structurally similar to retroviruses and are bounded by long terminal repeats. This is a family of eukaryotic Gag or capsid-related retrotranspon-related proteins. There is a central motif QGXXEXXXXXFXXLXXH that is common to Retroviridae gag-proteins, but is poorly conserved.

\ \ \N \N \N 23637 IPR005163

This small triple helical domain has been predicted to assume a topology similar to helix-turn-helix domains. These domains are found at the C-terminus of proteins related to P32157.

\ \N \N \N 23638 IPR005164

This family is found in pairs in Allantoicases, forming the majority of the protein. These proteins allow the use of purines as secondary nitrogen sources in nitrogen-limiting conditions through the reaction:

 allantoate + H(2)0 =  (-)-ureidoglycolate + urea

\ \N \N \N 23639 IPR005165

Anthrax bacilli produce a set of three proteins, protective antigen, lethal factor (LF; 90 kD), and edema factor, which are known collectively as anthrax toxin (ATx). These proteins are nontoxic individually, but act in binary or ternary combinations to produce shock-like symptoms and death. LF is a Zn2+-protease that cleaves several mitogen-activated protein kinase kinases, kills macrophages, and causes death of the host [MEDLINE:21225892].

\ \N \N \N 23640 IPR005166

A family of a vain specific viral glycoproteins that forms a receptor-binding gp85 polypeptide that is linked through disulfide to a membrane-spanning gp37 spike. Gp85 confers a high degree of subgroup specificity for interaction with distinct cell receptors [MEDLINE:86189950].

\ \N viral envelope ; GO:0019031 \N 23641 IPR005167

Bunyavirus has three genomic segments: small (S), middle-sized (M), and large (L). The S segment encodes the nucleocapsid and a non-structural protein. The M segment codes for two glycoproteins, G1 and G2, and another non-structural protein (NSm). The L segment codes for an RNA polymerase. This family contains the G1 glycoprotein which is the viral attachment protein [MEDLINE:96130172].

\ \N \N virus-host interaction ; GO:0019048 23642 IPR005168

\ \N \N \N 23643 IPR005169

Helicobacter pylori is the most common world-wide infection and plays an important role in pathogenesis of peptic ulcers. The CagA (cytotoxin-associated gene A ) protein is a cell-surface antigen which may play a role in determining the relative virulence of the viral strains.

\ \N \N \N 23644 IPR005170

This small domain is found in a family of proteins with the CBS IPR002550 domain and two CBS domains with this domain found at the C-terminus of the proteins, the domain is also found at the C-terminus of some Na⁺/H⁺ antiporters. This domain is also found in CorC that is involved in Magnesium and cobalt efflux. The function of this domain is uncertain but might be involved in modulating transport of ion substrates.

\ \N \N \N 23630 IPR005155

This family of proteins includes Q08962, the 60S ribosome subunit biogenesis protein Nip7. Many other members of this family are hypothetical proteins of no known function.

\ \N \N \N 23631 IPR005156

Members of this family are predicted to be lipoproteins. The function of these proteins is unknown.

\ \N \N \N 23632 IPR005158

Found in the DNRI/REDD/AFSR family of regulators, this region of AFSR (P25941) along with the C-terminal region is capable of independently directing actinorhodin production.

\ \N \N \N 23633 IPR005159

The WCCH motif is found in a retrotransposons and Gemini viruses. A specific function has not been associated to this motif [MEDLINE:21486800].

\ \N \N \N 23634 IPR005160

The Ku heterodimer (composed of Ku70 P12956.

\ \N \N \N 23629 IPR005154

This represents a family of -glucuronidases (CAZY:GH_67.

\ \ \N \N \N 23628 IPR005153

This domain is found in the MbtH protein O05821 as well as at the N-terminus of the antibiotic synthesis protein NIKP1. This domain is about 70 amino acids long and contains 3 fully conserved tryptophan residues. Many of the members of this family are found in known antibiotic synthesis gene clusters.

\ \N \N \N 23627 IPR005152

These lipases are expressed and secreted during the infection cycle of these pathogens. In particular, Candida albicans has a large number of different lipases, possibly reflecting broad lipolytic activity, which may contribute to the persistence and virulence of C. albicans in human tissue [MEDLINE:21014758].

\ \N \N \N 23626 IPR005151

Peptidase family S41B appears to represent a group of proteins related to Tricorn protease. This enzyme is found in a number of bacteria, including Thermoplasma acidophilum and appears to be responsible for degrading oliopeptides, probably derived from the proteosome.

\ \ \N \N \N 23624 IPR005149

Members of this family are transcriptional regulators that appear to be related to the MarR family IPR000835 a protein that is involved in negative regulation of phenolic acid metabolism.

\ \N \N \N 23625 IPR005150

Cellulose, an aggregate of unbranched polymers of -1,4-linked glucose residues, is the major component of wood and thus paper, and is synthesized by plants, most algae, some bacteria and fungi, and even some animals. The genes that synthesize cellulose in higher plants differ greatly from the well-characterized genes found in Acetobacter and Agrobacterium sp. More correctly designated as "cellulose synthase catalytic subunits", plant cellulose synthase (CesA) proteins are integral membrane proteins, approximately 1,000 amino acids in length. There are a number of highly conserved residues, including several motifs shown to be necessary for processive glycosyltransferase activity [MEDLINE:97057296].

\ cellulose synthase (UDP-forming) activity ; GO:0016760 membrane ; GO:0016020 cellulose biosynthesis ; GO:0030244 23618 IPR005143

This domain is found a a large family of transcriptional regulators. This domain specifically binds to autoinducer molecules.

\ \N \N \N 23619 IPR005144

The ATP-cone is an evolutionarily mobile, ATP-binding regulatory domain [MEDLINE:20393173].

\ \N \N \N 23620 IPR005145

The function of this domain is unknown, it is found in P32579.

\ \N \N \N 23621 IPR005146

This domain is found in tRNA synthetase subunits as well as in some non tRNA synthetase proteins.

\ \N \N \N 23622 IPR005147

This domain is found in phenylalanin-tRNA synthetase subunits.

\ \N \N \N 23623 IPR005148

\ \

This domain is found at the N-terminus of Arginyl tRNA synthetase, also called additional domain 1 (Add-1). It is about 140 residues long and it has been suggested that this domain will be involved in tRNA recognition [MEDLINE:98409547].

\ \ \N \N \N 23616 IPR005141

This domain is found in the release factor eRF1 which terminates protein biosynthesis by recognizing stop codons at the A site of the ribosome and stimulating peptidyl-tRNA bond hydrolysis at the peptidyl transferase center. The crystal structure of human eRF1 is known [MEDLINE:20139983]. The overall\ shape and dimensions of eRF1 resemble a tRNA molecule with domains 1, 2, and 3 of eRF1 corresponding to the anticodon loop,\ aminoacyl acceptor stem, and T stem of a tRNA molecule, respectively. The position of the essential GGQ motif at an exposed tip\ of domain 2 suggests that the Gln residue coordinates a water molecule to mediate the hydrolytic activity at the peptidyl\ transferase center. A conserved groove on domain 1, 80 A from the GGQ motif, is proposed to form the codon recognition site [MEDLINE:20139983].

\ \

This domain is also found in other proteins which may also be involved in translation termination

\ \ \N \N \N 23617 IPR005142

\ \

This domain is also found in other proteins which may also be involved in translation termination but this awaits experimental verification.

\ \ \N \N \N 23608 IPR005132 This is a family of bacterial lipoproteins. The function of RlpA is not well understood, but it has been shown to act as a prc mutant suppressor in Escherichia coli [MEDLINE:96165273]. This family contains a conserved region in the middle of RlpA. \ \ \N \N \N 23609 IPR005133

This is a family of small, transmembrane proteins believed to be components of Na+/H+ and K+/H+ antiporters. Members, including proteins designated\ MnhG from Staphylococcus aureus and PhaG from Rhizobium meliloti, show some\ similarity to chain L of the NADH dehydrogenase I, which also translocates protons.

\ \ \N \N \N 23610 IPR005134 This conserved hypothetical protein family with four predicted transmembrane regions is found in E. coli, Haemophilus influenzae, and Helicobacter pylori, among completed genomes.\ \ \N \N \N 23611 IPR005135

This large family of proteins includes magnesium dependent endonucleases and a large number of phosphatases involved in intracellular signalling [MEDLINE:20299260]. This family includes: AP endonuclease proteins (EC: 4.2.99.18), DNase I proteins (EC: 3.1.21.1), Synaptojanin an inositol-1,4,5-trisphosphate phosphatase (EC: 3.1.3.56) and\ Sphingomyelinase (EC: 3.1.4.12).

\ \ \N \N \N 23612 IPR005137

The BtpA protein is tightly associated with the thylakoid membranes, where it stabilizes the reaction centre proteins of photosystem I.

\ \N \N \N 23613 IPR005138

This is the N-terminal domain of aerolysin and pertussis toxin which contains a type-C lectin like fold.

\ \N \N \N 23614 IPR005139 This domain is found in peptide chain release factors.\ \N \N \N 23615 IPR005140

\ \

This domain is also found in other proteins for which the precise molecular function is unknown. Many of them are from\ Archaebacteria. These proteins may also be involved in translation termination but this awaits experimental verification.

\ \ \N \N \N 23607 IPR005131 L-serine dehydratase (EC: 4.2.1.13) is found as a heterodimer of

and

chain or as a fusion of the two chains in a single protein. This enzyme catalyses the deamination of serine to form pyruvate and is part of the gluconeogenesis pathway.\ \ \N \N \N 23603 IPR005127 During infection, the intestinal protozoan parasite Giardia lamblia undergoes continuous antigenic variation which is determined by diversification of the parasite's major surface antigen, named VSP (variant surface protein).\ \ \N \N \N 23606 IPR005130

L-serine dehydratase (EC: 4.2.1.13) is found as a heterodimer of and chain or as a fusion of the two chains in a single protein. This enzyme catalyses the deamination of serine to form pyruvate. This enzyme is part of the gluconeogenesis pathway.

\ \ \N \N \N 23604 IPR005128 Alpha-acetolactate decarboxylase (EC: 4.1.1.5) plays a dual role in the cell: (i) it catalyzes the second step of the acetoin pathway, \

 (S)-2-hydroxy-2-methyl-3-oxobutanoate = (R)-2-acetoin + CO2

and thus potentially the internal pH of cells\ and (ii) it controls the pool of

-acetolactate during leucine\ and valine synthesis.\ \ \N \N \N 23605 IPR005129

Bacterial periplasmic transport systems require the function of a specific substrate-binding protein, located in the periplasm, and several cytoplasmic membrane transport components. In Escherichia coli K-12, the arginine-ornithine transport system requires an\ arginine-ornithine-binding protein and the lysine-arginine-ornithine (LAO) transport system includes a LAO-binding protein. Both\ periplasmic proteins can be phosphorylated by a single kinase, ArgK [MEDLINE:90110252] resulting in reduced levels of transport activity of the periplasmic transport systems that\ include each of the binding proteins. The ArgK protein acts as an ATPase enzyme and as a kinase.

\ \ \N \N \N 23602 IPR005126 Within the NapC/NirT family of cytochrome c proteins, some members, such as NapC P33932, bind five haems. This family aligns the common N-terminal region that contains four haem-binding C-X(2)-CH motifs.\ \N \N \N 23601 IPR005124 This family represents the eukaryotic vacuolar (H+)-ATPase (V-ATPase) G subunit. V-ATPases generate an acidic environment in several intracellular compartments. Correspondingly, they are found as membrane-attached proteins in several organelles. They are also found in the plasma membranes of some specialized cells.\ V-ATPases consist of peripheral (V1) and membrane integral (V0) heteromultimeric complexes. The G subunit is part of the V1 subunit, but is also thought to be\ strongly attached to the V0 complex. It may be involved in the coupling of ATP degradation to H+ translocation.\ \ \N \N \N 23597 IPR005120 This family contains proteins that are involved in nonsense mediated mRNA decay, a process that is triggered by premature stop codons in mRNA. The family includes Smg-4 [MEDLINE:21261951] and UPF3.\ \ \N \N \N 23598 IPR005121

This is the anticodon binding domain found in some phenylalanyl tRNA synthetases. The domain has a ferredoxin fold [MEDLINE:99377256], [MEDLINE:97169444].

\ \ \N \N \N 23599 IPR005122

Uracil-DNA glycosylase (EC: 3.2.2.-) (UNG) is a DNA repair enzyme that excises uracil residues from DNA by cleaving the N-glycosylic bond. Uracil in DNA can arise as a result of misincorportation of dUMP residues by DNA\ polymerase or deamination of cytosine. The sequence of uracil-DNA glycosylase is extremely well conserved [MEDLINE:90059899].

\ \ \N \N \N 23600 IPR005123

This family contains members of the 2-oxoglutarate (2OG) and Fe(II)-dependent oxygenase superfamily [MEDLINE:21174434]. This family includes the C-terminal of prolyl 4-hydroxylase subunit. The holoenzyme has the activity (EC: 1.14.11.2)\ catalysing the reaction:

 Procollagen L-proline + 2-oxoglutarate + O2 = procollagen trans-\
                                      4-hydroxy-L-proline + succinate + CO2.

The full enzyme consists of a alpha2 beta2 complex with the subunit contributing most of the parts of the active site [MEDLINE:95273376]. The family also includes lysyl hydrolases, isopenicillin\ synthases and AlkB.

\ \ \N \N \N 23589 IPR005112

This region is always found associated with IPR001194.

\ \N \N \N 23590 IPR005113 This region is always found associated with IPR001194.\ \N \N \N 23591 IPR005114 This short domain is found in multiple copies in bacterial helicase proteins. The domain is predicted to contain 3

helices. The function of this domain may be to bind nucleic acid.\ \N \N \N 23588 IPR005111

This domain is found in proteins involved in biosynthesis of molybdopterin cofactor however the exact molecular function of this domain is uncertain. The structure of this domain is\ known [MEDLINE:21416011] and forms an incomplete barrel.

\ \ \N \N \N 23596 IPR005119 The structure of this domain is known and is similar to the periplasmic binding proteins [MEDLINE:97454788]. This domain is found in members of the LysR family of prokaryotic transcriptional regulatory proteins IPR000847 which share sequence similarities over approximately 280 residues including a putative helix-turn-helix DNA-binding motif at their N terminus.\ \ \N \N \N 23594 IPR005117 Sulfite and Nitrite reductases are key to both biosynthetic assimilation of sulfur and nitrogen and dissimilation of oxidized anions for energy transduction [MEDLINE:96008578]. Two copies of this repeat are found in Nitrite and Sulfite reductases\ and form a single structural domain.\ \ \N \N \N 23595 IPR005118

This domain is found in proteins necessary for strand-specific repair in DNA such as TRCF in E.coli. A lesion in the template strand blocks the RNA polymerase complex (RNAP). The RNAP-DNA-RNA complex is specifically recognised by TRCF which releases RNAP and the truncated transcript.

\ \ \N \N \N 23592 IPR005115

This domain is found duplicated in bacterial membrane proteins of unknown function and contains three transmembrane helices. The conserved glycines are suggestive of an ion channel.

\ \N \N \N 23593 IPR005116

The TOBE domain [MEDLINE:20288039] (Transport-associated OB) always occurs as a dimer as the C-terminal strand of each domain is supplied by the partner. It is probably involved in the recognition of small ligands such as molybdenum (P46930), and is found in ABC transporters immediately after the ATPase domain.

\ \N \N \N 23581 IPR005104 This domain is always found with a pair of CBS domains IPR000644. This region may be distantly related to the HrcA proteins of prokaryotes.\ \N \N \N 23582 IPR005105

This domain is found associated with the CBS domain (IPR000644), conserving the DXD motif. This strongly suggests that proteins containing this domain are also nucleotidyltransferases.

\ \N \N \N 23583 IPR005106

This domain adopts a Rossman NAD binding fold. The C-terminal domain of homoserine dehydrogenase contributes a single helix to this structural domain, which is not included in the Pfam model.

\ \N \N \N 23584 IPR005107

Proteins containing this domain form structural complexes with other known families, such as IPR000674.

\ \N \N \N 23585 IPR005108

The HELP (Hydrophobic ELP) domain is found in EMAP and EMAP-like proteins (ELPs) [MEDLINE:21638433], [MEDLINE:95081130]. Although called a domain it contains a predicted transmembrane helix and may not form a globular domain. It is also not clear if these proteins localize to membranes.

\ \N \N \N 23586 IPR005109 The members of this family (Anp1, Van1 and Mnn9) are membrane proteins required for proper Golgi function. These proteins colocalize within the cis Golgi, where they are physically associated in two distinct complexes [MEDLINE:98094364].\ \N \N \N 23587 IPR005110

Proteins in this family contain two structural domains. One of these contains the conserved DGXA motif. This region is found in proteins involved in biosynthesis of molybdopterin cofactor however the exact molecular function of\ this region is uncertain.

\ \ \N \N \N 23577 IPR005100 This short region of similarity is found in two tandem copies in Supt5 proteins that are involved in chromatin regulation. The function of this region is unknown.\ \N \N \N 23578 IPR005101

Deoxyribodipyrimidine photolyase (EC: 4.1.99.3) (DNA photolyase) is a DNA repair enzyme. It binds to UV-damaged DNA containing pyrimidine dimers and, upon absorbing a near-UV photon (300 to 500 nm), breaks the cyclobutane ring\ joining the two pyrimidines of the dimer. DNA photolyase is an enzyme that\ requires two choromophore-cofactors for its activity: a reduced FADH2 and\ either 5,10-methenyltetrahydrofolate (5,10-MTFH) or an oxidized 8-hydroxy-5-\ deazaflavin (8-HDF) derivative (F420). The folate or deazaflavin chromophore\ appears to function as an antenna, while the FADH2 chromophore is thought to\ be responsible for electron transfer. On the basis of sequence similarities\ DNA photolyases can be grouped into two classes. The first class contains\ enzymes from Gram-negative and Gram-positive bacteria, the halophilic\ archaebacteria Halobacterium halobium, fungi and plants. Class 1 enzymes bind\ either 5,10-MTHF (E.coli, fungi, etc.) or 8-HDF (S.griseus, H.halobium).

\ \

Proteins containing this domain also include Arabidopsis cryptochromes 1 (CRY1) and 2 (CRY2), which are blue light photoreceptors that mediate blue light-induced gene\ expression.

\ \ \ \ \N \N \N 23580 IPR005103

\ The only known activity within this family is that of endoglucanase (EC: 3.2.1.4) CAZY:GH_61\ \ \N \N \N 23579 IPR005102

The structure of this module is known [MEDLINE:20534886] and consists of an Ig-like fold. The function of this domain is unknown, but might be involved in mediating interaction with carbohydrates.

\ \N \N \N 23575 IPR005098 This domain is found in a number of worm proteins and has no known function. The boundaries of the presumed domain are rather uncertain.\ \N \N \N 23576 IPR005099 This non-structural protein is one of two found in pneumoviruses. The protein is about 140 amino acids in length. The NS1 protein appears to be important for efficient replication but not essential [MEDLINE:20438131]. The NS1 protein has been shown by yeast two-hybrid to interact with the viral P protein [MEDLINE:20404882]. This protein is also known as\ the 1C protein. It has also been shown that NS1 can potently inhibit transcription and RNA replication [MEDLINE:98105793].\ \ \N \N \N 23573 IPR005096 This family is specific to Borrelia burgdorferi. The protein is encoded on extrachromosomal DNA and is of unknown function.\ \N \N \N 23574 IPR005097 This family comprised of three structural domains that can not be separated in the linear sequence. In some organisms this enzyme is found as a bifunctional polypeptide with lysine ketoglutarate reductase (PF). The\ saccharopine dehydrogenase can also function as a saccharopine reductase.\ \ \N \N \N 23560 IPR005083

This family of proteins is a member of the C55 peptidase group and contains proteins such as the bacterial YopJ proteases.

\ \ \N \N \N 23561 IPR005084

The carbohydrate-binding module, family 6 CAZY:GH_6 was previously known as cellulose-binding domain family VI (CBD VI). The cellulose-binding function has beendemonstrated in one case on amorphous cellulose and xylan. Some of these modules also bind -1,3-glucan.

\ \ carbohydrate binding activity ; GO:0030246 \N \N 23562 IPR005085

Carbohydrate-binding module, family 25 CAZY:GH_25 has a starch-binding function as demonstrated in one case.

\ \N \N \N 23563 IPR005086 This domain is found in a number of alkaline cellulases.\ \N \N \N 23564 IPR005087

This domain is found in association with IPR001547).

\ \N \N \N 23565 IPR005088 This domain is found in a number of bacterial cellulases.\ \N \N \N 23566 IPR005089

\ \ Carbohydrate-binding module, family 25 CAZy GH_25 has a starch-binding function as demonstrated in one case.\ \ \ \N \N \N 23558 IPR005081

All peptidases classified as unknown, have an unidentified catalytic mechanism.

Sporulation in bacteria such as Bacillus subtilis involves the formation of a polar septum, which divides the sporangium into a mother cell and a\ forespore. The sigma E factor, which is encoded within the spoIIG operon, is a cell-specific regulatory protein that directs\ gene transcription in the mother cell. Sigma E is synthesized as an inactive proprotein pro-sigma E, which is converted to the\ mature factor by the putative processing enzyme SpoIIGA. This enzyme belongs to the U4 peptidase family.

\ \ aspartic-type endopeptidase activity ; GO:0004190 \N sporulation (sensu Bacteria) ; GO:0030436 23559 IPR005082

All peptidases classified as unknown, have an unidentified catalytic mechanism.

This family of proteins is a member of the U9 peptidase group and plays a role in the head assembly of bacteriophage T4.

\ \ peptidase activity ; GO:0008233 \N proteolysis and peptidolysis ; GO:0006508 23571 IPR005094 Relaxases/mobilization proteins are required for the horizontal transfer of genetic information contained on plasmids that occurs during bacterial conjugation. The relaxase, in conjunction with several auxiliary proteins, forms the relaxation complex or relaxosome. Relaxases nick duplex DNA in a specific manner by catalysing\ trans-esterification [MEDLINE:98010342]. \ \ \N \N \N 23572 IPR005095

EspA is the prototypical member of this family. EspA, together with EspB, EspD and Tir are exported by a type III secretion system. These proteins are essential for attaching and effacing lesion formation. EspA is a structural protein and a major component of a large, transiently expressed, filamentous surface organelle which\ forms a direct link between the bacterium and the host cell [MEDLINE:98211927], [MEDLINE:20223633].

\ \ \N \N \N 23569 IPR005092

This family of trans-activating transcriptional regulators (TATR), also known as intermediate early protein 1, are common to the Nucleopolyhedroviruses.

\ \N \N \N 23570 IPR005093

This is a family of Leviviridae RNA replicases. The replicase is also known as RNA-dependent RNA polymerase.

\ \N \N \N 23568 IPR005091

The major surface protein (MSP1) of the cattle pathogen Anaplasma is a heterodimer comprised of MSP1a and MSP1b. This family is the MSP1b chain. The MSP1 proteins are putative adhesins for bovine erythrocytes.

\ \ \N \N \N 23567 IPR005090

Proteins in this group have homology with the RepC protein of Agrobacterium Ri and Ti plasmids [MEDLINE:95083744]. They may be involved in plasmid replication and stabilization functions.

\ \N \N \N 23554 IPR005077

This is a family of evolutionary conserved cysteine proteases with strict specificity. Proteins in this family belong to the C11 peptidase family.

\ \ cysteine-type endopeptidase activity ; GO:0004197 \N proteolysis and peptidolysis ; GO:0006508 23555 IPR005078

This is a group of proteins of unknown function which are members of the C54 peptidase family.

\ \ \N \N \N 23557 IPR005080

All peptidases classified as unknown, have an unidentified catalytic mechanism.

This is a family of proteins which initiate the degradation of small, acid-soluble proteins during spore germination.

\ \ peptidase activity ; GO:0008233 \N spore germination ; GO:0009847 23556 IPR005079

This is a family of enzymes which catalyse the final step in penicillin biosynthesis. They are members of the C45 peptidase family.

\ \ \N \N penicillin biosynthesis ; GO:0042318 23552 IPR005075

Metalloproteases are the most diverse of the four main types of protease, with more than 30 families identified to date [MEDLINE:95405261]. In these enzymes, a divalent cation, usually zinc, activates the water molecule. The metal ion is held in place by amino acid ligands, usually three in number. The known metal ligands are His, Glu, Asp or Lys and at least one other residue is required for catalysis, which may play an electrophillic role. Of the known metalloproteases, around half contain an HEXXH motif, which has been shown in crystallographic studies to form part of the metal-binding site [MEDLINE:95405261]. The HEXXH motif is relatively common, but can be more stringently defined for metalloproteases as abXHEbbHbc, where 'a' is most often valine or threonine and forms part of the S1' subsite in thermolysin and neprilysin, 'b' is an uncharged residue, and 'c' a hydrophobic residue. Proline is never found in this site, possibly because it would break the helical structure adopted by this motif in metalloproteases [MEDLINE:95405261].

Metalloproteases can be split into five clans, and futher sub-divided into families, on the basis of their metal binding residues.

\ \

The majority of zinc-dependent metallopeptidases (with the notable exception\ of the carboxypeptidases) share a common pattern of primary structure [MEDLINE:89121072],[MEDLINE:91372401]\ in the part of their sequence involved in the binding of zinc, and can be\ grouped together as a superfamily, known as the metzincins, on the basis of\ this sequence similarity. They can be classified into a number of distinct\ families, one of which, family M4, contains thermostable thermolysins (EC: 3.4.24.27), and related thermolabile neutral\ proteases (bacillolysins) (EC: 3.4.24.28) from various species of Bacillus.

\ \ zinc ion binding activity ; GO:0008270 extracellular ; GO:0005576 proteolysis and peptidolysis ; GO:0006508 23553 IPR005076

Glycosyltransferase family 6 CAZY:GT_6 comprises enzymes with three known activities; -1,3-galactosyltransferase (EC: 2.4.1.151); -1,3 N-acetylgalactosaminyltransferase (EC: 2.4.1.40); -galactosyltransferase (EC: 2.4.1.37).

\ \ transferase activity, transferring hexosyl groups ; GO:0016758 membrane ; GO:0016020 carbohydrate metabolism ; GO:0005975 23550 IPR005073

All peptidases classified as unknown, have an unidentified catalytic mechanism.

This is a family of penicillin-insensitive murein endopeptidases involved in the removal of murein from the sacculus by cleaving the peptide bonds between neighbouring strands in mature murein.

\ \ murein DD-endopeptidase activity ; GO:0008931 periplasmic space (sensu Gram-negative Bacteria) ; GO:0030288 \N 23551 IPR005074

Lantibiotic and non-lantibiotic bacteriocins are synthesized as precursor peptides containing N-terminal extensions (leader peptides) which are cleaved off during\ maturation. Most non-lantibiotics and also some lantibiotics have leader peptides of the so-called double-glycine type. These leader peptides share consensus\ sequences and also a common processing site with two conserved glycine residues in positions -1 and -2. The double- glycine-type leader peptides are unrelated to\ the N-terminal signal sequences which direct proteins across the cytoplasmic membrane via the sec pathway. Their processing sites are also different from typical\ signal peptidase cleavage sites, suggesting that a different processing enzyme is involved.

Peptide bacteriocins are exported across the cytoplasmic membrane by a\ dedicated ATP-binding cassette (ABC) transporter. The ABC transporter is the maturation protease and its proteolytic domain resides in the N-terminal part of the\ protein [MEDLINE:95405261]. This peptidase domain is found in a wide range of ABC transporters, however the presumed catalytic cysteine and histidine are not conserved in all\ members of this family.

\ \ protein transporter activity ; GO:0008565 integral to membrane ; GO:0016021 protein transport ; GO:0015031 23546 IPR005069 This family of worm proteins has no known function.\ \N \N \N 23547 IPR005070 Expression of the envelope (Env) glycoprotein is essential for viral particle egress. This feature is unique to the Spumavirinae, a subclass of the Retroviridae. \ \N viral envelope ; GO:0019031 \N 23548 IPR005071 This family of worm proteins has no known function\ \N \N \N 23549 IPR005072

Metalloproteases can be split into five clans, and futher sub-divided into families, on the basis of their metal binding residues.

\ \

Protein G1, named after the vaccinia virus protein, is a metalloendopeptidase expressed by many Poxviridae which appears to play a role in the maturation of viral proteins.

\ \ zinc ion binding activity ; GO:0008270 \N viral assembly, maturation, egress, and release ; GO:0019067 23540 IPR005063 Transposase proteins are necessary for efficient DNA transposition. This family represents bacterial IS1 transposases. \ \N \N DNA transposition ; GO:0006313 23541 IPR005064

This is a protein family of unknown function.

\ molecular_function unknown ; GO:0005554 periplasmic space (sensu Gram-negative Bacteria) ; GO:0030288 \N 23542 IPR005065

Platelet-activating factor acetylhydrolase (PAF-AH) is a subfamily of phospholipase A2, IPR001211, responsible for inactivation of platelet-activating factor through cleavage of an acetyl group. Three known PAF-AHs are the brain heterotrimeric PAF-AH Ib, the extracellular,\ plasma PAF-AH (pPAF-AH), and the intracellular PAF-AH isoform II (PAF-AH II).

\ \ \ 2-acetyl-1-alkylglycerophosphocholine esterase activity ; GO:0003847\ \ 2-acetyl-1-alkylglycerophosphocholine esterase complex ; GO:0008247\ \N \N lipid catabolism ; GO:0016042 23543 IPR005066

This domain is found in molybdopterin cofactor (Mo-co) oxidoreductases. It is involved in dimer formation, and has an Ig-fold structure [MEDLINE:98088796].

\ \ oxidoreductase activity ; GO:0016491 \N \N 23544 IPR005067

Fatty acid desaturases are enzymes that catalyze the insertion of a double bond at the delta position of fatty acids.

\ \

There seem to be two distinct families of fatty acid desaturases which do not\ seem to be evolutionary related.

\ \

Family 1 is composed of:

\ \

- Stearoyl-CoA desaturase (SCD) (EC: 1.14.19.1) [MEDLINE:89359271].

\ \ \

Family 2 is composed of:

\ \

- Plants stearoyl-acyl-carrier-protein desaturase (EC: 1.14.19.1) [MEDLINE:91172837], these\ enzymes catalyze the introduction of a double bond at the delta(9) position\ of steraoyl-ACP to produce oleoyl-ACP. This enzyme is responsible for the\ conversion of saturated fatty acids to unsaturated fatty acids in the\ synthesis of vegetable oils.

- Cyanobacteria desA [MEDLINE:90370121], an enzyme that can introduce a second cis double\ bond at the delta(12) position of fatty acid bound to membranes\ glycerolipids. DesA is involved in chilling tolerance; the phase transition\ temperature of lipids of cellular membranes being dependent on the degree\ of unsaturation of fatty acids of the membrane lipids.

\ \ acyl-[acyl-carrier-protein] desaturase activity ; GO:0045300 \N fatty acid metabolism ; GO:0006631 23545 IPR005068

This repeat is found in the tail fibers of phage, for example protein K Q37842\ \ \ [MEDLINE:95407087] but bacterial homologues have also been identified. The repeats are about 40 residues long.

\ \ \N \N \N 23529 IPR005052 Lectins are structurally diverse proteins that bind to specific carbohydrates. This family includes the VIP36 P49256 lectins. These two proteins were the first recognized members of a family of animal lectins similar (19-24%) to the leguminous plant lectins [MEDLINE:94265253]. The alignment for this family aligns\ residues lying towards the N-terminus, where the similarity of VIP36 and ERGIC-53 is greatest. However, while Fiedler and Simons [MEDLINE:94265253] identified these proteins as a\ new family of animal lectins, this alignment also includes yeast sequences. ERGIC-53 is a 53kD protein, localized to the intermediate region between the endoplasmic\ reticulum and the Golgi apparatus (ER-Golgi-Intermediate Compartment, ERGIC). It was identified as a calcium-dependent, mannose-specific lectin [MEDLINE:97022115]. Its dysfunction\ has been associated with combined factors V and VIII deficiency OMIM:227300 OMIM:601567, suggesting an important and substrate-specific role for ERGIC-53 in\ the glycoprotein- secreting pathway [MEDLINE:97022115],[MEDLINE:99192442].\ \ \N membrane ; GO:0016020 \N 23530 IPR005053 This family includes of the MobA protein from the E. coli plasmid RSF1010, and the MobL protein from the Thiobacillus ferrooxidans plasmid PTF1. These sequences are mobilization proteins, which are essential for specific plasmid transfer.\ \ \N \N unidirectional conjugation ; GO:0009291 23531 IPR005054 The members of this family are derived from nepoviruses. Together with comoviruses and picornaviruses, nepoviruses are classified in the picornavirus superfamily of plus strand single-stranded RNA viruses. This family aligns several nepovirus coat protein sequences. In several cases, this is found at the C-terminus of the RNA2-encoded viral polyprotein. The coat protein consists of three trapezoid-shaped

-barrel domains, and\ forms a pseudo T = 3 icosahedral capsid structure [MEDLINE:98179933].\ \ structural molecule activity ; GO:0005198 viral capsid ; GO:0019028 \N 23532 IPR005055 The product of a gene expressed in the olfactory system of Drosophila melanogaster, OS-D, shares features common to vertebrate odorant-binding proteins, but has a primary structure unlike odorant-binding proteins.\ \ \N \N \N 23533 IPR005056 The matrix proteins of Pneumovirus virus are transcriptional processivity and antitermination factor and play a crucial role in viral assembly.\ \N viral envelope ; GO:0019031 viral assembly ; GO:0019068 23534 IPR005057

This is a protein family of unknown function.

\ molecular_function unknown ; GO:0005554 \N \N 23535 IPR005058

P4A is one of the most abundant structural proteins in the Vaccinia virion.

\ structural molecule activity ; GO:0005198 virion ; GO:0019012 \N 23536 IPR005059

The DNA-dependent RNA polymerase from vaccinia virions has a molecular weight of approximately 500,000 and can be dissociated into putative subunits of 140,000, 137,000, 37,000, 35,000, 31,000, 22,000, and 17,000 daltons. DNA-dependent RNA polymerase catalyses the transcription of DNA into RNA.

\ \ DNA-directed RNA polymerase activity ; GO:0003899 \N viral transcription ; GO:0019083 23537 IPR005060

The matrix (M) proteins of rabies virus (RV) plays a key role in both assembly and budding of progeny virions. A PPPY motif (PY motif or late-budding domain) is conserved in the M proteins. These PY motifs are important for virus budding and for mediating interactions with specific cellular proteins containing\ WW domains.

\ \ \N viral envelope ; GO:0019031 viral assembly, maturation, egress, and release ; GO:0019067 23538 IPR005061

This is a eukaryotic protein family of unknown function.

\ molecular_function unknown ; GO:0005554 \N \N 23539 IPR005062

This family of eukaryotic proteins brings together the yeast nuclear export factor Sac3 P46674, and mammalian GANP/MCM3-associated proteins, which facilitate the nuclear localization of MCM3, a protein that associates with chromatin in the G1 phase of the cell-cycle.

\ \ \N \N \N 23521 IPR005044

This is a Caenorhabditis protein family of unknown function.

\ \N \N \N 23522 IPR005045 Members of this family have no known function. They have been predicted to contain transmembrane helices.\ molecular_function unknown ; GO:0005554 membrane ; GO:0016020 \N 23523 IPR005046

This is a family Mycoplasma proteins of unknown function.

\ \N \N \N 23524 IPR005047

This is a Caenorhabditis protein family of unknown function.

\ molecular_function unknown ; GO:0005554 \N \N 23525 IPR005048

This is a domain of unknown function found in proteins of unknown function, DUF287.

\ \N \N \N 23526 IPR005049

This is a protein family of unknown function.

\ \N \N \N 23527 IPR005050

The expression of early nodulin (ENOD) genes has been well characterized in several legume species. Based on their biochemical attributes and expressionpatterns, they are postulated to have roles in cell structure, in the control of nodule ontogeny by the degradation of Nod factor, and in carbon metabolism [MEDLINE:20223721].

\ \ \N \N nodulation ; GO:0009877 23528 IPR005051 The UL46 protein (VP11/12) is produced in the late phase of Herpes virus infection in a manner highly dependent on viral DNA synthesis, and is mainly distributed at the edge of the nucleus in the cytoplasm. It is a tegument phosphoprotein reported to modulate the activity of UL48 (anti-TNF) protein.\ \ \N \N regulation of transcription, DNA-dependent ; GO:0006355 23517 IPR005040

This is a Caenorhabditis protein family of unknown function .

\ \N \N \N 23518 IPR005041 Adenoviruses (Ads) have evolved multiple mechanisms to evade the host immune response. Several of the immunomodulatory Ad proteins are encoded in early transcription unit 3 (E3). The E3B region is highly conserved among human Ads and codes for three proteins called 10.4K, 14.5K, and\ 14.7K - the E3/10.4K, 14.5K, and 14.7K proteins can protect cells from tumor necrosis\ factor

-mediated lysis.\ \ \N membrane ; GO:0016020 \N 23519 IPR005042

The pathogenicity gene, pthA, of Xanthomonas citri is required to elicit symptoms of Asiatic citrus canker disease; introduction of pthA into Xanthomonas strains that are mildly pathogenic or opportunistic on citrus confers the ability to\ induce cankers on citrus. Structurally, pthA is highly similar to avrBs3 and avrBsP\ from X. c. pv. vesicatoria and to avrB4, avrb6, avrb7, avrBIn, avrB101, and avrB102 from X. c. pv. malvacearum [MEDLINE:93043492].

\ \ \N \N pathogenesis ; GO:0009405 23520 IPR005043 Mammalian cellular apoptosis susceptibility (CAS) proteins are homologous to the yeast chromosome-segregation protein, CSE1 [MEDLINE:96036098]. This family aligns the C-terminal halves (approximately). CAS is involved in both cellular apoptosis and proliferation [MEDLINE:96234995], [MEDLINE:96181464]. Apoptosis is inhibited in CAS-depleted cells, while the expression of CAS\ correlates to the degree of cellular proliferation. Like CSE1, it is essential for the mitotic checkpoint in the cell cycle (CAS depletion blocks the cell in the G2 phase),\ and has been shown to be associated with the microtubule network and the mitotic spindle [MEDLINE:96181464], as is the protein MEK, which is thought to regulate the intracellular\ localization (predominantly nuclear vs. predominantly cytosolic) of CAS. In the nucleus, CAS acts as a nuclear transport factor in the importin pathway [MEDLINE:97462907]. The\ importin pathway mediates the nuclear transport of several proteins that are necessary for mitosis and further progression. CAS is therefore thought to affect the cell\ cycle through its effect on the nuclear transport of these proteins [MEDLINE:97462907]. Since apoptosis also requires the nuclear import of several proteins (such as P53 and\ transcription factors), it has been suggested that CAS also enables apoptosis by facilitating the nuclear import of at least a subset of these essential proteins [MEDLINE:98163433].\ \ importin-alpha export receptor activity ; GO:0008262 cytoplasm ; GO:0005737 cell proliferation ; GO:0008283 23508 IPR005031 Members of this family of enzymes from Streptomyces spp. are involved in polyketide (linear poly-

-ketones) synthesis.\ polyketide synthase activity ; GO:0016218 \N antibiotic biosynthesis ; GO:0017000 23509 IPR005032

This is a family of proteins related to the human Stromal Antigen proteins, SA-1 and SA-2. SA-1 appears to have no known function but another family member, yeast IRR1 protein (P40541) is believed to play a role in cell-cell interaction.

\ \N \N \N 23510 IPR005033

Named the YEATS family, after 'YNK7', 'ENL', 'AF-9', and 'TFIIF small subunit', this family also contains the GAS41 protein. All these proteins are thought to have a transcription stimulatory activity.

\ \N nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 23511 IPR005034

This putative domain is found in members of the Dicer protein family of dsRNA nucleases. This domain of about 100 amino acids has no known function, but does contain 3 possible zinc ligands.

\ \ \N \N \N 23512 IPR005035 Herpes simplex virus (HSV) is a large DNA virus, the genome of which encodes approximately 80 genes. The UL3 gene of HSV-2 is predicted to encode a 233 amino acid proteinwith a molecular mass of 26 kDa. Homologues of the UL3 protein are encoded only among alphaherpesviruses. The function of the UL3 protein of HSV remains unknown but it is known to localise to the nucleus and is a phosphoprotein [MEDLINE:99394691].\ \ \N \N \N 23513 IPR005036

This family consists of several eukaryotic proteins that are thought to be involved in the regulation of glycogen metabolism. For instance, the mouse PTG protein O08541 has been shown to interact with glycogen synthase, phosphorylase kinase, phosphorylase a: these three enzymes have key roles in the regulation of glycogen metabolism. PTG also binds the catalytic subunit of protein phosphatase 1 (PP1C) and localizes it to glycogen. Subsets of similar interactions have been\ observed with several other members of this family, such as the yeast PIG1, PIG2, GAC1 and GIP2 proteins. While the precise function of these proteins is not\ known, they may serve a scaffold function, bringing together the key enzymes in glycogen metabolism. This entry is a carbohydrate binding domain.

\ \ \N \N \N 23514 IPR005037

Members of this family are related to the pre mRNA splicing factor PRP38 from yeast [MEDLINE:92375062], therefore all the members of this family could be involved in splicing. This conserved region could be involved in RNA binding. The putative domain is about 180 amino acids in length. PRP38 is a unique component of the U4/U6.U5 tri-small\ nuclear ribonucleoprotein (snRNP) particle and is necessary for an essential step late in spliceosome maturation [MEDLINE:98250665].

\ \ \N \N \N 23515 IPR005038 This octapeptide repeat is found in several bacterial proteins. The function of this repeat is unknown.\ immunoglobulin binding activity ; GO:0019865 \N \N 23516 IPR005039 Prophages P1 and P7 exist as unit copy DNA plasmids in the bacterial cell. Maintenance of the prophage state requires the continuous expression of two repressors: (i) C1 is a protein which negatively regulates the expression of lytic genes including\ the C1 inactivator gene coi, and (ii) C4 is an antisense RNA which specifically inhibits the synthesis of an anti-repressor Ant.\ \ DNA binding activity ; GO:0003677 \N \N 23501 IPR005024

This is a family of eukaryotic proteins of no known function.

\ molecular_function unknown ; GO:0005554 \N \N 23502 IPR005025

NADPH-dependent FMN reductase (EC: 1.5.1.29) reduces FMN and also reduces riboflavin and FAD, although more slowly. Members of this family catalyse the reaction

\ \

NAD(P)H + FMN = NAD(P)(+) + FMNH(2).

\ \ \N \N \N 23503 IPR005026 The protein called postsynaptic density (PSD) is a specialized submembranous structure within which synaptic membrane proteins are\ linked to cytoskeleton and signalling proteins. Guanylate-kinase-associated protein (PSD-95/synapse-associated protein 90) is one of the major\ components of PSD, and functions as a scaffold protein for various ion\ channels and associated signalling molecules. \ \ \N \N cell-cell signaling ; GO:0007267 23504 IPR005027

Glycosyltransferase family 43 CAZY:GT_43 comprises enzymes with only one known activities; -glucuronyltransferase(EC: 2.4.1.-);.

\ \ galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase activity ; GO:0015018 membrane ; GO:0016020 \N 23505 IPR005028

This domain of unknown function is found in the intermediate/early proteins of the Herpes virus. Many of these proteins play a role in transcriptional regulation.

\ \N \N regulation of transcription, DNA-dependent ; GO:0006355 23506 IPR005029 The herpes simplex virus type 1 gene UL47 encodes the tegument proteins referred to collectively as VP13/14, which are believed to be differentially modified forms of the same protein. These proteins have been show to target to the nucleus. The function of this domain is unknown but it has been found in a number of Herpesviridae proteins. \ \N \N regulation of transcription, DNA-dependent ; GO:0006355 23507 IPR005030

This is a family of viral latent proteins whose function is not fully understood. A role in transcriptional regulation has been suggested [MEDLINE:20481634].

\ \N \N \N 23499 IPR005022

This family of proteins function as a trans-activator of viral late genes.

\ transcriptional activator activity ; GO:0016563 \N regulation of transcription, DNA-dependent ; GO:0006355 23500 IPR005023

All members of this family show similarity to the vaccinia virus late protein H2, which is often referred to by its gene name H2R. Members from this family all belong to the viral taxon Poxviridae.

\ \ \N \N \N 23496 IPR005019

This family of methyladenine glycosylases includes DNA-3-methyladenine glycosylase I (EC: 3.2.2.20) which acts as a base excision repair enzyme by severing the glycosylic bondof numerous damaged bases. The enzyme is constitutively expressed and is specific for the alkylated 3-methyladenine DNA.

\ \ DNA 3-methyladenine glycosylase I activity ; GO:0008725 \N DNA repair ; GO:0006281 23497 IPR005020

This is a family of Caenorhabditis elegans proteins of unknown function.

\ \N \N \N 23498 IPR005021 The majority of the members of this family are bacteriophage proteins, several of which are thought to be terminase large subunit proteins. There are also a number of bacterial proteins of unknown function.\ \ \N \N \N 23491 IPR005014

Actinobacillus pleuropneumoniae is the etiological agent of swine pleuropneumonia. The gene encoding an outer membrane lipoprotein A (OmlA) of Actinobacillus pleuropneumoniae has been cloned from several serotypes and is thought to exist as allelic variants [MEDLINE:99026959].

\ \N \N \N 23492 IPR005015

Thermostable directhemolysin (TDH) is considered an important virulence factor in Vibrio parahaemolyticus gastroenteritis and is a dimer composed of two identical subunit\ molecules of approximately 21 kDa. A number of biological properties have been attributed to TDH including hemolytic activity, enterotoxicity,\ cytotoxicity and cardiotoxicity [MEDLINE:21167651].

\ \ hemolysin activity ; GO:0015484 extracellular ; GO:0005576 pathogenesis ; GO:0009405 23493 IPR005016

This is a family of proteins which display differential expression in various tumour and cell lines. The function of these proteins is unknown.

\ \N membrane ; GO:0016020 \N 23494 IPR005017

This family includes TodX from Pseudomonas putida F1 Q51971. These are membrane proteins of uncertain function that are involved in toluene catabolism. Related proteins involved in the degradation of similar aromatic hydrocarbons are also in this family, such as CymD Q51971/>.

\ \ \N \N \N 23495 IPR005018

The DOMON domain is an 110-125 residue long domain which has been identifiedin the physiologically important enzyme dopamine -monooxygenase and in\ several other secreted and transmembrane proteins from both plants and\ animals. It has been named after DOpamine -MOnooxygenase N-terminal\ domain. The DOMON domain can be found in one to four copies and in association\ with other domains, such as the Cu-ascorbate dependent monooxygenase domain,\ the epidermal growth factor domain, the trypsin inhibitor-like domain (TIL), the SEA domain and the Reelin domain.\ The architectures of the DOMON domain proteins strongly suggest a function in\ extracellular adhesion [MEDLINE:21436381].

\ The sequence conservation is predominantly centered around patches of\ hydrophobic residues. The secondary structure prediction of the DOMON domain\ points to an all--strand fold with seven or eight core strands supported\ by a buried core of conserved hydrophobic residues. There is a chraracteristic\ motif with two small positions (Gly or Ser) corresponding to a conserved turn\ immediately C-terminal to strand three. It has been proposed that the DOMON\ domain might form a -sandwich structure, with the strands distributed into\ two sheets as is seen in many extracellular adhesion domains such as the\ immunoglobulin, fibronectin type III, cadherin and PKD domains [MEDLINE:21436381].

\ \ dopamine-beta-monooxygenase activity ; GO:0004500 \N catecholamine metabolism ; GO:0006584 23490 IPR005013

Members of this family are involved in asparagine-linked protein glycosylation. In particular, dolichyl-diphosphooligosaccharide-protein glycosyltransferase (DDOST), also known as oligosaccharyltransferase (EC: 2.4.1.119), transfers the high-mannose sugar GlcNAc(2)-Man(9)-Glc(3) from a dolichol-linked donor to an asparagine acceptor in\ a consensus Asn-X-Ser/Thr motif. In most eukaryotes, the DDOST complex is composed of three subunits, which in humans are described as a 48kDa subunit,\ ribophorin I, and ribophorin II. However, the yeast DDOST appears to consist of six subunits (, , gamma, delta, epsilon, zeta). The yeast subunit is a\ 45kDa polypeptide, previously discovered as the Wbp1 protein, with known sequence similarity to the human 48kDa subunit and the other orthologues. This family\ includes the 48kDa-like subunits from several eukaryotes; it also includes the yeast DDOST subunit Wbp1.

\ \ dolichyl-diphospho-oligosaccharide-protein glycosyltransferase activity ; GO:0004579 endoplasmic reticulum membrane ; GO:0005789 N-linked glycosylation via asparagine ; GO:0018279 23487 IPR005010

This is a family of phosphoproteins of unknown function expressed by Rhadovirus.

\ \ \N \N \N 23488 IPR005011 This family of proteins appear to contain a leucine zipper [MEDLINE:20346896] and may therefore be a family of transcription factors.\ \N \N \N 23489 IPR005012

Daxx is a ubiquitously expressed protein that functions, in part, as a transcriptional co-repressor through its interaction with a growing numberof nuclear, DNA-associated proteins. Human Daxx contains four\ structural domains commonly found in transcriptional regulatory proteins: two predicted paired amphipathic helices, an acid-rich domain and a\ Ser/Pro/Thr (SPT)-rich domain. The post-translational modification status of the SPT-domain of hDaxx regulates its association with\ transcription factors such as Pax3 and ETS-1, effectively bringing hDaxx to sites of active transcription.\ Through its presence at the site of active transcription, hDaxx could then be able to associate with acetylated histones present in the nucleosomes and\ Dek that is associated with chromatin. Through its association with the SPT-domain of hDaxx, histone deacetylases may also\ be brought to the site of active transcription. As a consequence, nucleosomes in the vicinity of the site of active transcription will have the histone tails\ deacetylated, allowing the deactylated tail to bind to DNA, thereby leading to an inactive chromatin structure and transcriptional repression [MEDLINE:22135751].

The Daxx protein (also known as the Fas-binding protein) is thought to play a role in apoptosis as a component of nuclear promyelocytic leukemia\ protein (PML) oncogenic domains (PODS). Daxx associates with PODs through a direct interaction with\ PML, a critical component of PODs. The interaction is a dynamic, cell cycle regulated\ event and is dependent on the post-translational modification of PML by the small ubiquitin-related modifier SUMO-1.

\ \ \N \N \N 23486 IPR005009 Vaccinia virus, the prototypic poxvirus, possesses a double-stranded DNA genome of 191,686 base pairs capable of encoding approximately 200 proteins. Virion enzymes produce mature viral mRNA with eukaryotic features,\ including a 5' cap and a 3' poly(A) tail. Vaccinia virus mRNA capping enzyme is a multifunctional protein with RNA triphosphatase, RNA guanylyltransferase, RNA\ (guanine-7) methyltransferase, and transcription termination factor activities. The protein is a heterodimer of 95- and 33-kDa\ subunits encoded by the vaccinia virus D1 and D12 genes, respectively. The capping reaction entails transfer of GMP from\ GTP to the 5'-diphosphate end of mRNA via a covalent enzyme-(lysyl-GMP) intermediate.\ \ mRNA (guanine-N7)-methyltransferase activity ; GO:0004482 \N mRNA capping ; GO:0006370 23483 IPR005006

This is a family of proteins expressed by members of the Poxviridae.

\ \N \N \N 23484 IPR005007

This is a family of proteins expressed by members of the Poxviridae.

\ \N \N \N 23485 IPR005008

This family represents the Poxvirus rifampicin resistance protein. The failure to isolate genotypic variants of Poxvirus family members encoding a predicted C-terminal truncated form of these proteins, suggests that the C terminus of the molecule may be essential to protein function, and, in turn, that this function may be essential to viral\ replication. It has been proposed that possession of a\ gene encoding a member of this polypeptide family might represent a defining molecular characteristic of the Poxviridae [MEDLINE:96201427].

\ \ \N \N response to antibiotic ; GO:0046677 23475 IPR004998

This is a family of early or early-intermediate transcription factors. This family includes EBV BRLF1 and similar ORF 50 proteins from other herpesviruses.

\ transcriptional activator activity ; GO:0016563 \N regulation of transcription, DNA-dependent ; GO:0006355 23476 IPR004999

The family is the capsid assembly protein, which binds DNA and may be involved in anchoring DNA in the capsid.

\ DNA binding activity ; GO:0003677 \N viral capsid assembly ; GO:0019069 23477 IPR005000

This family includes 2,4-dihydroxyhept-2-ene-1,7-dioic acid aldolase (EC: 4.1.2.-) and 4-hydroxy-2-oxovalerate aldolase (EC: 4.1.2.-).

\ aldolase activity ; GO:0016228 \N \N 23478 IPR005001

The bacterial Hfq protein is an abundant RNA-binding protein which modulates the stability or the translation of mRNAs and has recently been shown to interact with small regulatory RNAs in Escherichia coli. Hfq is involved also in the expression of many cellular proteins and a variety of\ metabolic pathways. More recently, the multiple roles of the protein were correlated with its capacity to affect the translation and the stability\ of several mRNAs and to interact with many different small regulatory RNAs. It has been suggested that changes\ in RNA conformation might explain the multiple effects of Hfq on mRNA metabolism.

\ \

The Hfq protein of E. coli is an 11 kDa polypeptide that forms a hexameric ring-shaped structure. Structural studies have suggested that the -4 strand in one molecule dimerises with the -5 strand of a neighbouring subunit to form the hexamer. These two strands move with a concerted mobility which may explain the stability of the entire structure [MEDLINE:22090777].

\ \ RNA binding activity ; GO:0003723 \N \N 23479 IPR005002 This enzyme (EC: 5.4.2.8) is involved in the synthesis of the GDP-mannose and dolichol-phosphate-mannose required for a number of critical mannosyl transfer reactions.\ phosphomannomutase activity ; GO:0004615 cytoplasm ; GO:0005737 mannose biosynthesis ; GO:0019307 23480 IPR005003

This is a repeat found in the tail fibres of many bacteriophage and homologous bacterial proteins.

\ structural molecule activity ; GO:0005198 \N \N 23481 IPR005004

This is a family of proteins expressed by members of the Poxviridae.

\ \N \N \N 23482 IPR005005

The vaccinia virus F12L gene encodes a 65 kDa protein that is expressed late during infection and is important for plaque formation, EEV production and virulence. The F12L protein\ is located on intracellular enveloped virus (IEV) particles, but is absent from immature virions, intracellular mature virus\ and cell-associated enveloped virus. F12L shows co-localization with endosomal compartments\ and microtubules and appears to play a role in the the transport of IEV particles to the cell surface on microtubules [MEDLINE:21623851] .

\ \ \N \N viral life cycle ; GO:0016032 23461 IPR004984

This domain is found along with a C-terminal domain (IPR004890) in a group of Mycoplasma lipoproteins of unknown function.

\ \N \N \N 23462 IPR004985

Adenoviruses have evolved multiple mechanisms to evade the host immune response. Several of the immunomodulatory proteins are encoded in early transcription unit 3 (E3).

\ \N \N viral-host defense evasion ; GO:0019049 23463 IPR004986 The gene III product (P15) of cauliflower mosaic virus (CaMV) is a DNA binding protein in which the DNA binding activity is located on its C-terminal part. A family of related proteins is expressed by other members of the Caulimoviridae.\ \ DNA binding activity ; GO:0003677 \N \N 23464 IPR004987

This is a family of proteins of unknown function.

\ molecular_function unknown ; GO:0005554 \N \N 23465 IPR004988

This is a family of proteins of unknown function.

\ \N \N \N 23466 IPR004989 This domain is found in Actinomycetales proteins of unknown function\ molecular_function unknown ; GO:0005554 \N \N 23467 IPR004990 This is a family of hypothetical proteins from cereal crops.\ \N \N \N 23468 IPR004991

This is a family of related bacterial toxins.

\ toxin activity ; GO:0015070 \N \N 23469 IPR004992

This is a family of related bacterial proteins with roles in ethanolamine and carbon dioxide metabolism.

\ \N \N \N 23470 IPR004993 Transcription of the gene family, GH3, has been shown to be specifically induced by the plant hormone auxin. The auxin-responsive GH3 gene promoter is composed of multiple auxin response elements (AuxREs), and each\ AuxRE contributes incrementally to the strong auxin inducibility to the promoter.\ \ \N \N \N 23471 IPR004994 Members of this family are gamma-Butyrobetaine hydroxylase enzymes (EC: 1.14.11.1).\ oxidoreductase activity ; GO:0016491 \N \N 23472 IPR004995 Dormant Bacillus subtilis spores germinate in the presence of particular nutrients called germinants. The spores are thought to recognize germinants through receptor proteins encoded by the gerA family of operons, which includes gerA, gerB, and\ gerK. The GerA proteins are predicted to be membrane associated.\ \ \N integral to membrane ; GO:0016021 spore germination ; GO:0009847 23473 IPR004996

This is a family of proteins expressed by members of the Herpesviridae.

\ \N \N viral genome replication ; GO:0019079 23474 IPR004997

This is an accessory subunit of Herpesvirus DNA polymerase that acts to increase the processivity of polymerisation.

\ DNA polymerase processivity factor activity ; GO:0030337 \N viral genome replication ; GO:0019079 23455 IPR004978

Stanniocalcin (STC) is a calcium- and phosphate-regulating hormone produced in bony fish by the corpuscles of Stannius, which are located close to the kidney. It is a major antihypercalcemic hormone in fish. Recent results\ suggest that the biological repertoires of STCs in mammals will be considerably larger than in fish and may not be limited to\ mineral metabolism.

\ \ hormone activity ; GO:0005179 extracellular ; GO:0005576 \N 23456 IPR004979

\ \

\ \ transcription factor activity ; GO:0003700 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 23457 IPR004980

This is a non-structural protein found in members of the Tenuivirus family.

\ \N \N \N 23458 IPR004981

This is a family of tryptophan 2,3-dioxygenase (EC: 1.13.11.11) enzymes involved in tryptophan metabolism, which catalyse the reaction:

 L-Tryptophan + O(2) = L-Formylkynurenine

\ \ tryptophan 2,3 dioxygenase activity ; GO:0004833 \N tryptophan metabolism ; GO:0006568 23459 IPR004982

This is a family of mainly hypothetical Schizosacchoromyces pombe proteins. Their function is unknown but the family includes at least one protein up-regulated during meiosis.

\ molecular_function unknown ; GO:0005554 \N \N 23460 IPR004983

The Mlp (for Multicopy Lipoprotein) family of lipoproteins is found in Borrelia species [MEDLINE:98147709]. This family were previously known as 2.9 lipoprotein genes [MEDLINE:20002587]. These surface expressed genes may represent new candidate vaccinogens for Lyme disease [MEDLINE:98147709]. Members of this family generally are downstream of four ORFs called A,B,C and D\ that are involved in hemolytic activity.

\ \ \N \N \N 23448 IPR004971 This is a family of viral mRNA capping enzymes. The enzyme catalyses the first two reactions in the mRNA cap formation pathway. It is a heterodimer consisting of a large and small subunit. This entry is the large subunit. \ \N \N mRNA capping ; GO:0006370 23449 IPR004972

This family is the Poxvirus P4B major core protein. It is a precursor for one of the two most abundant structural components of the virion (major core proteins 4A and 4B).

\ \N \N \N 23450 IPR004973

The Poxvirus DNA-directed RNA polymerase (EC: 2.7.7.6) catalyses DNA-template-directed extension of the 3'-end of an RNA strand by one nucleotide at a time. The enzyme consists of at least eight subunits, this is the 18 kDa subunit.

\ DNA-directed RNA polymerase activity ; GO:0003899 \N viral transcription ; GO:0019083 23451 IPR004974

The Poxvirus RNA polymerase-associated transcription specificity factor Rap94 associates with RNA polymerase and may mediate binding of the core polymerase to VetF. It is required for transcription of early genes.

\ transcription factor activity ; GO:0003700 \N \N 23452 IPR004975 The Poxvirus trans-activator protein A1 is a general late promoter trans-activator. It is active in the intermediate stages of infection.\ \N \N \N 23453 IPR004976 Poly(A) polymerase (EC: 2.7.7.19) catalyses template-independent extension of the 3'-end of a DNA or RNA strand by one nucleotide at a time. The Poxvirus enzyme creates the 3'(poly)A tail of mRNAs, and is a heterodimer of a catalytic and a regulatory subunit. This is the catalytic subunit. \ polynucleotide adenylyltransferase activity ; GO:0004652 \N mRNA processing ; GO:0006397 23454 IPR004977

\ \ \

The S25 ribosomal protein is a compnent of the 40S ribosomal subunit.

\ \ \N \N \N 23442 IPR004965 Paralemmin is a membrane-associated protein that may play a role in control of cell shape. There are two isoforms of the protein, isoform 2 is predominant during infancy and levels of isoform 1 increase with age.\ \N \N \N 23443 IPR004966 The Pox virus Ag35 surface protein is an evelope protein known as protein H5.\ \N viral envelope ; GO:0019031 \N 23444 IPR004967 This family includes Poxvirus C7 and F8A proteins.\ \N \N \N 23445 IPR004968 This protein is necessary for viral DNA replication, and is a nucleic acid independent nucleoside triphosphatase. \ \ \N \N \N 23446 IPR004969

Proteins in this group show homology to vaccinia virus I1L (Late) encoded protein.

\ \N \N \N 23447 IPR004970

Proteins in this group show homology to vaccinia virus I7L (Late) encoded protein. Protein I7 is expressed in thelate phase of infection [MEDLINE:88215015].

\ \ \N \N \N 23438 IPR004961 The Proteobacterial lipase chaperone is a lipase helper protein which seems to assist in the folding of extracellular lipase during its passage through the periplasm.\ chaperone activity ; GO:0003754 \N protein folding ; GO:0006457 23439 IPR004962 Mab-21 is a homeotic regulator homologue. The protein is found in eukayrotes. \ \N \N \N 23440 IPR004963 This family contains a number of uncharacterised proteins. Some of these are thought to be putative pectinacetylesterases.\ \N \N \N 23441 IPR004964 The phenazine biosynthesis proteins A and B are involved in the biosynthesis of this antibiotic. Phenazine is a nitrogen-containing heterocyclic molecule with important implications in virulence, competition and biological control.\ \N \N antibiotic biosynthesis ; GO:0017000 23430 IPR004953 The human EB1 protein was originally discovered as a protein interacting with the C-terminus of the APC protein. This interaction is often disrupted in colon cancer, due to deletions affecting the APC C-terminus. Several EB1 orthologues are also included in this family. The\ interaction between EB1 and APC has been shown to have a potent synergistic effect on microtubule polymerization. Neither of EB1 or\ APC alone has this effect. It is thought that EB1 targets APC to the + ends of microtubules, where APC promotes microtubule\ polymerization. This process is regulated by APC phosphorylation by Cdc2, which disrupts APC-EB1 binding. Human EB1 protein can\ functionally substitute for the yeast EB1 homologue Mal3. In addition, Mal3 can substitute for human EB1 in promoting microtubule\ polymerization with APC. \ \ \ microtubule binding activity ; GO:0008017 \N \N 23431 IPR004954

The viral enhancin protein, or enhancing factor, is involved in disruption of the peritrophic membrane and fusion of nucleocapsids with mid-gut cells.

\ \ \N \N viral life cycle ; GO:0016032 23432 IPR004955

This family includes the gp64 glycoprotein from baculovirus as well as other viruses. The gp64 protein is a phosphoglycoprotein located on the surface of both infected cells and budding virions. The protein may play a role in fusion of the viral envelope with the endosomal membrane for viral entry into cells.

\ \N viral envelope ; GO:0019031 virus-host interaction ; GO:0019048 23433 IPR004956 The Foamy virus BEL 1 protein is a transcriptional activator, and the BEL 2 protein may play an important role in the viral life cycle.\ \N \N \N 23434 IPR004957 The Spumavirus gag protein is a core viral polyprotein that undergoes specific enzymatic cleavages in vivo to yield the mature protein.\ \N viral capsid ; GO:0019028 \N 23435 IPR004958 This is a family of Herpes virus UL4 proteins, which are related to HSV-1, HSV-2, EHV-1 58, and VZV 56 proteins.\ \N \N \N 23436 IPR004959 This family includes IpaB, which is an invasion plasmid antigen from Shigella [MEDLINE:21129586], as well as EvcA from Escherichia coli. Members of this family seem to be involved in pathogenicity of some enterobacteria. However the exact function of this component is not clear. \ \ \ \N \N pathogenesis ; GO:0009405 23437 IPR004960 The bacterial lipid A biosynthesis protein, or lipid A biosynthesis (KDO)2-(lauroyl)-lipid IVA acyltransferase (EC 2.3.1.-), transfers myristate or laurate, activated on ACP, to the lipid IVA moiety of (KDO)2-(lauroyl)-lipid IVA during lipopolysaccharide core biosynthesis.\ acyltransferase activity ; GO:0008415 integral to membrane ; GO:0016021 lipopolysaccharide core region biosynthesis ; GO:0009244 23418 IPR004941 The function of the FP protein is not known. The protein is missing in baculovirus (Few Polyhedra) mutants [MEDLINE:96332533]. \ \N \N \N 23419 IPR004942

This family includes proteins that are about 100 amino acids long. Members of this family of proteins are associated with both flagellar outer arm dynein and Drosophila and rat brain cytoplasmic dynein. We propose that roadblock/LC7 family members may modulate specific dynein\ functions [MEDLINE:99332306].

\ \ \ \N \N \N 23420 IPR004943 This family includes Lepidopteran low molecular weight (30 kDa) lipoprotein, which is an extracellular protein of unknown function. Biosynthesis occurs in a stage-dependent fashion in the fat body. \ molecular_function unknown ; GO:0005554 extracellular ; GO:0005576 \N 23421 IPR004944 These proteins are activators of cyclin-dependent kinase 5. They are heterodimers of a catalytic subunit and a regulatory subunit. \ cyclin-dependent protein kinase 5 activator activity ; GO:0016534 cyclin-dependent protein kinase 5 activator complex ; GO:0016533 \N 23422 IPR004945 The function of the Coronavirus 6B and 7B proteins is not known.\ \N \N \N 23423 IPR004946

This family of cucumovirus proteins may be long-distance movement proteins.

\ \N \N \N 23424 IPR004947 Deoxyribonuclease II (EC: 3.1.22.1) hydrolyses DNA under acidic conditions with a preference for double-stranded DNA. It catalyses the endonucleolytic cleavage of DNA to 3'-phosphomononucleotide and 3'-phosphooligonucleotide end-products. The enzyme may play a role in apoptosis.This family also includes hypothetical proteins from Caenorhabditis elegans.\ \ deoxyribonuclease II activity ; GO:0004531 \N DNA metabolism ; GO:0006259 23425 IPR004948 This family includes hypothetical ATP-binding proteins from prokaryotes.\ molecular_function unknown ; GO:0005554 \N \N 23426 IPR004949 This family includes Arabidopsis proteins of unknown function. \ \N \N \N 23427 IPR004950 This family includes Caenorhabditis elegans proteins of unknown function. \ \N \N \N 23428 IPR004951 This family includes Caenorhabditis elegans proteins of unknown function. \ \N \N \N 23429 IPR004952 This family includes several proteins of unknown function. Members of this family may be involved in nitrogen fixation, since they are found within nitrogen fixation operons. \ \N \N \N 23409 IPR004932

RER1 family proteins are involved in involved in the retrieval of some endoplasmic reticulum membrane proteins from the early golgi compartment. The C terminus of yeast Rer1p interacts with a coatomer complex [MEDLINE:21135885].

\ \ \ \N integral to membrane ; GO:0016021 \N 23410 IPR004933 There are several antigenic variants in Rickettsia tsutsugamushi, and a type-specific antigen (TSA) of 56-kilodaltons located on the rickettsial surface is responsible for the variation [MEDLINE:89212887], [MEDLINE:92316959]. TSA proteins are probably integral membrane proteins. \ \ \ \N integral to membrane ; GO:0016021 \N 23411 IPR004934 Tropomodulin is a novel tropomyosin regulatory protein that binds to the end of erythrocyte tropomyosin and blocks head-to-tail association of tropomyosin along actin filaments [MEDLINE:92129352]. Limited proteolysis shows this protein is composed of two domains. The\ amino terminal domain contains the tropomyosin binding function [MEDLINE:20485523]. \ \ \ tropomyosin binding activity ; GO:0005523 cytoskeleton ; GO:0005856 \N 23412 IPR004935 Tymoviruses are single stranded RNA viruses. This family includes a protein of unknown function that has been named based on its molecular weight. Tymoviruses such as the ononis yellow mosaic tymovirus encode only three proteins. Of these two are overlapping\ this protein overalps a larger ORF that is thought to be the polymerase [MEDLINE:90021186]. \ \ molecular_function unknown ; GO:0005554 \N \N 23413 IPR004936 The UL21 protein appears to be a dispensable component in herpesviruses [MEDLINE:94202278].\ \N \N \N 23414 IPR004937 Members of this family transport urea across membranes. The family includes a bacterial homologue.\ \ urea transporter activity ; GO:0015204 integral to membrane ; GO:0016021 urea transport ; GO:0015840 23415 IPR004938 Plant cell walls are crucial for development, signal transduction, and disease resistance in plants. Cell walls are made of cellulose, hemicelluloses, and pectins. Xyloglucan (XG), the principal load-bearing hemicellulose of dicotyledonous plants, has a terminal fucosyl\ residue. This fucosyltransferase adds this residue [MEDLINE:99301928]. \ \ galactoside 2-alpha-L-fucosyltransferase activity ; GO:0008107 membrane ; GO:0016020 cell wall biosynthesis ; GO:0042546 23416 IPR004939 The anaphase-promoting complex subunit 10 is a nuclear protein involved in cell division.\ \N \N \N 23417 IPR004940 This family corresponds to a short 100 residue region found in adhesins and hypothetical adhesin-like proteins from Mycoplasmas.\ \ \N \N \N 23408 IPR004931 Prothymosin

and parathymosin are two ubiquitous small acidic nuclear proteins that are thought to be involved in cell cycle progression, proliferation, and cell differentiation [MEDLINE:20311124]. \ \ \ \N \N \N 23405 IPR004928

Photosystem I, a membrane complex found in the chloroplasts of plants and cyanobacteria uses light energy to transfer electrons from plastocyanin to ferredoxin PUB00003191. \ The electron transfer components of the photosystem include the primary electron donor \ chlorophyll P-700 and 5 electron acceptors: chlorophyll (A0), phylloquinone (A1) and \ three 4Fe-4S iron-sulphur centres, designated Fx, Fa and Fb. The role of this protein, subunit VI or PsaH, may be in docking of the light harvesting \ complex I antenna to the core complex.

\ \ \N photosystem I reaction center ; GO:0009538 photosynthesis ; GO:0015979 23406 IPR004929

This protein is involved in host lysis. This family is not considered to be a peptidase according to the MEROPs database.

\ \ \N \N cytolysis ; GO:0019835 23407 IPR004930 This family is the Pneumovirus nucleocapsid protein. It is the most abundant protein in the virion and an important element in conferring helical symmetry on the nucleoprotein core as well as interacting with the M protein during virion formation.\ \N viral nucleocapsid ; GO:0019013 \N 23403 IPR004926

Members of this family are similar to late embryogenesis abundant proteins. Members of the family have been isolated in a number of different screens. However, the molecular function of these proteins remains obscure.

\ \ \ \N \N response to stress ; GO:0006950 23404 IPR004927

Mercury is a highly toxic metal. Toxicity can result from three differentmercurial forms: elemental, inorganic ion and organomercurial compounds. The\ ability of bacteria to detoxify mercurial compounds by reduction and\ volatilisation is conferred by the Mer genes, which are usually plasmid\ encoded (although chromosome resistance determinants have also occasionally\ been identified) [MEDLINE:97311403]. Organomercurial lyase (MerB), also known as alkylmercury lyase (EC: 4.99.1.2), mediates the first\ of the two steps in the microbial detoxification of organomercurial salts\ (the other catalysed by mercuric reductase). \

Organomercurial lyase catalyses the protonolysis of the C-Hg bond in a wide\ range of organomercurial salts (primary, secondary, tertiary, alkyl, vinyl,\ allyl and aryl) to Hg(II) and the respective organic compound [MEDLINE:20018188]:\

RHg(+) + H(+) = RH + Hg(2+)\

Hg(II) is subsequently detoxified by mercuric reductase. \

The enzyme has been purified to homogeneity in Escherichia coli and has been found\ to be a 22.4kDa monomer with no detectable cofactors or metal ions.

\ \ \ \ alkylmercury lyase activity ; GO:0018836 \N organomercury catabolism ; GO:0046413 23395 IPR004918 In the budding yeast Saccharomyces cerevisiae, cell division control protein Cdc37 is required for the productive formation of Cdc28-cyclin complexes. Cdc37 may be a kinase targeting subunit of Hsp90 [MEDLINE:97384991]. \ \N \N regulation of cell cycle ; GO:0000074 23396 IPR004919 This family includes prokaryotic proteins of unknown function.\ molecular_function unknown ; GO:0005554 \N \N 23397 IPR004920

Proteins in this group are Caenorhabditis elegans proteins of unknown function.

\ \N \N \N 23398 IPR004921 This family represents a group of plasmid encodes proteins specifically found in Borrelia and that currently do not show any similarity to any other proteins outside the Borrelia genus. Proteins within this family are about 450 residues long and are found to be expanded in\ Borrelia burgdorferi. The function of this protein is unknown. \ \ \N \N \N 23399 IPR004922 Expression-site-associated gene (ESAG) proteins are thought to be involved in variant surface glycoprotein (VSG) activation.\ \N \N \N 23400 IPR004923 The Saccharomyces cerevisiae iron permease FTR1 is a plasma membrane permease for high-affinity iron uptake. Also included in this family are bacterial hypothetical integral membrane proteins.\ \N membrane ; GO:0016020 \N 23401 IPR004924

The flagellar basal body consists of four rings (L,P,S and M) surrounding the flagellar rod, which is believed to transmit motor rotation to the filament [MEDLINE:90172414]. The M ring is integral to the inner membrane of the cell, and may be connected to the rod via the S (supramembrane) ring, which lies just distal to it. The L and P rings reside in the outer membrane and periplasmic space, respectively.The FlgA protein is involved in the assembly of the flageller P-ring. It may associate with FlgF on the rod constituting a structure essential for the P-ring assembly, or may act as a modulator protein for P-ring assembly.

\ \N periplasmic space (sensu Gram-negative Bacteria) ; GO:0030288 flagella biogenesis ; GO:0009296 23402 IPR004925 HpaB encodes part of the 4-hydroxyphenylacetate 3-hydroxylase from Escherichia coli [MEDLINE:94357932]. HpaB is part of a heterodimeric enzyme that also requires HpaC. The enzyme is NADH-dependent and uses FAD as the redox chromophore. This family also includes\ PvcC, which may play a role in one of the proposed hydroxylation steps of pyoverdine chromophore biosynthesis [MEDLINE:99315810]. \ \ \ oxidoreductase activity ; GO:0016491 \N \N 23386 IPR004909 This family includes the Sugar beet yellow virus heat shock protein 90 homologue and other hypothetical proteins.\ \N \N \N 23387 IPR004910

The Drosophila gene, Yippee, reveals a novel family of putative zinc binding proteins highly conserved among eukaryotes.

\ \N \N \N 23388 IPR004911 This family includes the two characterized human gamma-interferon-inducible lysosomal thiol reductase (GILT) sequences [MEDLINE:88298888], [MEDLINE:20105543]. It also contains several other eukaryotic putative proteins with similarity to GILT [MEDLINE:21383621]. The aligned region contains three conserved cysteine residues. In addition, the two GILT sequences possess a C-X(2)-C motif that is\ shared by some of the other sequences in the family. This motif is thought to be associated with disulphide bond reduction. \ \ \ \N \N \N 23389 IPR004912 The function of this protein is unknown. It has a conserved amino terminus of 50 residues followed by a positively charged tail, suggesting it may interact with nucleic acid. \ \ \N viral capsid ; GO:0019028 \N 23390 IPR004913

The function of the herpesvirus glycoprotein J is unknown.

\ \N \N \N 23391 IPR004914 This family includes various protein that are involved in antirestriction. The ArdB protein efficiently inhibits restriction by members of the three known families of type I systems of Escherichia coli [MEDLINE:93328690]. \ \ \N \N \N 23392 IPR004915

This family represents the Bunyavirus NS-S family. Bunyavirus has three genomic segments: small (S), middle-sized (M), and large (L). The S segment encodes the nucleocapsid and a non-structural protein. The M segment codes for two glycoproteins, G1 and G2, and\ another non-structural protein (NSm). The L segment codes for an RNA polymerase.

\ \ \ \N \N \N 23393 IPR004916 Ubiquinone biosyntheis proteins, COQ7, are central metabolic regulatory proteins. They are members of a protein family, that contain two repeats of about 90 amino acids, that contains two conserved motifs. One of these DXEXXH may be part of an enzyme active site. \ \N \N ubiquinone biosynthesis ; GO:0006744 23394 IPR004917 This protein is found in various caulimoviruses. It codes for an 18 kDa protein (PII), which is dispensable for infection but which is required for aphid transmission of the virus [MEDLINE:84005872]. This protein interacts with the PIII protein [MEDLINE:20069337]. \ \ \ \N \N viral transmission ; GO:0019089 23385 IPR004908 ATP synthase (EC: 3.6.3.14) is a multisubunit non-phosphorylated ATPase that is involved in the transport of ions. V-type (vacuolar) ATPases are responsible for acidifying a variety of intracellular compartments in eukaryotic cells. V-ATPase is a heteromultimeric enzyme composed of a peripheral catalytic V1 complex of components A to H, attached to an integral membrane V0 proton pore complex, components A, C, C', C'' and D. This family represents subunit H of the peripheral V1 complex of vacuolar ATPase, which is responsible for activating ATPase activity and coupling ATPase activity to proton flow.\ ATP binding activity ; GO:0005524 \N proton transport ; GO:0015992 23381 IPR004903 Bacterial surface layer proteins are S-layer precursor proteins. The S-layer is a paracrystalline mono-layered assembly of proteins which coat the surface of bacteria.\ \ structural constituent of cell wall ; GO:0005199 S-layer ; GO:0030115 \N 23382 IPR004905 This family represents the Tombusvirus P19 core protein.\ \N virion ; GO:0019012 \N 23383 IPR004906 This family includes Caenorhabditis elegans vacuolar assembly protein and several uncharacterised proteins which may be putative transposases.\ \N \N \N 23384 IPR004907

ATP synthase (EC: 3.6.3.14) is a multisubunit non-phosphorylated ATPase that is involved in the transport of ions. V-type (vacuolar) ATPases are responsible for acidifying a variety of intracellular compartments in eukaryotic cells. V-ATPase is a heteromultimeric enzyme composed of a peripheral catalytic V1 complex of components A to H, attached to an integral membrane V0 proton pore complex, components A, C, C', C'' and D. This family represents subunit C of the peripheral V1 complex of vacuolar ATPase, which is responsible for the assembly of the catalytic sector of the enzyme and probably has a specific function in its catalytic activity.

\ ATP binding activity ; GO:0005524 \N proton transport ; GO:0015992 23378 IPR004900 The Poxvirus P35 protein is an immunodominant envelope protein.\ \N viral envelope ; GO:0019031 \N 23379 IPR004901 This family includes several uncharacterised eukaryotic proteins.\ \N \N \N 23380 IPR004902 This is a family of Rhabdovirus nucleocapsid proteins. These protein undergo phosphorylation.\ \N viral nucleocapsid ; GO:0019013 \N 23377 IPR004899

Bordetella pertussis is a Gram-negative, aerobic coccobacillus that causes pertussis (whooping cough), especially in young children\ \ \ \ [MEDLINE:89264462]. Once present in the lungs, the bacterium attaches to ciliated pulmonary epithelial cells via a collection of outer membrane proteins, all of which are virulence \ factors.

Pertactin, or P69 protein, is one of these virulence factors. Pertactin and\ filamentous haemagglutinin have been identified as Bordetella adhesins [MEDLINE:92407514]. Both proteins contain an arg-gly-asp (RGD) motif that promotes binding to integrins, known to be important in cell mobility and development. The\ production of most Bordetella virulence factors (including pertactin) is \ controlled by a two-component signal transduction system, comprising the\ BvgA regulator and the BvgS sensor [MEDLINE:20399103]. Pertactin shares a high level of similarity with other Bordetella adhesins, such as BrkA. The protein is\ first produced as a 93kDa precursor. Upon secretion into the extracellular\ environment, a 30kDa domain at the C-terminus remains in the outer membrane,\ while the mature 60.4kDa pertactin molecule is released [MEDLINE:96196517].

The crystal structure of mature pertactin has been determined to 2.5A \ resolution by means of X-ray diffraction. The fold is characterised by a 16-stranded parallel -helix, with a V-shaped cross-section. Several between-strand amino-acid repeats form internal and external ladders. The helical structure is interrupted by several protruding loops that contain motifs associated with the activity of the protein. One such sequence - [GGXXP]5 - appears directly after the RGD motif, and may mediate interaction with epithelial cells. The C-terminal region of P.69 pertactin contains a [PQP]5 motif loop, which contains the major immunoprotective epitope [MEDLINE:96196517].

The superfamily also includes immunoglobulin A1 protease and adhesion penetration protein HAP.

\ \ \N \N \N 23376 IPR004898

Pectate lyase (EC: 4.2.2.2) is responsible for the maceration and soft-rotting of plant tissue. It catalyses the eliminative cleavage of pectate to produce oligosaccharides with 4-deoxy--D-gluc-4-enuronosyl groups at their non-reducing ends. Pectate lyase is an extracellular enzyme and is induced by pectin. It is subject to self-catabolite repression, and has been implicated in plant disease.

\ The structure and the folding kinetics of one member of this family, pectate lyase C\ (pelC)1 from Erwinia chrysanthemi has been investigated in some detail [MEDLINE:21924508]. PelC contains a parallel

-helix folding motif. The majority of the regular secondary structure is composed of parallel

-sheets (about\ 30%). The individual strands of the sheets are connected by unordered loops of varying length. The backbone is then formed by a large helix composed of

-sheets. There are two disulfide bonds in pelC and 12 proline residues. One of these prolines, Pro220, is involved in a cis peptide bond. he folding mechanism of pelC involves two slow phases that have been attributed to proline isomerization. \ \ pectate lyase activity ; GO:0030570 extracellular ; GO:0005576 \N 23368 IPR004890

This domain is found along with a central domain (IPR004984) in a group of Mycoplasma lipoproteins of unknown function.

\ molecular_function unknown ; GO:0005554 \N \N 23369 IPR004891 The mercury resistance protein, MerC, is an inner mebrane protein that mediates Hg²⁺ transport into the cytoplasm, thereby conferring mercury resistance.\ mercury ion transporter activity ; GO:0015097 membrane ; GO:0016020 mercury ion transport ; GO:0015694 23370 IPR004892 This family includes the M025 proteins, whose function is not known, but they occur in many eukaryotic genomes. The family also includes the conidiophore development protein HymA.\ \N \N \N 23371 IPR004893 Nitrogenase is a complex metalloenzyme composed of two proteins designated the Fe-protein and the MoFe-protein. Apart from these two proteins, a number of accessory proteins are essential for the maturation and assembly of nitrogenase. Even though\ experimental evidence suggests that these accessory proteins are required for nitrogenase activity, the exact roles played by many of\ these proteins in the functions of nitrogenase are unclear [MEDLINE:98189211]. Using yeast two-hybrid screening it has been shown that NifW can\ interact with itself as well as NifZ. \ \ \ \N \N nitrogen fixation ; GO:0009399 23372 IPR004894 This is a family of outer surface proteins from Borrelia. The function of these proteins is unknown.\ \N \N \N 23373 IPR004895 This family includes yeast hypothetical proteins and the uncharacterised rat prenylated rab acceptor protein PRA1.\ \N \N \N 23374 IPR004896 This protein is required for high-level transcription of the PUC operon. It is an integral membrane protein. The family includes other proteins form Rhodobacter eg. bacteriochlorophyll synthase.\ \N \N \N 23375 IPR004897 Paramyxoviral P genes are able to generate more than one product, using alternative reading frames and RNA editing. The P gene encodes the structural phosphoprotein P. In addition, it encodes several non-structural proteins present in the infected cell but not in\ the virus particle. This family includes phosphoprotein P and the non-structural phosphoprotein V from different paramyxoviruses.\ Phosphoprotein P is essential for the activity of the RNA polymerase complex which it forms with another subunit, L\ IPR001016. The P and V phosphoproteins are amino co-terminal, but diverge at their C-termini. This difference is generated by an RNA-editing mechanism in which one or two non-templated G residues are inserted into\ P-gene-derived mRNA. In measles virus and Sendai virus, one G residue is inserted and the edited transcript encodes the V protein. In\ mumps, simian virus type 5 and Newcastle disease virus, two G residues are inserted, and the edited transcript codes for the P\ protein [MEDLINE:21235800]. Being phosphoproteins, both P and V are rich in serine and threonine residues over their whole lengths. In addition, the\ V proteins are rich in cysteine residues at the C-termini [MEDLINE:94103756]. \ \ \ \N \N RNA metabolism ; GO:0016070 23367 IPR004889 H2-forming N5,N10-methylenetetrahydromethanopterin dehydrogenase (EC: 1.5.99.11), also known as coenzyme F420-dependent N(5),N(10)-methenyltetrahydromethanopterin reductase, catalyses an intermediate step in methanogenesis from CO(2) and H(2) in bacteria, the conversion of N(5),N(10)-methylenetetrahydromethanopterin and reduced co-enzyme F420 to 5-methyl-5,6,7,8-tetrahydromethanopterin and co-enzyme F420.\ coenzyme F420-dependent N5,N10-methylenetetrahydromethanopterin reductase activity ; GO:0018537 \N methanogenesis ; GO:0015948 23362 IPR004884 This is a group of uncharacterised proteins of unknown function.\ \N \N \N 23363 IPR004885

This is a group of proteins of unknown function from bacteriophages.

\ \N \N \N 23364 IPR004886 This family is a group of yeast glycolipid proteins anchored to the membrane. It includes Candida albicans pH-regulated protein, which is required for apical growth and plays a role in morphogenesis and Saccharomyces cerevisiae glycolipid anchored surface protein.\ \N \N \N 23365 IPR004887 Glutathione synthetase (EC: 6.3.2.3) (GSS) catalyses the conversion of gamma-L-glutamyl-L-cysteine and glycine to phosphate and glutathione in the presence of ATP. This is the second step in glutathione biosynthesis. In humans, defects in GSS are inherited in an autosomal recessive way and are the cause of severe metabolic acidosis, 5-oxoprolinuria, increased rate of hemolysis and defective function of the central nervous system.\ \ glutathione synthase activity ; GO:0004363 \N glutathione biosynthesis ; GO:0006750 23366 IPR004888

This is a family of eukaryotic enzymes belonging to glycosyl hydrolase family 63 (CAZY:GH_63). They catalyse the specific cleavage of the\ non-reducing terminal glucose residue from Glc(3)Man(9)GlcNAc(2). Mannosyl oligosaccharide glucosidase EC: 3.2.1.106 is the first enzyme in the N-linked oligosaccharide processing pathway.

\ \ \ mannosyl-oligosaccharide glucosidase (processing A-glucosidase I) activity ; GO:0004573 \N oligosaccharide metabolism ; GO:0009311 23346 IPR004868 Like DNA-directed DNA polymerase family B, members of this family are also DNA polymerase type B proteins. Those included here are found in plant and fungal mitochondria, and in viruses. \ \ DNA-directed DNA polymerase activity ; GO:0003887 \N DNA replication ; GO:0006260 23347 IPR004869 Members of this family are putative integral membrane proteins from bacteria. Several of the members are mycobacterial proteins. Many of the proteins contain two copies of this aligned region. The function of these proteins is not known, although it has been\ suggested that they may be involved in lipid transport [MEDLINE:20159300]. \ \ \N membrane ; GO:0016020 \N 23348 IPR004870 This is a family of nucleoporin proteins. Nucleoporins are the main components of the nuclear pore complex in eukaryotic cells, andmediate bidirectional nucleocytoplasmic transport, especially of mRNA and proteins. Two nucleoporin classes are known: one is\ characterised by the FG repeat IPR004325; the other is represented by this family, and lacks any repeats. \ \ \ \ nucleocytoplasmic transporter activity ; GO:0005487 nuclear pore ; GO:0005643 nucleocytoplasmic transport ; GO:0006913 23349 IPR004871 This family includes a region that lies towards the C-terminus of the cleavage and polyadenylation specificity factor (CPSF) A (160 kDa) subunit. CPSF is involved in mRNA polyadenylation and binds the AAUAAA conserved sequence in pre-mRNA. CPSF has also been\ found to be necessary for splicing of single-intron pre-mRNAs [MEDLINE:21314167]. The function of the aligned region is unknown but may be involved\ in RNA/DNA binding. \ \ \ nucleic acid binding activity ; GO:0003676 nucleus ; GO:0005634 \N 23350 IPR004872

This family of bacterial lipoproteins contains several antigenic members, that may be involved in bacterial virulence. Their precise function is unknown. However they are probably distantly related to IPR001638 which are solute binding proteins.

\ \ \N \N \N 23351 IPR004873 The BURP domain is found at the C-terminus of several different plant proteins. It was named after the proteins in which it was first identified: the BNM2 clone-derived protein from Brassica napus; USPs and USP-like proteins (Q06765); RD22 from Arabidopsis thaliana; and PG1beta from Lycopersicon esculentum. This domain is\ around 230 amino acid residues long. It possesses the following conserved features: two phenylalanine residues at its N-terminus; two\ cysteine residues; and four repeated cysteine-histidine motifs, arranged as: CH-X(10)-CH-X(25-27)-CH-X(25-26)-CH, where X can be\ any amino acid [MEDLINE:99005260]. The function of this domain is unknown. \ \ \N \N \N 23352 IPR004874 This is a group of Borrelia proteins that have not yet been characterised, but contain repeated regions.\ \N \N \N 23353 IPR004875

These proteins are probably endonucleases of the DDE superfamily. Transposase proteins are necessary for efficient DNA transposition. This domain is a member of the DDE superfamily, which contain three carboxylate residues that are believed to be responsible for coordinating metal ions needed for catalysis. The catalytic activity of this enzyme involves DNA cleavage at a specific site followed by a strand transfer reaction. Interestingly this family also includes the CENP-B protein. This domain in that protein appears to have lost the metal binding residues and is unlikely to have endonuclease activity. Centromere Protein B (CENP-B) is a DNA-binding protein\ localised to the centromere.

\ \ \ DNA binding activity ; GO:0003677 nucleus ; GO:0005634 \N 23354 IPR004876 Members of this family are Coronavirus proteins that are located in the nucleocapsid. They have no known function.\ \N \N \N 23355 IPR004877

Cytochrome b561 is a secretory vesicle-specific electron transport protein. It is an integral membrane protein, that binds two heme groups non-covalently.

\ \N integral to membrane ; GO:0016021 electron transport ; GO:0006118 23356 IPR004878

This is a group of uncharacterised proteins from eukaryotes.

\ \N \N \N 23357 IPR004879

This is a group of uncharacterised proteins.

\ \N \N \N 23358 IPR004880

This is a group of uncharacterised proteins.

\ \N \N \N 23359 IPR004881 This is a group of proteins of unknown function.\ molecular_function unknown ; GO:0005554 \N \N 23360 IPR004882

This is a group of proteins of unknown function.

\ \N \N \N 23361 IPR004883 This is a group of uncharacterised proteins of unknown function.\ \N \N \N 23344 IPR004866 This domain represents the N terminal domain in chitobiases and

-hexosaminidases EC: 3.2.1.52. It is composed of a

sandwich structure that is similar in structure to the cellulose binding domain of cellulase from Cellulomonas fimi [MEDLINE:96266355]. This suggests that this may be a carbohydrate binding domain. \ \ carbohydrate binding activity ; GO:0030246 \N \N 23345 IPR004867

\ This short domain is found in members of the glycoside hydrolase family 20 (CAZY:GH_20. The function of this domain is unknown. \ \ \ beta-N-acetylhexosaminidase activity ; GO:0004563 \N carbohydrate metabolism ; GO:0005975 23343 IPR004865 The function of this domain is unknown. It is about 105 amino acid residues in length and is predicted to be predominantly

helical. This domain is usually found at the amino terminus of protein that contain a SAND domain IPR000770. \ \ \N nucleus ; GO:0005634 \N 23339 IPR004860 This is a family of site-specific DNA endonucleases encoded by DNA mobile elements. Similar to the homing endonuclease LAGLIDADG/HNH domain (IPR001982), the members of this family are also LAGLIDADG endonucleases. \ endonuclease activity ; GO:0004519 \N \N 23340 IPR004861 This family consists of putative tyrosine phosphatase proteins, this function is inferred from several sequences at the top of the noise,such as the Raccoon poxvirus Protein-tyrosine phosphatase (P80994. \ \ \ \N \N \N 23341 IPR004863 This is the MH1 (MAD homology 1) domain found at the amino terminus of MAD related proteins. This domain can bind to DNA [MEDLINE:97373960]. This domain is separated from the MH2 domain by a non-conserved linker region. The crystal structure of the MH1 domain shows that a highly conserved 11 residue

hairpin is used to bind DNA in the major groove. Not all examples of MH1 can bind to DNA however. Smad2 cannot bind DNA and has a large insertion within the hairpin that presumably abolishes DNA binding. \ \ \N \N regulation of transcription, DNA-dependent ; GO:0006355 23342 IPR004864

Different types of LEA proteins are expressed at different stages of late embryogenesis in higher plant seed embryos and under conditions of dehydration stress. The function of these proteins is unknown. This family represents a group of LEA proteins that appear to be distinct from those in IPR004238.

\ \ \N \N response to dessication ; GO:0009269 23335 IPR004855

Transcription initiation factor IIA (TFIIA) is a heterotrimer, the three subunits being known as , , and gamma, in order of molecular weight. The N and C-terminal domains of the gamma subunit are represented in TFIIA_gamma and TFIIA_gamma_C (IPR003194. After initiation, the PIC does not completely dissociate from the promoter. Some components, including TFIIA, remain attached and re-initiate a subsequent round of transcription.

\ \ transcription initiation factor activity ; GO:0016986 nucleus ; GO:0005634 transcription initiation from Pol II promoter ; GO:0006367 23336 IPR004856

N-linked (asparagine-linked) glycosylation of proteins is mediated by a highly conserved pathway in eukaryotes, in which a lipid (dolicholphosphate)-linked oligosaccharide is assembled at the endoplasmic reticulum membrane prior to the transfer of the oligosaccharide\ moiety to the target asparagine residues. This oligosaccharide is composed of Glc(3)Man(9)GlcNAc(2). The addition of the three\ glucose residues is the final series of steps in the synthesis of the oligosaccharide precursor. Alg6 transfers the first glucose residue,\ and Alg8 transfers the second one [MEDLINE:94286561]. In the human alg6 gene, a C-T transition, which causes Ala333 to be replaced with Val, has\ been identified as the cause of a congenital disorder of glycosylation, designated as type Ic OMIM:603147 [MEDLINE:99289584].

\ \ \N \N \N 23337 IPR004858 Members of this family are multigene family 530 proteins from African swine fever viruses. These proteins may be involved in promoting survival of infected macrophages [MEDLINE:21136868].\ \ \N \N \N 23338 IPR004859 This family aligns residues towards the N-terminus of several proteins with multiple functions. The members of this family all appear topossess 5'-3' exonuclease activity EC:3.1.11.-. Thus, the aligned region may be necessary for 5'-3' exonuclease function. \ \ \ exonuclease activity ; GO:0004527 nucleus ; GO:0005634 \N 23333 IPR004853 This family consists entirely of aligned regions from Drosophila melanogaster proteins. O49724 contains three repeats of this region. In other proteins, the aligned region is located towards the C-terminus. The function of the aligned region is unknown. \ \ \N \N \N 23334 IPR004854 Post-translational ubiquitin-protein conjugates are recognized for degradation by the ubiquitin fusion degradation (UFD) pathway. Several proteins involved in this pathway have been identified [MEDLINE:95340540]. This family includes UFD1, a 40kD protein that is essential for\ vegetative cell viability [MEDLINE:95340540]. The human UFD1 gene is expressed at high levels during embryogenesis, especially in the eyes and in the\ inner ear primordia and is thought to be important in the determination of ectoderm-derived structures, including neural crest cells. In\ addition, this gene is deleted in the CATCH-22 (cardiac defects, abnormal facies, thymic hypoplasia, cleft palate and hypocalcaemia\ with deletions on chromosome 22) syndrome. This clinical syndrome is associated with a variety of developmental defects, all\ characterised by microdeletions on 22q11.2. Two such developmental defects are the DiGeorge syndrome OMIM:188400, and the\ velo-cardio- facial syndrome OMIM:145410. Several of the abnormalities associated with these conditions are thought to be due to\ defective neural crest cell differentiation [MEDLINE:97217785]. \ \ \N \N ubiquitin-dependent protein catabolism ; GO:0006511 23331 IPR004851 Flotillins are integral membrane proteins that have been shown to be present in several subcellular components, including caveolae (invaginated plasma membrane microdomains), lipid rafts (sphingolipid and cholesterol-rich, detergent-resistant plasma membrane\ microdomains), and the Golgi apparatus. The molecular function of flotillins remains uncertain. They are probably involved in organizing\ the structure of caveolae and lipid rafts, and other detergent resistant membrane domains. They may also be involved in signal\ transduction. Flotillins have been shown to accumulate in brain cells with the development of Alzheimer's pathology [MEDLINE:20396280]. Also included\ in this family are Reggie proteins, which are expressed in non-caveolar neuronal plasma membrane domains. \ \ \ \N flotillin complex ; GO:0016600 \N 23332 IPR004852

This is a family of distinct cytochrome c peroxidases (CCPs) that contain two haem groups. Similar to other cytochrome c peroxidases, they reduce hydrogen peroxide to water using c-type haem as an oxidizable substrate. However, since they possess two, instead of one, haem prosthetic groups, bacterial CCPs reduce hydrogen peroxide without the need to generate semi-stable free radicals. The two haem groups have significantly different redox potentials. The high potential (+320 mV) haem feeds electrons from electron shuttle proteins to the low potential (-330 mV) haem, where peroxide is reduced (indeed, the low potential site is known as the peroxidatic site) [MEDLINE:96164439]. The CCP protein itself is structured into two domains, eachcontaining one c-type haem group, with a calcium-binding site at the domain interface. This family also includes MauG proteins, whose similarity to di-haem CCP was previously recognized [MEDLINE:97346034].

\ \ \ \N \N electron transport ; GO:0006118 23327 IPR004847 Some members of this family are currently uncharacterised hypothetical proteins, but it has been suggested that they may play a role in transport. One member, the Rhizobium meliloti PhaE protein is a PH adaptation potassium efflux system transmembrane protein.\ \N \N \N 23328 IPR004848 This family of viral proteins is known as the 110 family [MEDLINE:90219204]. The function of members of this family is unknown. The family\ contains a central cysteine rich region with eight conserved\ cysteines. Some members of the family contains two copies of\ the cysteine rich region Swiss:P18560.\ \ \N \N \N 23329 IPR004849

This family resembles a larger family of bacterial and eukaryotic 6-phosphogluconate dehydrogenases (Gnd) but differs from it by a deep split in a UPGMA similarity clustering tree and the lack of a central region of about 140 residues. Among complete genomes, it is found is found in Bacillus subtilis and Mycobacterium tuberculosis, both of which also contain Gnd, and in Aquifex aeolicus.

\ \N \N \N 23330 IPR004850 Agrin is a multidomain heparan sulphate proteoglycan, that is a key organizer for the induction of postsynaptic specializations at the neuromuscular junction. Binding of agrin to basement membranes requires the amino terminal (NtA) domain [MEDLINE:97465865]. This region mediates\ high affinity interaction with the coiled-coil domain of laminins. The binding of agrin to laminins via the NtA domain is subject to\ tissue-specific regulation. The NtA domain-containing form of agrin is expressed in non-neuronal cells or in neurons that project to\ non-neuronal cell such as motor neurons. The structure of this domain is an OB-fold [MEDLINE:21366090]. \ \ \ \N \N \N 23326 IPR004846

This family includes: protein D that is involved in the general (type II) secretion pathway (GSP) within Gram-negative bacteria, a signal sequence-dependent process responsible for protein export [MEDLINE:93174466], [MEDLINE:95099573], [MEDLINE:92276315],[MEDLINE:93316842], [MEDLINE:94049125], [MEDLINE:95020523], [MEDLINE:94247349] and protein G from the type III secretion system.

A number of proteins are involved in the GSP; one of these is known as protein D (GSPD protein), the most probable location of which is the outer membrane [MEDLINE:90008916]. This suggests that protein D constitutes the apparatus of the accessory mechanism, and is thus involved in transporting exoproteins from the periplasm, across the outer membrane, to the extracellular environment.

The type III secretion system is of great interest, as it is used to transport virulence factors from the pathogen directly into the host cell and is only triggered when the bacterium comes into close contact with the host. The protein subunits of the system are very similar to those of bacterial flagellar biosynthesis. However, while the latter forms a ring structure to allow secretion of flagellin and is an integral part of the flagellum itself [MEDLINE:20032050], type III subunits in the outer membrane translocate secreted proteins through a channel-like structure. Protein G aids in the structural assembly of the invasion complex [MEDLINE:96310365].

\ \ \N \N protein secretion ; GO:0009306 23323 IPR004842 This is a family of K-Cl cotransporters. It includes bumetanide-sensitive sodium-(potassium)-chloride cotransporter, an electrically silent transporter system which is a mediator of sodium and chloride reabsorption. It plays a vital role in the regulation of ionic balance and cell volume. Bumetanide-sensitive sodium-(potassium)-chloride cotransporter belongs to the SLC12A family of transporters. \ cation:chloride symporter activity ; GO:0015377 integral to membrane ; GO:0016021 chloride transport ; GO:0006821 23324 IPR004843

Protein phosphorylation plays a central role in the regulation of cell functions [MEDLINE:88107662], causing the activation or inhibition of many enzymes involved in various biochemical pathways [MEDLINE:91092406]. Kinases and phosphatases are the enzymes responsible for this, and may themselves be subject to control through the action of hormones and growth factors [MEDLINE:88107662]. Serine/threonine (S/T) phosphatases catalyse the dephosphorylation of phosphoserine and phosphothreonine residues. In \ mammalian tissues four different types of PP have been identified and are known as PP1, PP2A, PP2B and \ PP2C. Except for PP2C, these enzymes are evolutionary related. The catalytic regions of the proteins are well conserved and have a slow mutation rate, suggesting that major changes in these regions are highly detrimental [MEDLINE:88107662].

The metallo-phosphoesterase motif is found in a large number of proteins invoved in phosphoryation. These include serine/threonine phosphatases, DNA polymerase, exonucleases, and other phosphatases.

\ \ hydrolase activity ; GO:0016787 \N \N 23325 IPR004845

A number of proteins are involved in the general secretion pathway (GSP); one of these is known as protein D (GSPD protein). Protein D is involved in the type II general secretion pathway within Gram-negative bacteria, a signal sequence-dependent process responsible for protein export [MEDLINE:93174466], [MEDLINE:95099573], [MEDLINE:92276315],[MEDLINE:93316842], [MEDLINE:94049125], [MEDLINE:95020523], [MEDLINE:94247349]. The most probable location of protein D is the outer membrane [MEDLINE:90008916]. This suggests that protein D constitutes the apparatus of the accessory mechanism, and is thus involved in transporting exoproteins from the periplasm, across the outer membrane, to the extracellular environment.

\ protein transporter activity ; GO:0008565 \N \N 23320 IPR004839 Aminotransferases share certain mechanistic features with other pyridoxal-phosphate dependent enzymes, such as the covalent binding of the pyridoxal-phosphate group to a lysine residue. On the basis of sequence similarity, these various enzymes can be grouped [MEDLINE:91115885] into class I and class II. This entry includes both subfamilies. \ transaminase activity ; GO:0008483 \N biosynthesis ; GO:0009058 23321 IPR004840 Amino acid permeases are integral membrane proteins involved in the transportof amino acids into the cell. A number of such proteins have been found to be\ evolutionary related [MEDLINE:89125644], [MEDLINE:90076962], [MEDLINE:93184721].\ These proteins seem to contain up to 12 transmembrane segments. The best conserved region\ in this family is located in the second transmembrane segment.\ \ amino acid-polyamine transporter activity ; GO:0005279 membrane ; GO:0016020 amino acid transport ; GO:0006865 23322 IPR004841

Amino acid permeases are integral membrane proteins involved in the transport of amino acids into the cell. A number of such proteins have been found to be evolutionary related [MEDLINE:89125644], [MEDLINE:90076962], [MEDLINE:93184721]. These proteins seem to contain up to 12 transmembrane segments. The best conserved region in this family is located in the second transmembrane segment.

This domain is found in a wide variety of permeases, as well as several hypothetical proteins.

\ \ \N membrane ; GO:0016020 transport ; GO:0006810 23319 IPR004838 Aminotransferases share certain mechanistic features with other pyridoxal-phosphate dependent enzymes, such as the covalent binding of the pyridoxal-phosphate group to a lysine residue. On the basis of sequence similarity, these various enzymes can be grouped [MEDLINE:91115885] into subfamilies, one of which is the class I.\ transaminase activity ; GO:0008483 \N biosynthesis ; GO:0009058 23316 IPR004835 Chitin synthase (EC: 2.4.1.16), also known as chitin-UDP acetyl-glucosaminyl transferase, is a plasma membrane-bound protein which catalyses the conversion of UDP-N-acettyl-D-glucosamine and {(1,4)-(N-acetyl-

-D-glucosaminyl)}(N) to UDP and {(1,4)-(N-acetyl-

-D-glucosaminyl)}(N+1). It plays a major role in cell wall biogenesis. \ \ transferase activity, transferring hexosyl groups ; GO:0016758 \N \N 23317 IPR004836

Na⁺/Ca²⁺ exchange proteins are involved in maintaining Ca²⁺ homeostasis ina wide variety of cell types. They are found in both the plasma membrane\ and intracellular organellar membranes, where they exchange Na⁺ for Ca²⁺ in\ an electrogenic manner. When located in the plasma membrane, they generally\ utilise the transmembrane (TM) Na⁺ concentration gradient in order to\ extrude Ca²⁺ from cells. Three mammalian isoforms have been cloned to date\ (NCX1-3), which consist of 920-970 amino acid residues that are predicted\ to possess 11 or 12 TM domains. Interestingly, they possess a short motif\ (~30 residues) that is similar to the Na⁺/K⁺-ATPase, although its function\ is unknown [MEDLINE:91047958], [MEDLINE:96394663].

\ \

NCX1 has been found to be predominantly expressed in the heart, where it\ plays an important role in excitation-contraction coupling, but it is also\ abundant in a variety of other tissues [MEDLINE:91047958]. NCX2 and NCX3 transcripts have\ been detected in the brain and skeletal muscle [MEDLINE:96394663], [MEDLINE:94292496]. Homologous Na⁺/Ca²⁺\ exchange proteins have also been found in C.elegans, D.melanogaster and\ squid.

\ \ calcium:sodium antiporter activity ; GO:0005432 membrane ; GO:0016020 calcium ion transport ; GO:0006816 23318 IPR004837 The sodium/calcium exchangers are a family of integral membrane proteins. This domain covers the integral membrane regions of these proteins. Sodium/calcium exchangers regulate intracellular Ca2+ concentrations in many cells; cardiac myocytes, epithelial cells, neurons retinal rod photoreceptors and smooth muscle cells [MEDLINE:91047958]. Ca2+ is moved into or out of the cytosol depending on Na+ concentration [MEDLINE:91047958]. In humans and rats there are 3 isoforms; NCX1 NCX2 and NCX3 [MEDLINE:96394663]. \ \N integral to membrane ; GO:0016021 \N 23308 IPR004827 The basic-leucine zipper (bZIP) transcription factors [MEDLINE:95299934], PUB00001084 of eukaryotic are proteins that contain a basic region mediating sequence-specific DNA-binding followed by a leucine zipper region (see IPR002158) required for dimerization.\ DNA binding activity ; GO:0003677 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 23309 IPR004828 These antibacterial peptides are found in bees. These heat-stable, non-helical peptides are active against a wide range of plant-associated bacteria and some human pathogens [MEDLINE:90005446]. This family contains a conserved region including the propeptide and apidaecin sequence.\ antibacterial peptide activity ; GO:0003797 \N defense response ; GO:0006952 23310 IPR004829

This domain was first thought to represent apidaecins, but has now been found in a variety of cell surface proteins. It is found in PAC protein, a cell surface antigen implicated in dental caries; cell surface antigens SpaA and SpaP; IGA FC receptor, also known as antigen; and agglutinin receptor.

\ \N \N \N 23311 IPR004830 Leucine-rich repeats are short sequence motifs present in over sixty proteins, all of which appear to be involved in protein-protein interactions [MEDLINE:96082955]. The superfamily of leucine-rich repeat proteins can be subdivided into at least six subfamilies, characterised by different lengths and consensus sequences of the repeats. It was proposed that the repeats from different subfamilies retain a similar superhelical fold, but differ in the three-dimensional structures of individual repeats [MEDLINE:98202568]. This signature describes a leucine-rich repeat variant with a novel repetitive protein structural motif [MEDLINE:97102423].\ \ \N \N \N 23312 IPR004831 This family groups hypothetical proteins from Synechococcus and Deinococcus. At present there is no known function for any of these proteins.\ \N \N \N 23313 IPR004832 Two related oncogenes, TCL-1 P56279.\ \N \N \N 23314 IPR004833 T-cell leukemia/lymphoma protein 1B (TCL1B protein), also known as syncytiotrophoblast-specific protein, is implicated in disease. It is activated in chronic T-cell leukemias. \ \ \N \N \N 23315 IPR004834 This region is found commonly in chitin synthases classes I, II and III EC: 2.4.1.16. Chitin a linear homopolymer of GlcNAc residues, it is an important component of the cell wall of fungi and is synthesised on the cytoplasmic surface of the cell membrane by membrane bound chitin synthases [MEDLINE:95291659]. \ chitin synthase activity ; GO:0004100 \N chitin biosynthesis ; GO:0006031 23306 IPR004825 The insulin family of proteins [MEDLINE:81052382] groups a number of active peptides which are evolutionaryrelated including insulin; relaxin; insulin-like growth factors I and II [MEDLINE:90322988]; mammalian\ Leydig cell-specific insulin-like peptide (gene INSL3) [MEDLINE:94075362] and early placenta insulin-like\ peptide (ELIP) (gene INSL4) [MEDLINE:96115599]; insect prothoracicotropic hormone (bombyxin) PUB00004620;\ locust insulin-related peptide (LIRP) PUB00004620; molluscan insulin-related peptides 1 to 5 (MIP)\ [MEDLINE:91330924]; and C. elegans insulin-like peptides [MEDLINE:98217375]. Structurally, all these peptides\ consist of two polypeptide chains (A and B) linked by two disulfide bonds. They all share a conserved\ arrangement of four cysteines in their A chain. The first of these cysteines is linked by a disulfide\ bond to the third one and the second and fourth cysteines are linked by interchain disulfide bonds to\ cysteines in the B chain. Insulin is involved in the regulation of normal glucose homeostasis, as well\ as other specific physiological functions [MEDLINE:80120725]. It is synthesised as a\ prepropeptide from which an endoplasmic reticulum-targeting sequence is cleaved to yield proinsulin.\ Prosinsulin contains regions A and B separated by an intervening connecting region, C. The\ connecting region is cleaved, liberating the active protein, which contains the A and B chains,\ held together by 2 disulphide bonds [MEDLINE:80054779].\ \ hormone activity ; GO:0005179 extracellular ; GO:0005576 physiological processes ; GO:0007582 23307 IPR004826

There are several different types of Maf transcription factors with different roles in the cell. MafG and MafH are small Mafs which lack a putative transactivation domain. They behave as transcriptional repressors when they dimerize among themselves. However they also serve as transcriptional activators by dimerizing with other (usually larger) basic-zipper proteins and recruiting them to specific DNA-binding sites. Maf transcription factors contain a conserved basic region leucine zipper (bZIP) domain, which mediates their dimerization and DNA binding property. Neural retina-specific leucine zipper proteins also belong to this family. Together with the basic region, the Maf extended homology region (EHR), conserved only within the Maf\ family, defines the DNA binding specific to Mafs. This structure enables Mafs to make a\ broader area of contact with DNA and to recognize longer DNA\ sequences. In particular, the two residues at the beginning of\ helix H2 are positioned to recognize the\ flanking region [MEDLINE:21912421]. Small Maf proteins heterodimerize with Fos and may act as competitive repressors of the NF2-E2 transcription factor.

In mouse, Maf1 may play an early role in axial patterning. Defects in these proteins are a cause of autosomal dominant retinitis pigmentosa.

\ \ DNA binding activity ; GO:0003677 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 23302 IPR004820

This family includes [MEDLINE:99225283]:

Cholinephosphate cytidyltransferase (P49585).
Glycerol-3-phosphate cytidyltransferase (P49585/>).

CTP:cholinephosphate cytidylyltransferase (CCT) is a key regulatory enzyme in phosphatidylcholine biosynthesis that catalyzes the formation of CDP-choline.\ A comparison of the catalytic domains of CCTs from a wide variety of organisms reveals a large number of completely conserved residues. There may be a role for the conserved HXGH sequence in catalysis. The membrane-binding domain in rat CCT has been defined, and it has been suggested that lipids may play a role in inactivating the enzyme. A phosphorylation domain has been described [MEDLINE:98036086].

\ \ \ nucleotidyltransferase activity ; GO:0016779 \N biosynthesis ; GO:0009058 23303 IPR004821 Protein families that contain at least one copy of this domain include citrate lyase ligase, pantoate-

-alanine ligase, glycerol-3-phosphate cytidyltransferase, ADP-heptose synthase, phosphocholine cytidylyltransferase, lipopolysaccharide core biosynthesis protein KdtB, the bifunctional protein NadR, and a number whose function is unknown. Many of these proteins are known to use CTP or ATP and release pyrophosphate.\ \N \N \N 23304 IPR004823 The TATA box binding protein associated factor (TAF) is part of the transcription initiation factor TFIID multimeric protein complex. TFIID plays a central role in mediating promoter responses to various activators and repressors. It binds tightly to TAFII-250 and directly interacts with TAFII-40. TFIID is composed of TATA binding protein (TBP)and a number of TBP-associated factors (TAFS). TAF proteins adopt a histone-like fold. \ transcription initiation factor activity ; GO:0016986 nucleus ; GO:0005634 transcription initiation ; GO:0006352 23305 IPR004824 Bombyxin (4K-prothoracicotropic hormone) is a brain peptide responsible for activation of prothoracic glands to produce ecdysone in insects. It is a heterodimer of a B chain and an A chain linked by two disulphide bonds, and is secreted. \ prothoracicotrophic hormone activity ; GO:0018445 extracellular ; GO:0005576 physiological processes ; GO:0007582 23301 IPR004817

This family represents the K+-dependent Na+/Ca+ exchanger 1 proteins. They are critical components of the visual transduction cascade, and control the calcium concentration of outer segments during light and darkness. Light causes a rapid lowering of cytosolic free calcium caused by extrusion via this protein, which plays a key role in light adaptation. It is an integral membrane protein which transports one calcium and one potassium ion in exchange for four sodium ions.

\ calcium, potassium:sodium antiporter activity ; GO:0008273 integral to membrane ; GO:0016021 vision ; GO:0007601 23294 IPR004810

An Escherichia coli gene designated purU has been identified and characterised. The gene codes for a 280-amino-acid protein, PurU (P37051). \ PurU is an enzyme that catalyses the hydrolysis of 10-formyltetrahydrofolate\ (formyl-FH4) to FH4 and formate \ [MEDLINE:95173107],[MEDLINE:94042872].

  10-formyltetrahydrofolate + H(2)O = formate +tetrahydrofolate

\ \

Formyl-FH4 hydrolase generates the formate that is used by purT-encoded \ 5'-phosphoribosylglycinamide transformylase for step three of de novo purine\ nucleotide synthesis. Formyl-FH4 hydrolase, a hexamer of 32kDa subunits,\ is activated by methionine and inhibited by glycine. Heterotropic \ cooperativity is observed for activation by methionine in the presence of \ glycine and for inhibition by glycine in the presence of methionine. \ These results suggest that formyl-FH4 hydrolase is a regulatory enzyme whose\ main function is to balance the pools of FH4 and C1-FH4 in response to \ changing growth conditions. The enzyme uses methionine and glycine to\ sense the pools of C1-FH4 and FH4, respectively.

\ \ \ formyltetrahydrofolate deformylase activity ; GO:0008864 \N 'de novo' IMP biosynthesis ; GO:0006189 23295 IPR004811 The functions of E. coli RelA and SpoT differ somewhat. RelA (EC: 2.7.6.5) produces pppGpp (or ppGpp) from ATP and GTP (or GDP). SpoT (EC: 3.1.7.2) degrades ppGpp,\ but may also act as a secondary ppGpp synthetase. The two proteins are strongly similar.\ In many species, a single homolog to SpoT and RelA appears reponsible for both ppGpp\ synthesis and ppGpp degradation. \

(p)ppGpp is a regulatory metabolite of the stringent response, but appears also to be\ involved in antibiotic biosynthesis in some species.

\ \ \N \N guanosine tetraphosphate (5'-ppGpp-3') metabolism ; GO:0015969 23296 IPR004812 The drug resistance transporter Bcr/CflA proteins are predicted to have 12 membrane-spanning regions. Members with known activity include Bcr\ (bicyclomycin resistance protein) in E. coli, Flor (chloramphenicol and florfenicol\ resistance) in Salmonella typhimurium DT104, and CmlA (chloramphenicol resistance) in\ Pseudomonas sp. plasmid R1033.\ \ transporter activity ; GO:0005215 integral to membrane ; GO:0016021 transport ; GO:0006810 23297 IPR004813 The transporter OPT family are transporters of small oligopeptides, demonstratedexperimentally in three different species of yeast. OPT1 is not a member of the ABC or PTR membrane transport families [MEDLINE:97195785].\ \ \N \N \N 23298 IPR004814 This protein represents a small family of integral membrane proteins from Gram-negative bacteria, Gram-positive bacteria, and archaeal species. Members of this family contain 15 to 18 GES predicted transmembrane regions, and this family has extensive homology to a family of yeast tetrapeptide transporters, including isp4 (Schizosaccharomyces pombe) and Opt1 (Candida albicans). EspB, an apparent equivalog from Myxococcus xanthus, shares an operon with a two component system regulatory protein, and is required for the normal timing of sporulation after the aggregation of cells. This is consistent with a role in transporting oligopeptides as signals across the membrane.\ \N \N \N 23299 IPR004815 These proteins are induced by heat shock and other stresses in E. coli, B. subtilis, and other species. The yeast member, designated PIM1, is located in the mitochondrial matrix, required for mitochondrial function, and also induced by heat shock.\ ATP binding activity ; GO:0005524 \N ATP-dependent proteolysis ; GO:0006510 23300 IPR004816

Hydroxymethylglutaryl-CoA reductase (NADPH) (EC: 1.1.1.34) catalyzes the NADP-dependent synthesis of mevalonate from 3-hydroxy-3-methylglutaryl-CoA [MEDLINE:91370847], [MEDLINE:89127221]. In vertebrates, HMG-CoA reductase is the rate-limiting enzyme in cholesterol biosynthesis. In plants, mevalonate is the precursor of all isoprenoid compounds. The reduction of HMG-CoA to mevalonate is regulated by feedback inhibition by sterols and non-sterol metabolites derived from mevalonate [MEDLINE:85261451], including cholesterol.

HMG-CoA reductase is a membrane bound glycoprotein that remains in the endoplasmic reticulum after synthesis and glycosylation [MEDLINE:89127221]. Structurally, it consists of 3 domains. An N-terminal region that contains a variable number of transmembrane segments (7 in mammals, insects and fungi; 2 in plants), a linker region and a C-terminal catalytic domain of approximately 400 amino-acid residues. Although little sequence similarity is found between the transmembrane domains of HMG-CoA reductases from different species, the C-terminal catalytic domain is well conserved. The structure of this region is predicted to consist of amphipathic helices flanking an extended -pleated sheet.

In archebacteria\ \ \ \ [MEDLINE:92210542] HMG-CoA reductase, which is involved in the biosynthesis of the isoprenoids side chains of lipids, seems to be cytoplasmic and lack the N-terminal hydrophobic domain.

Some bacteria, such as Pseudomonas mevalonii, can use mevalonate as the sole carbon source. These bacteria use an NAD-dependent HMG-CoA reductase (EC: 1.1.1.88) to deacetylate mevalonate into 3-hydroxy-3-methylglutaryl-CoA [MEDLINE:92210542]. The Pseudomonas enzyme is structurally related to the catalytic domain of NADP-dependent HMG-CoA reductases.

Synonym(s): 3-hydroxy-3-methylglutaryl-coenzyme A reductase, HMG-CoA reductase

\ \ hydroxymethylglutaryl-CoA reductase (NADPH) activity ; GO:0004420 endoplasmic reticulum membrane ; GO:0005789 lipid metabolism ; GO:0006629 23289 IPR004805 All proteins in this family for which functions are known are DNA polymerases. The group defines the

subunit of DNA polymerase III (EC: 2.7.7.7).\ \ 3'-5' exonuclease activity ; GO:0008408\ alpha DNA polymerase activity ; GO:0003889 cytoplasm ; GO:0005737 DNA replication ; GO:0006260 23290 IPR004806

All proteins in this family for which functions are known are components of a multiprotein complex used for targeting nucleotide excision repair to specific parts of the genome. Rad23 contains a ubiquitin-like domain that interacts with catalytically active proteasomes and two ubiquitin (Ub)-associated (UBA) sequences that bind Ub. Rad23 interacts with ubiquitinated cellular proteins through the\ synergistic action of its UBA domains.

\ \ \ In\ humans, Rad23 complexes with the XPC protein.

\ \ \N nucleus ; GO:0005634 nucleotide-excision repair ; GO:0006289 23291 IPR004807 All proteins in this family for which functions are known are DNA helicases that function in the nucleotide excision repair and are endonucleases that make the 3' incision next to DNA damage. They are part of a pathway requiring UvrA, UvrB, UvrC, and UvrD\ homologs.\ \ excinuclease ABC activity ; GO:0009381 excinuclease ABC complex ; GO:0009380 nucleotide-excision repair ; GO:0006289 23292 IPR004808 All proteins in this family for which functions are known are 5' AP endonucleases that function in base excision repair and the repair of abasic sites in DNA.\ \ nuclease activity ; GO:0004518 \N DNA repair ; GO:0006281 23293 IPR004809 Glutamine synthetase type I (or glutamate-ammonia ligase) has a dodecameric form, which can be subdivided into 1-

and 1-

forms. The phylogeny of the 1-

and 1-

forms appears polyphyletic. E. coli, Synechocystis PCC6803, Aquifex aeolicus, and the crenarcheon\ \ \ \ Sulfolobus acidocaldarius have form 1-

, while Bacillus subtilis,\ Thermotoga maritima, and various euryarchaea has form 1-

. The 1-

dodecamer\ from the crenarcheon Sulfolobus acidocaldarius differs from that in E. coli in that it is not\ regulated by adenylylation.\ \ glutamate-ammonia ligase activity ; GO:0004356 cytoplasm ; GO:0005737 nitrogen fixation ; GO:0009399 23285 IPR004801 This family of proteins models the IIC domain of the phosphotransferase system (PTS) for lactose. The IIC domain catalyzes the transfer of a phosphoryl group from the IIB domain to lactose. When the IIC component and IIB components are in the same polypeptide chain they are designated IIBC.\ protein-N(PI)-phosphohistidine-sugar phosphotransferase activity ; GO:0008982 integral to membrane ; GO:0016021 phosphoenolpyruvate-dependent sugar phosphotransferase system ; GO:0009401 23286 IPR004802 This family represents the only archaeal proteins markedly similar to bacterial TruB, the tRNA pseudouridine 55 synthase. However, among two related yeast proteins, the\ archaeal set matches yeast YLR175w far better than YNL292w. The first, termed\ centromere/microtubule binding protein 5 (CBF5), is an apparent rRNA pseudouridine\ synthase, while the second is the exclusive tRNA pseudouridine 55 synthase for both\ cytosolic and mitochondrial compartments. It is unclear whether the archaeal proteins in this family modify tRNA, rRNA, or both.\ \ \N \N \N 23287 IPR004803 The queuine tRNA-ribosyltransferase (tgt) EC: 2.4.2.29 catalyzes an exchange for the guanine base at position 34 of many tRNAs; this nucleotide is subsequently modified to queuosine. The\ Archaea have a closely related enzyme that catalyzes a base exchange for guanine at\ position 15 in some tRNAs, a site that is subsequently converted to the archaeal-specific\ modified base archaeosine (7-formamidino-7-deazaguanosine), while Archaeoglobus\ fulgidus has both enzymes.\ \ queuine tRNA-ribosyltransferase activity ; GO:0008479 \N queuosine biosynthesis ; GO:0008616 23288 IPR004804 The archaeosine tRNA-guanine transglycosylase (tgt) differs from the tgt of E. coli and other bacteria in the site of action and the modification that results. It exchanges 7-cyano-7-deazaguanine (preQ0) with guanine at position 15 of archaeal tRNA; this nucleotide is subsequently\ converted to archaeosine, found exclusively in the Archaea. In contrast, bacterial tgt catalyzes the exchange of preQ0 or preQ1\ for the guanine base at position 34; this nucleotide is subsequently modified to queuosine.\ Archeoglobus fulgidus has both enzymes, while some other Archaea have just this one.\ \ \N \N \N 23279 IPR004794 This entry describes the ribD protein as found in Escherichia coli. The N-terminal domain includes the conserved zinc-binding site region that is shared by proteins such as cytosine deaminase, mammalian apolipoprotein B mRNA editing protein, blasticidin-S deaminase, and Bacillus subtilis competence protein comEB. The C-terminal domain is homologous to the full length of yeast HTP reductase, a protein required for riboflavin biosynthesis. A number of archaeal proteins that may be related to the riboflavin biosynthesis protein contain only the C-terminal domain.\ \ 5-amino-6-(5-phosphoribosylamino)uracil reductase activity ; GO:0008703\ diaminohydroxyphosphoribosylaminopyrimidine deaminase activity ; GO:0008835 \N vitamin B2 biosynthesis ; GO:0009231 23280 IPR004796 The phosphotransferase system (PTS) consists of both the cellobiose specific and the lactose specific forms of the phosphotransferase system (PTS) IIC component. The IIC domain catalyzes the transfer of a phosphoryl group from the IIB domain to the substrate. When the IIC component and IIB components are in the same polypeptide chain they are designated IIBC.\

This family consists of the cellobiose specific form of the phosphotransferase system\ (PTS), IIC component.

\ \ protein-N(PI)-phosphohistidine-sugar phosphotransferase activity ; GO:0008982 integral to membrane ; GO:0016021 phosphoenolpyruvate-dependent sugar phosphotransferase system ; GO:0009401 23281 IPR004797 This is the DNA internalization-related competence protein ComEC/Rec2 family. Apparant orthologs are found in 5 species so far (Haemophilus influenzae, Escherichia coli, Bacillus subtilis, Neisseria gonorrhoeae, Streptococcus pneumoniae), of which all but E. coli are model systems for the study of competence for natural transformation. This protein is a predicted multiple membrane-spanning protein likely to be involved in DNA internalization.\ \N integral to membrane ; GO:0016021 establishment of competence for transformation ; GO:0030420 23282 IPR004798 This is a group of calcium/proton exchanger proteins. In Arabidopsis thaliana the transporter is responsible for maintaining low cytosolic-free Ca2+ concentrations in the plant cells by catalyzing pH gradient-energized vacuolar Ca2+ accumulation.\ \N \N \N 23283 IPR004799 Periplasmic protein thiol:disulfide oxidoreductase is involved in the biogenesis of c-type cytochromes as well as in disulfide bond formation in some periplasmic proteins. This group defines the DsbE subfamily\ disulfide oxidoreductase activity ; GO:0015036 periplasmic space (sensu Gram-negative Bacteria) ; GO:0030288 cytochrome biogenesis ; GO:0017004 23284 IPR004800 This is a family of closely related proteins with the phosphosugar-binding domain SIS (Sugar ISomerase) followed by two copies of the CBS (named after Cystathionine Beta Synthase) domain. The group includes GutQ, a protein of the glucitol operon and KpsF, a virulence factor involved in capsular polysialic acid biosynthesis in some pathogenic strains of E. coli.\ \N \N \N 23272 IPR004787

The comE locus is obligatory for bacterial cell competence - the process of internalizing the exogenous added DNA. comEA and comEC are required for transformability, whereas the products of comEB and of the overlapping comER, which is transcribed in the reverse direction, are dispensable [MEDLINE:95286482].

ComEA has been shown to be an integral membrane protein, as predicted from hydropathy analysis, with its C-terminal domain outside the cytoplasmic membrane. This C-terminal domain possesses a sequence with similarity to those of several proteins known to be involved in nucleic acid transactions including UvrC and a human protein that binds to the replication origin of the Epstein-Barr virus\ \ \ \ [MEDLINE:95286482].

\ \ \N integral to membrane ; GO:0016021 establishment of competence for transformation ; GO:0030420 23273 IPR004788 Ribose 5-phosphate isomerase (EC: 5.3.1.6), also known as phosphoriboisomerase, catalyses the conversion of D-ribose 5-phosphate to D-ribulose 5-phosphate in the non-oxidative branch of the pentose phosphate pathway.\ ribose-5-phosphate isomerase activity ; GO:0004751 \N pentose-phosphate shunt, non-oxidative branch ; GO:0009052 23274 IPR004789

ACT domains are linked to a wide range of metabolic enzymes that are regulated by amino acid concentration.Pairs of ACT domains bind specifically to a particular amino acid leading to regulation of the linked enzyme.

Acetolactate synthase (or acetohydroxyacid synthase) EC: 4.1.3.18 is a heterodimeric thiamine pyrophosphate enzyme with large and\ small subunits.

\ \ acetolactate synthase activity ; GO:0003984 \N branched chain family amino acid biosynthesis ; GO:0009082 23275 IPR004790

Isocitrate dehydrogenase (IDH) [MEDLINE:90046847], [MEDLINE:92042149] is an important enzyme of carbohydrate metabolism which catalyzes the oxidative decarboxylation of isocitrate into -ketoglutarate. IDH is either dependent on NAD⁺ (EC: 1.1.1.41) or on NADP⁺ (EC: 1.1.1.42). In eukaryotes there are at least three isozymes of IDH: two are located in the mitochondrial matrix (one NAD⁺-dependent, the other NADP⁺-dependent), while the third one (also NADP⁺-dependent) is cytoplasmic. In Escherichia coli the activity of a NADP⁺-dependent form of the enzyme is controlled by the phosphorylation of a serine residue; the phosphorylated form of IDH is completely inactivated.

The eukaryotic, NADP-dependent isocitrate dehydrogenases, are defined by this group that includes the cytosolic, mitochondrial, and chloroplast enzymes.

\ \ isocitrate dehydrogenase (NADP+) activity ; GO:0004450 \N main pathways of carbohydrate metabolism ; GO:0006092 23276 IPR004791 Excinuclease ABC complex is involved in DNA replication, recombination and repair. This group defines the C subunit.\ excinuclease ABC activity ; GO:0009381 excinuclease ABC complex ; GO:0009380 DNA repair ; GO:0006281 23277 IPR004792 This is a family of conserved hypothetical proteins that may include proteins with a dinucleotide-binding motif (Rossman fold), including oxidoreductases and dehydrogenases.\ \N \N \N 23278 IPR004793 Desulfoferrodoxin is a non-heme iron protein which contains two types of iron atoms per molecule, a desulfoferrodoxin-like FES(4) site, and an octahedral coordinated high-spin ferrous site with nitrogen/oxygen-containing ligands. The short N-terminal domain contains four conserved Cys for binding of the ferric iron atom, and is homologous to the small protein desulforedoxin. The remainder of the molecule binds the ferrous iron atom and is similar to neelaredoxin, a monomeric blue non-heme iron protein. The homolog from Treponema pallidum, although essentially a full length homolog, lacks three of the four Cys residues in the N-terminal domain; the domain may have lost ferric binding ability but may have some conserved structural role such as dimerization, or some new function. This protein is described in some articles as rubredoxin oxidoreductase (rbo), and its gene shares an operon with the rubredoxin gene in Desulfovibrio vulgaris Hildenborough.\ \N \N electron transport ; GO:0006118 23260 IPR004773 The proteins of the Trk family are derived from Gram-negative and Gram-positive bacteria, yeast and wheat. The proteins of E. coli K12 TrkH and TrkG as well as several yeast proteins have been functionally characterized.The E. coli TrkH and TrkG proteins are complexed to two peripheral membrane proteins, TrkA, an NAD-binding protein, and TrkE, an ATP-binding protein. This complex forms the potassium uptake system. This family is specific for the eukaryotic Trk system.\ potassium ion transporter activity ; GO:0015079 integral to membrane ; GO:0016021 potassium ion transport ; GO:0006813 23261 IPR004775 A group of uncharacterised proteins some of which are similar to various chains of the NADH-ubiquinone/plastoquinone (complex I).\ \N \N \N 23262 IPR004776 Proteins in this group are mostly uncharacterised and of unknown function.\ molecular_function unknown ; GO:0005554 integral to membrane ; GO:0016021 \N 23263 IPR004777 L-lysine exporter, LysE is an exporter, which: (i) structurally represents a new type of translocator; (ii) demonstrates that exporters are also present for primary metabolites such as amino acids; and (iii) serves in one physiological function to link import with export activity [MEDLINE:97126810].\ \N integral to membrane ; GO:0016021 \N 23264 IPR004778 Proteins in this group include,

A chemotactic transduction protein from Pseudomonas aeruginosa.

The homoserine/homoserine lactone efflux protein from Escherichia coli.

and a number of hypothetical proteins.

\ \ \N integral to membrane ; GO:0016021 \N 23265 IPR004779 This family includes,

the PecM protein from Erwinia chrysanthemi that is involved in pectinase, cellulase and blue pigment regulation.

a probable amino acid metabloite efflux pump from Escherichia coli.

and a number of uncharacterised proteins.

\ \ \N integral to membrane ; GO:0016021 \N 23266 IPR004780 Signal recognition particle protein is necessary for the efficient export of extra-cytoplasmic proteins. They bind to the signal sequence when it emerges from the ribosome.\ signal-recognition-particle GTPase activity ; GO:0008548 signal recognition particle ; GO:0005786 protein targeting ; GO:0006605 23267 IPR004782 L-fuculose phosphate aldolase EC: 4.1.2.17 is involved in energy metabolism.\ L-fuculose-phosphate aldolase activity ; GO:0008738 \N fucose metabolism ; GO:0006004 23268 IPR004783 Galactose-6-phosphate isomerase EC: 5.3.1.26 is involved in lactose catabolism. This family is specific for the LacA subunit.\ intramolecular isomerase activity, interconverting aldoses and ketoses ; GO:0016861 \N lactose catabolism ; GO:0005990 23269 IPR004784 Galactose-6-phosphate isomerase EC: 5.3.1.26 is involved in lactose catabolism. This family is specific for the LacB subunit.\ intramolecular isomerase activity, interconverting aldoses and ketoses ; GO:0016861 \N lactose catabolism ; GO:0005990 23270 IPR004785 Ribose 5-phosphate EC: 5.3.1.6 is involved in the non-oxidate branch of the pentose phospate pathway. This family defines isomerase B.\ ribose-5-phosphate isomerase activity ; GO:0004751 \N pentose-phosphate shunt ; GO:0006098 23271 IPR004786

Two dehydratases, dihydroxy-acid dehydratase (EC: 4.2.1.9) (gene ilvD or ILV3) and 6-phosphogluconatedehydratase (EC: 4.2.1.12) (gene edd) have been shown to be evolutionary related [MEDLINE:92325055]. Dihydroxy-acid\ dehydratase catalyzes the fourth step in the biosynthesis of isoleucine and valine, the dehydratation of\ 2,3-dihydroxy-isovaleic acid into -ketoisovaleric acid. 6-Phosphogluconate dehydratase catalyzes the\ first step in the Entner-Doudoroff pathway, the dehydratation of 6-phospho-D-gluconate into \ 6-phospho-2-dehydro-3-deoxy-D-gluconate. Another protein containing this signature is the E. coli hypothetical protein\ yjhG. The N-terminal part of the proteins contains a cysteine that could be involved in the binding of a\ 2Fe-2S iron-sulfur cluster [MEDLINE:94131281].

This family defines the 6-phosphogluconate dehydratases.

\ \ ketopantoaldase activity ; GO:0004456 \N Entner-Doudoroff pathway ; GO:0009255 23256 IPR004769 A number of enzymes, belonging to the lyase class, for which fumarate is asubstrate have been shown [MEDLINE:88193096], PUB00001722\ to share a short conserved sequence around a\ methionine which is probably involved in the catalytic activity of this type\ of enzymes.\

Adenylosuccinate lyase EC: 4.3.2.2 is involved in purine ribonucleotide biosynthesis.

\ \ adenylosuccinate lyase activity ; GO:0004018 \N purine ribonucleotide biosynthesis ; GO:0009152 23257 IPR004770 A single member of the NhaC family, a protein from Bacillus firmus, has been functionally characterized.It is involved in pH homeostasis and sodium extrusion. Members of the NhaC family are found in both Gram-negative bacteria and Gram-positive bacteria.\ sodium:hydrogen antiporter activity ; GO:0015385 integral to membrane ; GO:0016021 regulation of pH ; GO:0006885 23258 IPR004771

\ \ cation transporter activity ; GO:0008324 integral to membrane ; GO:0016021 cation transport ; GO:0006812 23259 IPR004772 The proteins of the Trk family are derived from Gram-negative and Gram-positive bacteria, yeast and wheat. The proteins of E. coli K12 TrkH and TrkG as well as several yeast proteins have been functionally characterized.The E. coli TrkH and TrkG proteins are complexed to two peripheral membrane proteins, TrkA, an NAD-binding protein, and TrkE, an ATP-binding protein. This complex forms the potassium uptake system.\ cation transporter activity ; GO:0008324 integral to membrane ; GO:0016021 cation transport ; GO:0006812 23246 IPR004759 Amino acid permeases are integral membrane proteins involved in the transportof amino acids into the cell. A number of such proteins have been found to be\ evolutionary related [MEDLINE:89125644], [MEDLINE:90076962], [MEDLINE:93184721].\ These proteins seem to contain up to 12 transmembrane segments. The best conserved region\ in this family is located in the second transmembrane segment.\ \

An example of the glutamate:g-aminobutyrate antiporter proteins is the amino acid transporter involved in extreme acid resistance from Shigella flexneri.

\ \ amino acid permease activity ; GO:0015359 integral to membrane ; GO:0016021 amino acid transport ; GO:0006865 23247 IPR004760 Amino acid permeases are integral membrane proteins involved in the transportof amino acids into the cell. A number of such proteins have been found to be\ evolutionary related [MEDLINE:89125644], [MEDLINE:90076962], [MEDLINE:93184721].\ These proteins seem to contain up to 12 transmembrane segments. The best conserved region\ in this family is located in the second transmembrane segment.\ \

In this family of L-type amino acid transporters one example is the high affinity methionine permease from yeast.

\ \ amino acid permease activity ; GO:0015359 integral to membrane ; GO:0016021 amino acid transport ; GO:0006865 23248 IPR004761 Amino acid permeases are integral membrane proteins involved in the transportof amino acids into the cell. A number of such proteins have been found to be\ evolutionary related [MEDLINE:89125644], [MEDLINE:90076962], [MEDLINE:93184721].\ These proteins seem to contain up to 12 transmembrane segments. The best conserved region\ in this family is located in the second transmembrane segment.\

Spore germination protein (amino acid permease) is involved in the response to the germinative mixture of L-asparagine, glucose, fructose and potassium ions (AFFK). These proteins could be amino acid transporters.

\ \ \N integral to membrane ; GO:0016021 spore germination ; GO:0009847 23249 IPR004762 Amino acid permeases are integral membrane proteins involved in the transportof amino acids into the cell. A number of such proteins have been found to be\ evolutionary related [MEDLINE:89125644], [MEDLINE:90076962], [MEDLINE:93184721].\ These proteins seem to contain up to 12 transmembrane segments. The best conserved region\ in this family is located in the second transmembrane segment.\

This family is specific for the yeast amino acid permeases.

\ \ amino acid permease activity ; GO:0015359 integral to membrane ; GO:0016021 amino acid transport ; GO:0006865 23250 IPR004763 This belongs to the family of H+/heavy metal cation antiporters. The cobalt/zinc/cadmium resistance protein, CzcA, is essential for the expression of cobalt, zinc and cadmium resistance.\ cation transporter activity ; GO:0008324 integral to membrane ; GO:0016021 cation transport ; GO:0006812 23251 IPR004764

Hydrophobe/amphiphile efflux-1 HAE1 is involved in toxin production and resistance processes.

\ transporter activity ; GO:0005215 integral to membrane ; GO:0016021 transport ; GO:0006810 23252 IPR004765 The Niemann-Pick C type protein is an integral membrane protein, which indicates that it is most likely involved in cholesterol transport or acts as some component of cholesterol\ homeostasis.\ The defective protein has been associated with Niemann-Pick disease which is described in humans as autosomal recessive lipidosis. It is characterized by the lysosomal accumulation of\ unestrified cholesterol.\ \ \N integral to membrane ; GO:0016021 cholesterol transport ; GO:0030301 23253 IPR004766

Patched transmembrane receptor for sonic hedgehog. May have a role in epidermal development.

\ patched receptor activity ; GO:0008158 integral to membrane ; GO:0016021 \N 23254 IPR004767 Characterized members of the RND superfamily all probably catalyze substrate efflux via an H+ antiport mechanism. These proteins are found ubiquitously in bacteria, archaea and eukaryotes. They fall into seven phylogenetic families. \

This family consists of\ uncharacterised putative transporters.

\ \ \N \N \N 23255 IPR004768 Oligopeptide transporter, peptide:H+ symporter supports the proton-coupled intake of oligopeptides of 2 to 4 amino acids. These proteins may constitute a major route for the absorption of the end products of protein digestion.\ oligopeptide transporter activity ; GO:0015198 integral to membrane ; GO:0016021 oligopeptide transport ; GO:0006857 23242 IPR004755 Amino acid permeases are integral membrane proteins involved in the transportof amino acids into the cell. A number of such proteins have been found to be\ evolutionary related [MEDLINE:89125644], [MEDLINE:90076962], [MEDLINE:93184721].\ These proteins seem to contain up to 12 transmembrane segments. The best conserved region\ in this family is located in the second transmembrane segment.\

Some proteins in this family are low-affinity, high capacity permeases involved in the transport of arginine, lysine and ornithine, the cationinc amino acids.

\ \ amino acid permease activity ; GO:0015359 integral to membrane ; GO:0016021 amino acid transport ; GO:0006865 23243 IPR004756 Amino acid permeases are integral membrane proteins involved in the transportof amino acids into the cell. A number of such proteins have been found to be\ evolutionary related [MEDLINE:89125644], [MEDLINE:90076962], [MEDLINE:93184721].\ These proteins seem to contain up to 12 transmembrane segments. The best conserved region\ in this family is located in the second transmembrane segment.\ \ amino acid permease activity ; GO:0015359 integral to membrane ; GO:0016021 amino acid transport ; GO:0006865 23244 IPR004757 Amino acid permeases are integral membrane proteins involved in the transportof amino acids into the cell. A number of such proteins have been found to be\ evolutionary related [MEDLINE:89125644], [MEDLINE:90076962], [MEDLINE:93184721].\ These proteins seem to contain up to 12 transmembrane segments. The best conserved region\ in this family is located in the second transmembrane segment.\ \ \N \N \N 23245 IPR004758 Amino acid permeases are integral membrane proteins involved in the transportof amino acids into the cell. A number of such proteins have been found to be\ evolutionary related [MEDLINE:89125644], [MEDLINE:90076962], [MEDLINE:93184721].\ These proteins seem to contain up to 12 transmembrane segments. The best conserved region\ in this family is located in the second transmembrane segment.\

Some proteins in this group are involved in the transport of the cationic amino acids (arginine,lysine and ornithine).

\ \ \N \N \N 23234 IPR004747 This family of proteins is involved in active transport of cyanate. The cyanate transporter in E.Coli is used to transport cyanate into the cell so it can be metabolized into ammonia and bicarbonate. This process is used to overcome the toxicity of environmental cyanate.\ transporter activity ; GO:0005215 integral to membrane ; GO:0016021 transport ; GO:0006810 23235 IPR004748 This family of proteins includes the ribitol and D-arabinitol transporters from Klebsiella pneumoniae and the

-ketoglutarate permease from Bacillus subtilis.\ transporter activity ; GO:0005215 integral to membrane ; GO:0016021 transport ; GO:0006810 23236 IPR004749 Organic cation transport proteins belong to this group. The protein from human is a sodium-dependent, high affinity carnitine transporter that also transports organic cations without the involvement of sodium. It is involved in the active cellular uptake of carnitine.\ ion transporter activity ; GO:0015075 integral to membrane ; GO:0016021 ion transport ; GO:0006811 23237 IPR004750 This family of proteins is an efflux system for lactose, glucose, aromatic glucosides and galactosides, cellobiose, maltose, a-methyl glucoside and other sugar compounds. They are found in both gram-negative and gram-postitive bacteria.\ sugar efflux transporter activity ; GO:0015542 integral to membrane ; GO:0016021 carbohydrate transport ; GO:0008643 23238 IPR004751

Drug antiporters which use the proton motive force for the active efflux of the drug [MEDLINE:98353314].

\ \N integral to membrane ; GO:0016021 \N 23239 IPR004752 The signal transducer encoded by ampG is essential for induction of chromosomal AmpC

-lactamase in Escherichia coli by

-lactam antibiotics and 'unspecific' inducers [MEDLINE:95291453]. The ampG protein probably acts as a permease in the

-lactamase induction system and in peptidoglycan recycling.\ \N \N \N 23240 IPR004753

Bacterial cell shape varies greatly between species, and characteristic morphologies are used for identification purposes. In addition to individual\ cell shape, the way in which groups of cells are arranged is also typical of\ some bacterial species, especially Gram-positive coccoids. For many years, it was believed that micro-organisms with other than\ spheroidal cell shapes maintained morphology by means of their external cell \ walls. Recently, however, studies of the Gram-positive rod Bacillus subtilis\ have revealed two related genes that are essential for the integrity of cell\ morphogenesis [MEDLINE:21185937]. Termed mreB and mbl, the gene products localise close to\ the cell surface, forming filamentous helical structures. Many \ homologues have been found in diverse bacterial groups, suggesting a common \ ancestor [MEDLINE:21429422].

The crystal structure of MreB from Thermotoga maritima has been resolved \ using X-ray crystallography [MEDLINE:21429422]. It consists of 19 -strands and 15 -\ helices, and shows remarkable structural similarity to eukaryotic actin. \ MreB crystals also contain proto-filaments, with individual proteins \ assembling into polymers like F-actin, in the same orientation. It is \ hypothesised therefore, that MreB was the forerunner of actin in early \ eukaryotes [MEDLINE:21587823].

\ \ \N \N \N 23241 IPR004754 Amino acid permeases are integral membrane proteins involved in the transportof amino acids into the cell. A number of such proteins have been found to be\ evolutionary related [MEDLINE:89125644], [MEDLINE:90076962], [MEDLINE:93184721].\ These proteins seem to contain up to 12 transmembrane segments. The best conserved region\ in this family is located in the second transmembrane segment.\

Proteins in this group catalyse an electroneutral exchange between arginine and ornithine to allow high-efficiency energy conversions in the arginine deiminase pathway.

\ \ amino acid-polyamine transporter activity ; GO:0005279 integral to membrane ; GO:0016021 amino acid transport ; GO:0006865 23221 IPR004733

The purine biosynthetic pathway in procaryotes enlists eleven enzymes, six of which use ATP. Enzymes 5 and 6 of this pathway, formylglycinamide ribonucleotide (FGAR) amidotransferase (PurL) and aminoimidazole ribonucleotide (AIR) synthetase (PurM) utilize ATP to activate the oxygen of an amide within their substrate toward nucleophilic attack by a nitrogen. AIR synthetase uses the product of PurL, formylglycinamidine ribonucleotide (FGAM) and ATP to make AIR, ADP and P(i).

\ phosphoribosylformylglycinamidine cyclo-ligase activity ; GO:0004641 cytoplasm ; GO:0005737 'de novo' IMP biosynthesis ; GO:0006189 23222 IPR004734

Multidrug resistance proteins are molecular pumps that participate in a low energy shock adaptive response in some bacteria. They mediate cellular resistance to toxicants such as cycloheximide (CYH), 4-nitroquinoline N-oxide (4-NQO), cadmium, and hydrogen peroxide in yeast [MEDLINE:97382256].

\ \N integral to membrane ; GO:0016021 \N 23223 IPR004736 Citrate-proton symport proteins allow the utilization of citrate as a sole source of carbon and energy. They are involved in the uptake of citrate across the boundary membrane with the concomitant export of a proton.\ transporter activity ; GO:0005215 integral to membrane ; GO:0016021 transport ; GO:0006810 23224 IPR004737 Nitrate transporters in E.coli are involved in excretion of nitrite produced by the dissimilatory reduction of nitrate.\ inorganic anion transporter activity ; GO:0015103 integral to membrane ; GO:0016021 inorganic anion transport ; GO:0015698 23225 IPR004738 In yeast the high-affinity transporter for external inorganic phosphate is not essential since a constitutive, low-affinity transporter exists. The induction of the yeast protein is depressed by phosphate starvation.\ inorganic phosphate transporter activity ; GO:0005315 integral to membrane ; GO:0016021 phosphate transport ; GO:0006817 23226 IPR004739 Glutamine amidotransferase (GATase) (EC: 2.4.2.-) activity involves the removal of the ammonia group from a glutamate molecule and its subsequent transfer to a specific substrate, thus creating a new \ carbon-nitrogen group on the substrate. This activity is found in a range of biosynthetic enzymes, \ including glutamine amidotransferase, anthranilate synthase component II, p-aminobenzoate, and \ glutamine-dependent carbamoyl-transferase (CPSase). Glutamine amidotransferase (GATase) domains can occur \ either as single polypeptides, as in glutamine amidotransferases, or as domains in a much larger \ multifunctional synthase protein, such as CPSase. On the basis of sequence similarities two classes of \ GATase domains have been identified [MEDLINE:87250264], [MEDLINE:84264639], class-I (also known as trpG-type) and \ class-II (also known as purF-type). Class-I GATase domains have been found in the following enzymes, the \ second component of anthranilate synthase and 4-amino-4-deoxychorismate (ADC) synthase; CTP synthase; GMP \ synthase; glutamine-dependent carbamoyl-phosphate synthase; phosphoribosylformylglycinamidine synthase II; \ and the histidine amidotransferase hisH.\ \

The N-terminal region of GMP synthase EC: 6.3.5.2 is recognised by this group.

\ \ ATP binding activity ; GO:0005524 \N GMP biosynthesis ; GO:0006177 23227 IPR004740 This family of proteins transports nucleosides at a high affinity. The transport mechanism is driven by proton motive force. This family includes nucleoside permease NupG and xanthosine permease from E.Coli.\ nucleoside transporter activity ; GO:0005337 integral to membrane ; GO:0016021 nucleoside transport ; GO:0015858 23228 IPR004741

Oxalate/formate antiporters and many, as yet, uncharacterised proteins belong to this group.

\ \N \N \N 23229 IPR004742

The sugar transporters belong to a family of membrane proteins responsiblefor the transport of various sugars in a wide range of prokaryotic and\ eukaryotic organisms [MEDLINE:85272595]. These integral membrane proteins are\ predicted to comprise twelve membrane spanning domains. It is likely that the\ transporters have evolved from an ancient protein present in living organisms\ before the divergence into prokaryotes and eukaryotes [MEDLINE:87115869]. In mammals,\ these proteins are expressed in a number of organs [MEDLINE:89008414]. Proteins transporting sugars and other substrates are related in this broader family.

\ \

Sialic acid transporters belong to this group.

\ \ carbohydrate transporter activity ; GO:0015144 integral to membrane ; GO:0016021 transport ; GO:0006810 23230 IPR004743 Proton-linked monocarboxylate transporters catalyse the rapid transport across the plasma membrane of many monocarboxylates such as lactate, pyruvate, branched-chain oxo acids derived from leucine, valine and isoleucine, and the ketone bodies acetoacetate,

-hydroxybutyrate and acetate.\ monocarboxylate porter activity ; GO:0015355 integral to membrane ; GO:0016021 organic anion transport ; GO:0015711 23231 IPR004744 D-galactonate transporters and other proteins that belong to the phthalate permease family are members of this group.\ transporter activity ; GO:0005215 integral to membrane ; GO:0016021 transport ; GO:0006810 23232 IPR004745 Na(+)-dependent inorganic phosphate cotransporter proteins belong to this group. The mammalian proteins are important for the resorption of phosphate by the kidney and may be involved in actively transporting phosphate into cells via sodium ion cotransport in the renal brush border membrane.\ phosphate transporter activity ; GO:0015114 integral to membrane ; GO:0016021 phosphate transport ; GO:0006817 23233 IPR004746 Benzoate transport proteins belong to this group. Benzyl alcohol, benzaldehyde, benzoate, and anthranilate are metabolized via catechol, cis,cis-muconate, and the

-ketoadipate pathway in some bacteria.\ \ transporter activity ; GO:0005215 integral to membrane ; GO:0016021 transport ; GO:0006810 23220 IPR004732

Transaldolase (EC: 2.2.1.2) catalyzes the reversible transfer of a three-carbon ketol unit from sedoheptulose 7-phosphate to glyceraldehyde 3-phosphate to form erythrose 4-phosphate and fructose 6-phosphate. This enzyme, together with transketolase, provides a link between the glycolytic and pentose-phosphate pathways. Transaldolase is an enzyme of about 34 Kd whose sequence has been well conserved throughout evolution. A lysine has been implicated [MEDLINE:94152171] in the catalytic mechanism of the enzyme; it acts as a nucleophilic group that attacks the carbonyl group of fructose-6-phosphate.

Transaldolase is evolutionary related [MEDLINE:95291446] to a bacterial protein of about 20 Kd (known as talC in Escherichia coli), whose exact function is not yet known.

\ \ transaldolase activity ; GO:0004801 cytoplasm ; GO:0005737 pentose-phosphate shunt ; GO:0006098 23213 IPR004725 Bcl-X is a dominant regulator of programmed cell death in mammalian cells. The long form (Bcl-X(L)) displays cell death repressor activity, but the short isoform\ (Bcl-X(S)) and the b-isoform (Bcl-Xb) promote cell death. Bcl-X(L), Bcl-X(S) and Bcl-Xb are three isoforms derived by alternative RNA splicing. Bcl-X(S)\ forms heterodimers with Bcl-2. Homologues of Bcl-X include the rat Bax and mouse Bak proteins which also influence\ apoptosis.\ \ apoptosis regulator activity ; GO:0016329 membrane ; GO:0016020 apoptosis ; GO:0006915 23214 IPR004726 The Caenorhabditis elegans mec-4 gene encodes a subunit of a candidate mechanosensitive ion channel that plays a critical role in touch reception [MEDLINE:96251674]. The product is a mechanosensory protein (denegrin). At least some of\ the proteins in this group form part of a mechano-transducing complex for touch sensitivity. Others include the acid-sensing ion channels, ASIC1-3 that are homo- or hetero-oligomeric neuronal H+-gated channels that mediate pain sensation\ in response to tissue acidosis. \ Mammalian ENaC is important for the maintenance of Na+ balance and the regulation of\ blood pressure. Three homologous ENaC subunits, a, b and g, have\ been shown to assemble to form the highly Na+-selective channel.\ \ ion channel activity ; GO:0005216 integral to membrane ; GO:0016021 ion transport ; GO:0006811 23215 IPR004727 Chloride channels have several functions including the regulation of cell volume, the stabilisation of the membrane potential, signal transduction and transepithelial transport.\ voltage-gated chloride channel activity ; GO:0005247 integral to membrane ; GO:0016021 chloride transport ; GO:0006821 23216 IPR004728 Members of the NSCC2 family have been sequenced from various yeast, fungal and animals species including Saccharomyces cerevisiae, Drosophila melanogaster and Homo sapiens. These proteins are the Sec62 proteins, believed to be associated with the Sec61 and Sec63 constituents of the general protein secretary systems of yeast microsomes. They are also the non-selective cation (NS) channels of the mammalian cytoplasmic membrane. The yeast Sec62 protein has been shown to be essential for cell growth. The mammalian NS channel proteins has been implicated in platelet derived growth factor(PGDF) dependent single channel current in fibroblasts. These channels are essentially closed in serum deprived tissue-culture cells and are specifically opened by exposure to PDGF. These channels are reported to exhibit equal selectivity for Na+, K+ and Cs+ with low permeability to Ca2+, and no permeability to anions.\ protein transporter activity ; GO:0008565 integral to membrane ; GO:0016021 protein transport ; GO:0015031 23217 IPR004729

The transient-receptor-potential calcium channel protein, TRP-CC, has also been called the store-operated calcium channel (SOC) protein. The prototypical members include the Drosophila melanogaster retinal proteins TRP and TRPL [MEDLINE:90180449]. SOC members of the family mediate the entry of extracellular Ca²⁺ into cells in response to depletion of intracellular Ca²⁺ stores and agonist stimulated production of inositol-1,4,5 trisphosphate (IP3). One member of the TRP-CC family, mammalian Htrp3, has been shown to form a tight complex with the IP3 receptor. This interaction is apparently required for IP3 to stimulate Ca²⁺ release via Htrp3.

The vanilloid receptor subtype 1 (VR1), which is the receptor for capsaicin and serves as a heat-activated ion channel in the pain pathway, is also a member of this family. The stretch-inhibitable non-selective cation channel (SIC) is identical to the vanilloid receptor throughout all of its first 700 residues, but it exhibits a different sequence in its last 100 residues. VR1 and SIC transport monovalent cations as well as Ca²⁺. VR1 is about 10 times more permeable to Ca²⁺ than to monovalent ions. Ca²⁺ overload probably causes cell death after chronic exposure to capsaicin.

\ \ ion channel activity ; GO:0005216 integral to membrane ; GO:0016021 ion transport ; GO:0006811 23218 IPR004730

Transaldolase is evolutionary related [MEDLINE:95291446] to a bacterial protein of about 20 Kd (known as talC in Escherichia coli), whose exact function is not yet known.

\ \ transaldolase activity ; GO:0004801 cytoplasm ; GO:0005737 pentose-phosphate shunt ; GO:0006098 23219 IPR004731

Transaldolase is evolutionary related [MEDLINE:95291446] to a bacterial protein of about 20 Kd (known as talC in Escherichia coli), whose exact function is not yet known.

\ \ \N \N carbohydrate metabolism ; GO:0005975 23208 IPR004720 Bacterial PTS transporters transport and concomitantly phosphorylate their sugar substrates, and typically consist of multiple subunits or protein domains.The Man family is unique in several respects among PTS permease families.

It is the only PTS family in which members possess a IID protein.

It is the only PTS family in which the IIB constituent is phosphorylated on a histidyl rather than a cysteyl residue.

Its permease members exhibit broad specificity for a range of sugars, rather than being specific for just one or a few sugars.

The mannose permease of Escherichia coli, for example, can transport and phosphorylate glucose, mannose, fructose, glucosamine, N-acetylglucosamine, and other sugars. Other members of this can transport sorbose, fructose and N-acetylglucosamine.

This family is specific for the IIB components of this family of PTS transporters.

\ \ protein-N(PI)-phosphohistidine-sugar phosphotransferase activity ; GO:0008982 cytoplasm ; GO:0005737 phosphoenolpyruvate-dependent sugar phosphotransferase system ; GO:0009401 23209 IPR004721 This homodimeric form of dihydroorotase EC: 3.5.2.3 is less common in microbial genomes than a related dihydroorotase that appears in a complex with aspartyltranscarbamoylase or as a\ homologous domain in multifunctional proteins of pyrimidine biosynthesis in higher\ eukaryotes.\ \ dihydroorotase activity ; GO:0004151 \N pyrimidine base biosynthesis ; GO:0019856 23210 IPR004722 Dihydroorotase multifunctional complex type EC: 3.5.2.3 in contrast to the homodimeric type of dihydroorotase found in E. coli, this family tends to appear in a large, multifunctional complex with aspartate transcarbamoylase. Homologous\ domains appear in multifunctional proteins of higher eukaryotes. In some species, including\ Pseudomonas putida and P. aeruginosa, this protein is inactive but is required as a\ non-catalytic subunit of aspartate transcarbamoylase (ATCase). In these species, a second,\ active dihydroorotase is also present.\ \ \N \N \N 23211 IPR004723

8-amino-7-oxononanoate synthase (EC: 2.3.1.47) is involved in biotin biosynthesis.

Synonym(s): AONS, 8-amino-7-ketopelargonate synthase, 7-keto-8-amino-pelargonic acid synthetase, 7-KAP synthetase

\ \ \ 8-amino-7-oxononanoate synthase activity ; GO:0008710\ \N \N biotin biosynthesis ; GO:0009102 23212 IPR004724 The epithelial Na+ channel (ENaC) proteins consist of sodium channels from animals and has no recognizable homologues in other eukaryotes or bacteria. The vertebrate ENaC proteins from epithelial\ cells cluster tightly together on the phylogenetic tree: voltage-insensitive ENaC\ homologues are also found in the brain. Eleven sequenced C. elegans proteins, including\ the degenerins, are distantly related to the vertebrate proteins as well as to each other. \

At least some of\ the proteins in this group form part of a mechano-transducing complex for touch sensitivity. Others include the acid-sensing ion channels, ASIC1-3 that are homo- or hetero-oligomeric neuronal H+-gated channels that mediate pain sensation\ in response to tissue acidosis. \ Mammalian ENaC is important for the maintenance of Na+ balance and the regulation of\ blood pressure. Three homologous ENaC subunits, a, b and g, have\ been shown to assemble to form the highly Na+-selective channel.

\ \ amiloride-sensitive sodium channel activity ; GO:0015280 integral to membrane ; GO:0016021 sodium ion transport ; GO:0006814 23205 IPR004716 Bacterial PTS transporters transport and concomitantly phosphorylate their sugar substrates, and typically consist of multiple subunits or protein domains.The Man family is unique in several respects among PTS permease families.

It is the only PTS family in which members possess a IID protein.

It is the only PTS family in which the IIB constituent is phosphorylated on a histidyl rather than a cysteyl residue.

Its permease members exhibit broad specificity for a range of sugars, rather than being specific for just one or a few sugars.

This family consists only of glucitol-specific transporters, and occur both in Gram-negative and Gram-positive bacteria.The system in E.Coli consists of a IIA protein, and a IIBC protein.

This family is specific for the IIA component.

\ \ protein-N(PI)-phosphohistidine-sugar phosphotransferase activity ; GO:0008982 cytoplasm ; GO:0005737 phosphoenolpyruvate-dependent sugar phosphotransferase system ; GO:0009401 23206 IPR004718 Bacterial PTS transporters transport and concomitantly phosphorylate their sugar substrates, and typically consist of multiple subunits or protein domains.The Man family is unique in several respects among PTS permease families.

It is the only PTS family in which members possess a IID protein.

It is the only PTS family in which the IIB constituent is phosphorylated on a histidyl rather than a cysteyl residue.

Its permease members exhibit broad specificity for a range of sugars, rather than being specific for just one or a few sugars.

The Fru family is a large and complex family which includes several sequenced fructose and mannitol-specific permeases as well as several putative PTS permeases of unknown specificities.The Fru family PTS systems typically have 3 domains, IIA, IIB and IIC, which may be found as 1 or more proteins. The fructose and mannitol transporters form separate phylogenetic clusters in this family.

This family is specific for the IIC domain of the mannitol PTS transporters.

\ \ protein-N(PI)-phosphohistidine-sugar phosphotransferase activity ; GO:0008982 integral to membrane ; GO:0016021 phosphoenolpyruvate-dependent sugar phosphotransferase system ; GO:0009401 23207 IPR004719 Bacterial PTS transporters transport and concomitantly phosphorylate their sugar substrates, and typically consist of multiple subunits or protein domains.The Man family is unique in several respects among PTS permease families.

It is the only PTS family in which members possess a IID protein.

It is the only PTS family in which the IIB constituent is phosphorylated on a histidyl rather than a cysteyl residue.

Its permease members exhibit broad specificity for a range of sugars, rather than being specific for just one or a few sugars.

The PTS Glucose-Glucoside (Glc) family includes permeases specific for glucose, N-acetylglucosamine and a large\ variety of a- and b-glucosides.

This family is specific for the IIC domain of the Glc family PTS transporters.

\ \ protein-N(PI)-phosphohistidine-sugar phosphotransferase activity ; GO:0008982 integral to membrane ; GO:0016021 phosphoenolpyruvate-dependent sugar phosphotransferase system ; GO:0009401 23204 IPR004715 Bacterial PTS transporters transport and concomitantly phosphorylate their sugar substrates, and typically consist of multiple subunits or protein domains.The Man family is unique in several respects among PTS permease families.

It is the only PTS family in which members possess a IID protein.

It is the only PTS family in which the IIB constituent is phosphorylated on a histidyl rather than a cysteyl residue.

Its permease members exhibit broad specificity for a range of sugars, rather than being specific for just one or a few sugars.

The The PTS Fructose-Mannitol (Fru) family is a large and\ complex family which includes several sequenced fructose and mannitol-specific permeases\ as well as several putative PTS \ permeases of unknown specificities.

The fructose permeases of this family phosphorylate\ fructose on the 1-position. Those of family 4.6 phosphorylate fructose on the 6-position. The\ Fru family PTS systems typically have 3 domains, IIA, IIB and IIC, which may be found as 1 or\ more proteins. The fructose and mannitol transporters form separate phylogenetic clusters in this family.

This family is specific for the IIA domain of the fructose PTS transporters. Also\ similar to the Enzyme IIA Fru subunits of the PTS is Enzyme IIA Ntr (nitrogen) found in E. coli\ and other organisms, which may play a solely regulatory role.

\ \ protein-N(PI)-phosphohistidine-sugar phosphotransferase activity ; GO:0008982 integral to membrane ; GO:0016021 phosphoenolpyruvate-dependent sugar phosphotransferase system ; GO:0009401 23202 IPR004713 Proteins of the Ca2+:Cation Antiporter (CaCA) family are found ubiquitously, having been identified in animals, plants, yeast, archaea and widely divergent bacteria.\ All of the characterized animal proteins catalyze Ca2+:Na+ exchange although some also\ transport K+. The NCX1 plasma membrane protein exchanges 3 Na+ for 1 Ca2+. The E.\ coli ChaA protein catalyzes Ca2+:H+ antiport but may also catalyze Na+:H+ antiport. All\ remaining well-characterized members of the family catalyze Ca2+:H+ exchange.\

This family is specific for the calcium ion/proton exchangers of the CacA family.

\ \ cation transporter activity ; GO:0008324 integral to membrane ; GO:0016021 cation transport ; GO:0006812 23203 IPR004714

CcoS from Rhodobacter capsulatus has been shown to be essential for incorporation of redox-active prosthetic groups (heme, Cu) into cytochrome cbb(3) oxidase. FixS of Bradyrhizobium japonicum appears to have the same function. Members of this family are found so far in organisms with a cbb3-type cytochrome oxidase, including Neisseria meningitidis, Helicobacter pylori, Campylobacter jejuni, Caulobacter crescentus, Bradyrhizobium japonicum, and Rhodobacter capsulatus.

\ \N \N \N 23195 IPR004706 The arsenical-resistance protein ACR3 is an integral membrane protein involved in resistance to arsenic compounds. This family also includes several bacterial hypothetical proteins.\ \N integral to membrane ; GO:0016021 \N 23196 IPR004707 Characterized members of the Resistance-Nodulation-Cell Division (RND) superfamily all probably catalyze substrate efflux via an H+ antiport mechanism. These proteins are found ubiquitously in bacteria, archaea and\ eukaryotes.\

This group includes the S. coelicolor ActII3 protein, which may play a role\ in drug resistance, and the M. tuberculosis MmpL7 protein, which catalyzes export of an\ outer membrane lipid, phthiocerol dimycocerosate.

\ \ \N integral to membrane ; GO:0016021 \N 23197 IPR004708 A number of enzymes, belonging to the lyase class, for which fumarate is asubstrate have been shown [MEDLINE:88193096], PUB00001722\ to share a short conserved sequence around a\ methionine which is probably involved in the catalytic activity of this type\ of enzymes.\ \

Aspartate ammonia-lyase EC: 4.3.1.1 catalyses the conversion of aspartate to fumarate.

\ \ aspartate ammonia-lyase activity ; GO:0008797 \N aspartate metabolism ; GO:0006531 23198 IPR004709

\ \ \ \ sodium:hydrogen antiporter activity ; GO:0015385 integral to membrane ; GO:0016021 regulation of pH ; GO:0006885 23199 IPR004710 Functionally characterized members of the bile Acid:Na+ Symporter (BASS) family catalyze Na+:bile acid symport. These systems have been identified in intestinal, liver and kidney tissues of animals.\ These symporters exhibit broad specificity, taking up a variety of non bile organic\ compounds as well as taurocholate and other bile salts. Functionally uncharacterised\ homologues are found in plants, yeast, archaea and bacteria.\ \ bile acid:sodium symporter activity ; GO:0008508 integral to membrane ; GO:0016021 organic anion transport ; GO:0015711 23200 IPR004711 The benzoate transporter family contains only a single characterised member, the benzoate transporter of Acinetobacter calcoaceticus, which functions as a benzoate/proton symporter.\ \N integral to membrane ; GO:0016021 \N 23201 IPR004712

\ \ \

This group is specific for the fungal members of this family.

\ \ sodium:hydrogen antiporter activity ; GO:0015385 integral to membrane ; GO:0016021 sodium ion transport ; GO:0006814 23192 IPR004703 Bacterial PTS transporters transport and concomitantly phosphorylate their sugar substrates, and typically consist of multiple subunits or protein domains.The Man family is unique in several respects among PTS permease families.

It is the only PTS family in which members possess a IID protein.

It is the only PTS family in which the IIB constituent is phosphorylated on a histidyl rather than a cysteyl residue.

Its permease members exhibit broad specificity for a range of sugars, rather than being specific for just one or a few sugars.

The only characterized member of this family of PTS transporters is the E. coli galactitol transporter. Gat family PTS systems typically have 3 components: IIA, IIB and IIC.

This family is specific for the IIC component of the PTS Gat family.

\ \ \N integral to membrane ; GO:0016021 phosphoenolpyruvate-dependent sugar phosphotransferase system ; GO:0009401 23193 IPR004704 Bacterial PTS transporters transport and concomitantly phosphorylate their sugar substrates, and typically consist of multiple subunits or protein domains.The Man family is unique in several respects among PTS permease families.

It is the only PTS family in which members possess a IID protein.

It is the only PTS family in which the IIB constituent is phosphorylated on a histidyl rather than a cysteyl residue.

Its permease members exhibit broad specificity for a range of sugars, rather than being specific for just one or a few sugars.

The mannose permease of E. coli, for example, can transport and phosphorylate glucose, mannose, fructose, glucosamine,N-acetylglucosamine, and other sugars. Other members of this can transport sorbose, fructose and N-acetylglucosamine.

This family is specific for the IID subunits of this family of PTS transporters.

\ \ \N integral to membrane ; GO:0016021 phosphoenolpyruvate-dependent sugar phosphotransferase system ; GO:0009401 23194 IPR004705

\ \ \

This group is specific for the bacterial members of this family.

\ \ \N \N \N 23186 IPR004697 The p-Aminobenzoyl-glutamate transporter family includes two transporters, the AbgT (YdaH) protein of E. coli and MtrF of Neisseria gonorrhoeae. AbgT is apparently cryptic in wild type cells, but when expressed on a high copy number plasmid, or when expressed at higher levels due to mutation, it allows utilization of p-aminobenzoyl-glutamate as a source of p-aminobenzoate for p-aminobenzoate auxotrophs. p-Aminobenzoate is a constituent of and a precursor for the biosynthesis of folic acid.\ transporter activity ; GO:0005215 integral to membrane ; GO:0016021 transport ; GO:0006810 23187 IPR004698 Members of the zinc (Zn2+)-Iron (Fe2+) permease (ZIP) family consist of proteins with eight putative transmembrane spanners. They are derived from animals, plants and yeast. They comprise a diverse family, with several paralogues in any one organism (e.g., at least five\ in Caenorabditis elegans, at least five in Arabidopsis thaliana and two in\ Saccharomyces cervisiae. The two S. cerevisiae proteins, Zrt1 and Zrt2, both probably\ transport Zn2+ with high specificity, but Zrt1 transports Zn2+ with ten-fold higher affinity\ than Zrt2. Some members of the ZIP family have been shown to transport Zn2+ while\ others transport Fe2+, and at least one transports a range of metal ions. The energy\ source for\ transport has not been characterized, but these systems probably function as secondary\ carriers.\ \ zinc ion transporter activity ; GO:0005385 integral to membrane ; GO:0016021 zinc ion transport ; GO:0006829 23188 IPR004699 Bacterial PTS transporters transport and concomitantly phosphorylate their sugar substrates, and typically consist of multiple subunits or protein domains.The Man family is unique in several respects among PTS permease families.

It is the only PTS family in which members possess a IID protein.

It is the only PTS family in which the IIB constituent is phosphorylated on a histidyl rather than a cysteyl residue.

Its permease members exhibit broad specificity for a range of sugars, rather than being specific for just one or a few sugars.

The Gut family consists only of glucitol-specific transporters, but these occur both in Gram-negative and Gram-positive bacteria.E. coli consists of IIA protein, a IIC protein and a IIBC protein.

This family is specific for the IIC component.

\ \ \N integral to membrane ; GO:0016021 phosphoenolpyruvate-dependent sugar phosphotransferase system ; GO:0009401 23189 IPR004700 Bacterial PTS transporters transport and concomitantly phosphorylate their sugar substrates, and typically consist of multiple subunits or protein domains.The Man family is unique in several respects among PTS permease families.

It is the only PTS family in which members possess a IID protein.

It is the only PTS family in which the IIB constituent is phosphorylated on a histidyl rather than a cysteyl residue.

Its permease members exhibit broad specificity for a range of sugars, rather than being specific for just one or a few sugars.

The mannose permease of E. coli, for example, can transport and phosphorylate glucose, mannose, fructose, glucosamine, N-acetylglucosamine, and other sugars. Other members of this can transport sorbose, fructose and N-acetylglucosamine.

This family is specific for the sorbose-specific IIC subunits of this family of PTS transporters.

\ \ \N integral to membrane ; GO:0016021 phosphoenolpyruvate-dependent sugar phosphotransferase system ; GO:0009401 23190 IPR004701 Bacterial PTS transporters transport and concomitantly phosphorylate their sugar substrates, and typically consist of multiple subunits or protein domains.The Man family is unique in several respects among PTS permease families.

It is the only PTS family in which members possess a IID protein.

It is the only PTS family in which the IIB constituent is phosphorylated on a histidyl rather than a cysteyl residue.

Its permease members exhibit broad specificity for a range of sugars, rather than being specific for just one or a few sugars.

The mannose permease of E. coli, for example, can transport and phosphorylate glucose, mannose, fructose, glucosamine, N-acetylglucosamine, and other sugars. Other members of this can transport sorbose, fructose and N-acetylglucosamine.

This family is specific for the IIA components.

\ \ \N integral to membrane ; GO:0016021 phosphoenolpyruvate-dependent sugar phosphotransferase system ; GO:0009401 23191 IPR004702 Bacterial PTS transporters transport and concomitantly phosphorylate their sugar substrates, and typically consist of multiple subunits or protein domains.The Man family is unique in several respects among PTS permease families.

It is the only PTS family in which members possess a IID protein.

It is the only PTS family in which the IIB constituent is phosphorylated on a histidyl rather than a cysteyl residue.

Its permease members exhibit broad specificity for a range of sugars, rather than being specific for just one or a few sugars.

The Gut family consists only of glucitol-specific permeases, but these occur both in Gram-negative and Gram-positive bacteria.E. coli consists of IIA protein, a IIC protein and a IIBC protein.

This family is specific for the IIBC component.

\ \ \N integral to membrane ; GO:0016021 phosphoenolpyruvate-dependent sugar phosphotransferase system ; GO:0009401 23179 IPR004690 The MSS family includes the monobasic malonate:Na+ symporter of Malonomonas rubra. It consists of two integral membrane proteins, MadL and MadM. The transporter is believed to catalyze the electroneutral reversible uptake of H+-malonate with one Na+, and both subunits have been shown to be essential for activity.\ \N \N \N 23180 IPR004691 The MSS family includes the monobasic malonate:Na+ symporter of Malonomonas rubra. It consists of two integral membrane proteins, MadL and MadM.The transporter is believed to catalyze the electroneutral reversible uptake of H+-malonate with one Na+, and both subunits have been shown to be essential for activity.\ \N \N \N 23181 IPR004692

\ \

SecG has two transmembrane\ domains, both of which contribute to the recognition of preprotein signal\ sequences by the translocation complex [MEDLINE:95378268]. The protein also undergoes\ membrane topology inversion when coupled to the SecA cycle [MEDLINE:21413957].

\ \ \ protein translocase activity ; GO:0015450 integral to membrane ; GO:0016021 protein secretion ; GO:0009306 23182 IPR004693 Marine diatoms such as Cylindrotheca fusiformis encode at least six silicon transport protein homologues which exhibit similar size and topology. One characterized member of the family (Sit1) functions in the energy-dependent uptake of either silicic acid [Si(OH)4] or silicate [Si(OH)3O-] by a Na⁺ symport mechanism. The system is found in marine diatoms which make their "glass houses" out of silicon.\ \N \N \N 23183 IPR004694 The Hydroxy/Aromatic Amino Acid Permease (HAAAP) family includes well characterized aromatic amino acid:H+ symport permeases and hydroxy amino acid permeases. This group is specific for hydroxy\ amino acid transporters and includes the serine permease, SdaC, of E. coli, and the\ threonine permease, TdcC, of E. coli.\ \ transporter activity ; GO:0005215 integral to membrane ; GO:0016021 transport ; GO:0006810 23184 IPR004695 Two members of the Tellurite-Resistance/Dicarboxylate Transporter (TDT) family have been functionally characterized. One is the TehA protein of E. coli which has been implicated in resistance to tellurite; the other is the Mae1\ protein of S. pombe which functions in the uptake of malate and other dicarboxylates by a\ proton symport\ mechanism. These proteins exhibit 10 putative transmembrane a-helical\ spanners (TMSs).\ \ \N integral to membrane ; GO:0016021 \N 23185 IPR004696 Functionally characterized members of the 6-8 TMS Triose-phosphate Transporter (TPT) family are derived from the inner envelope membranes of chloroplasts and nongreen plastids of plants. However,\ homologues are also present in yeast. Saccharomyces cerevisiae has three functionally\ uncharacterized TPT paralogues encoded within its genome. Under normal physiological\ conditions, chloroplast TPTs mediate a strict antiport of substrates, frequently exchanging\ an organic three carbon compound phosphate ester for inorganic phosphate (Pi).\

Normally, a triose-phosphate, 3-phosphoglycerate, or another phosphorylated C3\ compound made in the chloroplast during photosynthesis, exits the organelle into the\ cytoplasm of the plant cell in exchange for Pi. However, experiments with reconstituted\ translocator in artificial membranes indicate that transport can also occur by a\ channel-like uniport mechanism with up to 10-fold higher transport rates. Channel opening\ may be induced by a membrane potential of large magnitude and/or by high substrate\ concentrations. Nongreen plastid and chloroplast carriers, such as those from maize\ endosperm and root membranes, mediate transport of C3 compounds phosphorylated at\ carbon atom 2, particularly phosphenolpyruvate, in exchange for Pi. These are the\ phosphoenolpyruvate:Pi antiporters (PPT). Glucose-6-P has also been shown to be a\ substrate of some plastid translocators (GPT). The three types of proteins (TPT, PPT and\ GPT) are divergent in sequence as well as substrate specificity, but their substrate\ specificities overlap.

\ \ transporter activity ; GO:0005215 integral to membrane ; GO:0016021 transport ; GO:0006810 23170 IPR004681

DctM subunit Tripartite ATP-independent Periplasmic Transporter (TRAP-T) family permeases generally consist of three components, and these systems have so far been found in Gram-negative\ bacteria, gram-postive bacteria and\ archaea.

Only one member of the family has been both sequenced and functionally\ characterized. This system is the DctPQM\ system of Rhodobacter capsulatus\ \ \ \ [MEDLINE:97431499]. DctP is a periplasmic\ dicarboxylate (malate, fumarate, succinate) binding receptor that is\ biochemically well-characterized. DctQ is an integral cytoplasmic membrane protein with 4\ putative transmembrane a-helical\ spanners (TMSs). DctM is a second integral cytoplasmic membrane protein with 12\ putative TMSs. These proteins have been shown to be both necessary and sufficient for\ the proton motive\ force-dependent uptake of dicarboxylates into R. capsulatus.

\ \ \N integral to membrane ; GO:0016021 \N 23171 IPR004682

TRAP-T family proteins generally consist of three components, and these systems have so far been found in Gram-negative bacteria, Gram-postive bacteria and archaea. Only one member of the family has been both sequenced and functionally characterized. This system is the DctPQM system of Rhodobacter capsulatus. DctP is a periplasmic dicarboxylate (malate, fumarate, succinate) binding receptor that is biochemically well-characterized.

\ \N periplasmic space (sensu Gram-negative Bacteria) ; GO:0030288 transport ; GO:0006810 23172 IPR004683 This group describes a short protein (80-93 residues) homologous to the C-terminus of the flagellar biosynthetic protein FlhB. It is found so far only in species that also have FlhB. In a\ phylogenetic tree based on alignment of both this family and the homologous region of\ FlhB and its homologs, the members of this family form a monophyletic set.\ \ \N \N \N 23173 IPR004684 This family includes the characterized 2-Keto-3-Deoxygluconate transporters from Bacillus subtilis and Erwinia chrysanthemi. There are homologs of this protein found in both gram-positive and gram-negative bacteria.\ \ 2-keto-3-deoxygluconate:hydrogen symporter activity ; GO:0015649\ \N integral to membrane ; GO:0016021 carbohydrate transport ; GO:0008643 23174 IPR004685 Characterized members of the branched chain Amino Acid:Cation Symporter (LIVCS) family transport all three of the branched chain aliphatic amino acids (leucine (L), isoleucine (I) and valine (V)). They function by a Na+ or H+\ symport mechanism and display 12 putative \ transmembrane helical spanners.\ \ branched-chain aliphatic amino acid transporter activity ; GO:0015658 integral to membrane ; GO:0016021 branched-chain aliphatic amino acid transport ; GO:0015803 23175 IPR004686 The MTC family consists of a limited number of homologues, all from eukaryotes. One member of the family has been functionally characterized as a tricarboxylate carrier from rat liver mitochondria. The rat liver mitochondrial tricarboxylate carrier has been reported to transport citrate, cis-aconitate, threo-D-isocitrate, D- and L-tartrate, malate, succinate and phosphoenolpyruvate. It presumably functions by a proton symport mechanism. The rest of the characterized proteins appear to be sideroflexins involved in iron transport.\ cation transporter activity ; GO:0008324 membrane ; GO:0016020 cation transport ; GO:0006812 23176 IPR004687 The proteins of the MET family have 4 TMS regions and are located in late endosomal or lysosomal membranes. Substrates of the mouse MTP transporter include thymidine, both nucleoside and nucleobase analogues, antibiotics, anthracyclines, ionophores and steroid hormones. MET transporters may be involved in the subcellular compartmentation of steroid hormones and other compounds.Drug sensitivity by mouse MET was regulated by compounds that inhibit lysosomal function, interface with intracellular cholesterol transport, or modulate the multidrug resistance phenotype of mammalian cells. Thus, MET family members may compartmentalize diverse hydrophobic molecules, thereby affecting cellular drug sensitivity, nucleoside/nucleobase availability and steroid hormone responses.\ \N integral to membrane ; GO:0016021 \N 23177 IPR004688 This family is found in both Gram-negative and Gram-positive bacteria. The functionally characterized members of the family catalyze uptake of either Ni2+ or Co2+ in a proton motive force-dependent process. Topological analyses with the HoxN Ni2+ transporter of Ralstonia eutropha suggest that it possesses 8 TMSs with its N- and C-termini in the cytoplasm.\ nickel ion transporter activity ; GO:0015099 integral to membrane ; GO:0016021 nickel ion transport ; GO:0015675 23178 IPR004689 Nucleotide-sugar transporters (NSTs) are found in the Golgi apparatus and the endoplasmic reticulum of eukaryotic cells. Members of the family have been sequenced\ from yeast, protozoans and animals. Animals such as C. elegans possess many of these\ transporters. Humans have at least two closely related isoforms of the\ UDP-galactose:UMP exchange transporter.\

NSTs generally appear to function by antiport mechanisms, exchanging a nucleotide-sugar\ for a nucleotide. Thus, CMP-sialic acid is exchanged for CMP; GDP-mannose is\ preferentially exchanged for GMP, and UDP-galactose and UDP-N-acetylglucosamine are\ exchanged for UMP (or possibly UDP). Other nucleotide sugars (e.g., GDP-fucose,\ UDP-xylose, UDP-glucose, UDP-N-acetylgalactosamine, etc.) may also be transported in\ exchange for various nucleotides, but their transporters have not been molecularly\ characterized. Each compound appears to be translocated by its own transport protein.\ Transport allows the compound, synthesized in the cytoplasm, to be exported to the lumen\ of the Golgi apparatus or the endoplasmic reticulum where it is used for the synthesis of\ glycoproteins and glycolipids.

\ \ nucleotide-sugar transporter activity ; GO:0005338 integral to membrane ; GO:0016021 nucleotide-sugar transport ; GO:0015780 23160 IPR004671 The E. coli NhaB Na+:H+ Antiporter (NhaB) protein has 12 predicted TMS, and catalyses sodium/proton exchange. Unlike NhaA this activity is not pH\ dependent.\ \ sodium:hydrogen antiporter activity ; GO:0015385 integral to membrane ; GO:0016021 sodium ion transport ; GO:0006814 23161 IPR004672

The NhaD Na+:H+ Antiporter (NhaD) protein of Vibrio cholerae which has 12 putative TMS. It has been shown to catalyze Na+/H+ antiport, but Li+ is also a substrate.

\ \ \N \N \N 23162 IPR004673 These proteins are members of the L-Rhamnose Symporter (RhaT) family. This family includes two characterized members, both of which function as L-rhamnose:H+ symporters and have 10 GES predicted transmembrane domains.\ rhamnose transporter activity ; GO:0015153 integral to membrane ; GO:0016021 hexose transport ; GO:0008645 23163 IPR004674 Members of this family are alkylhydroperoxidases, which catalyze the reduction of peroxides to their corresponding alcohols via oxidation of cysteine residues. In these alkylhydroperoxidases, the cysteines are located in a conserved -CXXC- motif located towards the COOH terminus. In Mycobacterium tuberculosis, two non-homologous alkylhydroperoxidases, AhpD and AhpC, are found in the same operon.\ peroxidase activity ; GO:0004601 \N \N 23164 IPR004675 This group represents a 51-residue core region of homology among a family of mostly uncharacterized proteins of 110 to 227 amino acids. Most members of this family contain the motif Exxxxxx[SA]xxxxC[VIL]xCxxxH.\ Members of the family include the alkylhydroperoxidase AhpD of Mycobacterium\ tuberculosis, a macrophage infectivity potentiator peptide of Legionella pneumophila, and\ an uncharacterized peptide in the tetrachloroethene reductive dehalogenase operon of\ Dehalospirillum multivorans. Peptides containing this domain may\ have alkylhydroperoxidase or related antioxidant activity.\ \ \N \N \N 23165 IPR004676 These proteins are members of the Cadmium Resistance (CadD) Family (TC:2.A.77 protein that has been reported to possibly function in quaternary ammonium ion export.\ \N \N \N 23166 IPR004677 This family represents the largest subunit, I, of the ccb3-type cytochrome c oxidase EC: 1.9.3.1, with two protohemes and copper. It shows strong homology to subunits of other types of cytochrome\ oxidases. Species with this type, all from the Proteobacteria so far, include Neisseria\ meningitidis, Helicobacter pylori, Campylobacter jejuni, Rhodobacter sphaeroides,\ Rhizobium leguminosarum, and others.\ \ cytochrome c oxidase activity ; GO:0004129 respiratory chain complex IV (sensu Bacteria) ; GO:0045278 electron transport ; GO:0006118 23167 IPR004678 This family describes a di-heme subunit of approximately 26 kDa of the cbb3 type copper and heme-containing cytochrome oxidase EC: 1.9.3.1.\ \ cytochrome c oxidase activity ; GO:0004129 \N electron transport ; GO:0006118 23168 IPR004679 These proteins are members of the citrate:cation symporter (CCS) family (TC:2.A.24). These proteins have 12 GES predicted transmembrane regions. Most members of the CCS family catalyze citrate uptake with either Na+ or H+ as the cotransported cation. However, one member is specific for L-malate and probably functions by a proton symport mechanism.\ organic anion transporter activity ; GO:0008514 integral to membrane ; GO:0016021 organic anion transport ; GO:0015711 23169 IPR004680 This family includes two characterized citrate/proton symporters from Bacillus subtilis. CitM transports citrate complexed to Mg2+, while the CitH apparently transports citrate without Mg2+. The family also includes uncharacterized transporters, including a third paralog in Bacillus subtilis.\ citrate transporter activity ; GO:0015137 integral to membrane ; GO:0016021 citrate transport ; GO:0015746 23153 IPR004664 Members of this subfamily include ribonuclease BN (rbn) from Escherichia coli and homologs from a number of bacteria, including the largely uncharacterized BrkB (Bordetella resist killing by serum B) from Bordetella pertussis. Some members have an additional C-terminal domain. Paralogs from E. coli (yhjD) and Mycobacterium tuberculosis (Rv3335c) are part of a smaller, related subfamily that form their own cluster. Ribonuclease BN is a homodimer in E. coli and does not contain a nucleic acid component. Phage T4 encodes several tRNAs that require this host ribonuclease for maturation. However, host tRNAs with the normal universal 3 sequence of CCA do not appear to be substrates. The substrate specificity of RNase BN appears to be very narrow and its biological role is uncertain. It is one of five ribonucleases in E. coli for which any of the five can confer viability, with the order of efficacy being RNase T > RNase PH > RNase D > RNase II > RNase BN.\ ribonuclease activity ; GO:0004540 \N \N 23154 IPR004665 Members of this family have a related but highly variable long, highly charged insert near the amino end. The proteins differ in the specificity of RNA binding.\ ATP binding activity ; GO:0005524 \N transcription termination ; GO:0006353 23155 IPR004666 E. coli, RimK adds additional Glu residues to the native Glu-Glu C-terminus of ribosomal protein S6. Mutation of the Glu-Glu terminus to Lys-Glu blocked addition. S6 has the\ C-terminal sequence Glu-Glu in few species, suggesting the homolog of rimK may have a\ function other than S6 modification in those species. However, most species having a\ member of this protein subfamily do not have an S6 homolog ending in Glu-Glu.\ \ \N \N ribosome biogenesis ; GO:0007046 23156 IPR004667 These proteins are members of the ATP:ADP Antiporter (AAA) family, which consists of nucleotide transporters that have 12 GES predicted transmembrane regions. One protein from Rickettsia prowazekii functions to take up ATP from the eukaryotic cell cytoplasm into the bacterium in exchange for ADP. Five AAA family paralogues are encoded within the genome of R. prowazekii. This organism transports UMP and GMP but not CMP, and it seems likely that one or more of the AAA family paralogues are responsible. The genome of Chlamydia trachomatis encodes two AAA family members, Npt1 and Npt2, which catalyse ATP/ADP exchange and GTP, CTP, ATP and UTP uptake probably employing a proton symport mechanism. Two homologous adenylate translocators of Arabidopsis thaliana are postulated to be localized to the intracellular plastid membrane where they function as ATP importers.\ ATP binding activity ; GO:0005524 integral to membrane ; GO:0016021 transport ; GO:0006810 23157 IPR004668 These proteins are members of the C4-Dicarboxylate Uptake (Dcu) family. Most proteins in this family have 12 GES predicted transmembrane regions; however one member has 10 experimentally determined transmembrane regions with both the N- and C-termini localized to the periplasm. The two Escherichia coli proteins, DcuA and DcuB, transport aspartate, malate, fumarate and succinate, and function as antiporters with any two of these substrates. Since DcuA is encoded in an operon with the gene for aspartase, and DcuB is encoded in an operon with the gene for fumarase, their physiological functions may be to catalyze aspartate:fumarate and fumarate:malate exchange during the anaerobic utilization of aspartate and fumarate, respectively.\ C4-dicarboxylate transporter activity ; GO:0015556 integral to membrane ; GO:0016021 C4-dicarboxylate transport ; GO:0015740 23158 IPR004669 These proteins are members of the C4-dicarboxylate Uptake C (DcuC) family. DcuC has 12 GES predicted transmembrane regions, is induced only under anaerobic conditions, and is not repressed by glucose. DcuC may therefore function as a succinate efflux system during anaerobic glucose fermentation. However, when overexpressed, it can replace either DcuA or DcuB in catalyzing fumarate-succinate exchange and fumarate uptake.\ C4-dicarboxylate transporter activity ; GO:0015556 integral to membrane ; GO:0016021 C4-dicarboxylate transport ; GO:0015740 23159 IPR004670 The E. coli NhaA Na+:H+ Antiporter (NhaA) protein probably functions in the regulation of the internal pH when the external pH is alkaline. It also uses the H+ gradient to expel Na+ from the cell. Its activity is\ highly pH dependent.\ \ \N integral to membrane ; GO:0016021 regulation of pH ; GO:0006885 23146 IPR004657 This membrane-associated enzyme converts 1,4-dihydroxy-2-naphthoic acid (DHNA) to demethylmenaquinone, a step in menaquinone biosynthesis. A key reaction in the biosynthesis of menaquinone involves the conversion of the soluble\ bicyclic naphthalenoid compound 1, 4-dihydroxy-2-naphthoic acid (DHNA) to the\ membrane-bound demethylmenaquinone [MEDLINE:98241547].\ \ transferase activity ; GO:0016740 integral to membrane ; GO:0016021 vitamin K2 biosynthesis ; GO:0009234 23147 IPR004658 Slp superfamily members are present in the Gram-negative gamma proteobacteria Escherichia coli, which also contains a close paralog, Haemophilus influenzae and Pasteurella multocida and Vibrio cholera. The known members of the family to date share a motif LX[GA]C near the N-terminus, which is compatible with the possibility that the protein is modified into a lipoprotein with Cys as the new N-terminus. Slp from Escherichia coli is known to be a lipoprotein of the outer membrane and to be expressed in response to carbon starvation.\ \N membrane ; GO:0016020 \N 23148 IPR004659 Ribonuclease E (EC 3.1.4.-) is responsible for maturing 5S rRNA from its precursors from all the rRNA genes. It also cleaves RNA I, a molecule that controls the replication of ColE1 plasmid DNA. It is the major endoribonuclease participating in mRNA turnover in E. coli, and initiates decay of RNAs by cutting them internally near their 5'-end. It is able to remove poly A tails by an endonucleolytic process. Ribonuclease G is involved in processing of the 5' end of 16S rRNA, and may be involved in chromosome segregation and cell division too.\ ribonuclease activity ; GO:0004540 cytoplasm ; GO:0005737 RNA processing ; GO:0006396 23149 IPR004660 Most members of this family are pyruvate dehydrogenase complex, E1 component. It includes\ a counterexample from Pseudomonas putida, MdeB, that is active as an E1 component of\ an

-ketoglutarate dehydrogenase complex rather than a pyruvate dehydrogenase\ complex. The second pyruvate dehydrogenase complex E1 protein from Alcaligenes\ eutrophus, PdhE, complements an aceE mutant of E. coli but is not part of a pyruvate\ dehydrogenase complex operon, is more similar to the Pseudomonas putida MdeB than\ to E. coli AceE, and may have also have a different primary specificity.\ \ oxidoreductase activity ; GO:0016491 \N \N 23150 IPR004661 E. coli has two genes, sgaE and sgbE, that are very close homologs of araD, the known L-ribulose-5-phosphate 4-epimerase of E. coli. The function of these paralogs is unknown.\ The member of this family from Mycobacterium smegmatis is flanked by putative araB and\ araA genes, consistent with it also being araD.\ \ L-ribulose-phosphate 4-epimerase activity ; GO:0008742 \N L-arabinose catabolism ; GO:0019572 23151 IPR004662 This family describes N-acetylglutamate kinases (ArgB) of many prokaryotes and the N-acetylglutamate kinase domains of multifunctional proteins from yeasts as well as some, as yet, uncharacterised proteins.\ \ acetylglutamate kinase activity ; GO:0003991 cytoplasm ; GO:0005737 arginine biosynthesis ; GO:0006526 23152 IPR004663

This family represents a set of proteins with extensive C-terminal homology to the ATP-dependent protease La, product of the lon gene of Escherichia coli. Archaeal and bacterial proteins belong to this group. Because several species, including Thermotoga maritima and Treponema pallidum, contain both a close homolog of the lon protease and nearly full-length homolog\ of the members of this family, it has been suggested that there may also be a functional division between\ the two families.

Members of this family from Pyrococcus horikoshii and Pyrococcus abyssi each contain a\ predicted intein conserved region.

\ \ ATP binding activity ; GO:0005524 \N protein catabolism ; GO:0030163 23139 IPR004650 This family of proteins has so far been found in three archaeal species: Methanobacterium thermoautotrophicum, Methanococcus jannaschii, and Archaeoglobus\ fulgidus. Proteins are homologous to phosphoribosylformimino-5-aminoimidazole\ carboxamide ribotide isomerase (HisA) and, with lower similarity, to the cyclase HisF,\ both of which are enzymes of histidine biosynthesis. Each species with this protein also\ encodes HisA. However, the function of proteins in this group is unknown.\ \ \N \N \N 23140 IPR004651 Histidine is formed by several complex and distinct biochemical reactions catalysed by eight enzymes. Proteinsinvolved in steps 4 and 6 of the histidine biosynthesis pathway are contained in one family. These enzymes are called\ His6 and His7 in eukaryotes and HisA and HisF in prokaryotes. HisA is a phosphoribosylformimino-5-aminoimidazole\ carboxamide ribotide isomerase (EC: 5.3.1.16), involved in the fourth step of histidine biosynthesis. The bacterial HisF\ protein is a cyclase which catalyzes the cyclization reaction that produces D-erythro-imidazole glycerol phosphate during\ the sixth step of histidine biosynthesis. The yeast His7 protein is a bifunctional protein which catalyzes an \ amido-transferase reaction that generates imidazole-glycerol phosphate and 5-aminoimidazol-4-carboxamide. The latter is the\ ribonucleotide used for purine biosynthesis. The enzyme also catalyzes the cyclization reaction that produces \ D-erythro-imidazole glycerol phosphate, and is involved in the fifth and sixth steps in histidine biosynthesis.\

This family describes the histidine biosynthesis protein, HisF.

\ \ imidazoleglycerol phosphate synthase activity ; GO:0000107 imidazoleglycerol-phosphate synthase complex ; GO:0009382 histidine biosynthesis ; GO:0000105 23141 IPR004652 This family represents one branch of COG0042 (Predicted TIM-barrel enzymes, possibly dehydrogenases, nifR3 family) and includes NifR3 itself, from Rhodobacter\ capsulatus. \ The function of nifR3 is unknown, but it is found in an operon with\ nitrogen-sensing two component regulators in Rhodobacter capsulatus.\ Members of this family show a distant relationship to

(TIM) barrel enzymes such\ as dihydroorotate dehydrogenase and glycolate oxidase.\ \ molecular_function unknown ; GO:0005554 \N \N 23142 IPR004653 This family represents one branch of COG0042 (Predicted TIM-barrel enzymes, possibly dehydrogenases, nifR3 family) although NifR3 itself, a protein of unknown function associated with nitrogen regulation in Rhodobacter capsulatus, is not a member of this branch. Proteins in this family are found in species as diverse as the proteobacteria, a spirochete, a cyanobacterium, and\ Deinococcus radiodurans. They show a distant relationship to

(TIM) barrel enzymes such\ as dihydroorotate dehydrogenase and glycolate oxidase.\ \ molecular_function unknown ; GO:0005554 \N \N 23143 IPR004654 This family describes one branch of the ROK superfamily of proteins that may have activity as glucokinase although many proteins are as yet uncharacterised.\ glucokinase activity ; GO:0004340 cytoplasm ; GO:0005737 glycolysis ; GO:0006096 23144 IPR004655 Beta-ketoacyl-acyl carrier protein synthase III (FabH) in general initiate elongation in type II fatty acid synthase systems found in bacteria and plants is responsible for producing the multitude of fatty acid structures found\ in bacterial membranes [MEDLINE:20096678]. The two members of this subfamily from Bacillus subtilis differ from each other,\ and from FabH from E. coli, in acyl group specificity. \ Active site residues include Cys112, His244 and Asn274 of E. coli FabH. Cys-112 is the\ site of acyl group attachment.\ \ \ 3-oxoacyl-[acyl-carrier protein] synthase activity ; GO:0004315\ \N \N fatty acid biosynthesis ; GO:0006633 23145 IPR004656 This family of archaeal proteins shows considerable homology and identical active site residues to FabH, the

-ketoacyl-acyl carrier protein synthase III of bacteria and plants.\ The archaeal species in which it is found, however, do not have a readily detectable\ homolog of acyl carrier protein itself, suggesting the condensation of the acyl group with\ some other carrier.\ Closely related bacterial families include a polyketide antibiotic\ (2,4-diacetylphloroglucinol) biosynthesis protein from Pseudomonas fluorescens and an\ uncharacterized protein from Staphylococcus carnosus.\ Cys-112 of MJ1546 is the site of acyl group attachment by homology to FabH. His-234\ and Asn-237 are also active site residues.\ \ \N \N \N 23136 IPR004647 A number of Fe-S cluster-containing hydro-lyases share a conserved motif, including argininosuccinate lyase, adenylosuccinate lyase, aspartase, class I fumarate hydratase\ (fumarase), and tartrate dehydratase (see IPR000362). Proteins in this group represent\ a subset of closely related proteins or modules, including the E. coli tartrate dehydratase

chain and the C-terminal region of the class I fumarase (where the N-terminal region is\ homologous to the tartrate dehydratase

chain). The activity of the archaeal proteins in\ this group is unknown.\ \ lyase activity ; GO:0016829 \N \N 23137 IPR004648 Oligopeptide transporter OPT superfamily has two main branches. One branch contains a tetrapeptide transporter demonstrated experimentally in three different species of yeast. The other family contains\ EspB , a protein required for normal rather than delayed\ sporulation after cellular aggregation; its role is unknown but is compatible with transport of\ a signalling molecule.\ Homology between the two branches of the superfamily is seen most easily at the ends of\ the protein. The central regions are poorly conserved within each branch and may not be\ homologous between branches.\ \ \N \N \N 23138 IPR004649 Ribonuclease HII EC: 3.1.26.4 cleaves RNA from DNA-RNA hybrids. Archaeal members of this subfamily of RNase H are designated RNase HII and one has\ been shown to be active as a monomer. A member from Homo sapiens was characterized\ as RNase HI, large subunit.\ \ ribonuclease H activity ; GO:0004523 \N RNA metabolism ; GO:0016070 23132 IPR004643 L-serine dehydratase (EC: 4.2.1.13), also called serine deaminase, catalyses the conversion of L-serine and water to pyruvate and ammonia during gluconeogenesis from serine. The enzyme forms a heterooctamer of four

chains and four

chains. This family describes the

chain of an iron-sulfur-dependent L-serine dehydratase, as in Bacillus subtilis. A fairly deep split in a UPGMA tree separates members of this family of

chains from the homologous region of single chain forms such as found in E. coli. This family of enzymes is not homologous to the pyridoxal phosphate-dependent threonine deaminases and eukaryotic serine deaminases.\ L-serine ammonia-lyase activity ; GO:0003941 \N gluconeogenesis ; GO:0006094 23133 IPR004644 This enzyme is also called serine deaminase. L-serine dehydratase converts serine into pyruvate in the gluconeogenesis pathway from serine. This enzyme is comprised of a single chain in Escherichia coli, Mycobacterium tuberculosis, and several other species, but has separate

and

chains in Bacillus subtilis and related species. The

and

chains are homologous to the N-terminal and C-terminal regions, respectively, but are rather deeply branched in a UPGMA tree. This enzyme requires iron and dithiothreitol for activation in vitro, and is a predicted 4Fe-4S protein. Escherichia coli\ \ \ Pseudomonas aeruginosa have two copies of this protein.\ \ L-serine ammonia-lyase activity ; GO:0003941 \N gluconeogenesis ; GO:0006094 23134 IPR004645 This is a family of Tfx DNA-binding proteins, which is restricted to the archaea. Homology among the members is strongest in the helix-turn-helix-containing N-terminal region. Tfx from Methanobacterium thermoautotrophicum is associated with the operon for molybdenum formyl-methanofuran dehydrogenase and binds a DNA sequence near its promoter.\ DNA binding activity ; GO:0003677 \N \N 23135 IPR004646 A number of Fe-S cluster-containing hydro-lyases share a conserved motif, including argininosuccinate lyase, adenylosuccinate lyase, aspartase, class I fumarate hydratase\ (fumarase), and tartrate dehydratase (see IPR000362). Proteins in this group represent\ a subset of closely related proteins or modules, including the E. coli tartrate dehydratase

chain and the N-terminal region of the class I fumarase (where the C-terminal region\ is homologous to the tartrate dehydratase

chain). The activity of archaeal proteins in\ this group is unknown.\ \ lyase activity ; GO:0016829 \N \N 23128 IPR004639 This enzyme, glutamate-1-semialdehyde-2,1-aminomutase (glutamate-1-semialdehydeaminotransferase, GSA aminotransferase) EC: 5.4.3.8, catalyses the conversion of (S)-4-amino-5-oxopentanoate to 5-aminolevulinate during the second step of porphyrin biosynthesis by the C5 pathway. It contains a pyridoxal phosphate attached at a Lys residue at position 283 of the seed alignment. It is in the family of class III aminotransferases.\ \ glutamate-1-semialdehyde 2,1-aminomutase activity ; GO:0042286 cytoplasm ; GO:0005737 porphyrin biosynthesis ; GO:0006779 23129 IPR004640 This family describes the small subunit, Hsc20 (20K heat shock cognate protein) of a pair of proteins Hsc66-Hsc20, related to the DnaK-DnaJ heat shock proteins, which also serve as molecular chaperones. Hsc20, unlike DnaJ, appears not to have chaperone activity on its own, but to act solely as a regulatory subunit for Hsc66. The gene for Hsc20 in E. coli, hscB, is not induced by heat shock.\ co-chaperone activity ; GO:0003767 \N \N 23130 IPR004641 Ribonuclease HIII (EC 3.1.26.-) cleaves RNA from DNA-RNA hybrids. It catalyses endonucleolytic cleavage to 5'-phospho-monoesters. Two types of ribonuclease H in Bacillus subtilis, RNase HII (rnhB) and RNase HIII (rnhC), areboth known experimentally and are quite similar to each other. The only RNase H homolog in the Mycoplasmas resembles rnhC. Archaeal forms resemble HII more closely than HIII. This family describes bacterial RNase III.\ \ ribonuclease H activity ; GO:0004523 cytoplasm ; GO:0005737 RNA metabolism ; GO:0016070 23131 IPR004642

L-serine dehydratase (EC: 4.2.1.13)converts serine into pyruvate in the gluconeogenesis pathway from serine. This model describes the chain of an iron-sulfur-dependent L-serine dehydratase, found in Bacillus subtilis. A fairly deep split in a UPGMA tree separates members of this family of chains from the homologous region of single chain forms such as found in Escherichia coli. This family of enzymes is not homologous to the pyridoxal phosphate-dependent threonine deaminases and eukaryotic serine deaminases.

Synonym(s): Serine deaminase, L-hydroxyaminoacid dehydratase

\ \ L-serine ammonia-lyase activity ; GO:0003941 \N gluconeogenesis ; GO:0006094 23126 IPR004637 This is a very small family, with two known examples at the time of model creation. This enzyme is a pyridoxal phosphate-containing class III aminotransferase and is quite similar to 4-aminobutyrate aminotransferase (EC: 2.6.1.19). Diaminobutyrate-2-oxoglutarate transaminase (EC: 2.6.1.76) is a homotetramer which catalyses the conversion of L-2,4-diaminobutyrate and 2-oxoglutarate to L-glutamate and L-aspartic 4-semialdehyde during 1,3-diaminopropane biosynthesis.\ transaminase activity ; GO:0008483 \N biosynthesis ; GO:0009058 23127 IPR004638 This subfamily of drug efflux proteins, a part of the major faciliator family, is predicted to have 14 potential membrane-spanning regions. Members with known activities include EmrB (multiple drug resistance efflux pump) in E. coli, FarB (antibacterial fatty acid resistance) in Neisseria gonorrhoeae, TcmA (tetracenomycin C resistance) in Streptomyces glaucescens, etc. In most cases, the efflux pump is described as having a second component encoded in the same operon, such as EmrA of E. coli.\ \N integral to membrane ; GO:0016021 transport ; GO:0006810 23124 IPR004635

Signal peptides of secretory proteins seem to serve at least two important biological functions. First, they are required forprotein targeting to and translocation across membranes, such as the eubacterial plasma membrane and the endoplasmic\ reticular membrane of eukaryotes. Second, in addition to their role as determinants for protein\ targeting and translocation, certain signal peptides have a signaling function.

\ \ peptidase activity ; GO:0008233 \N \N 23125 IPR004636 This family of proteins, for which ornithine aminotransferases form an outgroup, consists mostly of proteins designated acetylornithine aminotransferase. However, the two very closely related members from E. coli are assigned different enzymatic activities. One is acetylornithine aminotransferase (EC: 2.6.1.11), ArgD, an enzyme of arginine biosynthesis, while another is succinylornithine aminotransferase, an enzyme of the argininesuccinyltransferase pathway, an ammonia-generating pathway of arginine catabolism [MEDLINE:98361920]. Members of this family may also act on ornithine, like ornithine aminotransferase (EC: 2.6.1.13) [MEDLINE:90337349] and on succinyldiaminopimelate, like N-succinyldiaminopmelate-aminotransferase (EC: 2.6.1.17, DapC, an enzyme of lysine biosynthesis) [MEDLINE:99175097].\ \ transaminase activity ; GO:0008483 \N arginine metabolism ; GO:0006525 23122 IPR004633 This family describes essentially the full length of an uncharacterized protein from Bacillus subtilis and correponding lengths of longer proteins from E. coli and Treponema pallidum. There is homology to one other group of proteins, type II sodium/phosphate (Na/Pi) cotransporters. A well-conserved repeated domain in this family, approximately 60 residues in length, is also repeated in the Na/Pi cotransporters, although with greater spacing between the repeats. The two families share additional homology in the region after the first repeat, share the properly of having extensive hydrophobic regions, and may be similar in function.\ \N membrane ; GO:0016020 \N 23123 IPR004634

During or shortly after pre-protein translocation, the signal peptide is removed by signal peptidases. The integral membrane protein, SppA (protease IV), of Escherichia coli was shown experimentally to degrade signal peptides. The member of this family from Bacillus subtilis has only been shown to be required for efficient processing of\ pre-proteins under conditions of hyper-secretion [MEDLINE:99386931]. These enzymes have a molecular mass around 67 kDa and a duplication such that the N-terminal half shares extensive homology with the C-terminal half and was shown in E. coli to form homotetramers. E. coli SohB, which is most closely homologous to the C-terminal duplication of SppA, is predicted to perform a similar function of small peptide degradation, but in the periplasm.\ Many prokaryotes have a single SppA/SohB homolog that may perform the function of either or both.

\ \ \ signal peptidase activity ; GO:0009003 integral to membrane ; GO:0016021 \N 23120 IPR004631 4-aminobutyrate aminotransferase eukaryotic (EC: 2.6.1.19) is a class III pyridoxal-phosphate-dependent aminotransferase. The enzyme catalyses the conversion of 4-aminobutanoate and 2-oxoglutarate into succinate semialdehyde and L-glutamate. The degree of sequence difference between this set and known bacterial examples is greater than the distance between either set the most similar enzyme with distinct function, and so the prokaryotic and eukaryotic sets have been placed into separate families. This family describes known eukaryotic examples of the enzyme. Alternate names include GABA transaminase, gamma-amino-N-butyrate transaminase, and

-alanine--oxoglutarate aminotransferase.\ \ 4-aminobutyrate aminotransferase activity ; GO:0003867\ \N \N aminobutyrate metabolism ; GO:0009448 23121 IPR004632

Eukaryotic 4-aminobutyrate aminotransferase (EC: 2.6.1.19) is a class III pyridoxal-phosphate-dependent aminotransferase. The enzyme catalyses the conversion of 4-aminobutanoate and 2-oxoglutarate into succinate semialdehyde and L-glutamate. The degree of sequence difference between this set and known bacterial examples is greater than the distance between either set the most similar enzyme with distinct function, and so the prokaryotic and eukaryotic sets have been placed into separate families.

This family describes known bacterial examples of the enzyme. The best archaeal matches are\ presumed but not trusted to have the equivalent function. E. coli has two isozymes. Alternate names include GABA transaminase, gamma-amino-N-butyrate transaminase, and -alanine--oxoglutarate aminotransferase.

\ \ \ 4-aminobutyrate aminotransferase activity ; GO:0003867\ \N \N aminobutyrate metabolism ; GO:0009448 23116 IPR004627 L-threonine 3-dehydrogenase (EC: 1.1.1.103) is a tetrameric, zinc-binding, NAD-dependent enzyme of threonine catabolism. It catalyses the conversion of L-threonine and NAD+ to L-2-amino-3-oxobutanoate and NADH. Closely related proteins include sorbitol dehydrogenase, xylitol dehydrogenase, and benzyl alcohol dehydrogenase. Eukaryotic examples of this enzyme have been demonstrated experimentally but do not appear in database search results. E. coli His-90 modulates substrate specificity and is believed part of the active site.\ L-threonine 3-dehydrogenase activity ; GO:0008743 \N threonine catabolism ; GO:0006567 23117 IPR004628

This Fe2+-requiring enzyme plays a role in D-glucuronate catabolism in Escherichia coli. Mannonate dehydratase converts D-mannonate to 2-dehydro-3-deoxy-D-gluconate. An apparent equivalog is found in a glucuronate utilization operon in Bacillus stearothermophilus T-6.

\ mannonate dehydratase activity ; GO:0008927 \N glucuronate catabolism ; GO:0006064 23118 IPR004629

The WecG member of this superfamily, believed to be UDP-N-acetyl-D-mannosaminuronic acid transferase, plays a role in enterobacterial common antigen (eca) synthesis in Escherichia coli. Another family member, the Bacillus subtilis TagA protein, is involved in the biosynthesis of the cell wall polymer poly(glycerol phosphate). The third family member, CpsF, CMP-N-acetylneuraminic acid synthetase has a role in the capsular polysaccharide biosynthesis pathway.

\ \N \N biosynthesis ; GO:0009058 23119 IPR004630 Members of this family are found so far only in one archaeal species, Archaeoglobus fulgidus, and in two related bacterial species, Haemophilus influenzae and Escherichia coli. It has 9 GES predicted transmembrane regions at conserved locations in all members. These proteins have a molecular weight of approximately 35 to 38 kDa.\ molecular_function unknown ; GO:0005554 \N \N 23112 IPR004623 Kdp is a high affinity ATP-driven K+ transport system in Escherichia coli. It is composed of three membrane-bound subunits, KdpA, KdpB and KdpC and one small peptide, KdpF. KdpA is the K+-transporting subunit of this complex. During assembly of the complex, KdpA and KdpC bind to each other. This interaction is thought to stabilize the complex. Data indicates that KdpC might connect the KdpA, the K+-transporting subunit, to KdpB, the ATP-hydrolyzing (energy providing) subunit [MEDLINE:99077600].\ potassium-transporting ATPase activity ; GO:0008556 integral to membrane ; GO:0016021 potassium ion transport ; GO:0006813 23113 IPR004624 Phosphonoacetate hydrolase PhnA is a novel carbon-phosphorus bond cleavage enzyme. The phnA gene is part of a large operon in Escherichia coli associated with alkylphosphonate uptake and carbon-phosphorus bond cleavage. PhnA is found in both gram positive and gram negative bacteria.\ \N \N \N 23114 IPR004625 Pyridoxal kinase (EC: 2.7.1.35) is required for the synthesis of pyridoxal-5-phosphate from vitamin B6, and catalyses the conversion of pyridoxal to pyridoxal 5'-phosphate in the presence of ATP. E. coli has an enzyme PdxK that acts in vitro as a pyridoxine/pyridoxal/pyridoxamine kinase,but mutants lacking PdxK activity retain a specific pyridoxal kinase, PdxY. PdxY acts in the salvage pathway of pyridoxal 5'-phosphate biosynthesis. Mammalian forms of pyridoxal kinase are more similar to PdxY than to PdxK. ThiD and related proteins form an outgroup.\ \ pyridoxal kinase activity ; GO:0008478 \N \N 23115 IPR004626 This uncharacterized protein is predicted to have many membrane-spanning domains.\ molecular_function unknown ; GO:0005554 \N \N 23111 IPR004622 DNA-directed DNA polymerase (EC: 2.7.7.7) catalyzes DNA-template-directed extension of the 3'-end of an RNA strand by one nucleotide at a time. DNA polymerase III is a complex, multichain enzyme responsible for most of the replicative synthesis in bacteria. The enzyme also has 3' to 5' exonuclease activity. It has a core composed of

, epsilon and theta chains, that associate with a tau subunit which allows the core dimerization to form the PolIII' complex. PolIII' associates with the gamma complex (gamma, delta, delta', psi and chi chains) and with the

chain. This domain is the N-terminal half of the delta' subunit of DNA polymerase III. Delta' is homologous to the gamma and tau subunits, which form an outgroup for phylogenetic comparison. The gamma/tau branch of the tree is much more tightly conserved than the delta' branch, and some members of that branch score more highly against this model than some proteins classisified as delta'. The noise cutoff is set to detect weakly scoring delta' subunits rather than to exclude gamma/tau subunits.\ \ 3'-5' exonuclease activity ; GO:0008408\ DNA-directed DNA polymerase activity ; GO:0003887 \N DNA replication ; GO:0006260 23105 IPR004616 Leucyl/phenylalanyl-tRNA--protein transferase (EC 2.3.2.-) transfers a Leu or Phe to the amino end of certain proteins to enable degradation. The N-terminal residue controls the biological half-life of many proteins via the N-end rule pathway.\ transferase activity, transferring amino-acyl groups ; GO:0016755 \N protein catabolism ; GO:0030163 23106 IPR004617

Diadenosine 5',5"'-P1,P4-tetraphosphate (Ap4A) is a regulatory metabolite of stress conditions. It is hydrolyzed to two ADP by Bis(5'-nucleosyl)-tetraphosphatase (symmetrical) (EC: 3.6.1.41). Alternate names include diadenosine-tetraphosphatase and Ap4A hydrolase.

\ bis(5'-nucleosyl)-tetraphosphatase (symmetrical) activity ; GO:0008803 \N \N 23107 IPR004618 Aspartate--ammonia ligase (asparagine synthetase) EC: 6.3.1.1 catalyses the conversion of L-aspartate to L-asparagine in the presence of ATP and ammonia. This family represents one of two non-homologous forms of aspartate--ammonia ligase found in E. coli. This type is also found in Haemophilus influenzae, Treponema pallidum and Lactobacillus delbrueckii, but appears to have a very limited distribution. The fact that the protein from the H. influenzae is more than 70% identical to that from the spirochete Treponema pallidum, but less than 65% identical to that from the closely related E. coli, strongly suggests lateral transfer.\ aspartate-ammonia ligase activity ; GO:0004071 cytoplasm ; GO:0005737 asparagine biosynthesis ; GO:0006529 23108 IPR004619

This is a family of proteins found in a single copy in at least ten different early completed bacterial genomes. The only characterized member of the family is Bvg accessory factor (Baf), a protein required, in addition to the regulatory operon bvgAS, for heterologous transcription of the Bordetella pertussis toxin operon (ptx) in Escherichia coli.

\ \N \N \N 23109 IPR004620 The enzyme activities methylenetetrahydrofolate reductase (EC: 1.5.1.20) and 5,10-methylenetetrahydrofolate reductase (FADH) (EC: 1.7.99.5) differ in that the former (assigned in many eukaryotes) is defined to use NADP+ as an acceptor, while the latter (assigned in many bacteria) is flexible with respect to the acceptor. Both convert 5-methyltetrahydrofolate to 5,10-methylenetetrahydrofolate. From a larger set of proteins assigned as one or the other, this family describes the subset of proteins found in bacteria, and currently designated 5,10-methylenetetrahydrofolate reductase. This protein is an FAD-containing flavoprotein.\ \ 5,10-methylenetetrahydrofolate reductase (FADH) activity ; GO:0008702\ \N \N methionine biosynthesis ; GO:0009086 23110 IPR004621 The enzyme activities methylenetetrahydrofolate reductase (EC: 1.5.1.20) and 5,10-methylenetetrahydrofolate reductase (FADH) (EC: 1.7.99.5) differ in that the former (assigned in many eukaryotes) is defined to use NADP+ as an acceptor, while the latter (assigned in many bacteria) is flexible with respect to the acceptor. Both convert 5-methyltetrahydrofolate to 5,10-methylenetetrahydrofolate. From a larger set of proteins assigned as one or the other, this family describes the subset of proteins found in eukaryotes, and currently designated methylenetetrahydrofolate reductase (EC: 1.5.1.20). This protein is an FAD-containing flavoprotein.\ methylenetetrahydrofolate reductase (NADPH) activity ; GO:0004489 \N methionine metabolism ; GO:0006555 23100 IPR004611 The DNA primase DnaG of E. coli and its apparent orthologs in other eubacterial species are approximately 600 residues in length. Within this set, a conspicuous outlier in percent identity, as seen in a UPGMA difference tree, is the branch containing the Mycoplasmas. This lineage is also unique in containing the small, DNA primase-related protein found in this family, which is homologous to the central third of DNA primase. Several small regions of sequence similarity specifically to Mycoplasma sequences rather than to all DnaG homologs suggests that the divergence of this protein from DnaG post-dated the separation of bacterial lineages. The function of this DNA primase-related protein is unknown.\ \N \N \N 23101 IPR004612 The Bacillus subtilis protein belonging to this family has been shown to be required for DNA recombination and repair.\ \N cytoplasm ; GO:0005737 DNA recombination ; GO:0006310 23102 IPR004613 This is a family of conserved hypothetical proteins, the members of which contain an ATP-binding domain at the N-terminal end of the protein. It is possibly part of a superfamily of

-lactmases.\ \N \N \N 23103 IPR004614 Phosphate acetyltransferase (EC: 2.3.1.8) catalyses the conversion of acetyl-CoA and phosphate to CoA and acetyl phosphate in the last two steps in the conversion of actetae to acetyl-CoA.\ acetyltransferase activity ; GO:0016407 \N \N 23104 IPR004615 DNA-directed DNA polymerase (EC: 2.7.7.7) catalyzes DNA-template-directed extension of the 3'-end of an RNA strand by one nucleotide at a time. DNA polymerase III is a complex, multichain enzyme responsible for most of the replicative synthesis in bacteria. The enzyme also has 3' to 5' exonuclease activity. It has a core composed of

chain. This family is the psi subunit, the small subunit of the DNA polymerase III holoenzyme in E. coli and related species, whose exact function is not known. It appears to have a narrow taxonomic distribution. It is not found so far outside the gamma subdivision proteobacteria.\ \ 3'-5' exonuclease activity ; GO:0008408\ DNA-directed DNA polymerase activity ; GO:0003887 \N DNA replication ; GO:0006260 23096 IPR004607 This family describes phosphoribosylglycinamide formyltransferase (GAR transformylase), one of several proteins in IPR002376 shows a long branchlength but membership in the family, while the formyltetrahydrofolate deformylases form a closely related outgroup.\ \ phosphoribosylglycinamide formyltransferase activity ; GO:0004644 \N 'de novo' IMP biosynthesis ; GO:0006189 23097 IPR004608 Methylmalonyl-CoA mutase (EC: 5.4.99.2) catalyses the isomerization of succinyl-CoA to methylmalonyl-CoA during the synthesis of propionate from tricarboxylic acid-cycle intermediates in propionic acid fermentation. The adenosylcobalamin-binding, catalytic chain of methylmalonyl-CoA mutase may form homodimers, as in mitochondrion and E. coli, or heterodimers with a shorter, homologous chain that does not bind adenosylcobalamin. This family is this non-catalytic

chain, as found in the enzyme from Propionibacterium freudenreichii, for which the 3-dimensional structure has been solved.\ methylmalonyl-CoA mutase activity ; GO:0004494 \N propionate fermentation ; GO:0019652 23098 IPR004609 The ATP-dependent DNA helicase RecG (EC 3.6.1.-) plays a critical role in recombination and DNA repair. It helps to process Holliday junction intermediates to mature products by catalysing branch migration. RecG has DNA unwinding activity characteristic of a DNA helicase with 3' to 5' polarity.\ ATP dependent DNA helicase activity ; GO:0004003 \N DNA recombination ; GO:0006310 23099 IPR004610 All proteins in this family are 5'-3' single-strand DNA exonucleases. These proteins are used in some aspects of mismatch repair, recombination, and recombinational repair. RecJ is a single-stranded DNA-specific endonuclease which is required for many types of recombination events, although the stringency of the requirement for RecJ appears to vary with the type of recombinational event monitored, and the other recombination gene products which are available.\ \ 5'-3' exonuclease activity ; GO:0008409\ \N \N DNA recombination ; GO:0006310 23092 IPR004603 All proteins in this family for which functions are known are G:T mismatch endonucleases that function in a specialized mismatch repair process used usually to repair G:T mismatches in specific sections of the genome. G:T mismatches are caused by deamination of 5-methylcytosine in DNA, and can lead to C-to-T transition mutations if not repaired. Vsr (very short patch repair protein repairs the mismatches in favour of the G-containing strand. In E. coli, this endonuclease nicks double-stranded DNA within the sequence CT(AT)GN or NT(AT)GG next to the thymidine residue, which is mismatched to 2'-deoxyguanosine. The incision is mismatch-dependent and strand specific.\ endonuclease activity ; GO:0004519 \N mismatch repair ; GO:0006298 23093 IPR004604

DNA repair protein RecN is thought to be DNA damage inducible and involved in recombinational processes. The N-terminal region of most of the bacterial RecN proteins sequenced to date contains an ATP/GTP binding domain within an SMC-like motif.\ SMC-like domains are involved in chromosomal scaffolding and segregation. It is possible that the function of RecN in homologous recombination is either\ structural or enzymatic or both. RecN may be involved in the proper positioning of the recombining segments of DNA, ensuring normal recombination. The\ observation that inactivation of this gene leads to a decreased transformation efficiency, as well as increased sensitivity to DNA-damaging agents, may be due to\ some defect in chromosomal partitioning or positioning during these recombination-dependent processes [MEDLINE:21666124]. The protein may function presynaptically\ to process double-stranded breaks to produce 3 single-stranded DNA\ intermediates during recombination.

\ \ ATP binding activity ; GO:0005524 \N DNA recombination ; GO:0006310 23094 IPR004605 All proteins in this family for which functions are known are 5'-3' DNA helicases that, as part of a complex with RuvA homologs serve as a 5'-3' Holliday junction helicase. RuvA specifically binds Holliday junctions as a sandwich of two tetramers and maintains the configuration of the junction. It forms a complex with two hexameric rings of RuvB, the subunit that contains helicase activity. The complex drives ATP-dependent branch migration of the Holliday junction recombination intermediate. The endonuclease RuvC resolves junctions.\ Holliday junction helicase activity ; GO:0009378 \N DNA recombination ; GO:0006310 23095 IPR004606 This is a multigene family of molybdenum-pterin binding proteins of about 70 amino acids in Clostridium pasteurianum, as a tandemly-repeated domain C-terminal to an unrelated domain in ModE, a molybdate transport gene repressor of E. coli, and in single or tandemly paired domains in several related proteins.\ molybdenum ion binding activity ; GO:0030151 \N \N 23086 IPR004596 All proteins in this family for which the functions are known are cell division inhibitors. In E. coli, SulA is one of the SOS regulated genes. Accumulation of SulA causes rapid cessation of cell division and the appearance of long, non-septate filaments. The expression of SulA is repressed by LexA. The N-terminus of SulA may be involved in recognising the cell division apparatus.\ \N inner membrane ; GO:0019866 SOS response ; GO:0009432 23087 IPR004597 The DNA-3-methyladenine glycosylase I family are a group of alkylation DNA glycosylases that function in base excision repair. DNA-3-methyladenine glycosylase I (EC: 3.2.2.20) catalyses the hydrolysis of the deoxyribose N-glycosidic bond of alkylated DNA, releasing 3-methyladenine from the damaged DNA. Its activity is controlled by product inhibition.\ DNA 3-methyladenine glycosylase I activity ; GO:0008725 \N DNA repair ; GO:0006281 23088 IPR004598 Members of this family are part of the TFIIH complex which is involved in the initiation of transcription and nucleotide excision repair. The core-TFIIH basal transcription factor complex has six subunits, this is the p52 subunit.\ transcription factor activity ; GO:0003700 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 23080 IPR004590

All proteins in this family for which functions are known bind single-stranded DNA and are involved in the the pairing of homologous DNA. RecT from Escherichia coli is a homotetramer which binds to single-stranded DNA and promotes the renaturation of complementary single-stranded DNA, and also plays a role in recombination. It is able to promote the annealing of complementary singleDNA strands and can catalyze the formation of joint molecules [MEDLINE:22159925].

\ \ DNA binding activity ; GO:0003677 \N DNA metabolism ; GO:0006259 23081 IPR004591 All proteins in this family for which functions are known are part of a multiprotein complex made up of homologs of RPA1, RPA2 and RPA3 that bind single-stranded DNA and function in the recognition of DNA damage for nucleotide excision repair. The complex binds to single-stranded DNA sequences participating in DNA replication in addition to those mediating transcriptional repression and activation, and stimulates the activity of cognate strand exchange protein Sep1. It cooperates with T-AG and DNA topoisomerase I to unwind template DNA containing the Simian Virus 40 origin of replication. This family is Replication factor-a protein 1 (RPA1)\ DNA binding activity ; GO:0003677 nucleus ; GO:0005634 DNA replication ; GO:0006260 23089 IPR004600 Members of this family are part of the TFIIH complex which is involved in the initiation of transcription and nucleotide excision repair. The core-TFIIH basal transcription factor complex has six subunits, this is the p34 subunit.\ transcription factor activity ; GO:0003700 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 23090 IPR004601 All proteins in this family for which functions are known are UV dimer endonucleases that function in an alternative nucleotide excision repair process.\ \N \N \N 23091 IPR004602

\ During the process of Escherichia coli nucleotide excision repair, DNA damage\ recognition and processing are achieved by the action of the uvrA, uvrB,\ and uvrC gene products [MEDLINE:93221456].\ The UvrC protein contain 4 conserved regions: a central region which interact\ with UvrB (Uvr domain), a Helix hairpin Helix (HhH) domain important for 5\ prime incision of damage DNA and the homology regions 1 and 2 of unknown\ function. UvrC homology region 2 is specific for UvrC proteins, whereas UvrC\ homology region 1 is also shared by few other nucleases.\ \ excinuclease ABC activity ; GO:0009381 excinuclease ABC complex ; GO:0009380 nucleotide-excision repair ; GO:0006289 23078 IPR004588

This protein previously of unknown biochemical function is essential in Escherichia coli. It has now been characterised as 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate synthase, which converts 2C-methyl-D-erythritol 2,4-cyclodiphosphate (ME-2,4CPP) into 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate in the sixth step of nonmevalonate terpenoid biosynthesis. The family is restricted to bacteria, where it is widely but not universally distributed. No homology can be detected between this family and other proteins.

\ \N \N terpenoid biosynthesis ; GO:0016114 23079 IPR004589

\ \ ATP dependent helicase activity ; GO:0008026 \N DNA metabolism ; GO:0006259 23085 IPR004595 All proteins in this family for which functions are known are components of the TFIIH complex which is involved in the initiation of transcription and nucleotide excision repair. The yeast transcription factor Ssl1 (Suppressor of stem-loop protein 1) is essential for translation initiation and affects UV resistance.\ \N nucleus ; GO:0005634 DNA repair ; GO:0006281 23084 IPR004594 Members of this family are involved in the direct repair of UV induced spore photoproducts (thymine dimer 5-thyminyl-5,6-dihydrothymine). The protein repairs UV radiation-induced DNA damage during spore germination by monomerization of these thymine dimers.\ damaged DNA binding activity ; GO:0003684 \N sporulation (sensu Bacteria) ; GO:0030436 23082 IPR004592 All proteins in this family for which functions are known are part of an exonuclease complex with sbcD homologs. This complex is involved in the initiation of recombination to regulate the levels of palindromic sequences in DNA. SbcC may have nuclease activity that is functionally related to one of the nuclease activities of the RecBCD enzyme (IPR004586).\ exonuclease activity ; GO:0004527 \N DNA metabolism ; GO:0006259 23083 IPR004593 All proteins in this family for which functions are known are double-stranded DNA exonuclease (as part of a complex with SbcC homologs). This complex functions in the initiation of recombination and recombinational repair and is particularly important in regulating the stability of DNA sections that can form secondary structures. This family is likely to be homologous to the MRE11 family.\ exonuclease activity ; GO:0004527 \N DNA metabolism ; GO:0006259 23076 IPR004585

Rad52 was identified in Saccharomyces cerevisiae as a component of the homologous recombination repair pathway and to play an important role in both meiotic and mitotic recombination. The human protein is highly homologous in both structure and function. In the presence of absence of DNA, Rad52 forms ring-shaped oligomers which bind both single and double stranded DNA, stimulating annealing of complimentary DNA strands and promoting ligation of both cohesive and blunt-end fragments. Rad52 may act as a recombination mediator, optimising catalysis of strand exchange by the Rad51 protein.

A C-terminal self-association domain has been identified that mediates formation of higher order oligomers of Rad52 rings. Formation of these oligomers may be important for interaction with more than one DNA molecule PUB00007686.

\ \N \N DNA recombination ; GO:0006310 23077 IPR004586 Exodeoxyribonuclease V, or RecBCD holoenzyme, (EC: 3.1.11.5) is a multifunctional nuclease with potent ATP-dependentexodeoxyribonuclease activity. Ejection of RecD, as occurs at chi recombinational hotspots, cripples exonuclease activity in favor of recombinagenic helicase activity. All proteins in this family for which functions are known are DNA-DNA helicases that are used as part of an exonuclease-helicase complex (made up of RecBCD homologs) that function to generate substrates for the initiation of recombination and recombinational repair. The complex catalyses exonucleolytic cleavage in either the 5' to 3' or 3' to 5' direction to yield 5-phosphooligonucleotides in the presence of ATP. This is the

subunit.\ \ exodeoxyribonuclease V activity ; GO:0008854 \N DNA repair ; GO:0006281 23073 IPR004582

To be effective as a mechanism that preserves genomic integrity, the DNA damage checkpoint must beextremely sensitive in its ability to detect DNA damage. In Saccharomyces cerevisiae the Ddc1/Rad17/Mec3 complex and Rad24 are DNA damage checkpoint components which may promote checkpoint\ activation by "sensing" DNA damage directly [MEDLINE:21549067]. Rad24 shares sequence homology with RF-c, a protein that recognizes DNA template/RNA primer hybrids during DNA replication. The\ Ddc1 complex has structural homology to proliferating-cell nuclear antigen (PCNA), which clamps onto\ DNA and confers processivity to DNA polymerases delta and epsilon. Rad24 is postulated to\ recognize DNA lesions and then recruit the Ddc1 complex to generate checkpoint signals.

\ \ \N nucleus ; GO:0005634 cell cycle ; GO:0007049 23074 IPR004583

In nucleotide excision repair (NER) in eukaryotes, DNA is incised on both sides of the lesion, resulting in the removal of a fragment ~25-30 nucleotides long. This isfollowed by repair synthesis and ligation. This reaction, in yeast, requires the damage binding factors Rad14, RPA, and the Rad4-Rad23 complex, the transcription factor TFIIH which contains the two DNA\ helicases Rad3 and Rad25, essential for creating a bubble structure, and the two endonucleases, the Rad1-Rad10 complex and Rad2, which incise the damaged\ DNA strand on the 5'- and 3'-side of the lesion, respectively [MEDLINE:20377834].

Homologues of all the above mentioned yeast genes, except for RAD7, RAD16, and MMS19, have been identified in humans, and mutations in these human genes\ affect NER in a similar fashion as they do in yeast, with the exception of XPC, the human counterpart of yeast RAD4. Deletion of RAD4 causes the same high level\ of UV sensitivity as do mutations in the other class 1 genes, and rad4 mutants are completely defective in incision. By contrast, XPC is required for\ the repair of nontranscribed regions of the genome but not for the repair of the transcribed DNA strand.

\ \ damaged DNA binding activity ; GO:0003684 nucleus ; GO:0005634 nucleotide-excision repair ; GO:0006289 23075 IPR004584

Rad50 is involved in recombination, recombinational repair, and/or non-homologous end joining. It is a component of an exonuclease complex with MRE11 homologs. The yeast Rad50/MRE11 complex possesses single-stranded endonuclease activity and ATP-dependent double-strand-specific exonuclease activity. Rad50 provides an ATP-dependent control of MRE11 by unwinding and repositioning DNA ends into the MRE11 active site. This family is distantly related to the SbcC family of bacterial proteins.

When the N- and\ C-terminal globular regions of Rad50 from Pyrococcus\ furiosus P58301 are co-expressed in E. coli, they spontaneously associate to\ form a stable complex that possesses ATP-binding and weak ATP-hydrolysing activities. The\ structure formed is known as the Rad50 catalytic domain (Rad50cd1). In the presence of ATP, two\ Rad50cd1 molecules interact via their ATP-binding and highly conserved 'signature' motifs to form a\ dimer. As ATP is buried deep within this dimer interface, the two Rad50cd1 molecules may have to completely disengage after ATP hydrolysis to allow the\ release of ADP before binding of a new ATP molecule. ATP binding is also accompanied by a 30�\ rotation of two distinct domains within each Rad50cd1 part of the dimer. This rotation and dimerization\ creates a positively charged surface which, potentially, could provide a DNA-binding site capable of\ accommodating two DNA molecules.

The Mre11-docking site within Rad50 has been mapped to two 40-residue heptad-repeat\ sequences that lie adjacent to the N- and C-terminal ATPase segments. A\ distinct region within this domain forms a conserved hydrophobic patch that is believed to be the\ actual Mre11-binding site and lies immediately adjacent to the putative\ DNA-binding site of Rad50. As Rad50 dimerizes in the presence of ATP and forms a stoichiometric\ complex with Mre11 (one Mre11 subunit binding to one Rad50 subunit), it is possible that the MR\ complex forms a closely coordinated DNA-binding unit that has the potential to act on two DNA\ molecules simultaneously. Within this unit, ATP-dependent control of nuclease action might\ be achieved via Rad50 unwinding or repositioning DNA ends into the active-site of Mre11 [MEDLINE:22147075].

\ \ ATP binding activity ; GO:0005524 \N DNA repair ; GO:0006281 23071 IPR004579 All proteins in this family for which functions are known are components in a multiprotein endonuclease complex (usually made up of Rad1 and Rad10 homologs). This complex is used primarily for nucleotide excision repair but also for some aspects of recombination repair. In yeast, Rad10 works as a heterodimer with Rad1, and is involved in nucleotide excision repair of DNA damaged with UV light, bulky adducts or cross-linking agents. The complex forms an endonuclease which specifically degrades single-stranded DNA.\ endonuclease activity ; GO:0004519 nucleus ; GO:0005634 DNA repair ; GO:0006281 23072 IPR004580

During DNA replication, lesion bypass is an important cellular response to unrepaired damage in the genome. In the yeast Saccharomyces cerevisiae, Rad6 and Rad18 are required for both the error-free and error-prone lesion bypass mechanisms. The RAD18 gene encodes a RING-finger protein with single-stranded DNA binding activity that interacts with the\ ubiquitin-conjugating enzyme RAD6.

\ \ damaged DNA binding activity ; GO:0003684 nucleus ; GO:0005634 DNA repair ; GO:0006281 23067 IPR004575

MAT1 (menage a trois 1) is a RING finger protein with a characteristic C3HC4 motif located in the N-terminal domain. MAT1 stabilizes the cyclin H-CDK7 complex to form a functional CDK-activating kinase (CAK) enzymatic complex which then goes on to activate many of the CDK enzymes intimately involved in the cell cycle [MEDLINE:20460544]. CDK7 forms a stable complex with cyclin H and MAT1 in vivo only when phosphorylated on either one\ of two residues (Ser164 or Thr170) in its T-loop. The requirement for MAT1 for the activation of CAK can be by-passed by the phosphorylation of CDK7 on the T-loop. The two mechanisms for CDK7 complex stabilization and activationMAT1 addition and T-loop phosphorylationwhich can operate\ independently in vitro, actually cooperate under physiological conditions to maintain complex integrity. With prolonged exposure to elevated temperature,\ dissociation to monomeric subunits occurs in vivo when CDK7 is dephosphorylated, even in the presence of MAT1 [MEDLINE:21340267].

The Cyclin H-MAT1-CDK7 complex also forms part of TFIIH, a multiprotein complex required for both transcription and DNA repair.

\ \ \N nucleus ; GO:0005634 cell cycle ; GO:0007049 23068 IPR004576 All proteins in this family for which functions are known are DNA-dependent ATPases that function in the process of transcription-coupled DNA repair in which the repair of the transcribed strand of actively transcribed genes is repaired at a higher rate than the repair of non-transcribed regions of the genome and than the non-transcribed strand of the same gene. A lesion in the template strand blocks the RNA polymerase complex (RNAP). The RNAP-DNA-RNA complex is specifically recognised by TcrF, which releases RNAP and the truncated transcript. The TcrF may replace RNAP at the lesion site and then recruit the UvrA/B/C repair system.\ ATP binding activity ; GO:0005524 \N DNA repair ; GO:0006281 23069 IPR004577 All proteins in this family for which functions are known are 8-oxo-guanaine DNA glycosylases that function in base excision repair. The enzyme incises DNA at 8-oxoG residues, and excises 7,8-dihydro-8-oxoguanine from damaged DNA. It has

-lyase activity that nicks DNA 3' to the lesion.\ purine-specific oxidized base lesion DNA N-glycosylase activity ; GO:0008534 nucleus ; GO:0005634 DNA repair ; GO:0006281 23070 IPR004578 All proteins in this superfamily for which functions are known are DNA polymerases. DNA-directed DNA polymerase (EC: 2.7.7.7) catalyzes DNA-template-directed extension of the 3'-end of an RNA strand by one nucleotide at a time. In eukaryotes there are five DNA polymerases,

, gamma, delta and epsilon, which are responsible for different reactions of DNA synthesis. This family includes, among others, the

catalytic subunit, which is a replicative polymerase when in a complex with DNA primase, as well as archaebacterial DNA polymerase.\ DNA-directed DNA polymerase activity ; GO:0003887 nucleus ; GO:0005634 DNA replication ; GO:0006260 23065 IPR004573

The reading frame, encoding this protein, was originally interpreted as two reading frames, fmu and fmv. The recombinant protein from E. coli was shown to methylate only C967 of small subunit (16S) ribosomal RNA and to produce only m5C at that position. The family is built from bacterial sequences only. Eukaryotic homologs include Nop2, a protein required for processing pre-rRNA, that is likely also a rRNA methyltransferase, although thefine specificity may differ. Cutoff scores are set to avoid treating archaeal and eukaroytic homologs automatically as functionally equivalent, although they may have very similar roles.

\ \ \N \N \N 23066 IPR004574 Proteins repair alkylation damage to DNA. The Escherichia coli alkB gene product protects against cell killing by S(N)2-alkylating agents through DNA repair by a novel direct reversal DNA repair mechanism: the oxidative demethylation of N1-methyladenine or N3-methylcytosine DNA lesions. This reaction occurs on both single- and double-stranded DNA, and requires AlkB-bound non-heme Fe(2+), O(2) and

-ketogluterate to oxidize the offending methyl group. This is followed by the release of succinate, CO(2) and formaldehyde, and the restoration of undamaged A or C in DNA [MEDLINE:22406496].\ \N \N DNA repair ; GO:0006281 23063 IPR004571 NAD(P) transhydrogenase (EC: 1.6.1.1), a tetramer composed of 2

and 2

subunits, is an integral membrane protein that couples the proton transport across the membrane to the reversible transfer of hydride ion equivalents between NAD and NADP. This family is the is the

subunit. An alternate name is pyridine nucleotide transhydrogenase

subuint. The N-terminal region is homologous to alanine dehydrogenase. In some species, such as Rhodospirillum rubrum, the

chain is replaced by two shorter chains, both with some homology to the full-length

chain modeled here. These score below the trusted cutoff.\ NAD(P)+ transhydrogenase (AB-specific) activity ; GO:0008750 \N proton transport ; GO:0015992 23064 IPR004572 Protoporphyrinogen oxidase (EC: 1.3.3.4) oxidizes protoporphyrinogen IX to protoporphyrin IX, a precursor of heme and chlorophyll, in the penultimate step in heme and porphyrin biosynthesis. Bacillus subtilis HemY also has coproporphyrinogen III to coproporphyrin III oxidase activity in a heterologous expression system, although the role for this activity in vivo is unclear. This protein is a flavoprotein and has a

dinucleotide binding motif near the aminoend.\ \ protoporphyrinogen oxidase activity ; GO:0004729 \N porphyrin biosynthesis ; GO:0006779 23058 IPR004566 Pantothenate kinase (EC: 2.7.1.33) catalyzes the rate-limiting step in the biosynthesis of coenzyme A, the conversion of pantothenate to D-4'-phosphopantothenate in the presence of ATP. It is very well conserved from E. coli to B. subtilis, but differs considerably from known eukaryotic forms, described in a separate family. It has been shown to be a homodimer in E. coli and is regulated by feedback inhibition by CoA and its thioesters.\ ATP binding activity ; GO:0005524 cytoplasm ; GO:0005737 coenzyme A biosynthesis ; GO:0015937 23059 IPR004567

Pantothenate kinase (EC: 2.7.1.33) catalyses the conversion of CAATP and pantothenateto to ADP and D-4'-phosphopantothenate, in the key regulatory step in the biosynthesis of coenzyme A (CoA). This family describes a eukaryotic form of pantothenate kinase, characterized from the fungus Emericella nidulans and with similar forms known in several other eukaryotes. It differs in a number of biochemical properties (such as inhibition by acetyl-CoA) from eubacterial PanK and shows little sequence similarity.

\ \N \N \N 23060 IPR004568 This domain is active in transferring the phophopantethiene prosthetic groupto its attachment site on enzymes and carrier proteins. Many members of the family containing this domain are small proteins that act on the acyl carrier protein involved in fatty acid biosynthesis. Some members are domains of larger proteins involved specialized pathways for the synthesis of unusual molecules including polyketides, atypical fatty acids, and antibiotics.\ \ \N \N \N 23061 IPR004569 PdxJ is required in the biosynthesis of pyridoxine (vitamin B6), a precursor to the enzyme cofactor pyridoxal phosphate. PdxJ catalyses condensation of 1-amino-3-oxo-4-(phosphohydroxy)propan-2-one and 1-deoxy-D-xylulose-5-phosphate to form pyridoxine-5'-phosphate. The product of that reaction is oxidized by PdxH to pyridoxal 5'-phosphate.\ \N cytoplasm ; GO:0005737 pyridoxine biosynthesis ; GO:0008615 23062 IPR004570 CDP-diacylglycerol--glycerol-3-phosphate 3-phosphatidyltransferase (EC: 2.7.8.5), also known as phosphatidylglycerophosphate synthase, glycerophosphate phosphatidyltransferase and PGP synthase, catalyses the conversion ofCDP-diacylglycerol and glycerol-3-phosphate to CMP and 3-(3-phosphatidyl)-glycerol 1-phosphate in the commited step to the synthesis of acidic phospholipids. It is an integral membrane protein. A number of related enzymes are quite similar in both sequence and catalytic activity, including Saccharamyces cerevisiae YDL142c, now known to be a cardiolipin synthase. There may be problems with incorrect transitive annotation of near homologs as authentic CDP-diacylglycerol--glycerol-3-phosphate 3-phosphatidyltransferase.\ CDP-diacylglycerol-glycerol-3-phosphate 3-phosphatidyltransferase activity ; GO:0008444 integral to membrane ; GO:0016021 phospholipid biosynthesis ; GO:0008654 23053 IPR004561 Isochorismate synthase interconverts chorismate and isochorismate. In E. coli, different loci encode isochorismate synthases for the pathways of menaquinone biosynthesis and enterobactin biosynthesis and fail to complement each other. Among isochorismate synthases, the N-terminal domain is poorly conserved.\ isochorismate mutase activity ; GO:0008909 \N biosynthesis ; GO:0009058 23054 IPR004562 One member of this group of proteins is bovine lipoyltransferase, which transfers the lipoyl group from lipoyl-AMP to the specific Lys of lipoate-dependent enzymes. However, it does not first activate lipoic acid with ATP to create lipoyl-AMP and pyrophosphate. Another member of this group, lipoate-protein ligase A from E. coli, catalyzes both the activation and the transfer of lipoate. Homology between the two is full-length, except for the bovine mitochondrial targeting signal, but is strongest toward the N-terminus.\ \N \N \N 23055 IPR004563 Apolipoprotein N-acyltransferase (EC 2.3.1.-) transfers the acyl group to lipoproteins and is involved in lipoprotein biosynthesis. It is an integral membrane protein.\ N-acyltransferase activity ; GO:0016410 integral to membrane ; GO:0016021 lipoprotein biosynthesis ; GO:0042158 23056 IPR004564

This protein, LolA, is known so far only in the gamma subdivision of the Proteobacteria. In Escherichia coli, lipoproteins are anchored to the\ periplasmic side of either the inner or outer membrane through N-terminal lipids, depending on the lipoprotein-sorting signal present at\ position 2 [MEDLINE:22028954]. Five Lol proteins are involved in the sorting and outer membrane localization of lipoproteins. LolCDE, an ATP\ binding cassette (ABC) transporter, in the inner membrane releases outer membrane-directed lipoproteins from the inner membrane in an ATP-dependent manner, leading to the formation of a water-soluble complex between the lipoprotein and the molecular chaperone, LolA. The LolA-lipoprotein complex crosses the periplasm and then\ interacts with outer membrane receptor LolB, which is essential for the anchoring of lipoproteins to the outer membrane.

E. coli lipoproteins are anchored to the inner or outer membrane depending on the residue at position 2. Aspartate at this\ position makes lipoproteins specific to the inner membrane, whereas other residues cause the release of lipoproteins from the inner\ membrane.

\ \ \N periplasmic space (sensu Gram-negative Bacteria) ; GO:0030288 protein transport ; GO:0015031 23057 IPR004565

This protein, LolB, is known so far only in the gamma subdivision of the Proteobacteria. It is a processed, lipid-modified outer membrane protein. In Escherichia coli, lipoproteins are anchored to the\ periplasmic side of either the inner or outer membrane through N-terminal lipids, depending on the lipoprotein-sorting signal present at\ position 2 [MEDLINE:22028954]. Five Lol proteins are involved in the sorting and outer membrane localization of lipoproteins. LolCDE, an ATP\ binding cassette (ABC) transporter, in the inner membrane releases outer membrane-directed lipoproteins from the inner membrane in an ATP-dependent manner, leading to the formation of a water-soluble complex between the lipoprotein and LolA. The LolA-lipoprotein complex crosses the periplasm and then\ interacts with outer membrane receptor LolB, which is essential for the anchoring of lipoproteins to the outer membrane.

\ \ \N external outer membrane (sensu Gram-negative Bacteria) ; GO:0009279 protein transport ; GO:0015031 23051 IPR004559 Experimentally determined examples of oxygen-independent coproporphyrinogen IIIoxidase, an enzyme that replaces HemF function under anaerobic conditions, belong to a family of proteins called HemN (IPR004558 and to prevent accumulation of coproporphyrinogen III under anaerobic conditions, but the exact role of this protein is still uncertain. It is found in a number of species that do not synthesize heme de novo.\ \ coproporphyrinogen oxidase activity ; GO:0004109 cytoplasm ; GO:0005737 porphyrin biosynthesis ; GO:0006779 23052 IPR004560 This family shows similarity to other isomerases. Putative identification ashexulose-6-phosphate isomerase has been reported. This family is conserved at better than 40% identity among the four known examples from three species: Escherichia coli (SgbU and SgaU), Haemophilus influenzae, and Mycoplasma pneumoniae. The rarity of the family, high level of conservation, and proposed catabolic role suggests lateral transfer may be a part of the evolutionary history of this protein.\ \ intramolecular isomerase activity, interconverting aldoses and ketoses ; GO:0016861 \N carbohydrate metabolism ; GO:0005975 23049 IPR004557

These proteins exhibit homology to the Saccharomyces cerevisiae (yeast) ORF YDR140w (FYV9). No known function has been described for this yeast ORF though the null mutant is viable and exhibits K1 killer toxin hypersensitivity. Members of this entry are weakly related to the yeast ORF YNL063w which is a putative S-adenosyl-methionine-dependent methyltransferase [MEDLINE:99237242]. Members of this entry are found in archaeal, bacterial and eukaryotic lineages.

\ methyltransferase activity ; GO:0008168 \N \N 23050 IPR004558 This family represents HemN, the oxygen-independent coproporphyrinogen III oxidase that replaces HemF function under anaerobic conditions. HemN catalyses the anaerobic transformation of coproporhyrinogen-III into protoporphyrinogen-IX during porphyrin biosynthesis. Several species, including E. coli, Helicobacter pylori, and Aquifex aeolicus, have both a member of this family and a member of another, closely related family for which there is no evidence of coproporphyrinogen III oxidase activity. Members of this family have a perfectly conserved motif PYRT[SC]YP in a region N-terminal to the region of homology with the related uncharacterized protein.\ coproporphyrinogen oxidase activity ; GO:0004109 cytoplasm ; GO:0005737 porphyrin biosynthesis ; GO:0006779 23047 IPR004555 The opcA gene is found immediately downstream of zwf, the glucose-6-phosphatedehydrogenase (G6PDH) gene, in a number of species, including Mycobacterium\ tuberculosis, Streptomyces coelicolor, Nostoc punctiforme, and Synechococcus sp. PCC 7942. In the latter, disruption of opcA was shown to block assembly of G6PDH into active oligomeric forms. The protein is thought to play a role in the functional assembly of glucose-6-phosphate dehydrogenase.\ \ \N \N \N 23048 IPR004556 The gene hemK from E. coli was found to contribute to heme biosynthesis and originally suggested to be protoporphyrinogen oxidase [MEDLINE:95189105]. Functional analysis of the nearest homolog in Saccharomyces cerevisiae, YNL063w, finds it is not protoporphyrinogen oxidase and sequence analysis suggests that HemK homologs have S-adenosyl-methionine-dependent methyltransferase activity [MEDLINE:99237242]. Homologs are found, usually in a single copy, in nearly all completed genomes, but varying somewhat in apparent domain architecture. Both E. coli and H. influenzae have two members rather than one. The members from the Mycoplasmas have an additional C-terminal domain.\ protein methyltransferase activity ; GO:0008276 \N protein amino acid methylation ; GO:0006479 23042 IPR004550 L-asparaginase catalyses the conversion of L-asparagine to L-aspartate. Two related families of asparaginase (L-asparagine amidohydrolase, EC: 3.5.1.1) are designated type I and type II according to the terminology in E. coli, which has both: L-asparaginase I is a low-affinity enzyme found in the cytoplasm, while L-asparaginase II is a high-affinity periplasmic enzyme synthesized with a cleavable signal sequence. This familydescribes L-asparaginases related to type II of E. coli. Both the cytoplasmic and the cell wall asparaginases of Saccharomyces cerevisiae belong to this set. Members of this set from Acinetobacter glutaminasificans and Pseudomonas fluorescens are described as having both glutaminase and asparaginase activitities. All members are homotetrameric.\ \ asparaginase activity ; GO:0004067 \N asparagine metabolism ; GO:0006528 23043 IPR004551 Diphthine synthase (EC: 2.1.1.98), also known as diphthamide biosynthesis S-adenosylmethionine-dependent methyltransferase, participates in the modification of a specific His of elongation factor 2 of eukarotes and archaea to diphthamide. It is required for the methylation step in dipthamide biosynthesis. The protein was characterized in Saccharomyces cerevisiae and designated DPH5.\ diphthine synthase activity ; GO:0004164 \N peptidyl-diphthamide biosynthesis from peptidyl-histidine ; GO:0017183 23044 IPR004552 This domain describes the core homologous region of a collection of related proteins, several of which are known to act as 1-acyl-sn-glycerol-3-phosphate acyltransferases (EC: 2.3.1.51). Proteins scoring above the trusted cutoff are likely to have the same general activity, which is to convert acyl-CoA and 1-acyl-SN-glycerol 3-phosphate to CoA and 1,2-diacyl-SN-glycerol 3-phosphate. However, there is variation among characterized members as to whether the acyl group can be donated by acyl carrier protein or coenzyme A, and in the length and saturation of the donated acyl group. 1-acyl-sn-glycerol-3-phosphate acyltransferase is also called 1-AGP acyltransferase,\ lysophosphatidic acid acyltransferase, and LPA acyltransferase.\ \ \ 1-acylglycerol-3-phosphate O-acyltransferase activity ; GO:0003841\ \N membrane ; GO:0016020 phospholipid biosynthesis ; GO:0008654 23045 IPR004553 Most known examples of hydroxymethylglutaryl-CoA reductase are NADP-dependent (EC: 1.1.1.34) from eukaryotes and archaea, involved in the biosynthesis of mevalonate from 3-hydroxy-3-methylglutaryl-CoA. This family, in contrast, is built from the two examples in completed genomes of sequences closely related to the degradative, NAD-dependent hydroxymethylglutaryl-CoA reductase of Pseudomonas mevalonii, a bacterium that can use mevalonate as its sole carbon source.\ hydroxymethylglutaryl-CoA reductase activity ; GO:0042282 \N lipid metabolism ; GO:0006629 23046 IPR004554 This model represents archaeal examples of the enzyme hydroxymethylglutaryl-CoAreductase (NADP) (EC: 1.1.1.34) and the catalytic domain of eukaryotic examples, which also contain a hydrophobic N-terminal domain. This enzyme synthesizes mevalonate, a precursor of isopentenyl pyrophosphate (IPP), a building block for the synthesis of cholesterol, isoprenoids, and other molecules. A related hydroxymethylglutaryl-CoA reductase, typified by an example from Pseudomonas mevalonii, is NAD-dependent and catabolic.\ \ hydroxymethylglutaryl-CoA reductase (NADPH) activity ; GO:0004420 integral to membrane ; GO:0016021 lipid metabolism ; GO:0006629 23041 IPR004549 This family represents the biotin carboxylase subunit found usually as a component of acetyl-CoA carboxylase. Acetyl-CoA carboxylase (EC: 6.4.1.2) is a heterohexamer of biotin carboxyl carrier protein, biotin carboxylase (EC: 6.3.4.14), and two subunits of carboxyl transferase in a 2:2 complex. In the first step of long-chain fatty acid synthesis, biotin carboxylase catalyses the carboxylation of the carrier protein and then the transcarboxylase transfers the carboxyl group to form malonyl-coA. Homologous domains are found in eukaryotic forms of acetyl-CoA carboxylase and in a number of other carboxylases (e.g. pyruvate carboxylase). In some systems, the biotin carboxyl carrier protein and this protein (biotin carboxylase) may be shared by different carboxyltransferases. However, this model is not intended to identify the biotin carboxylase domain of propionyl-coA carboxylase. The model should hit the full length of proteins, except for chloroplast transit peptides in plants. If it hits a domain only of a longer protein, there may be a problem with the identification.\ ligase activity ; GO:0016874 \N \N 23036 IPR004544 Initiation factor 2 (IF-2) is one of the three factors required for the initiation of protein biosynthesis in bacteria. IF-2 promotes the GTP-dependent binding of the initiator tRNA to the small subunit of the ribosome. IF-2 is a protein of about 70 to 95 Kd which contains a central GTP-binding domain flanked by a highly variable N-terminal domain and a more conserved C-terminal domain. Some members of this family undergo protein self splicing that involves a post-translational excision of the intein followed by peptide ligation.\ GTP binding activity ; GO:0005525 \N translational initiation ; GO:0006413 23037 IPR004545 Proteins of this family have been identified in a number of species as a nuclear(but not nucleolar) protein with a cell cycle dependence. Various names given to members of this family have included cell cycle protein p38-2G4, DNA-binding protein GBP16, and proliferation-associated protein 1. This protein is closely related to methionine aminopeptidase, a cobolt-binding protein.\ \ \N \N \N 23038 IPR004546 This family is the M subunit of the type I restriction-modification system, whose role is in methylation of specific adenine residues, which is required for both restriction and modification activities. Restriction-modification enzymes in general are responsible for the methylation of specific DNA sequences in order to prevent the host from digesting its own genome via its restriction enzymes. These methylases have the same sequence specificity as their corresponding restriction enzymes. The type I restriction and modification system is composed of three polypeptides R,M and S. The M and S subunits together form a methyltransferase that methylates two adenine residues in complementary strands of a bipartite DNA recognition sequence. In the presence of the R subunit, the complex can also act as an endonuclease, binding to the same target sequence but cutting the DNA some distance from this site.Whether the DNA is cut or modified depends on the methylation state of the target sequence. When the target site is unmodified, the DNA is cut. When the target site is hemimethylated, the complex acts as a maintenance methyltransferase, modifying the DNA so that both strands become methylated.\ The ECOR124/3 I enzyme recognizes 5'GAA(N7)RTCG in the DNA sequence.\ \ site-specific DNA-methyltransferase (adenine-specific) activity ; GO:0009007 \N DNA methylation ; GO:0006306 23039 IPR004547 Glucosamine-6-phosphate isomerase (EC: 3.5.99.6) catalyses the conversion of D-glucosamine 6-phosphate and water to D-fructose 6-phosphate in the N-acetylglucosamine utilization pathway. The enzyme was formerly classified as EC 5.3.1.10.\ This family also includes a closely related pair of proteins from Bacillus subtilis, one of which is uncharacterized but included as a member of the orthologous set.\ \ glucosamine-6-phosphate deaminase activity ; GO:0004342 \N N-acetylglucosamine metabolism ; GO:0006044 23040 IPR004548 Peptide chain release factor 3 increases the formation of ribosomal termination complexes and stimulates activity of RF-1 and RF-2. It binds to guanine nucleotides and has a strong preference for UGA stop codons. This translation releasing factor, RF-3 (prfC) was originally described as stopcodon-independent, in contrast to peptide chain release factor 1 (RF-1, prfA) and RF-2 (prfB). RF-1 and RF-2 are closely related to each other, while RF-3 is similar to elongation factors EF-Tu and EF-G; RF-1 is active at UAA and UAG and RF-2 is active at UAA and UGA. All bacteria and organelles have RF-1. The Mycoplasmas and organelles, which translate UGA as Trp rather than as a stop codon, lack RF-2. RF-3, in contrast, seems to be rare among bacteria and is found so far only in Escherichia coli and some other gamma subdivision Proteobacteria, in Synechocystis PCC6803, and in Staphylococcus aureus.\ \ translation release factor activity, codon specific ; GO:0016149 cytoplasm ; GO:0005737 translational termination ; GO:0006415 23034 IPR004542 Eukaryotic elongation factor 1 (EF-1) is responsible for the GTP-dependent binding of aminoacyl-tRNAs to the ribosomes [MEDLINE:91118231]. \ EF-1 is composed of four subunits: the

chain which binds GTP and aminoacyl-tRNAs,\ the gamma chain that probably plays a role in anchoring the complex to other cellular\ components and the

and delta (or

') chains. The

and delta chains are highly \ similar proteins that both stimulate the exchange of GDP bound to the

chain for \ GTP [MEDLINE:91002651]. The

and \ delta chains are hydrophilic proteins. Their C-terminus seems to be \ important for the nucleotide exchange activity, while the N-terminus is probably involved \ in the interaction with the gamma chain. The archaebacterial translation elongation factor aEF-1 is related. This family describes the archaeal translation elongation factor aEF-1

. The member from Sulfolobus solfataricus was demonstrated experimentally. It is a dimer that catalyzes the exchange of GDP for GTP on aEF-1

.\ \ translation elongation factor activity ; GO:0003746 \N translational elongation ; GO:0006414 23035 IPR004543 This family represents archaeal elongation factor 2, a protein more similar to eukaryotic EF-2 than to bacterial EF-G, both in sequence similarity and in sharing with eukaryotes the property of having a diphthamide (modified His) residue at a conserved position. The diphthamide can be ADP-ribosylated by diphtheria toxin in the presence of NAD. Elongation factor 2 promotes the GTP-dependent translocation of the nascent protein chain from the A-site to the P-site of the ribosome.\ GTP binding activity ; GO:0005525 cytoplasm ; GO:0005737 translational elongation ; GO:0006414 23027 IPR004535 In prokaryotes, the incorporation of selenocysteine as the 21st amino acid, encoded by TGA, requires several elements: SelC is the tRNA itself, SelD acts as a donor of reduced selenium, SelA modifies a serine residue on SelC into selenocysteine, and SelB is a selenocysteine-specific translation elongation factor. 3' or 5' non-coding elements of mRNA have been found as probable structures for directing selenocysteine incorporation.

This family describes the elongation factor SelB, a close homolog rf EF-Tu. It may function by replacing EF-Tu. A C-terminal domain not found in EF-Tu is in all SelB sequences in the seed alignment except that from Methanococcus jannaschii. This family should not include an equivalent protein for eukaryotes.

\ \ translation elongation factor activity ; GO:0003746 cytoplasm ; GO:0005737 selenocysteine incorporation ; GO:0001514 23028 IPR004536 In prokaryotes, the incorporation of selenocysteine as the 21st amino acid, encoded by TGA, requires several elements: SelC is the tRNA itself, SelD acts as a donor of reduced selenium, SelA modifies a serine residue on SelC into selenocysteine, and SelB is a selenocysteine-specific translation elongation factor. 3' or 5' non-coding elements of mRNA have been found as probable structures for directing selenocysteine incorporation. This family describes SelD, known as selenophosphate synthetase, selenium donor protein, and selenide,water dikinase. SelD provides reduced selenium for the selenium transferase SelA. This protein itself contains selenocysteine in many species; any sequence scoring above the trusted cutoff but not aligning to the beginning of the HMM is likely have selenocysteine residue incorrectly interpreted as a stop codon upstream of the given sequence.\ ATP binding activity ; GO:0005524 \N \N 23029 IPR004537 Tellurite resistance protein TehB is part of a tellurite-reducing operon tehA and tehB. When present in high copy number, TehB is responsible for potassium tellurite resistance, probably by increasing the reduction rate of tellurite to metallic tellurium within the bacterium.\ \N \N \N 23030 IPR004538 Hemolysins are exotoxins that attack blood cell membranes and cause cell rupture. The mechanism of action is not well defined. Hemolysin A is induced by sodium ribonucleate, and is produced by pathogenic bacterial strains. Hemolysin A from Treponema hyodysenteriae causes swine dysentry.\ hemolysin activity ; GO:0015484 \N \N 23031 IPR004539 Eukaryotic elongation factor 1 (EF-1) is responsible for the GTP-dependent binding of aminoacyl-tRNAs to the ribosomes [MEDLINE:91118231]. \ EF-1 is composed of four subunits: the

chain which binds GTP and aminoacyl-tRNAs,\ the gamma chain that probably plays a role in anchoring the complex to other cellular\ components and the

and delta (or

') chains. This family is the

subunit, and represents the counterpart of bacterial EF-Tu for the archaea (aEF-1

) and eukaryotes (eEF-1

).\ \ GTP binding activity ; GO:0005525 cytoplasm ; GO:0005737 translational elongation ; GO:0006414 23032 IPR004540 After peptide bond formation, translation elongation factor G of bacteria and organelles catalyzes the translocation of the tRNA-mRNA complex, with its attached nascent polypeptide chain, from the A-site to the P-site of the ribosome. Every completed bacterial genome has at least one copy, but some species have additional EF-G-like proteins. The closest homolog to canonical (e.g. E. coli) EF-G in the spirochetes clusters as if it is derived frommitochondrial forms, while a more distant second copy is also present. Synechocystis PCC6803 has a few proteins more closely related to EF-G than to any other characterized protein. Two of these resemble E. coli EF-G more closely than does the best match from the spirochetes; it may be that both function as authentic EF-G.\ \ GTP binding activity ; GO:0005525 \N translational elongation ; GO:0006414 23033 IPR004541 This family includes orthologs of translation elongation factor EF-Tu in bacteria, mitochondria, and chloroplasts, one of several GTP-binding translation factors found in the larger family of GTP-binding elongation factors. The eukaryotic conterpart, eukaryotic translation elongation factor 1 (eEF-1

), is excluded from this family. EF-Tu is one of the most abundant proteins in bacteria, as well as one of the most highly conserved, and in a number of species the gene is duplicated with identical function. When bound to GTP, EF-Tu can form a complex with any (correctly) aminoacylated tRNA except those for initiation and for selenocysteine, in which case EF-Tu is replaced by other factors. Transfer RNA is carried to the ribosome in these complexes for protein translation.\ GTP binding activity ; GO:0005525 \N translational elongation ; GO:0006414 23025 IPR004533 This enzyme, CDP-diacylglycerol--serine O-phosphatidyltransferase, is involved in phospholipid biosynthesis catalyzing the reaction CDP-diacylglycerol + L-serine = CMP + L-1-phosphatidylserine. Members of this family do not bear any significant sequence similarity to the corresponding E.coli protein.\ CDP-diacylglycerol-serine O-phosphatidyltransferase activity ; GO:0003882 \N phosphatidylcholine biosynthesis ; GO:0006656 23026 IPR004534 In prokaryotes, the incorporation of selenocysteine as the 21st amino acid, encoded by TGA, requires several elements: SelC is the tRNA itself, SelD acts as a donor of reduced selenium, SelA modifies a serine residue on SelC into selenocysteine, and SelB is a selenocysteine-specific translation elongation factor. 3-prime or 5-prime non-coding elements of mRNA have been found as probable structures for directing selenocysteine incorporation.

This family describes SelA. A close homolog of SelA is found in Helicobacter pylori, but all other required elements are missing and the protein is shorter at the N-terminus than SelA from other species. The trusted cutoff is set above the score generated for H. pylori putative SelA.

\ \ cysteinyl-tRNA(Ser) selenium transferase activity ; GO:0004125 cytoplasm ; GO:0005737 selenocysteine incorporation ; GO:0001514 23024 IPR004532

\ \

Class-II tRNA synthetases do not share a high degree of similarity, however at least three conserved regions are present [MEDLINE:94099781], [MEDLINE:91272282], [MEDLINE:91305088].

\ \

Phenylalanyl-tRNA synthetase (EC: 6.1.1.20) is an alpha2/beta2 tetramer composed of 2 subunits that belongs to class IIc. In eubacteria, a small subunit (pheS gene) can be designated as (E. coli) or subunit (see IPR002319). Reciprocally the large subunit\ (pheT gene) can be designated as (E. coli) or . In all other kingdoms the two subunits have equivalent length in eucaryota, and can be identified by specific signatures. The enzyme from Thermus thermophilus has an 2 2 type quaternary structure and is one of the most complicated members of the synthetase family. Identification of phenylalanyl-tRNA synthetase as a member of class II aaRSs was based only on sequence alignment of the small -subunit with other synthetases [MEDLINE:94257735].

\ \

This family describes the subunit. The subunits break into two subfamilies that are considerably different in sequence, length, and pattern of gaps (see also IPR002319/>). \ This family represents the subfamily that includes the subunit from bacteria other than spirochetes, as well as a chloroplast-encoded form from Porphyra purpurea. The chloroplast-derived sequence is considerably shorter at the N-terminal.

\ \ ATP binding activity ; GO:0005524 cytoplasm ; GO:0005737 phenylalanyl-tRNA aminoacylation ; GO:0006432 23023 IPR004531

\ \

Class-II tRNA synthetases do not share a high degree of similarity, however at least three conserved regions are present [MEDLINE:94099781], [MEDLINE:91272282], [MEDLINE:91305088].

\ \

This family describes the subunit. The subunits break into two subfamilies that are considerably different in sequence, length, and pattern of gaps (see also IPR002319/>). This family represents the subfamily that includes the subunit from eukaryotic cytosol, the archaea, and spirochetes.

\ \ ATP binding activity ; GO:0005524 cytoplasm ; GO:0005737 phenylalanyl-tRNA aminoacylation ; GO:0006432 23022 IPR004530

\ \

Class-II tRNA synthetases do not share a high degree of similarity, however at least three conserved regions are present [MEDLINE:94099781], [MEDLINE:91272282], [MEDLINE:91305088].

\ \

This family describes the mitochondrial phenylalanyl-tRNA synthetases. Unlike all other known phenylalanyl-tRNA synthetases, the mitochondrial form demonstrated from yeast is monomeric. It is similar to but longer than the subunit (PheS) of the 2 2 form found in bacteria, Archaea, and eukaryotes, and shares the characteristic motifs of class II aminoacyl-tRNA ligases.

\ \ ATP binding activity ; GO:0005524 cytoplasm ; GO:0005737 phenylalanyl-tRNA aminoacylation ; GO:0006432 23020 IPR004528 3-Deoxy-D-manno-octulosonate cytidylyltransferase (EC: 2.7.7.38) activates KDO, a required 8-carbon sugar, for incorporation into bacterial lipopolysaccharide in Gram negative bacteria. It acts as a homodimer and catalyses the conversion of CTP and 3-deoxy-D-manno-octulosonate into CMP-3-deoxy-D-manno-octulosonate and pyrophosphate.\ \ 3-deoxy-manno-octulosonate cytidylyltransferase activity ; GO:0008690\ \N cytoplasm ; GO:0005737 lipopolysaccharide biosynthesis ; GO:0009103 23021 IPR004529

\ \

Class-II tRNA synthetases do not share a high degree of similarity, however at least three conserved regions are present [MEDLINE:94099781], [MEDLINE:91272282], [MEDLINE:91305088].

\ \

This family describes the subunit, which shows some similarity to class II aminoacyl-tRNA ligases. Mitochondrial phenylalanyl-tRNA synthetase is a single polypeptide chain, active as a monomer, and similar to this chain rather than to the chain, but excluded from this family.

\ \ ATP binding activity ; GO:0005524 cytoplasm ; GO:0005737 phenylalanyl-tRNA aminoacylation ; GO:0006432 23018 IPR004526

\ \

Glutamyl-tRNA synthetase (EC: 6.1.1.17) is a class Ic synthetase and shows several similarities with glutaminyl-tRNA synthetase concerning structure and catalytic properties. It is an alpha2 dimer. To date one crystal structure of a glutamyl-tRNA synthetase (Thermus thermophilus) has been solved. The molecule has the form of a bent cylinder and consists of four domains. The N-terminal half (domains 1 and 2) contains the 'Rossman fold' typical for class I synthetases and resembles the corresponding part of E. coli GlnRS, whereas the C-terminal half exhibits a GluRS-specific structure [MEDLINE:98086161].\

\ \ ATP binding activity ; GO:0005524 cytoplasm ; GO:0005737 glutamyl-tRNA aminoacylation ; GO:0006424 23019 IPR004527

\ \

\ \ ATP binding activity ; GO:0005524 cytoplasm ; GO:0005737 glutamyl-tRNA aminoacylation ; GO:0006424 23017 IPR004525 Escherichia coli, Haemophilus influenzae, and Aquifex aeolicus each have a protein closely homologous to the C-terminal region of lysyl-tRNA synthetase (LysS). Multiple sequence alignment of these proteins with the homologous regions of collected LysS proteins shows that these proteins form a distinct set rather than just similar truncations of LysS, so they appear to be orthologous. The protein is termed GenX after its designation in E. coli. Its function is unknown.\ ATP binding activity ; GO:0005524 \N lysyl-tRNA aminoacylation ; GO:0006430 23016 IPR004524

\ \

Class-II tRNA synthetases do not share a high degree of similarity, however at least three conserved regions are present [MEDLINE:94099781], [MEDLINE:91272282], [MEDLINE:91305088].

\ \

Aspartyl tRNA synthetase EC: 6.1.1.12 is an alpha2 dimer that belongs to class IIb. Structural analysis combined with mutagenesis and enzymology data on the yeast enzyme point to a tRNA binding process that starts by a recognition event between the tRNA anticodon loop and the synthetase anticodon binding module [MEDLINE:20334700].

\ \

\ This family represents aspartyl-tRNA synthetases from the bacteria and from mitochondria. In some species, this enzyme aminoacylates tRNA for both Asp and Asn; Asp-tRNA(asn) is subsequently transamidated to Asn-tRNA(asn).

\ \ ATP binding activity ; GO:0005524 cytoplasm ; GO:0005737 aspartyl-tRNA aminoacylation ; GO:0006422 23015 IPR004523

\ \

Class-II tRNA synthetases do not share a high degree of similarity, however at least three conserved regions are present [MEDLINE:94099781], [MEDLINE:91272282], [MEDLINE:91305088].

\ \

\ This family represents aspartyl-tRNA synthetases from the eukaryotic cytosol and from the archaea. In some species, this enzyme aminoacylates tRNA for \ both Asp and Asn; Asp-tRNA(asn) is subsequently transamidated to Asn-tRNA(asn).

\ \ ATP binding activity ; GO:0005524 cytoplasm ; GO:0005737 aspartyl-tRNA aminoacylation ; GO:0006422 23010 IPR004518 This family of prokaryotic proteins has no known function. It includes the uncharacterized protein MazG in E. coli.\ \N \N \N 23011 IPR004519 DNA-directed RNA polymerase (EC: 2.7.7.6) catalyzes DNA-template-directed extension of the 3'-end of an RNA strand by one nucleotide at a time. This family seems to be confined to the archea and eukaryotic taxa and are quite dissimilar to E.coli RpoE. DNA-directed RNA polymerase III in eukaryotes consists of up to 15 different subunits, while that of the archae consists of 13 subunits.\ DNA-directed RNA polymerase activity ; GO:0003899 nucleus ; GO:0005634 transcription ; GO:0006350 23012 IPR004520

The GTP-binding domain of all TrmE/ThdF orthologues is found in the C-terminal portion of the molecule. The N-terminal half can be removed without affecting the GTP-binding/hydrolysis function of the GTP-binding domain. The last four amino acids of all orthologues of ThdF/TrmE are highly conserved, being either CIGK or CLGK. This matches the Caax (where 'a' represents an aliphatic amino acid, and 'x' represents any amino acid) motif for isoprenylation that anchors small GTP-binding proteins to cell membranes in eukaryotic cells. However, protein isoprenylation has never been shown to occur in bacteria. Interestingly, biochemical experiments have shown that the Escherichia\ coli TrmE protein peripherally associates with the membrane fraction [MEDLINE:21382759].

\ \

Although the biochemical properties of TrmE have been investigated for the E. coli and Thermotoga maritima proteins, nothing is known about the\ relationship of this protein to tRNA modification. Orthologues of TrmE are present in eukaryotes and\ bacteria, but are not present in archaea. In Saccharomyces cerevisiae, Mss1p is a nuclear-encoded mitochondrial protein that is the yeast orthologue of TrmE. Mss1p interacts with the 15S rRNA of the yeast mitochondria, which is\ equivalent to the 16S rRNA of bacteria. Subsequent analysis of the S. cerevisiae MTO1 gene suggests\ that MSS1 and MTO1 act together in a pathway involved in optimizing mitochondrial protein synthesis.

TrmE may play a role\ in tRNA processing and may be directly or indirectly involved in regulating ribosome function.

\ \ GTPase activity ; GO:0003924 \N tRNA modification ; GO:0006400 23013 IPR004521 This uncharacterized domain is found a number of enzymes and uncharacterized proteins, often at the C-terminus. It is found in some but not all members of a family of related tRNA-guanine transglycosylases (tgt), which exchange a guanine base for some modified base without breaking the phosphodiester backbone of the tRNA. It is also found in rRNA pseudouridine synthase, another enzyme of RNA base modification not otherwise homologous to tgt. It is found, again at the C-terminus, in two putative glutamate 5-kinases. It is also found in a family of small, uncharacterized archaeal proteins consisting mostly of this domain.\ \N \N \N 23014 IPR004522

\ \

Class-II tRNA synthetases do not share a high degree of similarity, however at least three conserved regions are present [MEDLINE:94099781], [MEDLINE:91272282], [MEDLINE:91305088].

\ \

AsparaginyltRNA synthetase (EC: 6.1.1.22) is an alpha2 dimer that belongs to class IIb.\ There is a striking similarity between asparaginyl-tRNA synthetases and archaeal/eukaryotic type aspartyl-tRNA synthetases (IPR004523). This family, AsnS, represents asparaginyl-tRNA synthetases from the three domains of life. Some species lack this enzyme and charge tRNA(asn) by misacylation with Asp, followed by transamidation of Asp to Asn.

\ \ ATP binding activity ; GO:0005524 cytoplasm ; GO:0005737 asparaginyl-tRNA aminoacylation ; GO:0006421 23007 IPR004515 Phosphoheptose isomerase is involved in lipopolysaccharide biosynthesis, and more specifically in the synthesis of glyceromannoheptose 7-phosphate. It may also have a role in virulence in Haemophilus ducreyi.\ phosphoheptose isomerase activity ; GO:0008968 cytoplasm ; GO:0005737 lipopolysaccharide core region biosynthesis ; GO:0009244 23008 IPR004516

\ \

Class-II tRNA synthetases do not share a high degree of similarity, however at least three conserved regions are present [MEDLINE:94099781], [MEDLINE:91272282], [MEDLINE:91305088].

\ \

Histidyl-tRNA synthetase (EC: 6.1.1.21) is an alpha2 dimer that belongs to class IIa. Every completed genome includes a histidyl-tRNA synthetase. Apparent second copies from Bacillus subtilis, Synechocystis sp., and Aquifex aeolicus are slightly shorter, more closely related to each other than to other hisS proteins, and not demonstrated to act as histidyl-tRNA synthetases (see IPR004517). The\ regulatory protein kinase GCN2 of Saccharomyces cerevisiae (YDR283c), and related proteins from other species designated eIF-2 kinase, have a domain closely related to histidyl-tRNA synthetase that may serve to detect and respond to uncharged tRNA(his), an indicator of amino acid starvation, but these regulatory proteins are not orthologous.

\ \ ATP binding activity ; GO:0005524 cytoplasm ; GO:0005737 histidyl-tRNA aminoacylation ; GO:0006427 23009 IPR004517

\ \

Class-II tRNA synthetases do not share a high degree of similarity, however at least three conserved regions are present [MEDLINE:94099781], [MEDLINE:91272282], [MEDLINE:91305088].

\ \

Histidyl-tRNA synthetase (EC: 6.1.1.21) is an alpha2 dimer that belongs to class IIa (see IPR004516 are slightly shorter, more closely related to each other than to other hisS proteins, and not demonstrated to act as histidyl-tRNA synthetases. The\ regulatory protein kinase GCN2 of Saccharomyces cerevisiae (YDR283c), and related proteins from other species designated eIF-2 kinase, have a domain closely related to histidyl-tRNA synthetase that may serve to detect and respond to uncharged tRNA(his), an indicator of amino acid starvation, but these regulatory proteins are not orthologous.

\ An unusual feature is that this putative second HisS is shorter at the C-terminus. It shows greater similarity to archaeal HisS than to other bacterial HisS. There is reason by analogy to suspect this second HisS may have a function other than (or in addition to) ligating His to its tRNA: the protein kinase DGCN2 of Drosophila has a C-terminal domain related to HisS that appears to detect uncharged tRNA(his), an indicator of amino acid starvation, and respond by phosphorylating eIF-2alpha.

\ \ \N cytoplasm ; GO:0005737 histidine biosynthesis ; GO:0000105 23002 IPR004510 TruB, the tRNA pseudouridine 55 synthase, converts uracil to pseudouridine in the T loop of most tRNAs of all three domains of life. This model is built on a seed alignment of bacterial proteins only. Saccharomyces cerevisiae protein YNL292w (Pus4) has been shown to be the pseudouridine 55 synthase of both cytosolic and mitochondrial compartments, active at no other position on tRNA and the only enzyme active at that position in the species. A distinct yeast protein YLR175w, (centromere/microtubule-binding protein CBF5) is an rRNApseudouridine synthase, and the archaeal set is much more similar to CBF5 than to Pus4. It is unclear whether the archaeal proteins found by this model are tRNA pseudouridine 55 synthases like TruB, rRNA pseudouridine synthases like CBF5, or (as suggested by the absence of paralogs in the Archaea) both. CBF5 likely has additional, eukaryotic-specific functions.\ \ pseudouridylate synthase activity ; GO:0004730 \N tRNA processing ; GO:0008033 23003 IPR004511 Phosphoadenosine phosphosulfate reductase (EC: 1.8.4.8), involved in the assimilation of inorganic sulfate, is designated cysH in bacteria and MET16 in Saccharomyces cerevisiae. Synonyms include phosphoadenosine phosphosulfate reductase and PAPS reductase. In a reaction requiring reduced thioredoxin and NADPH, it converts 3'-phosphoadenylylsulfate (PAPS) to sulfite and adenosine 3',5' diphosphate (PAP). A related family of plant enzymes, scoring below the trusted cutoff, differs in having a thioredoxin-like C-terminal domain, not requiring thioredoxin, and in having a preference for 5'-adenylylsulfate (APS) over PAPS.\ phosphoadenylyl-sulfate reductase (thioredoxin) activity ; GO:0004604 \N sulfate assimilation, phosphoadenylyl sulfate reduction by a phosphoadenylyl-sulfate reductase (thioredoxin) ; GO:0019379 23004 IPR004512 The ribosomal RNA large subunit methyltransferase J (EC 2.1.1.-) methylates the 23S rRNA. It specifically methylates the uridine in position 2552 of 23s rRNA in the 50S particle using S-adenosyl-L-methionine as a substrate. It was previously known as cell division protein ftsJ.\ rRNA (uridine) methyltransferase activity ; GO:0016436 \N rRNA processing ; GO:0006364 23005 IPR004513 FtsX is an integral membrane protein encoded in the same operon as signal recognition particle docking protein FtsY and FtsE. FtsE is a hydrophilic nucleotide-binding protein that associates with the inner membrane by means of association with FtsX; FtsE mutants are viable only in high salt, supporting possible roles in cell division, as previously indicated, or in transport.\ \N integral to membrane ; GO:0016021 cell cycle ; GO:0007049 23006 IPR004514

\ \

Glutaminyl-tRNA synthetase (EC: 6.1.1.18) is a class Ic synthetase and shows several similarities with glutamyl-tRNA synthetase concerning structure and catalytic properties. It is an alpha2 dimer.\ Glutaminyl-tRNA synthetase is a relatively rare synthetase, found in the cytosolic compartment of eukaryotes, in E. coli and a number of other Gram-negative bacteria, and in Deinococcus radiodurans. In contrast, the pathway to Gln-tRNA in mitochondria, Archaea, Gram-positive bacteria, and a number of other lineages is by misacylation with Glu followed by transamidation to correct the aminoacylation to Gln.

\ \ ATP binding activity ; GO:0005524 \N glutamyl-tRNA aminoacylation ; GO:0006424 22997 IPR004504 This group includes ATP-dependent proteases involved in both DNA repair and degradation of proteins, peptides, glycopeptides.\ ATP binding activity ; GO:0005524 \N DNA repair ; GO:0006281 22998 IPR004506 tRNA (5-methylaminomethyl-2-thiouridylate)-methyltransferase (EC: 2.1.1.61) catalyses the addition of 5-methylaminomethyl-2-thiouridylate to tRNAs using S-adenosyl-L-methionine as a substrate and releasing S-adenosyl-L-homocysteine. The enzyme is cytoplasmic and is involved in tRNA processing.\ tRNA (5-methylaminomethyl-2-thiouridylate) methyltransferase activity ; GO:0004808 cytoplasm ; GO:0005737 tRNA processing ; GO:0008033 22999 IPR004507 In E.coli the protein has been shown to be involved in the third step of ubiquinone biosynthesis catalyzing the reaction:

3-octaprenyl-4-hydroxybenzoate = 2-octaprenylphenol + CO2

The knockout of this gene has confers sensitivity to phenylacrylic acids in yeast.\ \ carboxy-lyase activity ; GO:0016831 \N \N 23000 IPR004508 This enzyme, involved in the assimilation of inorganic sulfate, is closely related to the thioredoxin-dependent PAPS reductase of Bacteria (CysH) and Saccharomyces cerevisiae. However, it has its own C-terminal thioredoxin-like domain and is not thioredoxin-dependent. Also, it has a substrate preference for 5'-adenylylsulfate (APS) over 3'-phosphoadenylylsulfate (PAPS) so the pathway does not require an APS kinase (CysC) to convert APS to PAPS. Arabidopsis thaliana appears to have three isozymes, all able to complement Escherichia coli CysH mutants (even in backgrounds lacking thioredoxin or APS kinase) but likely localized to different compartments in Arabidopsis.\ oxidoreductase activity, acting on sulfur group of donors, disulfide as acceptor ; GO:0016671 \N sulfate reduction, APS pathway ; GO:0019421 23001 IPR004509 This domain is found in competence protein ComEA and closely related proteins from a number of species that exhibit competence for transformation by exongenous DNA, including Streptococcus pneumoniae, Bacillus subtilis, Neisseria meningitidis, and Haemophilus influenzae. This domain represents a region of two tandem copies of a helix-hairpin-helix domain, each about 30 residues in length. Limited sequence similarity can be found among some members of this family N-terminal to this domain.\ \N \N \N 22993 IPR004500

\ \

Class-II tRNA synthetases do not share a high degree of similarity, however at least three conserved regions are present [MEDLINE:94099781], [MEDLINE:91272282], [MEDLINE:91305088].

\ \

This family includes the enzyme from Escherichia coli that contains all three of the conserved consensus motifs characteristic of class II aminoacyl-tRNA synthetases [MEDLINE:97215833] and the enzyme from the spirochete Borrelia burgdorferi.

\ \ ATP binding activity ; GO:0005524 cytoplasm ; GO:0005737 protein biosynthesis ; GO:0006412 22994 IPR004501 This family of proteins consists of both the cellobiose specific and the lactose specific forms of the phosphotransferase system (PTS) IIC component. The IIC domain catalyzes the transfer of a phosphoryl group from the IIB domain to the substrate. When the IIC component and IIB components are in the same polypeptide chain they are designated IIBC.\ \N integral to membrane ; GO:0016021 phosphoenolpyruvate-dependent sugar phosphotransferase system ; GO:0009401 22995 IPR004502 This family of proteins includes thioredoxins, glutaredoxins, protein-disulfide isomerases, and others, some of which have several such domains. The sequence of proteins in this group at the redox-active disufide site, CPYC, matches glutaredoxins rather than thioredoxins, although overall the sequence seems closer to thioredoxins. Proteins may be involved in a ribonucleotide-reducing system component distinct from thioredoxin or glutaredoxin.\ electron transporter activity ; GO:0005489 \N electron transport ; GO:0006118 22996 IPR004503

\ \

Class-II tRNA synthetases do not share a high degree of similarity, however at least three conserved regions are present [MEDLINE:94099781], [MEDLINE:91272282], [MEDLINE:91305088].

\ \

Seryl-tRNA synthetase (EC: 6.1.1.11) exists as monomer and belongs to class IIa [MEDLINE:95302522].\ The seryl-tRNA synthetases from a few of the archaea that belong to this group are different from the set of mutually more closely related seryl-tRNA synthetases from eubacteria, eukaryotes, and other archaea (IPR002317).

\ \ ATP binding activity ; GO:0005524 \N seryl-tRNA aminoacylation ; GO:0006434 22987 IPR004494 MauM ferredoxin-type protein is involved in methylamine utilization. NapG ferredoxin-type protein is associated with nitrate reductase activity.\ \N \N electron transport ; GO:0006118 22988 IPR004495 The methionyl-tRNA synthetase (metG) (EC: 6.1.1.10) is a class I amino acyl-tRNA ligase. This family describes a region of the methionyl-tRNA synthetase that is present at the C-terminus of MetG in some species (Escherichia coli, Bacillus subtilis, Thermotoga maritima, Methanobacterium thermoautotrophicum), and as a separate

chain in Aquifex aeolicus. It is absent in a number of other species (e.g. Mycoplasma genitalium, Mycobacterium tuberculosis), while Pyrococcus horikoshii has both a full length MetG and a second protein homologous to the

chain only.\ ATP binding activity ; GO:0005524 cytoplasm ; GO:0005737 protein biosynthesis ; GO:0006412 22989 IPR004496

Members of this family are the ferredoxin-type protein subunits of nitrate reductase. These NapF proteins are involved in electron transfer, and contain iron-sulphur centres similar to\ those of bacterial-type 4FE-4S ferredoxins.

\ \ electron transporter activity ; GO:0005489 \N electron transport ; GO:0006118 22990 IPR004497 NADH-plastoquinone oxidoreductase subunit I (EC: 1.6.5.3) catalyses the conversion of plastoquinone and NADH to plastoquinol and NAD(+). The enzyme binds two 4FE-4S clusters at iron-sulphur centres which are similar to those of the bacterial-type 4FE-4S ferredoxins.\ NADH dehydrogenase (ubiquinone) activity ; GO:0008137 \N electron transport ; GO:0006118 22991 IPR004498 Ribosomal protein L11 methyltransferase (EC: 2.1.1.-) is required for the methylation of ribosomal protein L11. It forms a bifunctional operon in Escherichia coli with panF (pantothenate transport).\ protein methyltransferase activity ; GO:0008276 \N protein amino acid methylation ; GO:0006479 22992 IPR004499

\ \

Class-II tRNA synthetases do not share a high degree of similarity, however at least three conserved regions are present [MEDLINE:94099781], [MEDLINE:91272282], [MEDLINE:91305088].

\ \

Prolyl tRNA synthetase (EC: 6.1.1.15) exists in two forms, which are loosely related. The first form, is present in the majority of eubacteria species. The second one, present in some eubacteria, is essentially present in archaea and eukaryota. \ Prolyl-tRNA synthetase belongs to class IIa.

\ \

This family includes the archaeal enzymes and the prolyl-specific domain of a human multifunctional tRNA ligase.

\ \ ATP binding activity ; GO:0005524 cytoplasm ; GO:0005737 protein biosynthesis ; GO:0006412 22979 IPR004485 This protein is involved in cobalamin (vitamin B12) biosynthesis and porphyrin biosynthesis. It converts cobyric acid to cobinamide by the addition of aminopropanol on the F carboxylic group. It is part of the cob operon.\ \N integral to membrane ; GO:0016021 vitamin B12 biosynthesis ; GO:0009236 22980 IPR004486 This is the small subunit of a heterodimer which catalyzes the reaction CO + H2O + Acceptor = CO2 + Reduced acceptor and is involved in the synthesis of acetyl-CoA from CO2 and H2.\ \N \N one-carbon compound metabolism ; GO:0006730 22981 IPR004487 A member of the ATP-dependent proteases clpX has ATP-dependent chaperone activity and is required for specific ATP-dependent proteolytic activities expressed by ClpPX. The protease is also found to be involved in stress tolerance in Bacillus subtilis and is essential for the efficient acquisition of genes specifying type IA and IB restriction.\ ATP binding activity ; GO:0005524 \N \N 22982 IPR004488 The CorA transport system is the primary Mg2+ influx system of Salmonella typhimurium and Escherichia coli. It has an unusual membrane topology, with a large, soluble, highly charged periplasmic N-terminal domain with three transmembrane segments in a shorter, hydrophobic C-terminal domain. It has been suggested that the CorA Mg2+ transport system forms the major Mg2+ uptake system in the bacteria and archaea but that some family members may have a function other than Mg2+ transport [MEDLINE:98448512].\ magnesium ion transporter activity ; GO:0015095 membrane ; GO:0016020 magnesium ion transport ; GO:0015693 22983 IPR004489 Succinate dehydrogenase and fumarate reductase are reverse directions of the same enzymatic interconversion, succinate + FAD+ = fumarate + FADH2 (EC: 1.3.99.1). In Escherichia coli, the forward and reverse reactions are catalyzed by distinct complexes: fumarate reductase operates under anaerobic conditions and succinate dehydrogenase operates under aerobic conditions. This group also includes a region of the B subunit of a cytosolic archaeal fumarate reductase.\ oxidoreductase activity ; GO:0016491 \N electron transport ; GO:0006118 22984 IPR004490 The glc locus of Escherichia coli encodes the subunits of glycolate oxidase and the glc regulator protein. The subunit GlcD is similar to that of several D-lactate dehydrogenases, including that of E. coli. Glycolate oxidase has been found to have some D-lactate dehydrogenase activity.\ glycolate oxidase activity ; GO:0008891 glycolate oxidase complex ; GO:0009339 \N 22985 IPR004491 The heat-shock protein HslVU from Escherichia coli is a protein-activated ATPase as well as an ATP-dependent proteinase [MEDLINE:98389714]. The proteasome-related peptidase subunit is HslU.\ HslUV protease activity ; GO:0009377 HslUV protease complex ; GO:0009376 \N 22986 IPR004493

\ \

Leucyl tRNA synthetase (EC: 6.1.1.4) is an monomer that belongs to class Ia. There are two different families of leucyl-tRNA synthetases. This family includes both archaeal and cytosolic eukaryotic leucyl-tRNA synthetases.

\ \ ATP binding activity ; GO:0005524 cytoplasm ; GO:0005737 protein biosynthesis ; GO:0006412 22965 IPR004471 This gene is part of the azl operon which is involved in branched-chain amino acid transport. Overexpression of this gene results in resistance to a leucine analog, 4-azaleucine. The protein has 5 potential transmembrane motifs.\ \N integral to membrane ; GO:0016021 transport ; GO:0006810 22966 IPR004472 The enzyme is involved in biotin biosynthesis and catalyses the reaction (CO2 + 7,8-diaminononanoate + ATP = dethiobiotin + phosphate + ADP). The enzyme binds ATP and requires magnesium as a co-factor. The Thr residue at position seven of the seed alignment is necessary for the binding of ATP.\ ATP binding activity ; GO:0005524 \N biotin biosynthesis ; GO:0009102 22967 IPR004473

This gene is part of the type I restriction and modification system which is composed of three polypeptides R (restriction endonuclease), M (modification) and S (specificity). This group of enzymes recognize specific short DNA sequences and have an absolute requirement for ATP (or dATP) and S-adenosyl-L-methionine. They also catalyse the reactions of EC: 2.1.1.72 and EC: 2.1.1.73, with similar site specificity [J. Mol. Biol. 271 (3), 342-348 (1997)]. Members of this family are assumed to differ from each other in DNA site specificity.

\ type I site-specific deoxyribonuclease activity ; GO:0009035 \N DNA restriction ; GO:0009307 22968 IPR004474 This entry describes a domain of unknown function that is found in the predicted extracellular domain of a number of putative membrane-bound proteins. One of these is protein psr, described as a penicillin binding protein 5 (PDP-5) synthesis repressor. Another is Bacillus subtilis LytR, described as a transcriptional attenuator of itself and the LytABC operon, where LytC is N-acetylmuramoyl-L-alanine amidase. A third is CpsA, a putative regulatory protein involved in exocellular polysaccharide biosynthesis. These proteins share the property of having a short putative N-terminal cytoplasmic domain and transmembrane domain forming a signal-anchor.\ \N \N \N 22969 IPR004475 This family represents the large subunit, DP2, of a two subunit novel archaebacterial replicative DNA polymerase first characterized for Pyrococcus furiosus. The structure of DP2 appears to be organized as a ~950 residue component separated from a ~300 residue component by a ~150 residue intein. The other subunit, DP1, has sequence similarity to the eukaryotic DNA polymerase delta small subunit.\ DNA-directed DNA polymerase activity ; GO:0003887 \N DNA catabolism ; GO:0006308 22970 IPR004476

This family is defined to identify a pair of paralogous 3' exoribonucleases in Escherichia coli, plus the set of proteins apparently orthologous to one or the other in other eubacteria. VacB was characterized originally as required for the expression of virulence genes, but is now recognized as the exoribonuclease RNase R (Rnr). Its paralog in Escherichia coli and Haemophilus influenzae is designated exoribonuclease II (Rnb). Both are involved in the degradation of mRNA, and consequently have strong pleiotropic effects that may be difficult to disentangle. Both these proteins share domain-level similarity (RNB, S1) with a considerable number of other proteins, and full-length similarity scoring below the trusted cutoff to proteins associated with various phenotypes but uncertain biochemistry; it may be that these latter proteins are also 3' exoribonucleases.

\ ribonuclease activity ; GO:0004540 \N RNA metabolism ; GO:0016070 22971 IPR004477

\ \N \N \N 22972 IPR004478 This family of putative lipoproteins contains a consensus site for lipoprotein signal sequence cleavage. Escherichia coli contains several lipoproteins in addition to the major outer membrane lipoprotein. Members of this family are often localized in the cytoplasmic membrane and are attached to it by a lipid anchor.\ \N \N \N 22973 IPR004479 This protein family is represented by a single member in nearly every completed large (> 1000 genes) prokaryotic genome. In Rhizobium meliloti, a species in which the exo genes make succinoglycan, a symbiotically important exopolysaccharide, exsB is located nearby and affects succinoglycan levels, probably through polar effects on exsA expression or the same polycistronic mRNA. In Arthrobacter viscosus, the homologous gene is designated ALU1 and is associated with an aluminum tolerance phenotype. The function is unknown.\ molecular_function unknown ; GO:0005554 \N \N 22974 IPR004480 This family groups a number of hypothetical proteins from different organisms which are related to glutaredoxin proteins.\ \N \N \N 22975 IPR004481 This is a family of bacterial and archaeal proteins that is homologous, except for lacking a central region of ~ 250 amino acids and an N-terminal region of > 100 residues, to a functionally proven potassium-dependent sodium-calcium exchanger of the rat.\ \N \N \N 22976 IPR004482

This family includes several bacterial hypothetical proteins. These proteins are a subset of the magnesium chelatase, ChlI subunit family.

\ \N \N \N 22977 IPR004483 Eukaryotic members of this family have been characterized as binding certain single-stranded G-rich DNA sequences (GGGGT and GGGCT). A number of related proteins are characterised as helicases.\ ATP binding activity ; GO:0005524 \N \N 22978 IPR004484 This family describes cobyrinic acid a,c-diamide synthase, the cobB (cbiA in Salmonella) protein of cobalamin biosynthesis. It is responsible for the amidation of carboxylic groups at positions A and C of either cobyrinic acid or hydrogenobrynic acid. NH(2) groups are provided by glutamine and one molecule of ATP hydrogenolyzed for each amidation.\ cobyrinic acid a,c-diamide synthase activity ; GO:0042242 \N vitamin B12 biosynthesis ; GO:0009236 22956 IPR004462 This domain is found as essentially the full length of desulforedoxin, a 37-residue homodimeric non-heme iron protein. It is also found as the N-terminal domain of desulfoferrodoxin (rbo), a homodimeric non-heme iron protein with 2 Fe atoms per monomer in different oxidation states. This domain binds the ferric rather than the ferrous Fe of desulfoferrodoxin. Neelaredoxin, a monomeric blue non-heme iron protein, lacks this domain.\ iron ion binding activity ; GO:0005506 \N electron transport ; GO:0006118 22957 IPR004463 UDP-3-O-(R-3-hydroxymyristoyl)-GlcNAc deacetylase from Escherichia coli , LpxC, was previously designated EnvA. This enzyme is involved in lipid-A precursor biosynthesis. It is essential for cell viability.\ \ UDP-3-O-[3-hydroxymyristoyl] N-acetylglucosamine deacetylase activity ; GO:0008759 \N lipid A biosynthesis ; GO:0009245 22958 IPR004464 The GlpX protein is involved in glycerol metabolism but its exact function is unknown. It is induced by but not required for growth in glycerol.\ \N \N glycerol metabolism ; GO:0006071 22959 IPR004465 Ribonucleotide reductases (RNRs) are enzymes that provide the precursors of DNA synthesis. The three characterized classes of RNRs differ by their metal cofactor and their stable organic radical. The exact function of nrdI within the ribonucleotide reductases has not yet been fully characterised.\ \N \N \N 22960 IPR004466 This family of orthologous proteins shows a weak but significant similarity to the central region of the DnaG-type DNA primase. The region of similarity is termed the Toprim (topoisomerase-primase) domain and is also shared by RecR, OLD family nucleases, and type IA and II topoisomerases.\ \N \N \N 22961 IPR004467 Orotate phosphoribosyl transferase (OPRTase) is involved in the biosynthesis of pyrimidine nucleotides. Alpha-D-ribosyldiphosphate 5-phosphate (PRPP) and orotate are utilized to form pyrophosphate and orotidine 5 -monophosphate (OMP) in the presence of divalent cations, preferably Mg2+. In a number of eukaryotes, this protein is fused to a domain that catalyses the reaction (EC: 4.1.1.23). The combined activity of EC: 2.4.2.10 and EC: 4.1.1.23 is termed uridine 5 -monophosphate synthase. The conserved Lys (K) residue at position 101 of the seed alignment has been proposed as the active site for the enzyme.\ orotate phosphoribosyltransferase activity ; GO:0004588 \N pyrimidine nucleotide biosynthesis ; GO:0006221 22962 IPR004468 CTP synthase is involved in pyrimidine ribonucleotide/ribonucleoside metabolism. The enzyme catalyzes the reaction L-glutamine + H2O + UTP + ATP = CTP + phosphate + ADP + L-glutamate. The enzyme exists as a dimer of identical chains that aggregates as a tetramer. This gene has been found circa 500 bp 5 upstream of enolase in both

(Nitrosomonas europaea) and gamma (Escherichia coli) subdivisions of proteobacterium\ \ \ [MEDLINE:98377731].\ \ CTP synthase activity ; GO:0003883 \N pyrimidine nucleotide biosynthesis ; GO:0006221 22963 IPR004469 Phosphoserine phosphatase (SerB), (EC: 3.1.3.3), also known as O-phosphoserine phosphohydrolase, is involved in both serine and glycine biosynthesis. It catalyzes the reaction 3-phospho-serine + H2O = L-serine + phosphate, which is the last step in the biosynthesis of serine from carbohydrates. The reaction proceeds via the formation of a phosphoryl-enzyme intermediate. It acts as a homodimer, and requires magnesium as a cofactor.\ phosphoserine phosphatase activity ; GO:0004647 \N serine biosynthesis ; GO:0006564 22964 IPR004470 ZPR1 was shown experimentally to bind approximately two moles of zinc, and has two copies of a domain homologous to this protein, each containing a putative zinc finger of the form CXXCX(25)CXXC. ZPR1 binds the tyrosine kinase domain of epidermal growth factor receptor but is displaced by receptor activation and autophosphorylation after which it redistributes in part to the nucleus. The proteins described by this family by analogy may be suggested to play a role in signal transduction (see also IPR004457).\ zinc ion binding activity ; GO:0008270 \N \N 22942 IPR004447 This is a family of C-terminal peptidases with different substrates in different species, including processing of D1 protein of the photosystem II reaction center in higher plants, and cleavage of a peptide of 11 residues from the precursor form of penicillin-binding protein in Escherichia coli.\ serine-type peptidase activity ; GO:0008236 \N proteolysis and peptidolysis ; GO:0006508 22943 IPR004449 Phosphohistidine phosphatase SixA (EC: 3.1.3.-) from Escherichia coli exhibits phosphatase activity towards the HPT domain of the ArcB sensor involved in the multistep his-asp phosphorelay.\ phosphohistidine phosphatase activity ; GO:0008969 \N \N 22944 IPR004450 Threonine synthase (EC: 4.2.3.1) is involved in threonine biosynthesis. It catalyses the conversion of O-phospho-L-homoserine and water into L-threonine and orthophosphate, using pyridoxal phosphate as a cofactor. The pyridoxal-phosphate binding site is a Lys (K) residue. The enzyme is distantly related to the serine/threonine dehydratases which are also pyridoxal-phosphate dependent enzymes.\ threonine synthase activity ; GO:0004795 \N threonine biosynthesis ; GO:0009088 22945 IPR004451 This family of conserved hypothetical proteins includes proteins of unknown function from archaebacteria.\ molecular_function unknown ; GO:0005554 \N \N 22946 IPR004452 Members of this family have a perfect 4Fe-4S binding motif C-x(2)-C-x(2)-C-x(3)-CP followed by either a perfect or imperfect (the first Cys replaced by Ser) second copy. Members probably bind two 4fe-4S iron-sulfur clusters.\ \N \N \N 22947 IPR004453 This is a family of putative iron-sulfur cluster binding proteins. These proteins contain the IPR001450 signature for 4Fe-4S ferredoxins iron-sulfur binding proteins.\ \N \N \N 22948 IPR004454 The archaeal proteins containing this domain are as yet uncharacterised and of unknown function.\ molecular_function unknown ; GO:0005554 \N \N 22949 IPR004455 The function of F420-dependent NADP reductase is the transfer of electrons from reduced coenzyme F420 into an electron transport chain. It catalyses the reduction of F420 with NADP(+) and the reduction of NADP(+) with F420H(2).\ \N \N electron transport ; GO:0006118 22950 IPR004456

Phosphonopyruvate decarboxylase is involved in the biosynthesis of bialaphos. The enzyme catalyzes the formation of phosphonoacetaldehyde from phosphonopyruvate. This enzyme requires thiamine diphosphate and Mg2+ as cofactors. This family describes a set of proteins in the archaebacteria (two each in Methanococcus jannaschii, Methanobacterium thermoformicicum, and Archaeoglobus fulgidus) and in Aquifex aeolicus (1 member) that is related to but unlikely to be authentic phosphonopyruvate decarboxylase.

\ heavy metal binding activity ; GO:0005505 \N \N 22951 IPR004457 An orthologous protein found once in each of the completed archaeal genomes corresponds to a zinc finger-containing domain repeated as the N-terminal and C-terminal halves of the mouse protein ZPR1. ZPR1 is an experimentally proven zinc-binding protein that binds the tyrosine kinase domain of the epidermal growth factor receptor (EGFR); binding is inhibited by EGF stimulation and tyrosine phosphorylation, and activation by EGF is followed by some redistribution of ZPR1 to the nucleus. By analogy, other proteins with the ZPR1 zinc finger domain may be regulatory proteins that sense protein phosphorylation state and/or participate in signal transduction (see also IPR004470).\ zinc ion binding activity ; GO:0008270 \N \N 22952 IPR004458 Translation initiation factor aIF-2 functions in the early stages of protein synthesis by forming a ternary complex with GTP and the initiator tRNA. The factor is a heterotrimer composed of an

and gamma chain. This is the

subunit.\ translation initiation factor activity ; GO:0003743 \N translational initiation ; GO:0006413 22953 IPR004459 Cobyric acid synthase (CobQ) catalyses amidations at positions B, D, E, and G on adenosylcobyrinic A,C-diamide in the biosynthesis of cobalamin. NH(2) groups are provided by glutamine, and one molecule of ATP is hydrogenolysed for each amidation.\ enzyme activity ; GO:0003824 \N vitamin B12 biosynthesis ; GO:0009236 22954 IPR004460 Acetyl-CoA decarbonylase/synthase (ACDS) is a multienzyme complex (carbon monoxide dehydrogenase is a synonym). The ACDS complex carries out an unusual reaction involving the reversible cleavage and synthesis of acetyl-CoA in methanogens. The family contains the IPR001450 signature for 4Fe-4S ferredoxins [C-x(2)-C-x(2)-C-x(3)-C-[PEG]] between residues 448-462 of the model.\ carbon monoxide dehydrogenase activity ; GO:0018492 \N acetyl-CoA metabolism ; GO:0006084 22955 IPR004461 The carbon monoxide dehydrogenase

subunit (EC: 1.2.99.2) catalyses the interconversion of CO and CO2 and the synthesis of acteyl-coA from the methylated corrinoid/iron sulphur protein, CO and CoA. Nomenclature follows the description for Methanosarcina thermophila. The complex is also found in Archaeoglobus fulgidus, not considered a methanogen, but is otherwise generally associated with methanogenesis.\ carbon monoxide dehydrogenase activity ; GO:0018492 \N acetyl-CoA metabolism ; GO:0006084 22935 IPR004438 Oligoendopeptidase F (PepF) from Lactococcus lactis hydrolyzes peptides of 7 and 17 amino acids with fairly broad specificity. Differences in substrate specificity should be expected in other species. The gene is duplicated in Lactococcus lactis on the plasmid that bears it. A shortened second copy is found in Bacillus subtilis.\ metalloendopeptidase activity ; GO:0004222 \N \N 22936 IPR004439 Several NAD- or NADP-dependent dehydrogenases, including 3-isopropylmalate dehydrogenase, tartrate dehydrogenase, and the multimeric forms of isocitrate dehydrogenase, share a nucleotide binding domain unrelated to that of lactate dehydrogenase and its homologs. These enzymes dehydrogenate their substates at a H-C-OH site adjacent to a H-C-COOH site; the latter carbon, now adjacent to a carbonyl group, readily decarboxylates.

Prokaryotic NADP-dependent isocitrate dehydrogenases (EC: 1.1.1.42) resemble their NAD-dependent counterparts and 3-isopropylmalate dehydrogenase (an NAD-dependent enzyme) more closely than they resemble eukaryotic NADP-dependent isocitrate dehydrogenases.

\ isocitrate dehydrogenase (NADP+) activity ; GO:0004450 \N tricarboxylic acid cycle ; GO:0006099 22937 IPR004440 The RNA methyltransferase, TrmH family, group 2 are part of the trmH (spoU) family of rRNA methylases that are involved in tRNA and rRNA base modification.\ RNA methyltransferase activity ; GO:0008173 \N RNA modification ; GO:0009451 22938 IPR004441 The RNA methyltransferase, TrmH family, group 3 are part of the trmH (spoU) family of rRNA methylases that are involved in tRNA and rRNA base modification.\ RNA methyltransferase activity ; GO:0008173 \N RNA modification ; GO:0009451 22939 IPR004443 The C-terminal region of yjeF from Escherichia coli shows similarity to hydroxyethylthiazole kinase (thiM) and other enzymes involved in thiamine biosynthesis. Saccharomyces cerevisiae YKL151C and Bacillus subtilis yxkO match the yjeF C-terminal domain but lack this region. The proteins in this group are of unknown function.\ molecular_function unknown ; GO:0005554 \N \N 22940 IPR004445 This is a family of sodium/glutamate symporters (glutamate permeases), which catalyse the sodium-dependent uptake of extracellular glutamate. The protein is located in the inner membrane.\ glutamate:sodium symporter activity ; GO:0015501 integral to membrane ; GO:0016021 glutamate transport ; GO:0015813 22941 IPR004446 In a number of species, including Escherichia coli, the histidine biosynthetic enzymes imidazole glycerol phosphate dehydratase and histidinol phosphatase are found together in the bifunctional protein HisB. This family represents a protein closely related to the histidinol phosphatase domain of HisB. The protein is found both in Helicobacter pylori, for which the histidine biosynthetic pathway appears to be absent, and in species that also have a bifunctional HisB protein.\ molecular_function unknown ; GO:0005554 \N \N 22928 IPR004430 Homoaconitase, aconitase, and 3-isopropylmalate dehydratase have similar overall structures. All are dehydratases (EC: 4.2.1.-) and bind a Fe-4S iron-sulfur cluster. 3-isopropylmalate dehydratase is split into large (leuC) and small (leuD) chains in eubacteria. Several pairs of archaeal proteins resemble the leuC and leuD pair in length and sequence but even more closely resemble the respective domains of homoaconitase, and their identity is uncertain. The archaeal leuC-like proteins are not included in group.\ \ 3-isopropylmalate dehydratase activity ; GO:0003861\ \ 3-isopropylmalate dehydratase complex ; GO:0009316\ \N \N leucine biosynthesis ; GO:0009098 22929 IPR004431 Homoaconitase, aconitase, and 3-isopropylmalate dehydratase have similar overall structures. All are dehydratases (EC: 4.2.1.-) and bind a Fe-4S iron-sulfur cluster. 3-isopropylmalate dehydratase is split into large (leuC) and small (leuD) chains in eubacteria. Several pairs of archaeal proteins resemble the leuC and leuD pair in length and sequence but even more closely resemble the respective domains of homoaconitase, and their identity is uncertain. The archaeal leuD-like proteins are not included in group.\ \ 3-isopropylmalate dehydratase activity ; GO:0003861\ \ 3-isopropylmalate dehydratase complex ; GO:0009316\ \N \N leucine biosynthesis ; GO:0009098 22930 IPR004433 2-oxoglutarate decarboxylase/SHCHC synthase (menD) is a thiamine pyrophosphate enzyme involved in menaquinone biosynthesis.\ \ 2-oxoglutarate decarboxylase activity ; GO:0008683\ \N \N vitamin K2 biosynthesis ; GO:0009234 22931 IPR004434 Several NAD- or NADP-dependent dehydrogenases, including 3-isopropylmalate dehydrogenase, tartrate dehydrogenase, and the multimeric forms of isocitrate dehydrogenase, share a nucleotide binding domain unrelated to that of lactate dehydrogenase and its homologs. These enzymes dehydrogenate their substates at a H-C-OH site adjacent to a H-C-COOH site; the latter carbon, now adjacent to a carbonyl group, readily decarboxylates.

Mitochondrial NAD-dependent isocitrate dehydrogenases (IDH) resemble prokaryotic NADP-dependent IDH and 3-isopropylmalate dehydrogenase (an NAD-dependent enzyme) more closely than they resemble eukaryotic NADP-dependent IDH. The mitochondrial NAD-dependent isocitrate dehydrogenase is believed to be an (2)--gamma heterotetramer. All subunits are homologous and belog to this group.

The NADP-dependent IDH of Thermus aquaticus thermophilus strain HB8 resembles these NAD-dependent IDH, except for the residues involved in cofactor specificity, much more closely than it resembles other prokaryotic NADP-dependent IDH, including that of Thermus aquaticus strain YT1.

\ isocitrate dehydrogenase (NAD+) activity ; GO:0004449 mitochondrion ; GO:0005739 tricarboxylic acid cycle ; GO:0006099 22932 IPR004435 This molybdenum cofactor biosynthesis enzyme is similar to the urease accessory protein UreG and to the hydrogenase accessory protein HypB, both GTP hydrolases involved in loading nickel into the metallocenters of their respective target enzymes. The apparent ortholog from Aquifex is truncated at the carboxyl end. The archaeal orthologs from Methanocaldococcus jannaschii and Methanothermobacter thermoautotrophicum have an extension of about 50 residues, while Archaeoglobus fulgidus has a separate ORF of 49 amino acids closely homologous to that C-terminal extension.\ GTP binding activity ; GO:0005525 \N Mo-molybdopterin cofactor biosynthesis ; GO:0006777 22933 IPR004436 The monomeric type of isocitrate dehydrogenase (EC: 1.1.1.42) has been found so far in a small number of species, including Azotobacter vinelandii, Corynebacterium glutamicum, Rhodomicrobium vannielii, and Neisseria meningitidis. It is NADP-specific.\ isocitrate dehydrogenase (NADP+) activity ; GO:0004450 \N tricarboxylic acid cycle ; GO:0006099 22934 IPR004437 This group of chromosomal and plasmid partition proteins are related to ParB, including Spo0J, RepB, and SopB. Spo0J has been shown to bind a specific DNA sequence that, when introduced into a plasmid, can serve as partition site. Study of RepB, which has nicking-closing activity, suggests that it forms a transient protein-DNA covalent intermediate during the strand transfer reaction.\ DNA binding activity ; GO:0003677 \N plasmid partitioning (sensu Bacteria) ; GO:0030542 22924 IPR004425 These proteins of unknown function are currently found only among the archaea.\ molecular_function unknown ; GO:0005554 \N \N 22925 IPR004426 These proteins of unknown function are currently found only among the archaea.\ molecular_function unknown ; GO:0005554 \N \N 22926 IPR004428

Phosphatidylserine decarboxylase is synthesized as a single chain precursor. Generation of the pyruvoyl active site from a Ser is coupled to cleavage of a Gly-Ser bond between the larger () and smaller ( chains). It is an integral membrane protein. Protein in this group have many regions of homology to known phosphatidylserine decarboxylases, including the Gly-Ser motif for chain cleavage and active site generation, but have a shorter amino end and a number of deletions along the length of the alignment to the phosphatidylserine decarboxylases. It is unclear whether these proteins are a form of phosphatidylserine decarboxylase or a related enzyme. They are found in Neisseria gonorrhoeae, Mycobacterium tuberculosis, and several archaeal species, all of which lack known phosphatidylserine decarboxylase.

\ molecular_function unknown ; GO:0005554 \N \N 22927 IPR004429 Several NAD- or NADP-dependent dehydrogenases, including 3-isopropylmalate dehydrogenase, tartrate dehydrogenase, and the dimeric forms of isocitrate dehydrogenase, share a nucleotide binding domain unrelated to that of lactate dehydrogenase and its homologs. These enzymes dehydrogenate their substates at a H-C-OH site adjacent to a H-C-COOH site; the latter carbon, now adjacent to a carbonyl group, readily decarboxylates. Among these decarboxylating dehydrogenases of hydroxyacids, overall sequence homology indicates evolutionary history rather than actual substrate or cofactor specifity, which may be toggled experimentally by replacement of just a few amino acids. 3-isopropylmalate dehydrogenase is an NAD-dependent enzyme and should have a sequence resembling HGSAPDI around residue 340. The subtrate binding loop should include a sequence resembling E[KQR]X(0,1)LLXXR around residue 115.\ \ 3-isopropylmalate dehydrogenase activity ; GO:0003862\ \N cytoplasm ; GO:0005737 leucine biosynthesis ; GO:0009098 22916 IPR004416 Glucose-inhibited division protein A, GidA appears to be present in all complete eubacterial genomes so far, as well as Saccharomyces cerevisiae. The function of these proteins is unknown.\ molecular_function unknown ; GO:0005554 \N \N 22917 IPR004417 The gid proteins are present in relatively few bacteria but very tightly conserved where they occur. The function of these proteins is unknown. They are closely related to gidA (glucose-inhibited division protein A), which appears to be present in all complete eubacterial genomes so far and in Saccharomyces cerevisiae.\ molecular_function unknown ; GO:0005554 \N \N 22918 IPR004418 Homoaconitase is known only as a fungal enzyme from two species, where it is part of an unusual lysine biosynthesis pathway.\ homoaconitate hydratase activity ; GO:0004409 \N lysine biosynthesis ; GO:0009085 22919 IPR004419 These hydrogenase expression/formation proteins (hupD, hynC, hoxM) are believed to be metal binding and may be involved in processing or hydrogenase. They may be peptidase/proteases.\ heavy metal binding activity ; GO:0005505 \N protein processing ; GO:0016485 22920 IPR004420 The hydrogenase maturation protease (hycI) are involved in protein modification and repair.\ metalloendopeptidase activity ; GO:0004222 \N protein modification ; GO:0006464 22921 IPR004421 The hydrogenase maturation protein (HypF)/transcriptional regulator (hupY) appears to have an acylphosphatase domain. These proteins may regulate the expression of hydrogenase genes.\ \N \N \N 22922 IPR004422 These kinases are of unknown specificity and belong to the GHMP family, group 1. They have an amino-terminal domain probably related to ATP binding and are found so far only in the archaea.\ \N \N \N 22923 IPR004424 4-diphosphocytidyl-2C-methyl-D-erythritol kinase is a member of the family of GHMP kinases that were previously designated as conserved hypothetical protein YchB or as isopentenyl monophosphate kinase. In Lycopersicon esculentum (tomato) and Escherichia coli the protein has been indentified as 4-diphosphocytidyl-2C-methyl-D-erythritol kinase, an enzyme of the deoxyxylulose phosphate pathway of terpenoid biosynthesis.\ \ 4-diphosphocytidyl-2C-methyl-D-erythritol kinase activity ; GO:0008698\ \N \N terpenoid biosynthesis ; GO:0016114 22913 IPR004413 In many species, Gln-tRNA ligase is missing. tRNA(Gln) is misacylated with Glu after which a heterotrimeric amidotransferase converts Glu to Gln. This group represents the chain of the heterotrimer, encoded by the gatB gene called glutamyl-tRNA(Gln) amidotransferase, B subunit EC: 6.3.5.-. This enzyme functions as an alternative to a direct Gln-tRNA synthetase (Gln-tRNA ligase) in mitochondria, chloroplasts, gram-positive bacteria, cyanobacteria, and the archaea.

The archaea have an Asp-tRNA(Asn) amidotransferase instead of an Asp-tRNA ligase. In the archaea a paralog of gatB is found, here designated gatB_rel, that is a candidate B subunit of the Asp-tRNA(Asn) amidotransferase. The gatA-encoded subunit may be shared by gatB and gatB_rel.

\ glutamyl-tRNA(Gln) amidotransferase activity ; GO:0017068 \N protein biosynthesis ; GO:0006412 22914 IPR004414 The aspartyl-tRNA(Asn) amidotransferase, B subunit or designated here gatB_rel, is found only in the archaea. It is paralogous to the gatB-encoded subunit of Glu-tRNA(Gln) amidotransferase. The archaea have an Asp-tRNA(Asn) amidotransferase instead of an Asp--tRNA ligase, but the genes have not been identified. It is likely that this protein replaces gatB in Asp-tRNA(Asn) amidotransferase but that both enzymes share gatA.\ molecular_function unknown ; GO:0005554 \N \N 22915 IPR004415 In many species, Gln-tRNA ligase is missing. tRNA(Gln) is misacylated with Glu after which a heterotrimeric amidotransferase converts Glu to Gln. The glutamyl-tRNA(Gln) amidotransferase, C subunit EC: 6.3.5.- represents a small protein of the heterotrimer that appears to be important to the stability of the amidase subunit encode by gatA. Its function may not be required in every organism that expresses gatA and gatB. This enzyme functions as an alternative to a direct Gln-tRNA synthetase (Gln-tRNA ligase) in mitochondria, chloroplasts, gram-positive bacteria, cyanobacteria, and the archaea.

The archaea have an Asp-tRNA(Asn) amidotransferase instead of an Asp-tRNA ligase. In the archaea, a paralog of gatB is found, here designated gatB_rel, that is a candidate B subunit of the Asp-tRNA(Asn) amidotransferase. The gatA-encoded subunit may be shared by gatB and gatB_rel.

\ glutamyl-tRNA(Gln) amidotransferase activity ; GO:0017068 \N protein biosynthesis ; GO:0006412 22909 IPR004409

The biotin operon of Escherichia coli contains 5 structural genes involved in the synthesis of biotin. Transcription of the operon is regulated via one of these proteins, BirA. BirA is an asymetric protein with 3 specific domains. The ligase reaction intermediate, biotinyl-5'-AMP, is the co-repressor that triggers DNA binding by BirA.The -helical N-terminal domain of the BirA protein has the helix-turn-helix structure of DNA-binding proteins with a central DNA recognition helix. BirA undergoes several conformational changes related to repressor function and the N-terminal DNA-binding function is connected to the rest of the molecule through a hinge which will allow relocation of the domains during the reaction [MEDLINE:99400973].

Two repressor molecules form the operator-repressor complex, with dimer formation occuring simultaneously with DNA binding. DNA-binding may cause a conformational change which allows this co-operative interaction. In the dimer structure, the -sheets in the central domain of each monomer are arranged side-by-side to form a single, seamless -sheet.

\ \ transcriptional repressor activity ; GO:0016564 \N regulation of transcription, DNA-dependent ; GO:0006355 22910 IPR004410 Malonyl CoA-acyl carrier protein transacylase EC: 2.3.1.39 is involved in fatty acid biosynthesis and transfers the malonyl moeity from coenzyme A to acyl-carrier protein.\ [acyl-carrier protein] S-malonyltransferase activity ; GO:0004314 \N fatty acid biosynthesis ; GO:0006633 22911 IPR004411 Coenzyme F420-reducing hydrogenase delta subunit (putative coenzyme F420 hydrogenase processing subunit), frhD, is not part of the active FRH heterotrimer, but is probably a protease required for maturation involved in protein modification and repair. Alternative name: 8-hydroxy-5-deazaflavin (F420) reducing hydrogenase (FRH) subunit delta.\ hydrogenase activity ; GO:0008901 \N \N 22912 IPR004412 In many species, Gln-tRNA ligase is missing. tRNA(Gln) is misacylated with Glu after which a heterotrimeric amidotransferase converts Glu to Gln. This group represents the amidase chain of the heterotrimer, encoded by the gatA gene called glutamyl-tRNA(Gln) amidotransferase, A subunit EC: 6.3.5.-. This enzyme functions as an alternative to a direct Gln-tRNA synthetase (Gln-tRNA ligase) in mitochondria, chloroplasts, gram-positive bacteria, cyanobacteria, and the Archaea.

\ glutamyl-tRNA(Gln) amidotransferase activity ; GO:0017068 \N protein biosynthesis ; GO:0006412 22905 IPR004405

The Drosophila melanogaster protein pelota is proposed to act in protein translation. It can replace the budding yeast protein DOM34, and is closely related to a set of archaeal proteins. This family contains a proposed RNA binding motif, and is homologous to a family of peptide chain release factors.In Drosophila melanogaster it is required prior to the first meiotic division for spindle formation and nuclear envelope breakdown during spermatogenesis. It is also required for normal eye patterning and for mitotic divisions in the ovary. The meiotic defect in pelota mutants may be a complex result of a protein translation defect, as suggested in yeast by ribosomal protein RPS30A being a multicopy suppressor, and by an altered polyribosome profile in DOM34 mutants rescued by RPS30A.

\ \ \N nucleus ; GO:0005634 protein biosynthesis ; GO:0006412 22906 IPR004406 Synonym(s): Citrate hydro-lyase, Aconitase

Aconitate hydratase 2 EC: 4.2.1.3 is involved in energy metabolism as part of the TCA cycle. It catalyses the formation of cis-aconitate from citrate. Aconitase has an active (4FE-4S) and an inactive (3FE-4S) form. The active (4FE-4S) cluster is part of the catalytic site that interconverts citrate, cis-aconitase and isocitrate.

\ \ aconitate hydratase activity ; GO:0003994 \N tricarboxylic acid cycle ; GO:0006099 22907 IPR004407 Two groups of proteins form acetolactate from two molecules of pyruvate. Acetolactate synthase, large subunit, biosynthetic type EC: 4.1.3.18 also catalyzes the formation of acetohydroxybutyrate from pyruvate and 2-oxobutyrate, an early step in the branched chain amino acid biosynthesis; it is therefore also termed acetohydroxyacid synthase. In bacteria, this catalytic chain is associated with a smaller regulatory chain in an alpha2/beta2 heterotetramer. Acetolactate synthase is a thiamine pyrophosphate enzyme. In this type, FAD and Mg²⁺ are also found. Several isozymes of this enzyme are found in Escherichia coli K12, one of which contains a frameshift in the large subunit gene and is not expressed.\ acetolactate synthase activity ; GO:0003984 \N branched chain family amino acid biosynthesis ; GO:0009082 22908 IPR004408

The biotin operon of Escherichia coli contains 5 structural genes involved in the synthesis of biotin. Transcription of the operon is regulated via one of these proteins, the biotin ligase BirA. BirA is an asymetric protein with 3 specific domains - an N-terminal DNA-binding domain, a central catalytic domain and a C-terminal of unknown function. The ligase reaction intermediate, biotinyl-5'-AMP, is the co-repressor that triggers DNA binding by BirA.The -helical N-terminal domain of the BirA protein has the helix-turn-helix structure of DNA-binding proteins with a central DNA recognition helix. BirA undergoes several conformational changes related to repressor function and the N-terminal DNA-binding function is connected to the rest of the molecule through a hinge which will allow relocation of the domains during the reaction [MEDLINE:99400973]. Biotin-binding causes a large structural change thought to facilitate ATP-binding.

Two repressor molecules form the operator-repressor complex, with dimer formation occuring simultaneously with DNA binding. DNA-binding may also cause a conformational change which allows this co-operative interaction. In the dimer structure, the -sheets in the central domain of each monomer are arranged side-by-side to form a single, seamless -sheet.

The apparent orthologs among the eukaryotes are larger proteins that contain a domain with high sequence homology to BirA.

\ \ biotin-[acetyl-CoA-carboxylase] ligase activity ; GO:0004077 \N protein modification ; GO:0006464 22895 IPR004394 The gene iojap is a pattern-striping gene in maize, reflecting a chloroplast development defect in some cells. Maize has two RNA polymerases in plastids, but the plastid-encoded one, similar to bacterial RNA polymerases, is missing in iojap mutants. The role of iojap in chloroplast development, and the role of its bacterial orthologs modeled here, is unclear.\ molecular_function unknown ; GO:0005554 \N \N 22896 IPR004395

This is a family of conserved hypothetical proteins. In Escherichia coli, this protein flanks the DNA repair protein MutY, also called micA.

\ methyltransferase activity ; GO:0008168 \N \N 22897 IPR004396 This is a family of conserved hypothetical proteins. There are potential GTP binding sites: VGLPNVGK(8-15) and VDIAG(71-75) in the model.\ molecular_function unknown ; GO:0005554 \N \N 22898 IPR004398 This is a family of conserved hypothetical proteins, which includes a putative methylase.\ molecular_function unknown ; GO:0005554 \N \N 22899 IPR004399 Phosphomethylpyrimidine kinase (EC: 2.7.4.7), also known as HMP-phosphate kinase, catalyses the phosphorylation of HMP-P to HMP-PP in the reaction: ATP + 4-amino-2-methyl-5-phosphomethylpyrimidine = ADP + 4-amino-2-methyl-5-diphosphomethylpyrimidine during the biosynthesis of thiamine.\ phosphomethylpyrimidine kinase activity ; GO:0008972 \N thiamin biosynthesis ; GO:0009228 22900 IPR004400 This is a GTP hydrolase for assembly of the nickel metallocenter of urease. A similar protein, hypB, is an accessory protein for expression of hydrogenase, which also uses nickel. They play a central role in nitrogen metabolism.\ nickel ion binding activity ; GO:0016151 \N protein complex assembly ; GO:0006461 22901 IPR004401 The function of this protein is unknown. It is restricted to Bacteria and the plant Arabidopsis. The plant form contains an additional N-terminal region that may serve as a transit peptide and shows a close relationship to the cyanobacterial member, suggesting that it is a chloroplast protein. Members of this family are found in a single copy per bacterial genome, but are broadly distributed. A member is present even in the minimal gene complement of Mycoplasm genitalium. \ molecular_function unknown ; GO:0005554 \N \N 22902 IPR004402 Purine nucleoside phosphorylase EC: 2.4.2.1 also called inosine phosphorylase (pnp) cleave guanosine or inosine to respective bases and sugar-1-phosphate molecules. These enzymes are involved in the salvage of nucleotides and nucleosides.\ purine-nucleoside phosphorylase activity ; GO:0004731 \N nucleobase, nucleoside, nucleotide and nucleic acid metabolism ; GO:0006139 22903 IPR004403 These proteins are translation factors that have been characterized in eukaryotes as the non-GTP-binding subunit of a cytosolic heterodimer that acts as a translation release factor for all three stop codons. Members of this orthologous family are found in Eukarya and Archaea. The name used should be eRF1 for the Archaea and aRF1 for the Eukarya. Alternative names include eRF1, SUP45, omnipotent suppressor protein 1.\ translation release factor activity, codon specific ; GO:0016149 cytoplasm ; GO:0005737 translational termination ; GO:0006415 22904 IPR004404

Two dehydratases, dihydroxy-acid dehydratase (EC: 4.2.1.9) (gene ilvD or ILV3) and 6-phosphogluconatedehydratase (EC: 4.2.1.12) (gene edd) have been shown to be evolutionary related [MEDLINE:92325055]. Dihydroxy-acid\ dehydratase catalyzes the fourth step in the biosynthesis of isoleucine and valine, the dehydratation of\ 2,3-dihydroxy-isovaleic acid into -ketoisovaleric acid. 6-Phosphogluconate dehydratase catalyzes the\ first step in the Entner-Doudoroff pathway, the dehydratation of 6-phospho-D-gluconate into \ 6-phospho-2-dehydro-3-deoxy-D-gluconate. Another protein containing this signature is the Escherichia coli hypothetical protein\ yjhG. The N-terminal part of the proteins contains a cysteine that could be involved in the binding of a\ 2Fe-2S iron-sulfur cluster [MEDLINE:94131281].

\ \

\ \ Dihydroxy-acid dehydratase EC: 4.2.1.9 contains a catalytically essential [4Fe-4S] cluster. It catalyzes the fourth step in valine and isoleucine biosynthesis.

\ \ dihydroxy-acid dehydratase activity ; GO:0004160 \N branched chain family amino acid biosynthesis ; GO:0009082 22883 IPR004382

This family of conserved hypothetical proteins groups bacterial proteins of unknown function.

\ molecular_function unknown ; GO:0005554 \N \N 22884 IPR004383 This family of conserved hypothetical proteins groups bacterial proteins of unknown function.\ molecular_function unknown ; GO:0005554 \N \N 22885 IPR004384 These proteins are part of the trmH (spoU) family of rRNA methylases. The spoU gene of Escherichia coli codes for a protein that shows strong similarities to previously characterized 2'-O-methyltransferases [MEDLINE:97465955]. TrmH is a tRNA (guanosine-2'-O-)-methyltransferase (EC: 2.1.1.34), which specifically methylates guanosine-18 in various tRNAs using S-adenosyl-L-methionine.\ RNA methyltransferase activity ; GO:0008173 \N \N 22886 IPR004385 Members of this family include uncharacterized proteins of about 200 amino acids from Escherichia coli (2 proteins), Haemophilus influenzae, Helicobacter pylori, and Bacillus subtilis, from among the currently completed prokaryotic genomes. It also includes the C-terminal half of a 361-amino acid protein, TrgB from Rhodobacter sphaeroides, shown experimentally to help confer tellurite resistance.\ \N \N \N 22887 IPR004386 This family represents a cluster of eubacterial proteins and a cluster of archaeal proteins, all of which are uncharacterized, from 85 to 102 residues in length, and similar in sequence. Short sequences show weaker signatures of evolutionary relatedness than long sequences, and these two clusters are short and, if truly related, highly divergent. The sequencing of new related sequences and/or characterization of examples from the eubacterial and archaeal groups should better illustrate the relationships among these proteins.\ \ molecular_function unknown ; GO:0005554 \N \N 22888 IPR004387 This family includes a region that hits the PDZ domain, found in a number of proteins targeted to the membrane by binding to a peptide ligand. The N-terminal region of this family contains a perfectly conserved motif HEXGH as found in a number of metalloproteinases, where the Glu is the active site and the His residues coordinate the metal cation.\ \N \N \N 22889 IPR004388 This family includes the Sua5, YciO, YrdC and YwlC proteins. There is a partial match to sua5, which is involved in regulation of translation initiation. The 3' end of sua5 has matches to sua5, BS3690 and weakly to AF0781 and BB0734.\ molecular_function unknown ; GO:0005554 \N \N 22890 IPR004389

\ \ \

This is the ribosomal protein L18 family. The archaebacterial and eukaryotic type rpL18 is not included in this family.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 22891 IPR004390 This family includes the cell division ABC transporter and the periplasmic substrate-binding protein FtsY. There is a weak division between FtsY and SRP54; both are GTPases. In Escherichia coli, ftsY is an essential gene located in an operon with cell division genes ftsE and ftsX, but its apparent function is as the signal recognition particle docking protein.\ GTP binding activity ; GO:0005525 \N \N 22892 IPR004391 Glutamate racemase (EC: 5.1.1.3) provides the (R)-glutamic acid required for cell wall biosynthesis. It converts L-glutamate to D-glutamate during peptidoglycan biosynthesis. The most closely related proteins differing in function are aspartate racemases.\ glutamate racemase activity ; GO:0008881 \N peptidoglycan biosynthesis ; GO:0009252 22893 IPR004392 The hydrogenase accessory protein HypB is a GTP hydrolase for assembly of nickel metallocenter of hydrogenase. A similar protein, ureG, is an accessory protein for urease, which also uses nickel.\ nickel ion binding activity ; GO:0016151 \N protein complex assembly ; GO:0006461 22894 IPR004393 Nicotinate-nucleotide pyrophosphorylase (EC: 2.4.2.19), also known as quinolinate phosphoribosyltransferase (decarboxylating), catalyses the conversion of nicotinate D-ribonucleotide, pyrophosphate and carbon dioxide into pyridine-2,3-dicarboxylate and 5-phospho-

-D-ribose 1-diphosphate in the de novo biosynthesis of NAD and NADP.\ nicotinate-nucleotide pyrophosphorylase (carboxylating) activity ; GO:0004514 \N pyridine nucleotide biosynthesis ; GO:0019363 22876 IPR004375

This family consists of conserved hypothetical proteins, about 150 amino acids in length, with no known function. The family is restricted to the bacteria. It includes three members in Escherichia coli K12 and three in Streptococcus pneumoniae.

\ \ molecular_function unknown ; GO:0005554 \N \N 22877 IPR004376

Members of this uncharacterized family share a motif approximating DXH(X25)GDXXD(X25)GNHD as found in several phosphoesterases, including the nucleases SbcD and Mre11. SbcD is a subunit of the SbcCD nuclease of Escherichia coli that can cleave DNA hairpins to unblock stalled DNA replication. All members of this family are archaeal.

\ \ molecular_function unknown ; GO:0005554 \N \N 22878 IPR004377 The seed members for this HMM are a paralogous family of Mycobacterium tuberculosis. Nearly all proteins scoring above the noise cutoff are from high-GC Gram-positive organisms. The members of this paralogous family of efflux proteins are all found in operons with ATP-binding chain partners. They are related to a putative daunorubicin resistance efflux protein of Streptomyces peucetius. This model represents a branch of a larger superfamily that also includes NodJ, a part of the NodIJ pair of nodulation-triggering signal efflux proteins. The members of this branch may all act in antibiotic resistance.\ drug transporter activity ; GO:0015238 membrane ; GO:0016020 \N 22879 IPR004378 The Mycobacterium tuberculosis paralogous family 11 groups a number of related hypothetical proteins from this organism. The function of these proteins is not yet known.\ molecular_function unknown ; GO:0005554 \N \N 22880 IPR004379 UDP-galactopyranose mutase (EC: 5.4.99.9) is involved in the conversion of UDP-GALP into UDP-GALF through a 2-keto intermediate, and contains FAD as a cofactor. The gene is known as glf, ceoA, and rfbD. It is known experimentally in Escherichia coli, Mycobacterium tuberculosis, and Klebsiella pneumoniae.\ \ UDP-galactopyranose mutase activity ; GO:0008767 \N lipopolysaccharide biosynthesis ; GO:0009103 22881 IPR004380 Asparate racemases (EC: 5.1.1.13) and some close homologs of function are related to the more common glutamate racemases, but form a distinct evolutionary branch. Members of this family are the aspartate racemase-related subset of amino acid racemases. Aspartate racemases act as homodimers and catalyse the conversion of L-aspartate to D-aspartate.\ racemase and epimerase activity, acting on amino acids and derivatives ; GO:0016855 \N amino acid metabolism ; GO:0006520 22882 IPR004381

This family of conserved hypothetical proteins includes glycerate kinase 2 (EC: 2.7.1.31) from several organisms. Glycerate kinase catalyses the phosphorylation of (R)-glycerate to 3-phospho-(R)-glycerate in the presence of ATP.

\ glycerate kinase activity ; GO:0008887 \N \N 22869 IPR004367

\ \ \

This is the C-terminal domain of cyclins.

\ \ \N nucleus ; GO:0005634 regulation of cell cycle ; GO:0000074 22870 IPR004368 This family consists of translation initiation factor IF-1 as found in bacteria and chloroplasts. This protein, about 70 residues in length, consists largely of an S1 RNA binding domain (IPR003029).\ translation initiation factor activity ; GO:0003743 \N translational initiation ; GO:0006413 22871 IPR004369

The family models a protein whose product is thought to suppress the function or expression of EbsB, a protein thought to be involved in cell wall metabolism. A crystallographic study of the member from Haemophilus influenzae (HI1434, YbaK) suggests a nucleotide binding function.

\ \N \N regulation of transcription, DNA-dependent ; GO:0006355 22872 IPR004370

4-Oxalocrotonate tautomerase (4-OT) catalyzes the isomerization of ,gamma-unsaturated enones to their ,-isomers. The enzyme is part of a plasmid-encodedpathway, which enables bacteria harboring the plasmid to use various aromatic hydrocarbons as their sole sources of carbon and energy. The\ enzyme is a barrel-shaped hexamer, which can be viewed as a trimer of dimers. The hexamer contains a hydrophobic core formed by three -sheets and\ surrounded by three pairs of -helices. Each 4-OT monomer of 62 amino acids has a relatively simple -- fold as described by the structure of the enzyme from Pseudomonas putida\ \ \ \ [MEDLINE:22047069]. The monomer begins\ with a conserved proline at the start of a -strand, followed by an -helix and a 3₁₀ helix preceding a second parallel -strand , and ends with\ a -hairpin near the C-terminus. The dimer results from antiparallel interactions between the -sheets and -helices of the two monomers, forming a\ four-stranded -sheet with antiparallel -helices on one side, creating two active sites, one at each end of the -sheet. Three dimers further\ associate to form a hexamer by the interactions of the strands of the C-terminal -hairpin loops with the edges of the four-stranded -sheets of neighboring\ dimers, creating a series of cross-links that stabilize the hexamer

Pro-1 of the mature protein functions as the general base while Arg-39 and an ordered water molecule each provide a hydrogen bond to the C-2 oxygen of substrate. Arg-39\ plays an additional role in the binding of the C-1 carboxylate group. Arg-11 participates both in substrate binding and in catalysis. It\ interacts with the C-6 carboxylate group, thereby holding the substrate in place and drawing electron density to the C-5 position. The hydrophobic nature of\ the active site, which lowers the pKa of Pro-1 and provides a favourable environment for catalysis, is largely maintained by Phe-50.

\ \

Because several Arg residues located near the active site are not conserved among all members of this family and because of the presence of fairly distantly related paralogs in Campylobacter jejuni, the family is regarded as not necessarily uniform in function.

\ \ \ isomerase activity ; GO:0016853 \N aromatic compound metabolism ; GO:0006725 22873 IPR004372 Acetate kinase is involved in the activation of acetate to acetyl CoA and in the secretion of acetate. It catalyzes the reaction ATP + acetate = ADP + acetyl phosphate.\ phosphotransferase activity, carboxyl group as acceptor ; GO:0016774 \N organic acid metabolism ; GO:0006082 22874 IPR004373 This family describes peptide chain release factor 1 (PrfA, RF-1), and excludes the related peptide chain release factor 2 (PrfB, RF-2). RF-1 helps recognize and terminate translation at UAA and UAG stop codons. The mitochondrial release factors are prfA-like, although not included above the trusted cutoff for this model. RF-1 does not have a translational frameshift.\ translation release factor activity, codon specific ; GO:0016149 cytoplasm ; GO:0005737 translational termination ; GO:0006415 22875 IPR004374 In many but not all taxa, there is a conserved real translational frameshift at a TGA codon. RF-2 helps terminate translation at TGA codons and can therefore regulate its own production by readthrough when RF-2 is insufficient. There is a superfamily IPR000352 of RF-1, RF-2, mitochondrial, RF-H, etc proteins.\ translation release factor activity, codon specific ; GO:0016149 cytoplasm ; GO:0005737 translational termination ; GO:0006415 22863 IPR004360 Glyoxalase I (EC: 4.4.1.5) (lactoylglutathione lyase) catalyzes the first step of the glyoxal pathway. S-lactoylglutathione is then converted by glyoxalase II to lactic acid [MEDLINE:93266575].Glyoxalase I is an ubiquitous enzyme which binds one mole of zinc\ per subunit. The bacterial and yeast enzymes are monomeric while the mammalian one is homodimeric. The sequence of glyoxalase I is well conserved. This domain is found in other related proteins including the Bleomycin resistance protein and dioxygenases eg. 4-hydroxyphenylpyruvate dioxygenase.\ \ \N \N \N 22864 IPR004361 Glyoxalase I (EC: 4.4.1.5) (lactoylglutathione lyase) catalyzes the first stepof the glyoxal pathway in the following reaction:\

\
glutathione + methylglyoxal = (R)-S-lactoylglutathione\

\ \ S-lactoylglutathione is then converted by glyoxalase II to lactic acid [MEDLINE:93266575].\ Glyoxalase I is a ubiquitous enzyme which binds one mole of zinc\ per subunit. The bacterial and yeast enzymes are monomeric while the mammalian\ one is homodimeric.\ The sequence of glyoxalase I is well conserved. In bacteria and mammals the\ enzyme is a protein of about 130 to 180 residues while in fungi it is about\ twice as long. In these organisms the enzyme is built out of the tandem repeat\ of a homologous domain.\ \ lactoylglutathione lyase activity ; GO:0004462 \N carbohydrate metabolism ; GO:0005975 22865 IPR004362

Methylglyoxal synthase (EC: 4.2.3.3) (MGS) [MEDLINE:99197296] catalyzes the conversion of dihydroxyacetone phosphate to methylglyoxal and phosphate. It provides bacteria with an alternative to triosephosphate isomerase for metabolizing dihydroxyacetone phosphate. Methylglyoxal synthase contains a domain shared by other enzymes. Other proteins containing this domain include purine biosynthesis protein PurH and carbamoyl phosphate synthetase.

\ enzyme activity ; GO:0003824 \N metabolism ; GO:0008152 22866 IPR004363 Methylglyoxal synthase (EC: 4.2.3.3) (MGS) [MEDLINE:99197296] catalyzes the conversion ofdihydroxyacetone phosphate to methylglyoxal and phosphate:\

\
Glycerone phosphate = methylglyoxal + phosphate\

\ It provides\ bacteria with an alternative to triosephosphate isomerase for metabolizing\ dihydroxyacetone phosphate.\ MGS is a small protein of about 13 to 17 kDa. An aspartate residue is involved\ in the catalytic mechanism.\ \ methylglyoxal synthase activity ; GO:0008929 cytoplasm ; GO:0005737 methylglyoxal biosynthesis ; GO:0019242 22867 IPR004364

\ \

Class-II tRNA synthetases do not share a high degree of similarity, however at least three conserved regions are present [MEDLINE:94099781], [MEDLINE:91272282], [MEDLINE:91305088].

\ \

This family includes the asparagine, aspartic acid and lysine tRNA synthetases.

\ \ ATP binding activity ; GO:0005524 cytoplasm ; GO:0005737 amino acid activation ; GO:0006418 22868 IPR004365

The OB-fold (oligonucleotide/oligosaccharide-binding fold) is found in all three kingdoms and its common architecture presents a\ binding face that has adapted to bind different ligands. The OB-fold is a five-stranded closed -barrel and the majority of OB-fold proteins use the\ same face for ligand binding or as an active site. Different OB-fold proteins use this 'fold-related\ binding face' to, variously, bind oligosaccharides, oligonucleotides, proteins, metal ions and catalytic\ substrates.

This entry contains OB-fold domains that bind to nucleic acids [MEDLINE:20288039]. It includes the anti-codon binding domain of lysyl, aspartyl, and asparaginyl -tRNA synthetases (See IPR004364. This domain is also found at the C terminus of bacterial DNA polymerase III chain.

\ \ nucleic acid binding activity ; GO:0003676 \N \N 22862 IPR004358

The term sensor refers to a family of proteins that respond to extra-cytoplasmic stimuli in bacteria. Sensors are usually linked to a 2-component regulatory system consisting of the sensor and a cytoplasmic regulator protein [MEDLINE:90136096].

The cytoplasmic C-terminal portions of the sensor proteins show marked sequence similarity and are responsible for kinase activity [MEDLINE:87017043].\ Some sensor proteins are cytoplasmic and may respond to several external stimuli. Sensors\ also show similarity to some regulatory proteins [MEDLINE:90136096]. The structure of CheA, a signal-transducing histidine kinase is known [MEDLINE:99142610]. The catalytic domain consists of several -helices packed over one face of a large anti-parallel sheet forming a loop which closes over the bound ATP. Hydrolysis of ATP is coupled to Mg ²⁺ release and conformational changes in the ATP-binding cavity.

\ \ \ two-component sensor molecule activity ; GO:0000155 \N signal transduction ; GO:0007165 22860 IPR004356

P pili, or fimbriae, are ~68A in diameter and 1 micron in length, the bulk of which is a fibre composed of the main structural protein PapA [MEDLINE:92204235].\ At its tip, the pilus is terminated by a fibrillum consisting of repeating\ units of the PapE protein. This, in turn, is topped by the adhesins, PapF\ and PapG, both of which are needed for receptor binding. The tip fibrillum\ is anchored to the main PapA fibre by the PapK pilus-adaptor protein. PapH,\ an outer membrane protein, then anchors the entire rod in the bacterial\ envelope [MEDLINE:95115757]. A cytoplasmic chaperone (PapD) assists in assembling the \ monomers of the macromolecule in the membrane.

All of the functional pap genes are arranged in a cluster (operon) on the \ Escherichia coli genome. It is believed that selective pressure exerted by the \ host's urinal and intestinal tract isoreceptors forced the spread of this \ operon to other strains via lateral transfer [MEDLINE:93023852]. PapB, encoded within the \ cluster, acts as a transcriptional regulator of the functional pap genes\ and is located in the bacterial cytoplasm [MEDLINE:89305531]. Its mechanism involves\ differential binding to separate sites in the cluster, suggesting that \ this protein is both an activator and repressor of pilus-adhesion \ transcription. The protein shares similarity with other E.coli fimbrial-\ adhesion transcription regulators, such as AfaA, DaaA and FanB.\

\ \ \N \N regulation of transcription, DNA-dependent ; GO:0006355 22861 IPR004357

Helicobacter pylori makes use of a type IV secretion system similar in mechanism to the conjugation machine of Agrobacterium tumefaciens\ \ \ \ [MEDLINE:20381412]. These machines\ secrete three different types of substrate: DNA conjugation intermediates,\ as in A.tumefaciens; multimeric proteins such as the pertussis toxin of\ Bordetella pertussis; and the CagA protein of H.pylori. CagA has been\ linked to the more severe forms of gastric ulcers and duodenal cancers [MEDLINE:20150113].\ Both CagA and the secretion system apparatus are encoded in the large\ pathogenicity island, termed cag [MEDLINE:20150113], possessed by the malignant disease-causing type I bacterial strains.

CagX is found on this pathogenicity island; mutants lacking the gene fail\ to induce pathogenicity in an infected mouse model. CagX is thought to play a role in the process of conjugation [MEDLINE:20150112].

\ \ \N \N pathogenesis ; GO:0009405 22858 IPR004354

REC114 is one of 10 genes required for initiation of meiotic recombination in Saccharomyces cerevisiae\ \ \ \ [MEDLINE:97412794]. Located on chromosome XIII, it is \ transcribed only in meiosis and has no detectable function in mitosis [MEDLINE:93223262].

REC114 has been shown to possess an intron and is one of only three genes\ in yeast with 3' introns [MEDLINE:97412794]. The 3' splice site utilised in REC114 is a\ very rare AAG sequence - only three other genes in yeast use this non-\ consensus sequence [MEDLINE:97412794]. It appears that the intron is not essential for\ expression of REC114 and is not absolutely required for meiotic function.\ Nevertheless, it is conserved in evolution - two other species of yeast\ contain an intron at the same location in their REC114 genes [MEDLINE:97412794].

\ \ \N \N meiotic recombination ; GO:0007131 22859 IPR004355

The CagA exotoxin is encoded in the last portion of the island, and\ mutants lacking the gene fail to induce IL-8 secretion, and to activate \ NF-kappa-B in vivo [MEDLINE:20150112]. CagA is believed to have a similar function to \ EPEC type III secreted effectors; both are tyrosine-phosphorylated once \ translocated into the target cell [MEDLINE:20150112], and allow engulfment by the host via\ rearrangement of the actin cytoskeleton.

\ \ toxin transporter activity ; GO:0019534 \N \N 22856 IPR004352

Eighty-one archaeal-like genes, ranging in size from 4-20kb, are clustered in 15 regions of the Thermotoga maritima genome [MEDLINE:99287316].\ Conservation of gene order between Thermotoga maritima and Archaea in many of these\ regions suggests that lateral gene transfer may have occurred between\ thermophilic Eubacteria and Archaea [MEDLINE:99287316].

One of the Thermotoga maritima sequences (hypothetical protein TM1410) \ shares similarity with Methanococcus jannaschii hypothetical protein MJ1477\ and with hypothetical protein DR0705 from Deinococcus radiodurans. The \ sequences are characterised by relatively variable N- and C-terminal domains,\ and a more conserved central domain. They share no similarity with any other \ known, functionally or structurally characterised proteins.

\ \ molecular_function unknown ; GO:0005554 \N \N 22857 IPR004353

The sequence of a 6.8kb DNA fragment from Saccharomyces cerevisiae chromosome VII has been analysed [MEDLINE:97051592]. The sequence was found to contain\ five open reading frames (ORFs) greater than 100 amino acids in length. One \ of these (a 73.5kDa protein) shares similarity with the 58.0kDa SPAC1D4.03C\ from Schizosaccharomyces pombe, and with hypothetical proteins from Homo \ sapiens, Drosophila melanogaster, Caenorhabditis elegans and Fugu rubripes.

The sequences are characterised by a variable N-terminal domain and a more\ conserved C-terminal domain. They share no similarity with any other known, \ functionally or structurally characterised proteins.

\ \ molecular_function unknown ; GO:0005554 \N \N 22853 IPR004348 The function of this family of plant proteins is unknown.\ \N \N \N 22854 IPR004349

The nitrogenase complex EC: 1.18.6.1 catalyses the conversion of molecular nitrogen to ammonia (nitrogen fixation). The complex is hexameric, consisting of 2 , 2 , and 2 delta subunits.

This family represents the delta\ subunit of a group of nitrogenases that do not utilise molybdenum (Mo) as a cofactor, but instead use either vanadium (V\ nitrogenases), or iron (alternative nitrogenases).

\ \ nitrogenase activity ; GO:0016163 \N nitrogen fixation ; GO:0009399 22855 IPR004350

\ Kv2.1 channels are expressed in the neurons. Essential for their function\ is protein phosphorylation dependent on protein kinase A. Three isoforms \ exhibiting temporal patterning during neuronal development have also been\ discovered, implying distinct roles for these channels in development PUB00009786.

\ \ voltage-gated potassium channel activity ; GO:0005249 integral to membrane ; GO:0016021 potassium ion transport ; GO:0006813 22849 IPR004344

Tubulins and microtubules are subjected to several post-translational modifications of which the reversible detyrosination/tyrosination of the carboxy-terminal end of most -tubulins has been extensively analysed. This\ modification cycle involves a specific carboxypeptidase and the activity of the tubulin-tyrosine ligase (TTL) [MEDLINE:20148025]. Tubulin-tyrosine ligase (TTL) catalyses the\ ATP-dependent post-translational addition of a tyrosine to the carboxy terminal end of detyrosinated -tubulin. The true\ physiological function of TTL has so far not been established. In\ normally cycling cells, the tyrosinated form of tubulin predominates. However, in breast cancer cells, the detyrosinated\ form frequently predominates, with a correlation to tumour aggressiveness [MEDLINE:21324320].

3-nitrotyrosine has\ been shown to be incorporated, by TTL, into the carboxy terminal end of detyrosinated -tubulin. This reaction is not\ reversible by the carboxypeptidase enzyme. Cells cultured in 3-nitrotyrosine rich medium showed evidence of altered\ microtubule structure and function, including altered cell morphology, epithelial barrier dysfunction, and apoptosis [MEDLINE:99272699].

\ \ tubulinyl-tyrosine ligase activity ; GO:0004835 \N protein modification ; GO:0006464 22850 IPR004345

This family includes members from a wide variety of eukaryotes. It includes the TB2/DP1 (deleted in polyposis) protein which in human is deleted in severe forms of familial adenomatous polyposis, an autosomal dominant oncological inherited disease.

The family also includes the plant protein of known similarity to TB2/DP1, the\ HVA22 abscisic acid-induced protein (e.g. Q07764), which is thought to be a regulatory protein.

\ \ \N \N \N 22851 IPR004346

This family includes the Helicobacter pylori protein CagE (see examples), which together with other proteins from the cag pathogenicity island (PAI), encodes a type IV transporter secretion system. The precise role of CagE is not known,\ but studies in animal models have shown that it is essential for pathogenesis in Helicobacter pylori induced gastritis and\ peptic ulceration [MEDLINE:20558380]. Indeed, the expression of the cag PAI has been shown to be essential for stimulating human gastric\ epithelial cell apoptosis in vitro [MEDLINE:21340388].

Similar type IV transport systems are also found in other bacteria. This family includes proteins from the trb and Vir conjugal transfer systems in\ Agrobacterium tumefaciens and homologues of VirB proteins from other species.

\ \ ATP binding activity ; GO:0005524 \N \N 22852 IPR004347 This family of proteins includes members that may be involved in the 20S proteasome complex of Actinomycetales. Their precise function is unknown.\ molecular_function unknown ; GO:0005554 \N \N 22843 IPR004338 This family of bacterial proteins includes a sodium-translocating NADH-ubiquinone oxidoreductase (i.e. a respiration linked sodium pump). In Vibrio cholerae, it negatively regulates the expression of virulence factors through inhibiting (by\ an unknown mechanism) the transcription of the transcriptional activator ToxT [MEDLINE:99179036]. The family also includes proteins\ involved in nitrogen fixation, RnfD and RnfE. The similarity of these proteins to NADH-ubiquinone oxidoreductases was\ previously noted [MEDLINE:97299785].\ \ \N membrane ; GO:0016020 transport ; GO:0006810 22844 IPR004339 The function of these herpesvirus proteins is unknown.\ \N \N \N 22845 IPR004340

Herpes simplex virus type 1 (HSV1) DNA replication in host cells is known to be mediated by seven viral-encoded proteins, three of which form a heterotrimeric DNA helicase-primase complex. This complex consists of UL5, UL8, and UL52\ subunits. Heterodimers consisting of UL5 and UL52 have been shown to retain both helicase and primase activities.\ Nevertheless, UL8 is still essential for replication: though it lacks any DNA binding or catalytic activities, it is involved in\ the transport of UL5-UL52 and it also interacts with other replication proteins.

The molecular mechanisms of the\ UL5-UL52 catalytic activities are not known. While UL5 is associated with DNA helicase activity and UL52 with DNA\ primase activity, the helicase activity requires the interaction of UL5 and UL52 [MEDLINE:99429603], [MEDLINE:21264531]. It is not known if the primase\ activity can be maintained by UL52 alone. The biological significance of UL52-UL8\ interaction is not known. Yeast two-hybrid analysis together with immunoprecipitation experiments have shown that the\ HSV1 UL52 region between residues 366-914 is essential for this interaction, while the first 349 N-terminal residues are\ dispensable [MEDLINE:99429603].

This family also includes protein UL70 from cytomegalovirus (CMV, a subgroup of the Herpesviridae)\ strains which, by analogy with UL52, is thought to have DNA primase activity. Indeed, CMV\ strains also possess a DNA helicase-primase complex, the other subunits being protein UL105 (with known similarity to\ HSV1 UL5) and protein UL102.

\ \ DNA primase activity ; GO:0003896 \N DNA replication ; GO:0006260 22846 IPR004341 The CAT RNA-binding domain is found at the amino terminus of a family of transcriptional antiterminator proteins, the Co-AntiTerminator (CAT) domain. This domain forms a dimer in the crystal structure [MEDLINE:97449148]. Transcriptional antiterminators of the BglG/SacY family are regulatory proteins that mediate the induction of sugar metabolizing operons in Gram-positive and Gram-negative bacteria. Upon activation, these proteins bind to specific targets in nascent mRNAs, thereby preventing abortive dissociation of the RNA polymerase from the DNA template [MEDLINE:20079504].\ \ RNA binding activity ; GO:0003723 \N regulation of transcription, DNA-dependent ; GO:0006355 22847 IPR004342

The EXS domain is named after ERD1/XPR1/SYG1 and proteins containing this motif include the C-terminal of the SYG1 G-protein associated signal transduction protein from Saccharomyces cerevisiae, and sequences that are thought to be murine leukaemia virus (MLV) receptors (XPR1. The N-terminal of these proteins often have an SPX domain (IPR004331.

While the N-terminal is thought to be involved in signal\ transduction, the role of the C-terminal is not known. This region of similarity contains\ several predicted transmembrane helices. This family also includes the ERD1 (ERD: ER retention defective) Saccharomyces cerevisiae\ proteins. ERD1 proteins are involved in the localization of endogenous endoplasmic reticulum (ER)\ proteins. erd1 null mutants secrete such proteins even though they possess the C-terminal HDEL ER lumen localization\ label sequence. In addition, null mutants also exhibit defects in the Golgi-dependent processing of several glycoproteins,\ which led to the suggestion that the sorting of luminal ER proteins actually occurs in the Golgi, with subsequent return of\ these proteins to the ER via 'salvage' vesicles [MEDLINE:90183957].

\ \ \N integral to membrane ; GO:0016021 \N 22848 IPR004343 The plus-3 domain is about 90 residues in length and is often found associated with the GYF domain (IPR003169). The function of plus-3 is uncertain. It is possible that this domain is involved in DNA binding as it has three conserved positively charged residues, hence this domain has been names the plus-3 domain. It is found in the yeast Rtf1 protein which may be a transcription elongation factor [MEDLINE:20469343].\ \ \N \N \N 22839 IPR004334 This family of poxvirus proteins is found in cytoplasmic sites of viral DNA replication [MEDLINE:20311222]. However, its function is unknown.\ \ \N \N \N 22840 IPR004335 Several members of this family are Borrelia burgdorferi plasmid proteins of unknown function.\ \N \N \N 22841 IPR004336 The molecular structure and function of the NS2 protein is not known. However, mutants lacking the NS2 grow at slower rates when compared to the wild-type yet NS2 is not essential for viral replication [MEDLINE:99102581].\ \ \N \N \N 22842 IPR004337 The astrovirus genome is apparently organized with nonstructural proteins encoded at the 5' end and structural proteins at the 3' end [MEDLINE:94076464]. Proteins in this family are encoded by astrovirus ORF2, one of the three astrovirus ORFs (1a, 1b, 2). The proteins contain a viral RNA-dependent RNA polymerase motif [MEDLINE:94076464]. The 87kDa precursor polyprotein\ undergoes an intracellular cleavage to form a 79kDa protein. Subsequently, extracellular trypsin cleavage yields the three\ proteins forming the infectious virion [MEDLINE:20111302].\ \ \N \N \N 22833 IPR004328 This functionally uncharacterised domain is found in a number of signal transduction proteins.\ \N \N signal transduction ; GO:0007165 22834 IPR004329 CcmE is the product of one of a cluster of Ccm genes that are necessary for cytochrome c biosynthesis in eubacteria. Expression of these proteins is induced when the organisms are grown under anaerobic conditions with nitrate or nitrite as\ the final electron acceptor.\ \ \N \N cytochrome biogenesis ; GO:0017004 22835 IPR004330

This domain was first identified in an Arabidopsis mutant, far1 (far-red-impaired response), which has reduced responsiveness to continuous far-red light, but responds normally to other light wavelengths. The\ FAR1 gene encodes a protein with no significant sequence similarity to any proteins of known function [MEDLINE:99375316]. The FAR1 protein\ contains a predicted nuclear localization signal and is targeted to the nucleus in transient transfection assays.

\ \

This domain is also found in members from other\ plant species, such as Arabidopsis thaliana and Oryza sativa (rice).

\ \ \N \N \N 22836 IPR004331

The SPX domain is named after SYG1/Pho81/XPR1 proteins. This 180 residue length domain is found at the amino terminus of a variety of proteins. In the yeast protein SYG1, the N-terminus directly binds to the G- protein subunit and inhibits transduction of the mating pheromone signal [MEDLINE:96029624] suggesting that all the members of this\ family are involved in G-protein associated signal transduction. The C-terminal of these proteins often have an EXS domain (IPR004342.

The N-termini of several proteins involved in the\ regulation of phosphate transport, including the putative phosphate level sensors PHO81 from\ Saccharomyces cerevisiae and NUC-2 from Neurospora crassa, are also members of this family [MEDLINE:97075801], [MEDLINE:20521942]. NUC-2 contains several ankyrin repeats (IPR004342/>).

Several members of this family are the XPR1 proteins: the\ xenotropic and polytropic retrovirus receptor confers susceptibility to infection with murine leukaemia viruses (MLV)\ \ \ \ [MEDLINE:99145559].\ The similarity between SYG1, phosphate regulators and XPR1 sequences has been previously noted, as has the\ additional similarity to several predicted proteins, of unknown function, from Drosophila melanogaster, Arabidopsis\ thaliana, Caenorhabditis elegans, Schizosaccharomyces pombe, and Saccharomyces cerevisiae\ \ \ \ [MEDLINE:99145559], [MEDLINE:99128339]. In addition, given\ the similarities between XPR1 and SYG1 and phosphate regulatory proteins, it has been proposed that XPR1 might be\ involved in G-protein associated signal transduction and may itself function as a phosphate sensor [MEDLINE:99145559].

\ \ \N \N \N 22837 IPR004332 The plant MuDR transposase domain is present in plant proteins that are presumed to be the transposases for Mutator transposable elements [MEDLINE:95402701], [MEDLINE:92090705]. The function of these proteins is unknown.\ \N \N \N 22838 IPR004333 The SBP plant protein domain is a sequence specific DNA-binding domain [MEDLINE:96158840]. Proteins with this domain probably function as transcription factors involved in the control of\ early flower development. The domain contains 10 conserved cysteine and histidine residues that probably are zinc\ ligands.\ \ DNA binding activity ; GO:0003677 nucleus ; GO:0005634 \N 22827 IPR004322 This is a family of bacterial plasmid DNA replication initiator proteins. These RepA proteins exist as monomers and dimers in equilibrium: monomers bind directly to repeated DNA sequences and thus\ activate replication; dimers repress repA transcription by binding an inversely repeated DNA operator. Dimer\ dissociation can occur spontaneously or may be mediated by Hsp70 chaperones.\ A similar RepA family of proteins found mainly in Escherichia coli is involved in plasmid replication (see IPR002584).\ \ DNA binding activity ; GO:0003677 extrachromosomal circular DNA ; GO:0005727 plasmid maintenance ; GO:0006276 22828 IPR004323 Several gene loci with a possible involvement in cellular tolerance to copper have been identified [MEDLINE:95349397]. One such locus in eubacteria and archaebacteria cutA, is thought to be involved in cellular tolerance to a wide variety of divalent cations\ other than copper. The cutA locus consists of two operons, of one and two genes. The CutA1 protein is a cytoplasmic\ protein, encoded by the single-gene operon and has been linked to divalent cation tolerance. It has no recognized\ structural motifs [MEDLINE:97405892]. This family also contains putative proteins from eukaryotes (human and Drosophila melanogaster).\ \ \N \N \N 22829 IPR004324 Members of this family are transmembrane proteins. Several are Leishmania putative proteins that are thought to be pteridine transporters [MEDLINE:20055929], [MEDLINE:95075382]. This family also contains five putative Arabidopsis thaliana proteins of unknown\ function as well as two predicted prokaryotic proteins (from the cyanobacteria Synechocystis and Synechococcus).\ \ \N membrane ; GO:0016020 \N 22830 IPR004325 The FG repeats are found in diverse nucleoporins and may mediate interactions with substrates to be transported through the nuclear pore [MEDLINE:95254630], [MEDLINE:21021984]. The repeats are also present in a family of\ helicases. Due to the shortness of this repeat it is not clear if its presence in the helicases has any biological significance.\ \ \N \N \N 22831 IPR004326

The Mlo-related proteins are a family of plant integral membrane proteins, first discovered in barley. Mutants lacking wild-type Mlo proteins show broad spectrum resistance to the powdery mildew fungus, and dysregulated cell death control, with spontaneous cell\ death in response to developmental or abiotic stimuli. Thus wild-type Mlo proteins are thought to be inhibitors of cell\ death whose deficiency lowers the threshold required to trigger the cascade of events that result in plant cell death.

Mlo\ proteins are localized in the plasma membrane and possess seven transmembrane regions; thus the Mlo family is the only\ major higher plant family to possess 7 transmembrane domains. It has been suggested that Mlo proteins function as\ G-protein coupled receptors in plants [MEDLINE:20044759]; however the molecular and biological functions of Mlo proteins is still unclear.

\ \ \N integral to membrane ; GO:0016021 cell death ; GO:0008219 22832 IPR004327 Phosphotyrosyl phosphatase activator (PTPA) proteins stimulate the phosphotyrosyl phosphatase (PTPase) activity of the dimeric form of protein phosphatase 2A (PP2A). PTPase activity in PP2A (in vitro) is relatively low when compared\ to the better recognized phosphoserine/ threonine protein phosphorylase activity. The specific biological role of PTPA is\ unknown, Basal expression of PTPA depends on the activity of a ubiquitous transcription factor, Yin Yang 1 (YY1). The\ tumour suppressor protein p53 can inhibit PTPA expression through an unknown mechanism that negatively controls\ YY1 [MEDLINE:21092868].\ \ phosphatase activator activity ; GO:0019211 \N \N 22824 IPR004319 This domain is found entirely in Mycoplasma pneumoniae proteins of unknown function. Another related domain (IPR004306) is also found entirely in mycoplasmal proteins of the MG032/MG096/MG288 family and both domains often occur together.\ molecular_function unknown ; GO:0005554 \N \N 22825 IPR004320 This family represents a number of Arabidopsis thaliana proteins of unknown function.\ \N \N \N 22826 IPR004321

The variable portion of the genes encoding immunoglobulins and T cell receptors are assembled from component V, D, and J DNAsegments by a site-specific recombination reaction termed V(D)J recombination. V(D)J recombination is targeted to\ specific sites on the chromosome by recombination signal sequences (RSSs) that flank antigen receptor gene segments. The RSS\ consists of a conserved heptamer (consensus, 5'-CACAGTG-3') and nonamer (consensus, 5'-ACAAAAACC-3') separated by a\ spacer of either 12 or 23 bp. Efficient recombination occurs between a 12-RSS and a 23-RSS, a restriction known as the 12/23 rule.

\ \

V(D)J recombination can be divided into two phases, DNA cleavage and DNA joining. DNA cleavage requires two lymphocyte-specific factors, the\ products of the recombination activating genes, RAG1 and RAG2, which together recognize the RSSs and create\ double strand breaks at the RSS-coding segment junctions [MEDLINE:21959427]. RAG-mediated DNA cleavage occurs in a synaptic complex\ termed the paired complex, which is constituted from two distinct RSS-RAG complexes, a 12-SC and a 23-SC (where SC stands for signal complex). The DNA cleavage reaction involves two distinct enzymatic steps, initial nicking that creates a 3'-OH between a coding\ segment and its RSS, followed by hairpin formation in which the newly created 3'-OH attacks a phosphodiester bond on the opposite DNA strand. This generates a\ blunt, 5' phosphorylated signal end containing all of the RSS elements, and a covalently sealed hairpin coding end.

\ \

The second phase of V(D)J recombination, in which broken DNA fragments are processed and joined, is less well characterized. Signal ends are typically joined\ precisely to form a signal joint, whereas joining of the coding ends requires the hairpin structure to be opened and typically involves nucleotide addition and deletion\ before formation of the coding joint. The factors involved in these processes include ubiquitously expressed proteins involved in the repair of DNA double strand\ breaks by nonhomologous end joining, terminal deoxynucleotidyl transferase, and Artemis protein.

\ \

In addition to their critical roles in RSS recognition and DNA cleavage, the RAG proteins may perform two distinct types of functions in the\ postcleavage phase of V(D)J. A structural function has been inferred\ from the finding that, after DNA cleavage in vitro, the DNA ends remain associated with the RAG proteins in a "four end" complex known as the cleaved signal\ complex. After release of the coding ends in vitro, and after coding joint formation in vivo, the RAG proteins remain in a\ stable signal end complex (SEC) containing the two signal ends. These postcleavage complexes may serve\ as essential scaffolds for the second phase of the reaction, with the RAG proteins acting to organize the DNA processing and joining events.

\ \

The second type of RAG protein-mediated postcleavage activity is the catalysis of phosphodiester bond hydrolysis and strand transfer reactions. The RAG proteins are capable of opening hairpin coding ends in vitro. The RAG proteins\ also show 3' flap endonuclease activity that may contribute to coding end processing/joining and can utilize the\ 3' OH group on the signal ends to attack hairpin coding ends (forming hybrid or open/shut joints) or virtually any DNA duplex (forming a transposition product).

\ \ \ DNA binding activity ; GO:0003677 nucleus ; GO:0005634 DNA recombination ; GO:0006310 22819 IPR004314 This domain is found in a number of Arabidopsis thaliana proteins of unknown function. A small number of the proteins that contain this domain are putative peptidases.\ \N \N \N 22820 IPR004315 The accessory gland of male insects is a genital tissue that secretes many components of the ejaculatory fluid, some of which affect the female's receptivity to courtship and her rate of oviposition. The protein is expressed exclusively in the\ male accessory glands of adult Drosophila melanogaster. During copulation it is transferred to the female genital tract where it is rapidly altered [MEDLINE:89053045].\ \ \N extracellular ; GO:0005576 mating ; GO:0007618 22821 IPR004316 This family includes proteins such as Drosophila saliva [MEDLINE:98413052], MtN3 involved in root nodule development [MEDLINE:96212994] and a protein involved in activation and expression of recombination activation genes (RAGs) [MEDLINE:96205347]. Although the molecular function of\ these proteins is unknown, they are almost certainly transmembrane proteins. This family contains a region of two\ transmembrane helices that is found in two copies in most members of the family.\ \ molecular_function unknown ; GO:0005554 membrane ; GO:0016020 \N 22822 IPR004317

Reoviruses are double-stranded RNA viruses that lack a membrane envelope. Their capsid is organized in two concentric icosahedral layers: an inner core and an outer capsid layer. The sigma1 protein is found in the outer capsid, and the sigma2 protein is found in the core. There are four other kinds of protein (besides sigma2) in the core, termed lambda 1-3, mu2. Interactions between sigma2 and lambda 1 and lambda 3 are thought to initiate core formation, followed by mu2 and lambda2 [MEDLINE:99139013].

Sigma1 is a trimeric protein, and is positioned at the 12 vertices of the icosahedral outer capsid layer. Its N-terminal fibrous tail, arranged as a triple coiled coil,\ anchors it in the virion, and a C-terminal globular head interacts with the\ cellular receptor [MEDLINE:21413935]. These two parts form by separate trimerization events.\ The N-terminal fibrous tail forms on the polysome, without the involvement\ of ATP or chaperones. The post- translational assembly of the C-terminal\ globular head involves the chaperone activity of Hsp90, which is associated\ with phosphorylation of Hsp90 during the process [MEDLINE:21413935]. Sigma1 protein acts\ as a cell attachment protein, and determines viral virulence, pathways of\ spread, and tropism. Junctional adhesion molecule has been identified as a\ receptor for sigma1 [MEDLINE:21135266]. In type 3 reoviruses, a small region, predicted to\ form a sheet, in the N-terminal tail was found to bind target cell surface\ sialic acid (i.e. sialic acid acts as a co-receptor) and promote apoptosis [MEDLINE:21184684].\ The sigma1 protein also binds to the lambda2 core protein [MEDLINE:97456587].

\ \ \N \N \N 22823 IPR004318

Members of this family are found in the parasite Babesia bigemina. Other rhoptry-associated proteins are found in Plasmodium falciparum but these do not belong to this family. Animal infection with Babesia bigemina may produce a pattern similar to human malaria [MEDLINE:20080134]. Rhoptry organelles form part of the apical complex in apicomplexan parasites.

Rhoptry-associated proteins are\ antigenic, and generate partially protective immune responses in infected mammals. Thus RAPs are among the targeted\ vaccine antigens for babesial (and malarial) parasites. However, RAP-1 proteins are encoded by by a multigene family;\ thus RAP-1 proteins are polymorphic, with B and T cell epitopes that are conserved among strains, but not across\ species [MEDLINE:98327208], [MEDLINE:98135662], [MEDLINE:98187931]. Antibodies to Babesia bigemina RAP-1 may also be helpful in the serological detection of Babesia bigemina infections [MEDLINE:99294770].

\ \ defense/immunity protein activity ; GO:0003793 \N \N 22809 IPR004304 This family includes amidohydrolases of formamide EC: 3.5.1.49 and acetamide EC: 3.5.1.-. The formamidase from Methylophilus methylotrophus forms a homotrimer suggesting that this may be a common property of other members of this family.\ hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides ; GO:0016811 \N metabolism ; GO:0008152 22810 IPR004305

Proteins containing this domain are found in all the three major phyla of life: archaebacteria, eubacteria, and eukaryotes. In Bacillus subtilis, TENA is one of a number of proteins that enhance the expression of extracellular enzymes, such as\ alkaline protease, neutral protease and levansucrase [MEDLINE:91100316].

The THI-4 protein, which is involved in thiamine biosynthesis, also contains this domain. The C-terminal part of these proteins consistently show significant sequence similarity to\ TENA proteins. This similarity was first noted with the Neurospora crassa THI-4 [MEDLINE:96269931]. The exact molecular function of\ this domain is uncertain.

\ \ \N \N \N 22811 IPR004306 This domain is found entirely in Mycoplasma pneumoniae proteins of unknown function. Another related domain (IPR004319) is found entirely in mycoplasmal proteins of the MG032/MG096/MG288 family and both domains often occur together.\ molecular_function unknown ; GO:0005554 \N \N 22812 IPR004307

Tryptophan-rich sensory protein (TspO) is an integral membrane protein that acts as a negative regulator of the expression of specific photosynthesis genes in response to oxygen/light [MEDLINE:95403350]. It is involved in the efflux of porphyrin\ intermediates from the cell. This reduces the activity of coproporphyrinogen III oxidase, which is thought to lead to the\ accumulation of a putative repressor molecule that inhibits the expression of specific photosynthesis genes. Several\ conserved aromatic residues are necessary for TspO function: they are thought to be involved in binding porphyrin\ intermediates [MEDLINE:20148770].

The rat mitochondrial peripheral benzodiazepine receptor (MBR) was shown to not only retain\ its structure within a bacterial outer membrane, but also to be able to functionally substitute for TspO in TspO- mutants,\ and to act in a similar manner to TspO in its in situ location: the outer mitochondrial membrane [MEDLINE:97289726]. The biological significance\ of MBR remains unclear. It is thought to be involved in a variety of cellular functions, including cholesterol\ transport in steroidogenic tissues.

\ \ \N integral to membrane ; GO:0016021 \N 22813 IPR004308 This family represents the catalytic subunit of glutamate-cysteine ligase (EC: 6.3.2.2), also known as gamma-glutamylcysteine synthetase (GCS). This enzyme catalyses the rate limiting step in the biosynthesis of glutathione.\ The eukaryotic enzyme is a dimer of a heavy chain and a light chain with all the catalytic activity exhibited by the heavy\ chain.\ \ glutamate-cysteine ligase activity ; GO:0004357 \N glutathione biosynthesis ; GO:0006750 22814 IPR004309

This is a domain of unknown function found in archaebacterial proteins of unknown function, often adjacent to DUF234 IPR004256.

\ molecular_function unknown ; GO:0005554 \N \N 22815 IPR004310 This protein is encoded by ORF3 of equine arteritis virus. The function is unknown.\ \N \N \N 22816 IPR004311

Proteins containing this domain include a number of Helicobacter pylori outer membrane proteins with multiple copies of this small conserved region.

\ toxin activity ; GO:0015070 external outer membrane (sensu Gram-negative Bacteria) ; GO:0009279 \N 22817 IPR004312 ATHILA is a group of Arabidopsis thaliana retrotransposons [MEDLINE:96123225] belonging to the Ty3/gypsy family of the long terminal repeat (LTR) class of eukaryotic retrotransposons[MEDLINE:98278792], [MEDLINE:20349905]. The central region of ATHILA retrotransposons contains two or\ three open reading frames (ORFs). This family represents the ORF1 product. The function of ORF1 is unknown.\ \ \N \N \N 22818 IPR004313

The two acireductone dioxygenase enzymes (ARD and ARD', previously known as E-2 and E-2') from Klebsiella pneumoniae share the same amino acid sequence Q9ZFE7, but bind different metal ions: ARD binds Ni2+, ARD' binds\ Fe2+ [MEDLINE:99098850]. ARD and ARD' can be experimentally interconverted by removal of the bound metal ion and reconstitution with\ the appropriate metal ion. The two enzymes share the same substrate, 1,2-dihydroxy-3-keto-5-(methylthio)pentene, but\ yield different products. ARD' yields the -keto precursor of methionine (and formate), thus forming part of the\ ubiquitous methionine salvage pathway that converts 5'-methylthioadenosine (MTA) to methionine. This pathway is\ responsible for the tight control of the concentration of MTA, which is a powerful inhibitor of polyamine biosynthesis and\ transmethylation reactions [MEDLINE:21264120]. ARD yields methylthiopropanoate, carbon monoxide and formate, and thus prevents the\ conversion of MTA to methionine. The role of the ARD catalysed reaction is unclear: methylthiopropanoate is cytotoxic,\ and carbon monoxide can activate guanylyl cyclase, leading to increased intracellular cGMP levels [MEDLINE:21264120], [MEDLINE:99098850].

This family also\ contains other proteins, whose functions are not well characterised.

\ \ \N \N \N 22807 IPR004302 Entomopoxviruses are a class of insect viruses whose virions are embedded in cytoplasmic occlusion bodies. The major component of these protective complexes is a protein called spheroidin/spindolin. Intermolecular disulfide bonds have been shown to play major roles in the formation and structure of these viral occlusion bodies [MEDLINE:90223988] some of which are spindle body proteins.\ \N viral capsid ; GO:0019028 \N 22808 IPR004303 Members of this family are found in mammals. In the presence of calcium ions, PAD enzymes EC: 3.5.3.15 catalyse the post-translational modification reaction responsible for the formation of citrulline residues in proteins. Several types of PAD enzymes are recognized (and included in the family) on the basis of molecular mass,\ substrate specificity, and tissue localization. The expression of type I PAD is known to be under the control of oestrogen\ [MEDLINE:99192810].\ \ protein-arginine deiminase activity ; GO:0004668 \N protein modification ; GO:0006464 22805 IPR004300

Glycoside hydrolase family 57 CAZY:GH_57) and 4--glucanotransferase (EC: 2.4.1.-).

\ \ enzyme activity ; GO:0003824 \N carbohydrate metabolism ; GO:0005975 22806 IPR004301 Nucleoplasmins are also known as chromatin decondensation proteins. They bind to core histones and transfer DNA to them in a reaction that requires ATP. This is thought to play a role in the assembly of regular nucleosomal arrays.\ \ nucleic acid binding activity ; GO:0003676 nucleus ; GO:0005634 \N 22798 IPR004293 Members of this family are non-structural proteins that are found in transmissible gastroenteritis coronavirus (TGEV) and porcine respiratory coronavirus (PRCV) isolates. These proteins\ are found on the same mRNA as another product, designated ORF3a. While ORF3a/b has been implicated in TGEV\ and PRCV pathogenesis, its precise role remains unclear [MEDLINE:20403263], [MEDLINE:99293500].\ \ \N \N \N 22799 IPR004294 Retinal pigment epithelial membrane proteins are abundantly expressed in retinal pigment epithelium, and binds plasma retinal binding protein. The family also includes the sequence related neoxanthin cleavage\ enzyme in plants and lignostilbene-

-dioxygenase in bacteria.\ \ \N \N \N 22800 IPR004295

This family includes the gp36 protein from retroviruses such as mouse mammary tumor virus (MMTV) and Human endogenous retrovirus (HERVs). The gp36 protein is an envelope protein that has a predicted transmembrane helix at its amino terminus.

\ \ \N viral capsid ; GO:0019028 \N 22801 IPR004296 This domain is located at the C-terminal region of a number of Caenorhabditis elegans proteins of unknown function.\ \N \N \N 22802 IPR004297 Members of this family are found in Solanaceae spp. plants, a taxonomic group (family) that includes pepper and tobacco plant species. Synthesis of these proteins is induced by tobacco mosaic virus (TMV) and salicylic acid [MEDLINE:93120622]; indeed they\ are thought to be involved in the development of systemic acquired resistance (SAR) after an initial hypersensitive\ response to microbial infection [MEDLINE:93120622], [MEDLINE:20347562]. SAR is characterized by long-lasting resistance to infection by a wide range of\ pathogens, extending to plant tissues distant from the initial infection site [MEDLINE:20347562].\ \ defense/immunity protein activity ; GO:0003793 \N systemic acquired resistance ; GO:0009627 22803 IPR004298 Nicotianamine synthase EC: 2.5.1.43 catalyzes the trimerization of S-adenosylmethionine to yield one molecule of nicotianamine. Nicotianamine has an important role in plant iron uptake mechanisms. Plants adopt two strategies (termed I and II) of iron acquisition. Strategy I is adopted by all higher plants except graminaceous plants, which adopt strategy II\ [MEDLINE:99289604], [MEDLINE:99137899]. In strategy I plants, the role of nicotianamine is not fully determined: possible roles include the formation of more\ stable complexes with ferrous than with ferric ion, which might serve as a sensor of the physiological status of iron within\ a plant, or which might be involved in the transport of iron [MEDLINE:99289604]. In strategy II (graminaceous) plants, nicotianamine is the\ key intermediate (and nicotianamine synthase the key enzyme) in the synthesis of the mugineic family (the only known\ family in plants) of phytosiderophores. Phytosiderophores are iron chelators whose secretion by the roots is greatly\ increased in instances of iron deficiency [MEDLINE:99137899].\ \ nicotianamine synthase activity ; GO:0030410 \N nicotianamine biosynthesis ; GO:0030418 22804 IPR004299 The MBOAT (membrane bound O-acyl transferase) family of membrane proteins contains a variety of acyltransferase enzymes. A conserved histidine has been suggested to be the active site residue [MEDLINE:20175785].\ \ \N \N \N 22794 IPR004289 Members of this family are functionally uncharacterised proteins from herpesviruses.\ \N \N \N 22795 IPR004290 Members of this family are functionally uncharacterised proteins from herpesviruses.\ \N \N \N 22796 IPR004291 Transposase proteins are necessary for efficient DNA transposition. This family includes the bacterial insertion sequence (IS) element, IS66, from Agrobacterium tumefaciens\ \ \ \ [MEDLINE:85063817]. IS66 may cause genetic and structural variations of the T region and\ the vir region of the octopine Ti plasmids [MEDLINE:85063817].\ \ \N \N \N 22797 IPR004292 The adenoviral protein 52K (named after the earliest known 52kDa members) is a DNA-binding protein [MEDLINE:96186720] that is probably involved in virion assembly.\ \N \N viral assembly ; GO:0019068 22793 IPR004288 This family consists exclusively of streptococcal competence stimulating peptide precursors, which are generally up to 50 amino acid residues long. In all the members of this family, the leader sequence is cleaved after two conserved glycine residues; thus the leader sequence is of the double- glycine type [MEDLINE:98012953]. Competence stimulating peptides (CSP) are small (less than 25 amino acid residues) cationic peptides. The N-terminal amino acid residue is negatively charged, either\ glutamate or aspartate. The C-terminal end is positively charged. The third residue is also positively charged: a highly\ conserved arginine [MEDLINE:98012953]. Some COMC proteins and their precursors (not included in this family) do not fully follow the\ above description.\

Functionally, CSP act as\ pheromones, stimulating competence for genetic transformation in streptococci. In streptococci, the (CSP mediated)\ competence response requires exponential cell growth at a critical density, a relatively simple requirement when\ compared to the stationary-phase requirement of Haemophilus, or the late-logarithmic- phase of Bacillus [MEDLINE:96074663]. All bacteria\ induced to competence by a particular CSP are said to belong to the same pherotype, because each CSP is recognized\ by a specific receptor (the signalling domain of a histidine kinase ComD). Pherotypes are not necessarily species-specific.\ In addition, an organism may change pherotype. There are two possible mechanisms for pherotype switching: horizontal\ gene transfer, and accumulation of point mutations. The biological significance of pherotypes and pherotype switching is\ not definitively determined. Pherotype switching occurs frequently enough in naturally competent streptococci to suggest\ that it may be an important contributor to genetic exchange between different bacterial species [MEDLINE:98012953].

\ \ pheromone activity ; GO:0005186 \N \N 22786 IPR004280 Members of this family are functionally uncharacterised proteins from herpesviruses.\ \N \N \N 22787 IPR004281 Interleukin 12 (IL-12) is a disulphide-bonded heterodimer consisting of a 35kDa

subunit and a 40kDa

subunit. It is involved in the stimulation and maintenance of Th1 cellular immune responses, including the normal host defence against various intracellular pathogens, such as Leishmania, Toxoplasma, measles virus and HIV. IL-12 also has an important role in pathological Th1 responses, such as in inflammatory bowel disease and multiple sclerosis. Suppression of IL-12 activity in such diseases may have therapeutic benefit. On the other\ hand, administration of recombinant IL-12 may have therapeutic benefit in conditions associated with pathological Th2\ responses [MEDLINE:21317397], [MEDLINE:98259427].\ \ growth factor activity ; GO:0008083 extracellular ; GO:0005576 immune response ; GO:0006955 22788 IPR004282 Members of this family are probable integral membrane proteins. Their molecular function is unknown. CemA proteins are found in the inner envelope membrane of chloroplasts but not in the thylakoid membrane [MEDLINE:96210582]. A cyanobacterial\ member of this family has been implicated in CO2 transport, but is probably not a CO2 transporter itself [MEDLINE:96210582].\ \ molecular_function unknown ; GO:0005554 integral to membrane ; GO:0016021 \N 22789 IPR004283 The late expression factor 2 (lef-2) protein from Nucleopolyhedrovirus is required for expression of late genes. The lef-2 protein has been shown to be specifically required for expression from the vp39 and polh promoters [MEDLINE:93188166].\ \ \N \N viral transcription ; GO:0019083 22790 IPR004284 Birnaviruses are ds RNA viruses. Non structural protein VP5 is found in RNA segment A. The function of this small viral protein is unknown.\ \ \N \N \N 22791 IPR004285 Members of this family are functionally uncharacterised.\ \N \N \N 22792 IPR004286 UL16 protein may play a role in capsid maturation including DNA packaging/cleavage [MEDLINE:98309064]. In immunofluorescence studies [MEDLINE:97124648], UL16 was localised to the nucleus of infected cells in areas containing high concentrations of HSV capsid proteins. These\ nuclear compartments have been described previously as viral assemblons [MEDLINE:96256775] and are distinct from compartments\ containing replicating DNA. Localization within assemblons argues for a role of UL16 encoded protein in capsid\ assembly or maturation [MEDLINE:97124648].\ \ \N \N \N 22783 IPR004277 Phosphatidyl serine synthase is also known as serine exchange enzyme (EC: 2.7.8.-). This family represents eukaryotic PSS I and II, membrane bound proteins that catalyse the replacement of the head group of a phospholipid (phosphotidylcholine or phosphotidylethanolamine) by L-serine.\ \ \N \N phosphatidylserine biosynthesis ; GO:0006659 22784 IPR004278 Caliciviruses are a small round-structured virus group defined by RNA-dependent RNA polymerase and capsid diversity.\ \N \N \N 22785 IPR004279 The perilipin family includes lipid droplet-associated protein (perilipin) and adipose differentiation-related protein (adipophilin). Perilipin is a modulator of adipocyte lipid metabolism and adipophilinis involved in the development and maintenance of adipose tissue. Other proteins belong to this group include TIP47, a cargo selection device for mannose 6-phosphate receptor trafficking [MEDLINE:98250059].\ \ \N \N \N 22769 IPR004263 Hereditary multiple exostoses (EXT) is an autosomal dominant disorder that is characterized by the appearance of multiple outgrowths of the long bones (exostoses) at their epiphyses [MEDLINE:98139867]. Mutations in two homologous genes, EXT1 and EXT2, are responsible for the EXT\ syndrome. The human and mouse EXT genes have at least two homologs in the invertebrate\ Caenorhabditis elegans, indicating that they do not function exclusively as regulators of bone growth.\ EXT1 and EXT2 have both been shown to encode glycosyltransferases involved in the chain\ elongation step of heparan sulfate biosynthesis [MEDLINE:98434521].\ \ \N membrane ; GO:0016020 cell growth and/or maintenance ; GO:0008151 22770 IPR004264 Proteins in this group are TNP1/EN/SPM-like transposon proteins with no known function mostly from Arabidopsis thaliana.\ \N \N \N 22771 IPR004265 This family contains a number of proteins which are induced during disease response in plants.\ \N \N response to pathogenic fungi ; GO:0009621 22772 IPR004266 This family contains the protein with a molecular mass of 26189 Da (P26) from beet necrotic yellow vein virus (BNYVV). The function of these proteins is unknown.\ \N \N \N 22773 IPR004267

This family represents the matrix protein, M2, of influenza C virus. The M1 protein is the product of a spliced mRNA (see IPR004271). Small quantities of the unspliced mRNA are found in the cell additionally encoding the M2 protein.

\ \ \N \N \N 22774 IPR004268 The MVIN-like protein is a putative integral membrane protein. The function is unknown.\ \N integral to membrane ; GO:0016021 pathogenesis ; GO:0009405 22775 IPR004269 This family includes the folate receptor which binds to folate and reduced folic acid derivatives and mediates delivery of 5-methyltetrahydrofolate to the interior of cells. These proteins are attached to the membrane by a GPI-anchor. A riboflavin-binding protein required for the transport of riboflavin to the developing oocyte in chicken also belong to this family.\ \ \N \N \N 22776 IPR004270 The E5 protein from papillomaviruses is about 80 amino acids long and contain three regions that have been predicted to be transmembrane

helices. The function of this protein is unknown.\ \N \N \N 22777 IPR004271

This family represents the matrix protein, M1, of influenza C virus. The M1 protein is the product of a spliced mRNA. Small quantities of the unspliced mRNA are found in the cell additionally encoding the M2 protein (see IPR004267).

\ \N viral capsid ; GO:0019028 \N 22778 IPR004272

This family contains the juvenile hormone binding protein of the tobacco hawkmoth (Manduca sexta ) [MEDLINE:94286603] as well as number of Drosophila proteins of unknown function. The juvenile hormone exerts pleiotropic functions during insect life cycles and its binding proteins regulate these functions.

Based on the similarity to the hormone binding protein it is suggested that the members of this family are odorant binding proteins.

\ \ molecular_function unknown ; GO:0005554 \N \N 22779 IPR004273

Dynein is a multisubunit microtubule-dependent motor enzyme that acts as the force generating protein of eukaryotic cilia and flagella. The cytoplasmic isoform of dynein acts as a motor for the intracellular retrograde motility of\ vesicles and organelles along microtubules.

Dynein is composed of a number of\ ATP-binding large subunits, intermediate size subunits and small subunits (see IPR001372).\ \ This family represents the C-terminal region of dynein heavy chain. The dynein heavy chain also exhibits ATPase activity and\ microtubule binding ability and acts as a motor for the movement of organelles and vesicles along microtubules.

\ \ dynein ATPase activity ; GO:0008567 dynein complex ; GO:0030286 microtubule-based movement ; GO:0007018 22780 IPR004274 The function of this domain is unclear. It is found in proteins of diverse function including phosphatases some of which may be active in active in ternary elongation complexes and a number of NLI interacting factors. In the phospatases this domain is often present N-terminal to the BRCT domain (IPR001357).\ \N \N \N 22781 IPR004275 In addition to the highly specific cell-mediated immune system, vertebrates possess an efficient host-defense mechanism against invading microorganisms which involves the synthesis of highly potent antimicrobial peptides with a large spectrum of activity. This family contains a number of these defence peptides secreted from the skin of amphibians, including the opiate-like\ dermorphins and deltorphins, and the antimicrobial dermoseptins and temporins.\ \ antimicrobial peptide activity ; GO:0003795 extracellular ; GO:0005576 defense response ; GO:0006952 22782 IPR004276

Glycosyltransferase family 28 CAZY:GT_28); -N-acetylglucosamine transferase (EC: 2.4.1.-).

\ \ transferase activity, transferring hexosyl groups ; GO:0016758 \N lipid glycosylation ; GO:0030259 22766 IPR004260 Pyrimidine dimer DNA glycosylases excise pyrimidine dimers by hydrolysis of the glycosylic bond of the 5' pyrimidine, followed by the intra-pyrimidine phosphodiester bond. One such enzyme is T4 endonuclease V, an enzyme responsible for the first step\ of a pyrimidine-dimer-specific excision-repair pathway [MEDLINE:91295981]. Bacteriophage T4 that are deficient in these enzymes are extremely sensitive to UV.\ \ \N \N DNA repair ; GO:0006281 22767 IPR004261 The hepatitis E virus structural protein 2 has a high basic amino acid content suggesting that it may play a role in viral genomic RNA encapsidation.\ structural molecule activity ; GO:0005198 \N \N 22768 IPR004262 This family represents the C-terminal region of the male sterility protein in a number of organisms. The Arabidopsis thaliana male sterility 2 (MS2) protein is involved in male gametogenesis. The MS2 protein shows sequence similarity to a jojoba protein (also a member of this group) that converts wax fatty acids to fatty alcohols. It has been suggested that a possible function of the MS2 protein may be as a fatty acyl reductase in the formation\ of pollen wall substances [MEDLINE:98012531].\ \ \N \N \N 22756 IPR004250 Somatostatin inhibits the release of the pituitary growth hormone, somatotropin and inhibits the release of glucagon and insulin from the pancreas of fasted animals. Cortistatin is a cortical neuropeptide with neuronal depressant and sleep-modulating properties [MEDLINE:96208649].\ hormone activity ; GO:0005179 extracellular ; GO:0005576 \N 22757 IPR004251

This is a Poxvirus protein family of unknown function.

\ \N \N \N 22758 IPR004252 Some members of this family are putative plant transposon proteins of unknown function. Some may be similar to leucine zipper transcription factors.\ \N \N \N 22759 IPR004253 This domain of unknown function is found in some Arabidopsis thaliana proteins. \ molecular_function unknown ; GO:0005554 \N \N 22760 IPR004254 Members of this family are integral membrane proteins. This family includes proteins that are hemolysin-III homologs.\ \N integral to membrane ; GO:0016021 \N 22761 IPR004255 This family of uncharacterised proteins is greatly expanded in Mycobacterium tuberculosis.\ molecular_function unknown ; GO:0005554 \N \N 22762 IPR004256 The DUF234 domain is present in a number of archaeabacterial proteins of unknown function.\ molecular_function unknown ; GO:0005554 \N \N 22763 IPR004257 This family contains a predicted structural envelope protein GP4 from equine arteritis virus (EAV).\ \N \N \N 22764 IPR004258 Severe Plasmodium falciparum malaria is characterized by excessive sequestration of infected and uninfected erythrocytes in the microvasculature of the affected organ. Rosetting, the adhesion of P. falciparum-infected erythrocytes to uninfected erythrocytes is a virulent parasite phenotype associated with the occurrence of severe malaria [MEDLINE:98080592]. The adhesive ligand P. falciparum erythrocyte membrane protein 1 (PfEMP1) is a rosetting protein that contains clusters of glycosaminoglycan-binding motifs.\ glycosaminoglycan binding activity ; GO:0005539 \N pathogenesis ; GO:0009405 22765 IPR004259 This family includes the M1 phosphoprotein non-structural RNA polymerase

subunit (EC: 2.7.7.48) from various strains of rabies virus\ \ \ [MEDLINE:91088333]. The M1 phosphoprotein is thought to be a\ component of the active polymerase, and may be involved in template binding.\ \ RNA-directed RNA polymerase activity ; GO:0003968 \N viral transcription ; GO:0019083 22743 IPR004237 The ability of bacteria to bind fibronectin is thought to enable the colonisation of wound tissue and blood clots. The fibronectin-binding protein is directly involved in the fibronectin-mediated adherence of the bacteria to epithelial cells [MEDLINE:92363585]. The fibronectin binding repeat is found in bacterial fibronectin binding proteins and serum opacity factor.\ \N cell wall (sensu Gram-positive Bacteria) ; GO:0009275 cell adhesion ; GO:0007155 22744 IPR004238 Different types of late embryogenesis abundant (LEA) proteins are expressed at different stages of late embryogenesis in higher plant seed embryos and under conditions of dehydration stress. They may be induced by abscisic acid. This domain may be repeated several times in these proteins whose function is unknown.\ \ \N \N \N 22745 IPR004239

This group comprises proteins of unknown function from Borrelia burgdorferi, the causitive organism of Lyme disease.

\ molecular_function unknown ; GO:0005554 \N \N 22746 IPR004240 The transmembrane 9 superfamily protein (TM9SF) may function as a channel or small molecule transporter. Proteins in this group are endosomal integral membrane proteins.\ transporter activity ; GO:0005215 integral to membrane ; GO:0016021 transport ; GO:0006810 22747 IPR004241 Light chain 3 (LC3) may function primarily as a MAP1A and MAP1B subunit and its expression may regulate the microtubule binding activity of of the neuronal microtubule-associated proteins (MAPs), MAP1A and MAP1B [MEDLINE:94209331]. Related proteins that belong to this group include the human ganglioside expression factor and a symbiosis-related fungal protein.\ \N \N \N 22748 IPR004242 This family includes a En/Spm-like transposable element, Tdc1 from carrot [MEDLINE:97324589]. The function of these proteins is unknown.\ \N \N \N 22749 IPR004243 This minor capsid protein may act as a link between the external capsid and the internal DNA-protein core. Residues at the C-terminal end of the protein may act as a protease cofactor leading to activation of the adenovirus proteinase [MEDLINE:86172221].\ \N viral capsid ; GO:0019028 \N 22750 IPR004244 Many human L1 elements are capable of retrotransposition. Some of these have been shown to exhibit reverse transcriptase (RT) activity [MEDLINE:97285120] although the function of many are, as yet, unknown.\ \N \N \N 22751 IPR004245 Members of this family are uncharacterised with a long conserved region that may contain several domains.\ molecular_function unknown ; GO:0005554 \N \N 22752 IPR004246 This family of uncharacterised proteins appears to be specific to Caenorhabditis elegans.\ molecular_function unknown ; GO:0005554 \N \N 22753 IPR004247 This family contains retroviral transactivating (Tat) proteins, from a variety of lentiviruses. The Tat protein may have a role in trans-activation of the viral long terminal repeat [MEDLINE:89098943].\ transcriptional activator activity ; GO:0016563 \N positive regulation of transcription ; GO:0045941 22754 IPR004248

Borrelia burgdorferi supercoiled plasmids encode multicopy tandem open reading frames called Orf-A, Orf-B, Orf-C and Orf-D. This family corresponds to Orf-D. The putative product of this gene has no known function [MEDLINE:96236048].

\ \ molecular_function unknown ; GO:0005554 \N \N 22755 IPR004249 The RPT2 protein is a signal transducer of the phototropic response in Arabidopsis thaliana. The RPT2 gene is light inducible; encodes a novel protein with putative phosphorylation sites, a nuclear localization signal, a BTB/POZ domain (IPR000210. The NPH3 protein is a NPH1 photoreceptor-interacting protein that is essential for phototropism.Phototropism of Arabidopsis thaliana seedlings in response to a blue light source is initiated by nonphototropic hypocotyl 1 (NPH1), a light-activated serine-threonine protein kinase [MEDLINE:20011525] ]. NPH3 is a member of\ a large protein family, apparently specific to higher plants, and may function as an adapter or scaffold protein to bring\ together the enzymatic components of a NPH1-activated phosphorelay [MEDLINE:20011525]. Many of the proteins in this group also contain the BTB/POZ domain (IPR000210/>) at the N-terminal.\ \ signal transducer activity ; GO:0004871 \N response to light ; GO:0009416 22734 IPR004228 Cryptophytes are unicellular photosynthetic algae that use a lumenally located light-harvesting system, which is distinct from the phycobilisome structure found in cyanobacteria and red algae. One of the key components of this system is water-soluble phycoerythrin (PE) 545 whose expression is enhanced by low light levels [MEDLINE:99362683]. Phycoerythrin (PE) 545 is a heterodimeric of

(1)

(2)betabeta subunits. Each

subunit carries a covalently linked 15,16-dihydrobiliverdin chromophore that probably acts as the final energy acceptor. The architecture of the heterodimer suggests that PE 545 may dock to an acceptor protein via a deep cleft and that energy may be transferred via this intermediary protein to the reaction center [MEDLINE:99362683].\ \ \N phycobilisome ; GO:0030089 photosynthesis ; GO:0015979 22735 IPR004229 Methylamine dehydrogenase (MADH) is an electron transfer protein that oxidises methylamine to amicyanin. It is a tetramer of two light (L) subunits and two heavy (H) subunits. The active site of the enzyme is located in the light subunit and is accessible via a hydrophobic channel between the heavy and light subunits.The redox cofactor of MADH is tryptophan tryptophylquinone [MEDLINE:93028362].\ amine dehydrogenase activity ; GO:0030058 periplasmic space (sensu Gram-negative Bacteria) ; GO:0030288 electron transport ; GO:0006118 22736 IPR004230 MutS, MutL and MutH are the three essential proteins for initiation of methyl-directed DNA mismatch repair to correct mistakes made during DNA replication in Escherichia coli. MutH cleaves a newly synthesized and unmethylated daughter strand 5' to the sequence d(GATC) in a hemi-methylated duplex. Activation of MutH requires the recognition of a DNA mismatch by MutS and MutL [MEDLINE:98151376].\ endonuclease activity ; GO:0004519 \N DNA modification ; GO:0006304 22737 IPR004231 The native inhibitor is resistant to fragmentation by proteases [MEDLINE:79187807]. It may play a defensive role against insect attack.\ metalloendopeptidase inhibitor activity ; GO:0008191 \N defense response ; GO:0006952 22738 IPR004232 Nitrile hydratase (EC: 4.2.1.84) is composed of two subunits,

and

and catalyzes the hydration of nitrile compounds to the corresponding amides.\ nitrile hydratase activity ; GO:0018822 \N nitrogen metabolism ; GO:0006807 22739 IPR004233

FokI (EC: 3.1.21.4) is a member of an unusual class of bipartite restriction enzymes that recognize a specific DNA sequence and cleave DNA nonspecifically a short distance away from that sequence. It is a type IIs restriction endonuclease [MEDLINE:98393685]. FokI contains amino- and carboxy-terminal domains corresponding to the DNA-recognition (IPR004234) and cleavage functions, respectively.

The catalytic domain contains only a single catalytic centre, raising the question of how monomeric FokI manages to cleave both DNA strands. The catalytic domain is sequestered in a 'piggyback' fashion by the recognition domain [MEDLINE:97357159].

\ \ type II site-specific deoxyribonuclease activity ; GO:0009036 \N DNA restriction ; GO:0009307 22740 IPR004234

The recognition domain is made of three smaller subdomains (D1, D2 and D3) which are evolutionarily related to the helix-turn-helix-containing DNA-binding domain of the catabolite gene activator protein CAP [MEDLINE:97357159].

\ \ type II site-specific deoxyribonuclease activity ; GO:0009036 \N DNA restriction ; GO:0009307 22741 IPR004235 Scytalone dehydratase (EC: 4.2.1.94) is a member of the group of enzymes involved in fungal melanin biosynthesis. It was first identified in a phytopathogenic fungus, Pyricularia oryzae, which causes rice blast disease. Scytalone dehydratase is a molecular target of inhibitor design efforts aimed at protecting rice plants from fungal disease [MEDLINE:99119201].\ hydro-lyase activity ; GO:0016836 \N melanin metabolism ; GO:0006582 22742 IPR004236

The serine proteases, trypsin family is almost totally confined to animals, although trypsin-likeenzymes are found in actinomycetes of the genera Streptomyces and\ Saccharopolyspora, and in the fungus Fusarium oxysporum\ \ \ \ [MEDLINE:95147689]. The enzymes\ are inherently secreted, being synthesised with a signal peptide that\ targets them to the secretory pathway. Animal enzymes are either secreted\ directly, packaged into vesicles for regulated secretion, or are retained\ in leukocyte granules [MEDLINE:95147689].

The -lytic protease prodomain is almost always found in association with the serine proteases, trypsin family in the bacterial enzymes (IPR001254.

\ \ serine-type peptidase activity ; GO:0008236 extracellular ; GO:0005576 proteolysis and peptidolysis ; GO:0006508 22731 IPR004224 Fumarate reductase couples the reduction of fumarate to succinate to the oxidation of quinol to quinone, in a reaction opposite to that catalysed by the related complex II of the respiratory chain (succinate dehydrogenase) [MEDLINE:20052158]. Three protein subunits contain the fumarate reductase complex. Subunit A contains the site of fumarate reduction and a covalently bound flavin adenine dinucleotide prosthetic group. Subunit B contains three iron-sulphur centres. The menaquinol-oxidizing subunit C (this family) consists of five membrane-spanning, primarily helical segments and binds two haem b molecules [MEDLINE:20052158].\ \ \N \N electron transport ; GO:0006118 22733 IPR004227 The bifunctional enzyme formiminotransferase-cyclodeaminase (FTCD) contains two active sites at different positions on the protein structure. This domain is for the formiminotransferase. The enzyme binds a gamma-linked polyglutamylated form of the tetrahydrofolate substrate and channels the product\ of the transferase reaction from the transferase active site to the cyclodeaminase active site [MEDLINE:20139690].\ \ transferase activity ; GO:0016740 \N metabolism ; GO:0008152 22732 IPR004226

The folding pathway of tubulins includes highly specific interactions with a series of cofactors (A, B, C, D and E) after they are released from the eukaryotic chaperonin CCT. Cofactors A and D capture and stabilise tubulin in a quasi-native conformation. Cofactor E binds to the cofactor D-tubulin complex, and interaction with cofactor C then causes the release of tubulin poypeptides in the native state. This family is the tubulin-specific chaperone A.

\ tubulin-specific chaperone activity ; GO:0017072 \N chaperonin-mediated tubulin folding ; GO:0007022 22716 IPR004209 Ferredoxin thioredoxin reductase is a [4FE-4S] protein which plays an important role in the ferredoxin/thioredoxin regulatory chain. It converts an electron signal (photoreduced ferredoxin) to a thiol signal (reduced thioredoxin), regulating enzymes by reduction of specific disulfide groups. It catalyses the light-dependent activation of several photosynthetis enzymes. Ferredoxin thioredoxin reductase is a heterodimer of subunit a and subunit b. Subunit a is the variable subunit, and b is the catalytic chain. This family is the

chain.\ ferredoxin reductase activity ; GO:0008937 \N electron transport ; GO:0006118 22717 IPR004210 The BESS motif is named after the proteins in which it is found (BEAF [MEDLINE:95300220], Suvar(3)7 [MEDLINE:90190836] and Stonewall [MEDLINE:96194052]). The motif is 40 amino acid residues long and is composed of two predicted

helices. Based on the protein in which it is found and the presence of conserved positively charged residues it is predicted to be a DNA binding domain. This domain appears to be specific to Drosophila.\ DNA binding activity ; GO:0003677 \N \N 22718 IPR004211 This domain is found in a family of proteins which includes phage T4 endonuclease VII, Mycobacteriophage gene 59, and other as yet uncharacterised proteins. Phage T4 endonuclease VII (Endo VII) recognizes a broad spectrum of DNA substrates ranging from branched DNAs to single base mismatches. The structure of this enzyme has been resolved and it was found that the monomers form an elongated, intertwined molecular dimer that exibits extreme domain swapping. Two pairs of antiparallel helices which form a novel 'four-helix cross' motif are the major dimerization elements [MEDLINE:99177160].\ endonuclease activity ; GO:0004519 \N \N 22719 IPR004212 This region of sequence similarity is found up to six times in a variety of proteins including GTF2I. It has been suggested that this may be a DNA binding domain [MEDLINE:98449952], [MEDLINE:99216421].\ \N \N \N 22720 IPR004213 The flt3 (fms-related tyrosine kinase 3) ligand is a short chain cytokine with a 4 helical bundle fold. It is a type I membrane protein which stimulates the proliferation of of early hematopoeitic cells, and synergises well with other colony stimulating factors and interleukins.\ cytokine activity ; GO:0005125 membrane ; GO:0016020 \N 22721 IPR004214 Conotoxins are small snail neurotoxins that block ion channels. Omega-conotoxins act at presynaptic membranes and bind and block the calcium channels.\ neurotoxin activity ; GO:0019847 extracellular ; GO:0005576 pathogenesis ; GO:0009405 22722 IPR004215 Prokaryotic glutathione synthetase EC: 6.3.2.3 (glutathione synthase) catalyses the conversion of gamma-L-glutamyl-L-cysteine and glycine to orthophosphate and glutathione in the presence of ATP. This is the second step in glutathione biosynthesis. The enzyme is inhibited by 7,8-dihydrofolate, methotrexate and trimethoprim. This domain is the N-terminus of the enzyme.\ glutathione synthase activity ; GO:0004363 \N glutathione biosynthesis ; GO:0006750 22723 IPR004216

L-fucose isomerase (EC: 5.3.1.25) converts the aldose L-fucose into the corresponding ketose L-fuculose during the first step in fucose metabolism using Mn2+ as a cofactor. The enzyme is a hexamer, forming the largest structurally known ketol isomerase, and has no sequence or structural similarity with other ketol isomerases. The structure was determined by X-ray crystallography at 2.5 A resolution [MEDLINE:98035055].

\ \ L-fucose isomerase activity ; GO:0008736 cytoplasm ; GO:0005737 fucose metabolism ; GO:0006004 22724 IPR004217 This is a putative zinc binding domain with four conserved cysteine residues. This domain is found in the human disease protein Deafness Dystonia Protein 1. Members of this family such as Tim9 and Tim10 are involved in mitochondrial protein import [MEDLINE:20553219]. Members of this family seem to be localised to the mitochondrial intermembrane space [MEDLINE:96291871].\ protein translocase activity ; GO:0015450 mitochondrial inner membrane ; GO:0005743 mitochondrial translocation ; GO:0006628 22725 IPR004218 Prokaryotic glutathione synthetase EC: 6.3.2.3 (glutathione synthase) catalyses the conversion of gamma-L-glutamyl-L-cysteine and glycine to orthophosphate and glutathione in the presence of ATP. This is the second step in glutathione biosynthesis. The enzyme is inhibited by 7,8-dihydrofolate, methotrexate and trimethoprim. This is the ATP-binding domain of the enzyme.\ ATP binding activity ; GO:0005524 \N glutathione biosynthesis ; GO:0006750 22726 IPR004219 TT virus (TTV), isolated initially from a Japanese patient with hepatitis of unknown aetiology, has since been found to infect both healthy and diseased individuals and numerous prevalence studies have raised questions about its role in unexplained hepatitis. ORF1 is a large 750 residue protein.\ \N \N \N 22727 IPR004220 5-carboxymethyl-2-hydroxymuconate isomerase (EC: 5.3.3.10) transforms 5-carboxymethyl-2-hydroxy-muconic acid into 5-oxo-pent-3-ene-1,2,5-tricarboxylic acid during the\ third step of the homoprotocatechuate catabolic pathway.\ \ \ 5-carboxymethyl-2-hydroxymuconate delta-isomerase activity ; GO:0008704\ \N \N aromatic compound metabolism ; GO:0006725 22728 IPR004221 Restriction endonuclease EcoRI (EC: 3.1.21.4) is a type II site-specific deoxyribonuclease, which catalyses the endonucleolytic cleavage of DNA, using magnesium as a cofactor, to give specific double-stranded fragments with terminal 5'-phosphates. Type II restriction endonucleases are characterized by their specificity for recognising and cleaving specific DNA sequences. The sequences of these endonucleases are surprisingly unrelated. Restriction endonuclease EcoRI recognises the DNA sequence GAATTC and cleaves after G-1.\ type II site-specific deoxyribonuclease activity ; GO:0009036 \N DNA restriction ; GO:0009307 22729 IPR004222 Methane monooxygenase (EC: 1.14.13.25) catalyses the oxidation of methane to methanol ion the presence of oxygen and NAD(P)H in methanotrophs. It has a broad specificity, hydroxylating many alkanes, and converting alkenes into the corresponding epoxides. In additional reactions CO is oxidized to CO(2), ammonia is oxidized to hydroxylamine, and some aromatic compounds and cyclic alkanes can also be hydroxylated, although more slowly. In Methylococcus capsulatus there are two forms of the enzyme, a soluble and a membrane-bound type. The soluble form consists of 3 components, A, B and C. Protein A is made up of 3 chains,

and gamma. This family is the gamma chain.\ methane monooxygenase activity ; GO:0015049 \N methane metabolism ; GO:0015947 22730 IPR004223 Vitamin B12 dependent methionine synthase EC: 2.1.1.13 (5-methyltetrahydrofolate--homocysteine S-methyltransferase) catalyses the conversion of 5-methyltetrahydrofolate and L-homocysteine to tetrahydrofolate and L-methionine as the final step in de novo methionine biosynthesis. The enzyme requires methylcobalamin as a cofactor. In humans, defects in this enzyme are the cause of autosomal recessive inherited methylcobalamin deficiency (CBLG), which causes mental retardation, macrocytic anemia and homocystinuria. Mild deficiencies in activity may result in mild hyperhomocysteinemia, and mutations in the enzyme may be involved in tumorigenesis. Vitamin B12 dependent methionine synthase is found in prokaryotes and eukaryotes, but in prokaryotes the cofactor is cobalamin.\ \ \ 5-methyltetrahydrofolate-homocysteine S-methyltransferase activity ; GO:0008705\ \N intracellular ; GO:0005622 methionine biosynthesis ; GO:0009086 22711 IPR004204 Cytochrome c oxidase, a 13 subunit complex, EC: 1.9.3.1 is the terminal oxidase in the mitochondrial electron transport chain. Thisfamily is composed of cytochrome c oxidase subunit VIc.\ \ cytochrome c oxidase activity ; GO:0004129 \N electron transport ; GO:0006118 22712 IPR004205

The ubiquinol-cytochrome C reductase complex (cytochrome bc1 complex) is a respiratory multi-enzyme complex [MEDLINE:98316377], which recognizes a mitochondrial targeting presequence. The bc1 complex contains 11 subunits: 3 respiratory subunits (cytochrome b, cytochrome c1 and Rieske protein), 2 core proteins and 6 low molecular weight proteins. This family represents the 9.5 kDa subunit of the complex. This subunit together with cytochrome B binds to ubiquinone.

\ ubiquinol-cytochrome c reductase activity ; GO:0008121 ubiquinol-cytochrome c reductase complex (sensu Eukarya) ; GO:0015008 electron transport ; GO:0006118 22713 IPR004206 The mRNA capping enzyme in yeasts is composed of two separate chains, a mRNA guanyltransferase and an RNA 5'-triphosphate. This is the

chain of mRNA capping enzyme which has triphosphatase activity. The

chain (polynucleotide 5'-phosphatase EC: 3.1.3.33) converts the 5'-triphosphate end of a nascent mRNA chain into a diphosphate in the first step of mRNA capping.The function of the capping enzyme also depends on the guanylyltransferase activity conferred by the

chain (see IPR001339).\ \ polynucleotide 5'-phosphatase activity ; GO:0004651 nucleus ; GO:0005634 mRNA capping ; GO:0006370 22714 IPR004207 Ferredoxin thioredoxin reductase is a [4FE-4S] protein which plays an important role in the ferredoxin/thioredoxin regulatory chain. It converts an electron signal (photoreduced ferredoxin) to a thiol signal (reduced thioredoxin), regulating enzymes by reduction of specific disulfide groups. It catalyses the light-dependent activation of several photosynthetis enzymes. Ferredoxin thioredoxin reductase is a heterodimer of subunit a and subunit b. Subunit a is the variable subunit, and b is the catalytic chain. This family is the

chain.\ ferredoxin reductase activity ; GO:0008937 \N electron transport ; GO:0006118 22715 IPR004208 A specific region of the influenza B virus NS1 protein, which includes part of its effector domain, blocks the covalent linkage of mouse ISG15 to its target proteins both in vitro and in infected cells. Of the several hundred proteins induced by interferon (IFN)

, the ubiquitin-like ISG15 protein is one of the most predominant. Influenza A virus employs a different strategy: its NS1 protein does not bind the ISG15 protein, but little or no ISG15 protein is produced during infection [MEDLINE:21099215].\ \N \N \N 22707 IPR004200

The -galactosidase enzymes (EC: 3.2.1.23) belong to the glycosyl hydrolase 42 family CAZY:GH_42. The enzyme catalyses the hydrolysis of terminal, non-reducing terminal -D-galactosidase residues. This domain is found in the carboxy-terminal portion of the small chain of dimeric -galactosidases, as well as in single chain -galactosidase.

\ \ beta-galactosidase activity ; GO:0004565 beta-galactosidase complex ; GO:0009341 carbohydrate metabolism ; GO:0005975 22710 IPR004203 Cytochrome c oxidase, a 13 sub-unit complex, EC: 1.9.3.1 is the terminal oxidase in the mitochondrial electron transport chain. Thisfamily is composed of cytochrome c oxidase subunit IV. The Dictyostelium discoideum member of this family is called COX VI. The Saccharomyces cerevisiae protein YGX6_YEAST appears to be the yeast COX IV subunit.\ \ cytochrome c oxidase activity ; GO:0004129 \N electron transport ; GO:0006118 22708 IPR004201 This domain has a double psi-

barrel fold and includes VCP-like ATPase and N-ethylmaleimide sensitive fusion protein N-terminal domains. Both the VAT and NSF N-terminal functional domains consist of two structural domains of which this is at the C-terminus. The VAT-N domain found in AAA ATPases (IPR003959.\ ATP binding activity ; GO:0005524 \N \N 22709 IPR004202 Cytochrome c oxidase, a 13 sub-unit complex, EC: 1.9.3.1 is the terminal oxidase in the mitochondrial electron transport chain. Thisfamily is composed of cytochrome c oxidase subunit VIIc. The yeast member of this family is called COX VIII\ \ cytochrome c oxidase activity ; GO:0004129 \N electron transport ; GO:0006118 22706 IPR004199

O-Glycosyl hydrolases (EC 3.2.1.-) are a widespread group of enzymes that hydrolyse the glycosidic bond between two or more carbohydrates, or between a carbohydrate and a non-carbohydrate moiety. A classification system for glycosyl hydrolases, based on sequence similarity, has led to the definition of 85 different families [MEDLINE:92082464], [MEDLINE:93356744], [MEDLINE:96257770], [MEDLINE:92121114], [MEDLINE:96097392], PUB00005672. This classification is available on the CAZy (CArbohydrate-Active EnZymes) web site [http://afmb.cnrs-mrs.fr/~pedro/CAZY/ghf.html]. Because the fold of proteins is better conserved than their sequences, some of the families can be grouped in 'clans'.

The -galactosidase enzymes (EC: 3.2.1.23) belong to the glycosyl hydrolase 42 family CAZY:GH_42. The enzyme catalyses the hydrolysis of terminal, non-reducing terminal -D-galactosidase residues. This domain is found in the amino-terminal portion of the small chain of dimeric -galactosidases, as well as in single chain -galactosidase.

\ \ beta-galactosidase activity ; GO:0004565 beta-galactosidase complex ; GO:0009341 carbohydrate metabolism ; GO:0005975 22703 IPR004196 The assembly of a macromolecular structure proceeds via a specific pathway of ordered events and occurs by changing of protein conformations as they join the assembly. The assembly process is aided by scaffolding proteins, which act as chaperones. In bacteriophages, scaffolding proteins B and D are responsible for procapsid formation. Copies of protein D (240) form the external scaffold, while 60 copies of protein B form the internal scaffold [MEDLINE:97449380]. The role of scaffolding protein D is in the production of viral single-stranded RNA.\ \N \N viral procapsid maturation ; GO:0046797 22704 IPR004197

Cellulases (Endoglucanases) EC: 3.2.1.4 catalyse the endohydrolysis of 1,4--D-glucosidic linkages in cellulose.\ This is the N-terminal ig-like domain of cellulase, enzymes containing this domain belong to family 9 of the glycoside hydrolases (CAZY:GH_9).

\ \ cellulase activity ; GO:0008810 \N carbohydrate metabolism ; GO:0005975 22705 IPR004198 Predicted zinc finger with eight potential zinc ligand binding residues. This domain is found in Jumonji [MEDLINE:21108725], and may have a DNA binding function. The mouse jumonji protein is required for neural tube formation, and is essential for normal heart development. It also plays a role in the down-regulation of cell proliferation signalling.\ \N nucleus ; GO:0005634 \N 22696 IPR004189

This transposase is essential for integration, replication-transposition and excision of Mu Bacteriophage DNA. Transposition requires transposase and a transposition enhancer, and the DNA can be transposed into multiple sites in bacterial genomes.

The crystal structure of the core domain of bacteriophage Mu transposase, MuA, has been determined. The first of two subdomains contains the active site and, despite very limited sequence homology, exhibits a striking similarity to the core domain of HIV-1 integrase. The enzymatic activity of MuA is known to be activated by formation of a DNA-bound tetramer of the protein [MEDLINE:95354202].

\ \ transposase activity ; GO:0004803 \N DNA integration ; GO:0015074 22697 IPR004190 The DNA polymerase processivity factor is a replisome sliding clamp subunit, which is responsible for tethering the catalytic subunit of DNA polymerase to the DNA during high speed replication. The crystal structure of the bacteriophage RB69 sliding clamp has been solved. It has shown that the peptide binds to the sliding clamp at the same position as that of a replication inhibitor peptide bound to PCNA. This suggests that the replication inhibitor protein p21CIP1 competes with eukaryotic polymerases for the same binding pocket on the clamp [MEDLINE:20004392].\ \N \N DNA replication ; GO:0006260 22698 IPR004191 The integrase family of site-specific recombinases catalyze a diverse array of DNA rearrangements in archaebacteria, eubacteria and yeast. The structure of theDNA binding domain of the the conjugative transposon Tn916 integrase protein was determined using NMR spectroscopy. The N-terminal domain was found to be structurally similar to the double stranded RNA binding domain (dsRBD). Experimental evidence suggests that the integrase protein interacts with DNA using residues located on the face of its three stranded

-sheet [MEDLINE:98328103].\ \ integrase activity ; GO:0008907 \N DNA integration ; GO:0015074 22699 IPR004192 The ubiquinol cytochrome c reductase (cytochrome bc1) complex is a respiratory chain that generates an elctrochemical potential coupled to ATP synthesis. The bc1 complex contains 11 subunits, 3 respiratory subunits (cytochrome B, cytochrome C1, Rieske protein), 2 core proteins and 6 low-molecular weight proteins. Each subunit of the cytochrome bc1 complex provides a single helix (this family) to make up the transmembrane region of the complex.\ ubiquinol-cytochrome c reductase activity ; GO:0008121 ubiquinol-cytochrome c reductase complex (sensu Eukarya) ; GO:0015008 electron transport ; GO:0006118 22700 IPR004193

\ Enzymes containing this domain belong to family 13 (CAZY:GH_13) of the glycosyl hydrolases. This domain is found in a range of enzymes that act on branched substrates ie. isoamylase, pullulanase and\ branching enzyme. Isoamylase hydrolyses 1,6-

-D-glucosidic branch linkages in glycogen, amylopectin and\ dextrin; 1,4-

-glucan branching enzyme functions in the formation of 1,6-glucosidic linkages of glycogen; and\ pullulanase is a starch-debranching enzyme.\ \ hydrolase activity, hydrolyzing O-glycosyl compounds ; GO:0004553 \N carbohydrate metabolism ; GO:0005975 22702 IPR004195 Bacteriophage lambda head decoration protein D stabilizes the head shell after the rearrangement of GP7 subunits of the head shell lattice that accompanies expansion of the head. There are approximately 420 copies of protein D per mature phage.\ \N viral capsid ; GO:0019028 \N 22701 IPR004194 Type II restriction endonucleases are characterized by their specificity for recognising and cleaving specific DNA sequences. The sequences of these endonucleases are surprisingly unrelated, however the structure of restriction endonuclease BamHI was determined at 1.95 A resolution, and shows a resemblance to the structure of endonuclease EcoRI [MEDLINE:94195433].\ type II site-specific deoxyribonuclease activity ; GO:0009036 \N DNA restriction ; GO:0009307 22695 IPR004188

\ \

Class-II tRNA synthetases do not share a high degree of similarity, however at least three conserved regions are present [MEDLINE:94099781], [MEDLINE:91272282], [MEDLINE:91305088].

\ \

Phenylalanyl-tRNA synthetase from Thermus thermophilus has an 2 2 type quaternary structure and is one of the most complicated members of the synthetase family. Identification of phenylalanyl-tRNA synthetase as a member of class II aaRSs was based only on sequence alignment of the small -subunit with other synthetases [MEDLINE:94257735]. This is the N-terminal domain of phenylalanyl-tRNA synthetase.

\ \ ATP binding activity ; GO:0005524 \N phenylalanyl-tRNA aminoacylation ; GO:0006432 22690 IPR004182 The GRAM domain is found in in glucosyltransferases, myotubularins and other putative membrane-associated proteins.\ \N \N \N 22691 IPR004183 The LigAB enzyme (a protocatechuate 4,5-dioxygenase EC: 1.13.11.8), of Sphingomonas paucimobilis oxidizes protocatechuate (or 3,4-dihydroxybenzoic acid, PCA). The enzyme belongs to the class III extradiol-type catecholic dioxygenase family, which catalyzes the ring-opening reaction of protocatechuate and related compounds [MEDLINE:99404941]. Other members of this family include 3,4-dihydroxyphenylacetate 2,3-dioxygenase (EC: 1.13.11.15) and 2,3-dihydroxyphenylpropionate 1,2-dioxygenase.\ oxidoreductase activity ; GO:0016491 \N aromatic compound metabolism ; GO:0006725 22692 IPR004184

Pyruvate formate-lyase EC: 2.3.1.54 (also known as formate C-acetyltransferase) is an enzyme which converts acetyl-CoA and formate to CoA and pyruvate.

 Acetyl-CoA + formate = CoA + pyruvate

In Escherichia coli, it uses a radical mechanism to reversibly cleave the C1-C2 bond of pyruvate using the Gly 734 radical and two cysteine residues (Cys 418, Cys 419) [MEDLINE:99436526].

\ \ formate C-acetyltransferase activity ; GO:0008861 cytoplasm ; GO:0005737 glucose metabolism ; GO:0006006 22693 IPR004185

\ Enzymes containing this domain belong to family 13 (CAZY:GH_13) of the glycosyl hydrolases. The maltogenic

-amylase is an enzyme which catalyses hydrolysis of (1-4)-

-D-glucosidic linkages in polysaccharides so as to remove successive

-maltose residues from the non-reducing ends of the chains in the conversion of starch to maltose. Other enzymes include neopullulanase, which hydrolyses pullulan to panose, and cyclomaltodextrinase, which hydrolyses cyclodextrins.\ \ hydrolase activity, hydrolyzing O-glycosyl compounds ; GO:0004553 \N carbohydrate metabolism ; GO:0005975 22694 IPR004186 The Epstein-Barr virus nuclear antigen 1 (EBNA1) binds to and activates DNAreplication from the latent origin of replication in Epstein-Barr virus. The crystal structure of the DNA-binding and dimerization domains were solved [MEDLINE:96006523], and it was found that EBNA1 appears to bind DNA via two independent regions, the core and the flanking DNA-binding domains. This DNA-binding domain has a ferredoxin-like fold.\ \ DNA binding activity ; GO:0003677 host cell nucleus ; GO:0042025 \N 22679 IPR004171 Members of this family are extremely potent competitive inhibitors of cAMP-dependent protein kinase activity. These proteins interact with the catalytic subunit of the enzyme after the cAMP-induced dissociation of its regulatory chains.\ cAMP-dependent protein kinase inhibitor activity ; GO:0004862 \N negative regulation of protein kinase activity ; GO:0006469 22680 IPR004172 The L27 domain is found in receptor targeting proteins Lin-2 and Lin-7, as well as some protein kinases and human MPP2 protein.\ \N \N \N 22681 IPR004173 This domain is predicted to be a small molecule binding domain, based on its occurrence with other domains [MEDLINE:21189415]. The domain is named after its three conserved histidine residues.\ binding activity ; GO:0005488 \N \N 22682 IPR004174 gpW is a 68 residue protein known to be present in phage particles. Extracts of phage-infected cells lacking gpW contain DNA-filled heads, and active tails, but no infectious virions. gpW is required for the addition of gpFII to the head, which is, in turn, required for the attachment of tails. Since gpFII and tails are known to be attached at the connector, gpW is also likely to assemble at this site. The addition of gpW to filled heads increases the DNase resistance of the packaged DNA, suggesting that gpW either forms a plug at the connector to prevent ejection of the DNA, or binds directly to the DNA. The large number of positively charged residues in gpW (its calculated pI is 10.8) is consistent with a role in DNA interaction [MEDLINE:21199556].\ \N \N viral assembly, maturation, egress, and release ; GO:0019067 22683 IPR004175 Members of this family are bacterial and archaeal RNA ligases that are able to ligate tRNA half molecules containing 2',3'-cyclic phosphate and 5' hydroxyl termini to products containing the 2',5' phosphodiester linkage. Each member of this family contains an internal duplication, each of which contains an HXTX motif that defines the family. The structure of a related protein is known [MEDLINE:20532513].\ \ 2'-5' RNA ligase activity ; GO:0008664\ \N \N RNA metabolism ; GO:0016070 22684 IPR004176 This short domain is found in one or two copies at the amino terminus of ClpA and ClpB proteins from bacteria and eukaryotes. The function of these domains is uncertain but they may form a protein binding site [MEDLINE:20545497]. The proteins are thought to be subunits of ATP-dependent proteases which act as chaperones to target the proteases to substrates.\ ATP binding activity ; GO:0005524 \N \N 22685 IPR004177 The DDHD domain is 180 residues long and contains four conserved residues that may form a metal binding site. The domain is named after these four residues. This pattern of conservation of metal binding residues is often seen in phosphoesterase domains. This domain is found in retinal degeneration B proteins, as well as a family of probable phospholipases.\ heavy metal binding activity ; GO:0005505 \N \N 22686 IPR004178 Small-conductance Ca2+-activated K+ channels (SK channels) are independent of voltage and gated solely by intracellular Ca2+. These membrane channels are heteromeric complexes that comprise pore-forming

-subunits and the Ca2+-binding protein calmodulin (CaM) [MEDLINE:21223356]. CaM binds to the SK channel through this the CaM-binding domain (CaMBD), which is located in an intracellular region of the

-subunit immediately carboxy-terminal to the pore. Channel opening is triggered when Ca2+ binds the EF hands in the N-lobe ofCaM. The structure of this domain complexed with CaM is known [MEDLINE:21223356]. This domain forms an elongated dimer with a CaM molecule bound at each end; each CaM wraps around three

-helices, two from one CaMBD subunit and one from the other.\ \ calcium-activated potassium channel activity ; GO:0015269 integral to membrane ; GO:0016021 potassium ion transport ; GO:0006813 22687 IPR004179 This domain was named after the yeast Sec63 (or NPL1) protein in which it was found. This protein is required for preprotein translocation. Other yeast proteins containing this domain include pre-mRNA splicing helicase BRR2, HFM1 protein and putative helicases.\ \N nucleus ; GO:0005634 \N 22688 IPR004180 This family of proteins are found in Borrelia burgdorferi. The proteins are about 190 amino acids long and have no known function.\ molecular_function unknown ; GO:0005554 \N \N 22689 IPR004181

Miz1 (Msx-interacting-zinc finger) is a zinc finger-containing protein with homology to the yeast protein, Nfi-1. Miz1 is a sequence specific DNA binding protein that can function as a positive-acting transcription factor. Miz1 binds to the homeobox protein Msx2, enhancing the specific DNA-binding ability of Msx2 [MEDLINE:97398443]. Other proteins containing this domain include the human pias family (protein inhibitor of activated STAT protein).

\ zinc ion binding activity ; GO:0008270 \N \N 22676 IPR004168 This protein motif is found in the PEVK region of the titin protein. Titin is a muscle protein which may be involved in muscle assembly and maintaining structural integrity of sarcomeres. It may have protein kinase activity.\ structural constituent of muscle ; GO:0008307 \N muscle development ; GO:0007517 22677 IPR004169 This family of spider neurotoxins are thought to be calcium ion channel inhibitors.\ neurotoxin activity ; GO:0019847 extracellular ; GO:0005576 pathogenesis ; GO:0009405 22678 IPR004170 The WWE domain is named after three of its conserved residues and is predicted to mediate specific protein-protein interactions in ubiquitin and ADP ribose conjugation systems.\ \N \N \N 22670 IPR004162 The seven in absentia (sina) gene was first identified in Drosophila. The Drosophila Sina protein is essential for the determination of the R7 pathway in photoreceptor cell development: the loss of functional Sina results in the transformation of the R7 precursor cell to a non- neuronal cell type. The Sina protein contains an N-terminal RING finger domain zf-C3HC4. Through this domain, Sina binds E2 ubiquitin-conjugating enzymes (UbcD1) Sina also interacts with Tramtrack (TTK88) via PHYL. Tramtrack is a transcriptional repressor that blocks photoreceptor determination, while PHYL down-regulates the activity of TTK88. In turn, the activity of PHYL requires the activation of the Sevenless receptor tyrosine kinase, a process essential for R7 determination. It is thought that thus Sina targets TTK88 for degradation, therefore promoting the R7 pathway. Murine and human homologues of Sina have also been identified. The human homologue Siah-1 [MEDLINE:98066768] ] also binds E2 enzymes (UbcH5) and through a series of physical interactions, targets

-catenin for ubiquitin degradation. Siah-1 expression is enhanced by p53, itself promoted by DNA damage. Thus this pathway links DNA damage to

-catenin degradation [MEDLINE:97410311], [MEDLINE:21286882]. Sina proteins, therefore, physically interact with a variety of proteins. The N-terminal RING finger domain that binds ubiquitin conjugating enzymes is described in zf-C3HC4, and does not form part of the alignment for this family. The remainder C-terminal part is involved in interactions with other proteins, and is included in this alignment. In addition to the Drosophila protein and mammalian homologues, whose similarity was noted previously, this family also includes putative homologues from Caenorhabditis elegans, Arabidopsis thaliana.\ \N nucleus ; GO:0005634 development ; GO:0007275 22674 IPR004166 Proteins containing this domain consist of a novel group of eukaryotic protein kinase catalytic domains, which have no detectable similarity to conventional kinases. Proteins include myosin heavy chain kinases [MEDLINE:95122486], [MEDLINE:97207233] and Elongation Factor-2 kinase and a bifunctional ion channel [MEDLINE:21108343].\ ATP binding activity ; GO:0005524 \N protein amino acid phosphorylation ; GO:0006468 22675 IPR004167 A small domain of the E2 subunit of 2-oxo-acid dehydrogenases that is responsible for the binding of the E3 subunit. Proteins containing this domain include the branched-chain

-keto acid dehydrogenase complex of bacteria, which catalyses the overall conversion of

-keto acids to acyl-CoA and carbon dioxide; and the E-3 binding protein of eukaryotic pyruvate dehydrogenase.\ acyltransferase activity ; GO:0008415 \N metabolism ; GO:0008152 22671 IPR004163 Coenzyme A (CoA) transferases belong to an evolutionary conserved [MEDLINE:92325057], [MEDLINE:97467359] family of enzymes catalyzing the reversible transfer of CoA from one carboxylic acid to another. They have been identified in many prokaryotes and in mammalian tissues. The bacterial enzymes are heterodimer of two subunits (A and B) of about 25 Kd each while eukaryotic SCOT consist of a single chain which is colinear with the two bacterial subunits. This entry corresponds to a region in the N-terminal of the A subunit that may be implicated in the binding of CoA to the enzyme.\ CoA-transferase activity ; GO:0008410 \N metabolism ; GO:0008152 22672 IPR004164 Coenzyme A (CoA) transferases belong to an evolutionary conserved [MEDLINE:92325057], [MEDLINE:97467359] family of enzymes catalyzing the reversible transfer of CoA from one carboxylic acid to another. They have been identified in many prokaryotes and in mammalian tissues. The bacterial enzymes are heterodimer of two subunits (A and B) of about 25 Kd each while eukaryotic SCOT consist of a single chain which is colinear with the two bacterial subunits. This entry corresponds to a region in the N-terminal of the B subunit and contains a glutamate that is involved in the catalytic mechanism.\ CoA-transferase activity ; GO:0008410 \N metabolism ; GO:0008152 22673 IPR004165 Coenzyme A (CoA) transferases belong to an evolutionary conserved [MEDLINE:92325057], [MEDLINE:97467359] family of enzymes catalyzing the reversible transfer of CoA from one carboxylic acid to another. They have been identified in many prokaryotes and in mammalian tissues. The bacterial enzymes are heterodimer of two subunits (A and B) of about 25 Kd each while eukaryotic SCOT consist of a single chain which is colinear with the two bacterial subunits.\ CoA-transferase activity ; GO:0008410 \N metabolism ; GO:0008152 22667 IPR004159 Members of this family of hypothetical plant proteins are probably methyltransferases. Several of the aligned sequences either match the methyltransferase profile PS50124 (IPR001601). Q9ZQ84 contains both.\ molecular_function unknown ; GO:0005554 \N \N 22668 IPR004160 Elongation factor Tu consists of three structural domains, this is the third domain. This third domain adopts a

barrel structure, and is involved in binding to both charged tRNA [MEDLINE:96095207] and binding to EF-Ts (IPR001816.\ GTP binding activity ; GO:0005525 \N \N 22669 IPR004161 Elongation factor Tu consists of three structural domains, this is the second domain. This second domain adopts a

barrel structure, and is involved in binding to charged tRNA [MEDLINE:96095207]. This domain is also found in other proteins such as elongation factor G and translation initiation factor IF-2. This domain is structurally related to IPR004160, and in fact has weak sequence matches to this domain.\ GTP binding activity ; GO:0005525 \N \N 22666 IPR004158 The function of the plant proteins constituting this family is unknown.\ molecular_function unknown ; GO:0005554 \N \N 22665 IPR004157 This family consists of several eukaryotic Organic-Anion-Transporting Polypeptides (OATPs). Several have been identified mostly in human and rat. Different OATPs vary in tissue distribution and substrate specificity. Since the numbering of different OATPs in particular species was based originally on the order of discovery, similarly numbered OATPs in humans and rats did not necessarily correspond in function, tissue distribution and substrate specificity (in spite of the name, some OATPs also transport organic cations and neutral molecules). Thus, Tamai et al. [MEDLINE:20334260] initiated the current scheme of using digits for rat OATPs and letters for human ones. Prostaglandin transporter (PGT) proteins are also considered to be OATP family members. In addition, the methotrexate transporter OATK is closely related to OATPs. This family aligns residues towards the C-terminus. The family OATP_N (IPR004156. This similarity was not previously noted. Note: Members of this family are described (in the Swiss-Prot database) as belonging to the SLC21 family of transporters.\ transporter activity ; GO:0005215 membrane ; GO:0016020 transport ; GO:0006810 22663 IPR004155

These proteins contain a short bi-helical repeat that is related to HEAT. Cyanobacteria and red algae harvest light energy using macromolecular complexes known as phycobilisomes (PBS), peripherally attached to the photosynthetic membrane. The major components of PBS are the phycobiliproteins. These heterodimeric proteins are covalently attached to phycobilins: open-chain tetrapyrrole chromophores, which function as the photosynthetic light-harvesting pigments. Phycobiliproteins differ in sequence and in the nature and number ofattached phycobilins to each of their subunits. These proteins include the lyase enzymes that specifically attach particular phycobilins to apophycobiliprotein subunits. The most comprehensively studied of these is the CpcE/Flyase P31967.

All the reactions of the above lyases involve an apoprotein cysteine SH addition to a terminal delta 3,3'-double bond. Such a reaction is not possible in the case of phycoviolobilin (PVB), the phycobilin of -phycoerythrocyanin (-PEC). It is thought that in this case, PCB, not PVB, is first added to apo--PEC, and is then isomerized to PVB. The addition reaction has been shown to occur in the presence of either of the components of -PEC-PVB lyase PecE or PecF (or both). The isomerisation reaction occurs only when both PecE and PecF components are present, i.e. the PecE/F phycobiliprotein lyase is also a phycobilin isomerase [MEDLINE:20175401]. Another member of this family is the NblB protein, whose similarity to the phycobiliprotein lyases was previously noted [MEDLINE:99102226]. This constitutively expressed protein is not known to have any lyase activity. It is thought to be involved in the coordination of PBS degradation with environmental nutrient limitation. It has been suggested that the similarity of NblB to the phycobiliprotein lyases is due to the ability to bind tetrapyrrole phycobilins via the common repeated motif [MEDLINE:99102226].

\ \ \N phycobilisome ; GO:0030089 \N 22664 IPR004156 This family consists of several eukaryotic Organic-Anion-Transporting Polypeptides (OATPs). Several have been identified mostly in human and rat. Different OATPs vary in tissue distribution and substrate specificity. Since the numbering of different OATPs in particular species was based originally on the order of discovery, similarly numbered OATPs in humans and rats did not necessarily correspond in function, tissue distribution and substrate specificity (in spite of the name, some OATPs also transport organic cations and neutral molecules). Thus, Tamai et al. [MEDLINE:20334260] initiated the current scheme of using digits for rat OATPs and letters for human ones. Prostaglandin transporter (PGT) proteins are also considered to be OATP family members. In addition, the methotrexate transporter OATK is closely related to OATPs. This family aligns residues towards the N-terminus. The family OATP_C (IPR004157. This similarity was not previously noted. Note: Members of this family are described (in the Swiss-Prot database) as belonging to the SLC21 family of transporters.\ transporter activity ; GO:0005215 membrane ; GO:0016020 transport ; GO:0006810 22657 IPR004149 DNA ligases catalyse the crucial step of joining the breaks in duplex DNA during DNA replication, repair and recombination, utilizing either ATP or NAD(+) as a cofactor [MEDLINE:20164478]. This domain is a small zinc binding motif that is presumably DNA binding. It is found only in NAD dependent DNA ligases.\ DNA ligase (NAD+) activity ; GO:0003911 \N DNA repair ; GO:0006281 22658 IPR004150 DNA ligases catalyse the crucial step of joining the breaks in duplex DNA during DNA replication, repair and recombination, utilizing either ATP or NAD(+) as a cofactor [MEDLINE:20164478]. This family is a small domain found after the adenylation domain DNA_ligase_N (IPR001679) in NAD dependent ligases. OB-fold domains generally are involved in nucleic acid binding.\ DNA ligase (NAD+) activity ; GO:0003911 \N DNA repair ; GO:0006281 22659 IPR004151 Caenorhabditis elegans Sre proteins are candidate chemosensory receptors. There are four main recognized groups of such receptors: Odr-10, Sra, Sro, and Srg. Sre (this family), Sra Sra and Srb Srb comprise the Sra group. All of the above receptors are thought to be G protein-coupled seven transmembrane domain proteins [MEDLINE:20047718], [MEDLINE:96028095]. The existence of several different chemosensory receptors underlies the fact that in spite of having only 20-30 chemosensory neurones, C. elegans detects hundreds of different chemicals, with the ability to discern individual chemicals among combinations [MEDLINE:20047718].\ transmembrane receptor activity ; GO:0004888 integral to membrane ; GO:0016021 chemosensory perception ; GO:0007606 22653 IPR004145 This domain is only found in fly proteins. It is found associated with YLP motifs (PF02757) in some proteins.\ molecular_function unknown ; GO:0005554 \N \N 22654 IPR004146 This short domain is rich in cysteines and histidines. The pattern of conservation is similar to that found in DAG_PE-bind (IPR002219), therefore we have termed this domain DC1 for divergent C1 domain. This domain probably also binds to two zinc ions. The function of proteins with this domain is uncertain, however this domain may bind to molecules such as diacylglycerol (A Bateman pers. obs.). This family are found in plant proteins.\ molecular_function unknown ; GO:0005554 \N \N 22655 IPR004147 This family includes ABC1 from yeast [MEDLINE:91293073] and AarF from E. coli\ \ \ [MEDLINE:98083065]. These proteins have a nuclear or mitochondrial subcellular location in eukaryotes. The exact molecular functions of these proteins is not clear, however yeast ABC1 suppresses a cytochrome b mRNA translation defect and is essential for the electron transfer in the bc 1 complex [MEDLINE:91293073] and E. coli AarF is required for ubiquinone production [MEDLINE:98083065]. It has been suggested that members of the ABC1 family are novel chaperonins [MEDLINE:91293073]. These proteins are unrelated to the ABC transporter proteins.\ \ \N \N \N 22656 IPR004148

\ \ \N \N endocytosis ; GO:0006897 22662 IPR004154 tRNA synthetases, or tRNA ligases are involved in protein synthesis. This domain is found in histidyl, glycyl, threonyl and prolyl tRNA synthetases [MEDLINE:99377256] it is probably the anticodon binding domain [MEDLINE:97228080].\ ATP binding activity ; GO:0005524 \N protein biosynthesis ; GO:0006412 22661 IPR004153 This repeat contains the conserved pattern CXCXC where X can be any amino acid. The repeat is found in up to five copies in Vascular endothelial growth factor C [MEDLINE:96203094]. In the salivary glands of the dipteran Chironomus tentans, a specific messenger ribonucleoprotein (mRNP) particle, the Balbiani ring (BR) granule, can be visualized during its assembly on the gene and during its nucleocytoplasmic transport. This repeat is found over 70 copies in the balbiani ring protein 3 (Q03376.\ \N \N \N 22660 IPR004152 The GAT domain is responsible for binding of GGA proteins to several members of the ARF family including ARF1 [MEDLINE:20211638] and ARF3. The GAT domain stabilizes membrane bound ARF1 in its GTP bound state, by interfering with GAP proteins [MEDLINE:21197947].\ protein transporter activity ; GO:0008565 Golgi stack ; GO:0005795 intra-Golgi transport ; GO:0006891 22652 IPR004144 NeuB is the prokaryotic N-acetylneuraminic acid (Neu5Ac) synthase. It catalyses the direct formation of Neu5Ac (the most common sialic acid) by condensation of phosphoenolpyruvate (PEP) and N-acetylmannosamine (ManNAc). This reaction has only been observed in prokaryotes; eukaryotes synthesise the 9-phosphate form, Neu5Ac-9-P, and utilize ManNAc-6-P instead of ManNAc. Such eukaryotic enzymesare not present in this family [MEDLINE:20334323]. This family also contains SpsE spore coat polysaccharide biosynthesis proteins.\ \ \N \N carbohydrate biosynthesis ; GO:0016051 22651 IPR004143 This domain is found in biotin protein ligase, lipoate-protein ligase A and B. Biotin is covalently attached at the active site of certain enzymes that transfer carbon dioxide from bicarbonate to organic acids to form cellular metabolites. Biotin protein ligase (BPL) is the enzyme responsible for attaching biotin to a specific lysine at the active site of biotin enzymes. Each organism probably has only one BPL. Biotin attachment is a two step reaction that results in the formation of an amide linkage between the carboxyl group of biotin and the epsilon-amino group of the modified lysine [MEDLINE:99400973]. Lipoate-protein ligase A (LPLA) catalyses the formation of an amide linkage between lipoic acid and a specific lysine residue in lipoate dependent enzymes [MEDLINE:94266793].\ enzyme activity ; GO:0003824 \N protein modification ; GO:0006464 22649 IPR004141 Strictosidine synthase (EC: 4.3.3.2) is a key enzyme in alkaloid biosynthesis. It catalyses the condensation of tryptamine with secologanin to form strictosidine.\ strictosidine synthase activity ; GO:0016844 \N biosynthesis ; GO:0009058 22650 IPR004142 This family consists of proteins from different gene families: Ndr1/RTP/Drg1, Ndr2, and Ndr3. Their similarity was previously noted [MEDLINE:20050077]. The precise molecular and cellular function of members of this family is still unknown, yet they are known to be involved in cellular differentiation events. The Ndr1 group was the first to be discovered. Their expression is repressed by the proto-oncogenes N-myc and c-myc, and in line with this observation, Ndr1 protein expression is down-regulated in neoplastic cells, and is reactivated when differentiation is induced by chemicals such as retinoic acid. Ndr2 and Ndr3 expression is not under the control of N-myc or c-myc. Ndr1 expression is also activated by several chemicals: tunicamycin and homocysteine induce Ndr1 in human umbilical endothelial cells; nickel induces Ndr1 in several cell types. Members of this family are found in wide variety of multicellular eukaryotes, including an Ndr1 type protein in Helianthus annuus (sunflower), known as Sf21. Interestingly, the highest scoring matches in the noise are all

hydrolases (IPR000073), suggesting that this family may have an enzymatic function.\ \N \N cell differentiation ; GO:0030154 22648 IPR004140 The Exo70 protein forms one subunit of the exocyst complex. First discovered in S. cerevisiae\ \ \ [MEDLINE:97133278], Exo70 and other exocyst proteins have been observed in several other eukaryotes, including humans. In S. cerevisiae, the\ exocyst complex is involved in the late stages of exocytosis, and is localized at the tip of the bud, the major site of exocytosis in yeast [MEDLINE:97133278]. Exo70 interacts with the Rho3 GTPase [MEDLINE:99223586]. This interaction mediates one of the three known functions of Rho3 in cell polarity: vesicle docking and fusion with the plasma membrane (the other two functions are regulation of actin polarity and transport of exocytic vesicles from the mother cell to the bud) [MEDLINE:20056094]. In humans, the functions of Exo70 and the exocyst complex are less well characterized: Exo70 is expressed in several tissues and is thought to also be involved in exocytosis [MEDLINE:98070770].\ \ \N exocyst ; GO:0000145 exocytosis ; GO:0006887 22643 IPR004134 This family is closely related to the Peptidase_C1 family (IPR000668), containing several prokaryotic and eukaryotic aminopeptidases and bleomycin hydrolases.\ \ cysteine-type endopeptidase activity ; GO:0004197 \N proteolysis and peptidolysis ; GO:0006508 22644 IPR004136 Members of this family catalyse the denitrification of a number of nitroalkanes using either FAD or FMN as a cofactor.\ oxidoreductase activity ; GO:0016491 \N electron transport ; GO:0006118 22645 IPR004137 Members of this family, also known as hybrid-cluster proteins, contain two Fe/S centers - a [4Fe-4S] cubane cluster, and a hybrid [4Fe-2S-2O] cluster. The physiological role of this protein is as yet unknown, although a role in nitrate/nitrite respiration has been suggested [MEDLINE:20117674].\ \N cytoplasm ; GO:0005737 electron transport ; GO:0006118 22646 IPR004138 This family represents herpes virus protein U79 and cytomegalovirus early phosphoprotein P34 (UL112).\ \N \N \N 22647 IPR004139

\ Alpha-1,3-mannosyl-glycoprotein

-1,2-N-acetylglucosaminyltransferase (GNT-I, GLCNAC-T I) EC: 2.4.1.101 transfers N-acetyl-D-glucosamine from UDP to high-mannose glycoprotein N-oligosaccharide. This is an essential step in the synthesis of complex or hybrid-type N-linked oligosaccharides. The enzyme is an integral membrane protein localized to the Golgi apparatus, and is probably distributed in all tissues. The catalytic domain is located at the C-terminus PUB00007032. These proteins are members of the glycosyl transferase family 13 (CAZY:GH_13)\ \ alpha-1,3-mannosylglycoprotein beta-1,2-N-acetylglucosaminyltransferase activity ; GO:0003827 Golgi membrane ; GO:0000139 N-linked glycosylation ; GO:0006487 22641 IPR004132 Kinetoplastid membrane protein 11 is a major cell surface glycoprotein of the parasite Leishmania donovani. It stimulates T-cell proliferation and may play a role in the immunlogy of the dieases Leishmaniasis.\ defense/immunity protein activity ; GO:0003793 \N positive regulation of cell proliferation ; GO:0008284 22642 IPR004133 This domain contains 9 conserved cysteines and is extracellular. Therefore the cysteines may form disulphide bridges. This family of proteins has been termed the DAN family [MEDLINE:98325381] after the first member to be reported. This family includes DAN, Cerberus and Gremlin. The gremlin protein is an antagonist of bone morphogenetic protein signaling. It is postulated that all members of this family antagonize different TGF

TGF-

ligands [MEDLINE:98325381].\ \N \N \N 22639 IPR004130 Members of this family are found in a range of archaea and eukaryotes and have hypothesised ATP binding activity.\ molecular_function unknown ; GO:0005554 \N \N 22640 IPR004131

The inorganic H+ pyrophosphatase (EC: 3.6.1.1) is a vacuolar-type H(+)-translocating inorganic pyrophosphatase which has long been considered to be restricted to plants and to a few species of phototrophic bacteria. However, in recent investigations, pyrophosphatases have been found in organisms as disparate as thermophilic Archaea and parasitic protists [MEDLINE:20026090]. It is an integral membrane protein and is suggested to have about 15 membrane spanning domains. Proton translocating inorganic pyrophosphatase, like\ H(+)-ATPase, acidifies the vacuoles and is pivotal to the vacuolar secondary active transport\ systems in plants.

\ \ hydrogen-translocating pyrophosphatase activity ; GO:0009678 membrane ; GO:0016020 proton transport ; GO:0015992 22636 IPR004126 Proteins in this group inhibit basic phospholipase A2 isozymes in snake's venom [MEDLINE:98055712].\ phospholipase inhibitor activity ; GO:0004859 extracellular ; GO:0005576 \N 22637 IPR004127 Members of this family are for the most part molecular chaperones capable of stabilising a variety of proteins.\ chaperone activity ; GO:0003754 prefoldin complex ; GO:0016272 protein folding ; GO:0006457 22638 IPR004129 Glycerophosphoryl diester phosphodiesterases display broad specificity for glycerophosphodiesters; glycerophosphocholine, glycerophosphoethanolamine, glycerophosphoglycerol, and bis(glycerophosphoglycerol) all of which are are hydrolysed by this enzyme.\ glycerophosphodiester phosphodiesterase activity ; GO:0008889 \N glycerol metabolism ; GO:0006071 22634 IPR004124

Sialidases (CAZY:GH_33.

The 1.8 A\ structure of trans-sialidase from leech (Macrobdella decora, Q27701) in complex with 2-deoxy-2, 3-didehydro-NeuAc was solved. The refined model comprising\ residues 81-769 has a catalytic -propeller domain, a N-terminal lectin-like domain and an irregular -stranded\ domain inserted into the catalytic domain [MEDLINE:98230750].

\ \ exo-alpha-sialidase activity ; GO:0004308 \N carbohydrate metabolism ; GO:0005975 22635 IPR004125

The signal recognition particle (SRP) is an oligomeric complex that mediates targeting and insertion of the signal sequence of exported proteins into the membrane of the endoplasmic reticulum. SRP \ consists of a 7S RNA and six protein subunits. One of these subunits, the 54 kD protein (SRP54), is \ a GTP-binding protein that interacts with the signal sequence when it emerges from the ribosome. The 54K subunit of the signal recognition particle has a two domain structure: the G-domain that binds GTP and the M-domain that binds the 7s RNA and also binds the signal sequence. The \ N-terminal 300 residues of SRP54 include the GTP-binding site (G-domain) (see IPR000897) and are evolutionary related \ to similar domains in other proteins [MEDLINE:94301771].

These proteins include E. coli and Bacillus \ subtilis ffh protein (P48), which seems to be the prokaryotic counterpart of SRP54; signal recognition \ particle receptor subunit (docking protein), an integral membrane GTP-binding protein which \ ensures, in conjunction with SRP, the correct targeting of nascent secretory proteins to the \ endoplasmic reticulum membrane; bacterial FtsY protein, which is believed to play a similar role to \ that of the docking protein in eukaryotes; the pilA protein from Neisseria gonorrhoeae, the homolog of \ ftsY; and bacterial flagellar biosynthesis protein flhF.

\ \ protein signal sequence binding activity ; GO:0008249 signal recognition particle ; GO:0005786 protein targeting ; GO:0006605 22633 IPR004123

Thioredoxins [MEDLINE:85277988], [MEDLINE:89340492], [MEDLINE:95308039], [MEDLINE:95308040] are small disulphide-containing redox proteins that have been found in all the kingdoms of living organisms. Thioredoxin serves as a general protein disulphide oxidoreductase. It interacts with a broad range of proteins by a redox mechanism based on reversible oxidation of 2 cysteine thiol groups to a disulphide, accompanied by the transfer of 2 electrons and 2 protons. The net result is the covalent interconversion of a disulphide and a dithiol.

Compared to human thioredoxin, human U5 snRNP-specific protein U5-15kD contains 37 additional residues that may cause structural changes which most likely form putative binding sites for other spliceosomal proteins or RNA. Although U5-15kD apparently lacks protein disulfide isomerase activity, it is\ strictly required for pre-mRNA splicing [MEDLINE:20079514].

\ \ \N spliceosome complex ; GO:0005681 mitosis ; GO:0007067 22630 IPR004120 Human T-cell leukemia virus type I (HTLV-I) is the etiological agent for adult T-cell leukemia (ATL), as well as for tropical spastic paraparesis (TSP) and HTLV-I associate myelopathy (HAM). A biological understanding of the\ involvement of HTLV-I and in ATL has focused significantly on the workings of the virally-encoded 40 kDa\ phospho-oncoprotein, Tat. Tat is a transcriptional activator. Its ability to modulate the expression and function of many\ cellular genes has been reasoned to be a major contributory mechanism explaining HTLV-I-mediated transformation of\ cells. In activating cellular gene expression, Tat impinges upon several cellular signal-transduction pathways, including\ those for CREB/ATF and NF-kappaB [MEDLINE:21225975].\ \ transcriptional activator activity ; GO:0016563 \N positive regulation of transcription ; GO:0045941 22631 IPR004121 Current genotyping systems for human herpesvirus 8 (HHV-8) are based on the highly variable gene encoding the K1 glycoprotein [MID: 11172090].\ \ \N \N \N 22632 IPR004122 The BAF protein protects retroviral DNA from autointegration [MEDLINE:98132624], thereby promoting the integration of the retroviral DNA into the host chromosome.\ DNA binding activity ; GO:0003677 \N \N 22623 IPR004113

Some oxygen-dependent oxidoreductases are flavoproteins that contain a covalently bound FAD group which is attached to a histidine via an 8--(N3-histidyl)-riboflavin linkage. The region around the histidine that binds the FAD group is conserved in these enzymes (see IPR006093).

\ \N \N \N 22624 IPR004114

The THUMP domain is shared by 4-thiouridine, pseudouridine synthases and RNA methylases[MEDLINE:21192780] and is probably an RNA-binding domain that adopts an / fold similar to that found in the C-terminal domain of translation initiation factor 3 and ribosomal protein S8. The THUMP domain probably functions by delivering a variety of RNA modification enzymes to their targets [MEDLINE:21192780].

This domain is found in the thiamine biosynthesis proteins (ThiI) (see IPR003720).

\ \ \N \N \N 22625 IPR004115 This domain is found in some members of the GatB and aspartyl tRNA synthetases.\ \ ATP binding activity ; GO:0005524 cytoplasm ; GO:0005737 protein biosynthesis ; GO:0006412 22626 IPR004116 Amelogenins play a role in biomineralization. They seem to regulate the formation of crystallites during the secretory stage of tooth enamel development and are thought to play a major role in the structural organization and mineralization of developing\ enamel. They are found in the extracellular matrix. Mutations in X-chromosomal amelogenin have been shown to cause amelogenesis\ imperfecta [MEDLINE:21127437].\ \ \N extracellular matrix ; GO:0005578 development ; GO:0007275 22627 IPR004117 All known members of this group are seven-transmembrane proteins that are candidate odorant receptors in Drosophila.\ odorant binding activity ; GO:0005549 membrane ; GO:0016020 olfaction ; GO:0007608 22628 IPR004118 A nonenveloped and single-stranded DNA virus designated TT virus (TTV) has been reported from Japan in association with hepatitis of unknown etiology [MEDLINE:99319011].\ \ \N \N \N 22629 IPR004119 This family includes proteins of unknown function. All known members of this group are proteins from drosophila and C. elegans.\ molecular_function unknown ; GO:0005554 \N \N 22617 IPR004106

The prolyl oligopeptidase family [MEDLINE:92062013], [MEDLINE:92384936], [MEDLINE:92384937] consist of a number of evolutionaryrelated peptidases whose catalytic activity seems to be provided by a charge\ relay system similar to that of the trypsin family of serine proteases, but\ which evolved by independent convergent evolution.

\ \

This unusual 7-stranded -propeller domain protects the catalytic triad of\ prolyl oligopeptidase (see IPR001375) with which it is almost always associated, excluding larger peptides and\ proteins from proteolysis in the cytosol.

\ \ serine-type endopeptidase activity ; GO:0004252 \N proteolysis and peptidolysis ; GO:0006508 22618 IPR004107

Proteins containing this domain cleave DNA substrates by a series of staggered cuts, during which the protein becomes covalently linked to the DNA through a catalytic tyrosine residue at the carboxy end of the alignment [MEDLINE:97238925], [MEDLINE:97433323].

The phage integrase N-terminal SAM-like domain is almost always found with the signature that defines the phage integrase family (see IPR002104).

\ \ \N \N DNA integration ; GO:0015074 22619 IPR004108 Proteins containing this domain may be involved in the mechanism of biological hydrogen activation and contain 4FE-4S clusters. They can use molecular hydrogen for the reduction of a variety of substances.\ \N \N \N 22620 IPR004109 The hepatitis C virus (HCV) nonstructural protein NS3 has been identified as a virus-encoded serine protease. It has been suggested that the NS3 serine protease of HCV is involved in cell transformation and that the ability to transform requires an active enzyme [MEDLINE:21165473].\ serine-type peptidase activity ; GO:0008236 \N viral transformation ; GO:0019087 22621 IPR004111

Several resistance mechanisms have been developed by Gram-negative bacteria against the broad-spectrum antibiotic tetracycline (Tc) [MEDLINE:95222589]. A common mechanism involves a membrane-associated protein (TetA) that exports the antibiotic out of the cell before it can attach to ribosomes and inhibit polypeptide chain growth. TetA expression is regulated by the Tet repressor (TetR). TetR occurs as a homodimer and uses 2 HTH motifs to bind tandem DNA operators, thereby blocking the expression of the associated genes, TetA and TetR.

The structure of the class D TetR repressor protein [MEDLINE:94204640] involves 10 -helices, with connecting turns and loops. The 3 N-terminal helices constitute the DNA-binding HTH domain, which has an inverse orientation compared with HTH motifs in other DNA-binding proteins. The core of the protein, formed by helices 5-10, is responsible for dimerisation and contains, for each monomer, a binding pocket that accommodates Tc in the presence of a divalent cation.

\ \ specific transcriptional repressor activity ; GO:0016566 \N negative regulation of transcription ; GO:0016481 22622 IPR004112

In bacteria two distinct, membrane-bound, enzyme complexes are responsible forthe interconversion of fumarate and succinate (EC: 1.3.99.1): fumarate\ reductase (Frd) is used in anaerobic growth, and succinate dehydrogenase (Sdh)\ is used in aerobic growth. Both complexes consist of two main components: a\ membrane-extrinsic component composed of a FAD-binding flavoprotein and an\ iron-sulfur protein; and an hydrophobic component composed of a membrane\ anchor protein and/or a cytochrome B.

In eukaryotes mitochondrial succinate dehydrogenase (ubiquinone) (EC: 1.3.5.1)\ is an enzyme composed of two subunits: a FAD flavoprotein and and iron-sulfur\ protein.

The flavoprotein subunit is a protein of about 60 to 70 Kd to which FAD is\ covalently bound to a histidine residue which is located in the N-terminal\ section of the protein [MEDLINE:89340438]. The sequence around that histidine is well\ conserved in Frd and Sdh from various bacterial and eukaryotic species [MEDLINE:92283874].

This family includes members that bind FAD such as the flavoprotein subunits from\ succinate and fumarate dehydrogenase, aspartate oxidase and the subunit of adenylylsulfate\ reductase.

\ \ oxidoreductase activity ; GO:0016491 \N electron transport ; GO:0006118 22616 IPR004105 This helical bundle domain is the homodimer interface of the signal transducing histidine kinase family.\ \ signal transducer activity ; GO:0004871 cytoplasm ; GO:0005737 signal transduction ; GO:0007165 22612 IPR004101

Proteins containing this domain include a number of related ligase enzymes that catalyse consecutive steps in the synthesis of peptidoglycan. Proteins also include folylpolyglutamate synthase that transfers glutamate to folylpolyglutamate and cyanophycin synthetase that catalyses the biosynthesis of the cyanobacterial reserve material multi-L-arginyl-poly-L-aspartate (cyanophycin) [MEDLINE:98314516].

The C-terminal domain is almost always associated with the cytoplasmic peptidoglycan synthetases, N-terminal domain (see IPR000713).

\ \ ligase activity ; GO:0016874 \N biosynthesis ; GO:0009058 22613 IPR004102 Poly(ADP-ribose) polymerase catalyses the covalent attachment of ADP-ribose units from NAD+ to itself and to a limited number of other DNA binding proteins, which decreases their affinity for DNA. Poly(ADP-ribose) polymerase is a regulatory component induced by DNA damage. The regulatory domain of the polymerase is almost always associated with the C-terminal catalytic domain (see IPR001290).\ \ NAD+ ADP-ribosyltransferase activity ; GO:0003950 nucleus ; GO:0005634 protein amino acid ADP-ribosylation ; GO:0006471 22614 IPR004103 Proteins containing this domain consists of a group of secreted bacterial lyase enzymes EC: 4.2.2.1 capable of acting on hyaluronan and chondroitin in the extracellular matrix of host tissues, contributing to the invasive capacity of\ the pathogen. This domain if almost always associated with the polysaccharide lyase family 8, N-terminal domain (see IPR003159).\ \ lyase activity ; GO:0016829 extracellular ; GO:0005576 \N 22615 IPR004104

Enzymes containing this domain utilise NADP or NAD, and are known as the GFO/IDH/MOCA family in Swiss-Prot.GFO is a glucose--fructose oxidoreductase, which converts D-glucose and D-fructose into\ D-gluconolactone and D-glucitol in the sorbitol-gluconate pathway. MOCA is a rhizopine catabolism\ protein which may catalyze the NADH-dependent dehydrogenase reaction involved in rhizopine catabolism.\ Other proteins belonging to this family include Gal80, a negative regulator for the expression of lactose and\ galactose metabolic genes; and several hypothetical proteins from yeast, E. coli and Bacillus.

The oxidoreductase, C-terminal domain is almost always associated with the oxidoreductase, N-terminal domain (see IPR000683).

\ \ oxidoreductase activity ; GO:0016491 \N metabolism ; GO:0008152 22610 IPR004099 Proteins containing this domain include both class I and class II oxidoreductases and also NADH oxidases and peroxidases.\ \ oxidoreductase activity ; GO:0016491 cytoplasm ; GO:0005737 electron transport ; GO:0006118 22611 IPR004100

\ \

\ \ \ \ \ \ \

Proteins containing this domain includes the ATP synthase and subunits the ATP synthase\ associated with flagella. The sequences of the and subunits are related and\ both contain a nucleotide-binding site for ATP and ADP. The N-terminal domain is almost\ always associated with the central region (see IPR000194).\

Vacuolar ATPases [MEDLINE:90078145] (V-ATPases) are responsible for acidifying a variety of\ intracellular compartments in eukaryotic cells. Like F-ATPases, they are\ oligomeric complexes of a transmembrane and a catalytic sector. The sequence\ of the largest subunit of the catalytic sector (70 kDa) is related to that of\ F-ATPase subunit, while a 60 kDa subunit, from the same sector, is related\ to the F-ATPases subunit [MEDLINE:89367309].\ Archaebacterial membrane-associated ATPases are composed of three subunits.\ The chain is related to F-ATPases chain and the chain is\ related to F-ATPases chain [MEDLINE:89367309].\ A protein highly similar to F-ATPase subunits is found [MEDLINE:93259961] in some\ bacterial apparatus involved in a specialized protein export pathway that\ proceeds without signal peptide cleavage. This protein is known as fliI in\ Bacillus and Salmonella, Spa47 (mxiB) in Shigella flexneri, HrpB6 in\ Xanthomonas campestris and yscN in Yersinia virulence plasmids.

In bacteria the chain is the regulatory subunit and the chain is the catalytic subunit. In V-type ATP synthase the archaeal chain is the catalytic subunit while the chain is the regulatory subunit.

\ \ \ hydrogen-transporting two-sector ATPase activity ; GO:0003936 proton-transporting two-sector ATPase complex ; GO:0016469 proton transport ; GO:0015992 22607 IPR004096 Central cellular functions such as metabolism, solute transport and signal transduction are regulated, in part, via binding of small molecules by specialized domains.The 4-vinyl reductase (4VR) domain is a predicted small molecular binding domain, that may bind to hydrocarbons [MEDLINE:21189415]. Proteins that contain this domain include a regulator of the phenol catabolic pathway and a protein involved in chlorophyll biosynthesis.\ \ \N \N \N 22608 IPR004097 This domain is called DHHA2 since it is often associated with the DHH domain (IPR001667.\ pyrophosphatase activity ; GO:0016462 cytoplasm ; GO:0005737 \N 22609 IPR004098

The splicing factor Prp18 is required for the second step of pre-mRNA splicing. PRP18 appears to\ be primarily associated with the U5 snRNP.

The structure of a large fragment of the Saccharomyces cerevisiae\ Prp18 is known [MEDLINE:20202581]. This fragment is fully active in yeast splicing in vitro and\ includes the sequences of Prp18 that have been evolutionarily conserved.\ The core structure consists of five -helices that adopt a novel fold. The\ most highly conserved region of Prp18, a nearly invariant stretch of 19 aa,\ forms part of a loop between two -helices and may interact with the\ U5 small nuclear ribonucleoprotein particles [MEDLINE:20202581].

\ \ pre-mRNA splicing factor activity ; GO:0008248 spliceosome complex ; GO:0005681 RNA splicing ; GO:0008380 22600 IPR004089

Bacterial chemotactic-signal transducers PUB00000988, PUB00000988 are proteins that respond tochanges in the concentration of attractants and repellents in the environment,\ and transduce a signal from the outside to the inside of the cell. These\ proteins undergo two covalent modifications: deamidation and reversible\ methylation. Attractants increase the level of methylation while repellents\ decrease it. The methyl groups are added by the methyl-transferase cheR and\ are removed by the methylesterase cheB.

\ \

All these proteins are composed of the same structural domains: a N-terminal\ region that resembles a signal peptide, but which is not removed from the\ mature protein and serves as a membrane-spanning region; a periplasmic\ domain of about 160 amino acids that forms the receptor domain; a second\ transmembrane region and finally a C-terminal cytoplasmic domain of about 300\ amino acids which contains the methylation sites.

The methyl-accepting sites are specific glutamate residues (some of these\ sites are translated as glutamine but are irreversibly deamidated by cheB).\ They are clustered in two regions of the cytoplasmic domain [MEDLINE:91236753].

\ \ signal transducer activity ; GO:0004871 membrane ; GO:0016020 signal transduction ; GO:0007165 22601 IPR004090

\ \

\ \ signal transducer activity ; GO:0004871 membrane ; GO:0016020 signal transduction ; GO:0007165 22606 IPR004095

The TGS domain is present in a number of enzymes, for example, in threonyl-tRNA synthetase (ThrRS), GTPase, and guanosine-3',5'-bis(diphosphate) 3'-pyrophosphohydrolase (SpoT) [MEDLINE:99377256]. The TGS domain is also present at the amino terminus of the uridine kinase from the spirochaete Treponema pallidum (but not any other organism, including the related spirochaete Borrelia burgdorferi).

TGS is a small domain that consists of ~50 amino acid residues and is predicted to possess a predominantly -sheet structure. There is no direct information\ on the functions of the TGS domain, but its presence in two types of\ regulatory proteins (the GTPases and guanosine polyphosphate phosphohydrolases/synthetases) suggests a ligand (most likely nucleotide)-binding, regulatory role [MEDLINE:99377256].

\ \ \N \N \N 22602 IPR004091

\ \

\ \ signal transducer activity ; GO:0004871 membrane ; GO:0016020 signal transduction ; GO:0007165 22603 IPR004092 The function of this repeat is unknown, but is found in a number of nuclear proteins. The repeat contains a completely conserved glutamate at its amino terminus that may be important for function.\ \ \N \N \N 22604 IPR004093 Staphylokinases and streptokinases are not proteases. They are involved in plasminogen activation. The three-dimensional structure of streptokinase is believed to contain two independently folded domains, each homologous to serine proteases [MEDLINE:83127125].\ plasminogen activator activity ; GO:0008243 \N \N 22605 IPR004094 A class of serine protease inhibitors characterized by a well conserved pattern of cysteine residues contain this signature. Many of the proteins that belong to this family are anti-coagulants.\ serine protease inhibitor activity ; GO:0004867 \N \N 22595 IPR004084

Spo11 is a meiosis-specific protein in yeast that covalently binds to DNAdouble-strand breaks (DSBs) during the early stages of meiosis [MEDLINE:20005938]. These DSBs initiate homologous recombination, which is required for chromosomal \ segregation and generation of genetic diversity during meiosis. Mouse and human homologues of Spo11 have been cloned and characterised. The proteins are 82% identical and share ~25% identity with other family members. Mouse Spo11 has been localised to chromosome 2H4, and human SPO11 to chromosome 20q13.2-q13.3, a region amplified in some breast and ovarian tumours [MEDLINE:20005938].

Similarity between SPO11 and archaebacterial TOP6A proteins points to \ evolutionary specialisation of a DNA-cleavage function for meiotic recombination [MEDLINE:20086432]. Note that the yeast SPO11 protein shares far less similarity to other SPO11 proteins than the human and mouse homologues do to each other.

\ \ DNA binding activity ; GO:0003677 \N meiotic recombination ; GO:0007131 22596 IPR004085

In all organisms, type II DNA topoisomerases are essential for untanglingchromosomal DNA. The structure of the DNA-binding core of the Methanococcus jannaschii DNA topoisomerase VI A subunit has been determined to 2.0A resolution. The overall structure of the subunit is unique, demonstrating that archaeal type II enzymes are distinct from other type II topoisomerases. Nevertheless, the core structure contains a pair of domains that are also found in type IA and classic type II topoisomerases. Such regions may form the basis of a DNA cleavage mechanism shared among these enzymes [MEDLINE:20012926] ].

The core A subunit is a dimer, with a deep groove spanning both protomers. The dimer architecture is such that DNA is thought to bind in the groove, across the A subunit interface, and the monomers are thought to separate during DNA transport [MEDLINE:20012926] ]. The A subunit of topoisomerase VI is similar to the meiotic recombination factor, Spo11.

\ \ DNA topoisomerase type II activity ; GO:0003918 \N DNA topological change ; GO:0006265 22597 IPR004086

The Gram-negative pathogen Escherichia coli causes several common bacterial illnesses in humans, including diarrhoea, neonatal meningitidis and urinary \ tract infections. Attachment to host tissues is essential for successful invasion, and requires interaction between a bacterial adhesive protein and \ its target receptor. This protein is usually supported on a larger structure \ made up of heteropolymeric fibres [MEDLINE:92204235]. Pyelonephritogenic E.coli\ specifically invade the uroepithelium by expressing between 100 and 300 \ pili on their cell surface. Pili are macromolecular structures that allow \ binding to a digalactoside receptor in the urinary tract.

P pili, or fimbriae, are ~68A in diameter and 1 micron in length, the\ bulk of which is a fibre composed of the main structural protein PapA [MEDLINE:92204235]. At its tip, the pilus is terminated by a fibrillum consisting of repeating units of the PapE protein. This, in turn, is topped by the adhesins, PapF and PapG, both of which are needed for receptor binding. The tip fibrillum \ is anchored to the main PapA fibre by the PapK pilus-adaptor protein. PapH, an outer membrane protein, then anchors the entire rod in the bacterial envelope [MEDLINE:95115757]. A cytoplasmic chaperone (PapD) assists in assembling the monomers of the macromolecule in the membrane.

PapE can vary its structure and antigenic properties according to the \ serotype strain of bacteria [MEDLINE:88169520], and therefore has the ability to evade host immune responses. A recent study into the assembly of P pili [MEDLINE:97075088] showed that both PapA and PapE automatically self-assemble into pilus \ rods and tip fibrillae, respectively, once released from the PapD chaperone.

\ \ \N fimbria ; GO:0009289 cell adhesion ; GO:0007155 22598 IPR004087 The K homology (KH) domain was first identified in the human heterogeneousnuclear ribonucleoprotein (hnRNP) K. It is an evolutionarily conserved\ sequence of around 70 amino acids that is present in a wide variety of quite\ diverse nucleic acid-binding proteins. Although it is not strictly proven the\ KH domain is suspected to bind RNA. Like many other RNA-binding motifs, KH\ motifs are found in one or multiple copies (14 copies in chicken vigilin) and,\ at least for hnRNP K (three KH domains) and FMR-1 (two KH domains), each motif\ is necessary for in vitro RNA binding activity, suggesting that they may\ function cooperatively or, in the case of single KH motif proteins (for\ example, Mer1p), independently [MEDLINE:94310455]. The domain has been found in a number of proteins including eukaryotic and prokaryotic RS3 ribosomal proteins; vertebrate fragile X mental retardation protein 1 (FMR1); yeast Pab1-binding protein 2 PBP2; human high-density lipoprotein binding protein; and human onconeural ventral antigen-1 (NOVA-1).\ The solution structure of the first KH domain of FMR1 [MEDLINE:97448673] and of the\ C-terminal KH domain of hnRNP K [MEDLINE:99299390] determined by nuclear magnetic resonance\ (NMR) revealed a

-alpha-

-beta-

structure.\ \ nucleic acid binding activity ; GO:0003676 \N \N 22599 IPR004088

The K homology (KH) domain was first identified in the human heterogeneousnuclear ribonucleoprotein (hnRNP) K. It is a domain of around 70 amino acids\ that is present in a wide variety of quite diverse nucleic acid-binding\ proteins [MEDLINE:94310455]. It has been shown to bind RNA [MEDLINE:97448673], [MEDLINE:99299390]. Like many other RNA-binding motifs, KH motifs are found in one or multiple copies (14 copies in chicken vigilin) and, at least for hnRNP K (three copies) and FMR-1 (two copies), each motif is necessary for in vitro RNA binding activity, suggesting that they may function cooperatively or, in the case of single KH motif proteins (for example, Mer1p), independently [MEDLINE:94310455].

According to structural [MEDLINE:97448673], [MEDLINE:99299390], [MEDLINE:21113148] analysis the KH domain can be separated in two groups. The first group or type-1 contain a --alpha--beta- structure, whereas in the type-2 the two last -sheet are located in the N terminal part of the domain (--beta--alpha-). Sequence similarity between these two folds are limited to a short region (VIGXXGXXI) in the RNA binding motif. This motif is located between helice 1 and 2 in type-1 and between helice 2 and 3 in type-2. Proteins known to contain a type-1 KH domain include bacterial polyribonucleotide nucleotidyltransferases (EC: 2.7.7.8); vertebrate fragile X mental retardation protein 1 (FMR1); eukaryotic heterogeneous nuclear ribonucleoprotein K (hnRNP K), one of at least 20 major proteins that are part of hnRNP particles in mammalian cells; mammalian poly(rC) binding proteins; Artemia salina glycine-rich protein GRP33; yeast PAB1-binding protein 2 (PBP2); vertebrate vigilin; and human high-density lipoprotein binding protein (HDL-binding protein).

\ \ nucleic acid binding activity ; GO:0003676 \N \N 22591 IPR004080

The complete nucleotide sequence of cDNA coding for the structural capsid polypeptides of foot-and-mouth disease virus (FMDV) has been determined. The FMDV capsid is composed of 60 icosahedral units, each of which comprises one copy each of proteins VP1, VP2, VP3 and VP4 [MEDLINE:82211814]. Specific enzymatic \ cleavages in vivo yield mature proteins. The VP1 coat protein contains the main antigenic determinants of the virion, and hence changes in its sequence must be responsible for the high antigenic variability of the virus.

The structure of FMDV has been determined to 2.9A resolution by means of \ X-ray diffraction. The virus shares similarities with other picorna-viruses, but also reveals unique features. The canyon found in other picornaviruses is absent, which has important implications for cell attachment. The most immunogenic portion of the capsid, which acts as a potent peptide vaccine, forms a disordered protrusion on the virus surface [MEDLINE:89143740].

\ \ structural molecule activity ; GO:0005198 viral capsid ; GO:0019028 \N 22592 IPR004081

N-acetylation by hepatic arylamine N-acetyltransferase (NAT) is a major route in the metabolism and detoxification of various drugs and foreign chemicals [MEDLINE:90253613]. NAT catalyses the conversion of acetyl-coA and arylamine to coA and N-acetylarylamine.

NAT is the target of a common genetic polymorphism of clinical relevance in\ humans [MEDLINE:90253613]. The N-acetylation polymorphism is determined by low or high NAT activity in liver [MEDLINE:91296815]. NAT has been implicated in the action and toxicity of amine-containing drugs, and in the susceptibility to cancer [MEDLINE:95004642] and systematic lupus erythematosus. Two highly similar human genes for NAT, termed NAT1 and NAT2, encode genetically invariant and variant NAT proteins, respectively [MEDLINE:91296815].

\ \ arylamine N-acetyltransferase activity ; GO:0004060 \N metabolism ; GO:0008152 22593 IPR004082 A total of 715 potential protein-coding genes have been identified in the nucleotide sequence of Arabidopsis thaliana chromosome 5, with an average gene density of 1 gene per 4001 bp [MEDLINE:20181125]. Amongst the gene products is a \ well-conserved family of 130.7kDa proteins that share no sequence similarity\ with any other known proteins. The sequences are characterised by an N-terminal domain of variable length, a central cysteine-rich region and a relatively acidic C-terminal domain. The sequences may possess a PHD finger.\ \ molecular_function unknown ; GO:0005554 \N \N 22594 IPR004083

The complete nucleotide sequence of Saccharomyces cerevisiae chromosome VIIIcontains 269 predicted or known genes (of 300bp or larger) [MEDLINE:94378003]. Of these, 59 had previously been identified; of the 210 novel genes, 65 encode putative proteins similar to other proteins of known or predicted function.

Amongst the gene products is a hypothetical 175.8kDa protein that belongs to\ a well-conserved family that shares no sequence similarity with any other known proteins. The sequences are characterised by an N-terminal domain of variable length, and a C-terminal WD-repeat-containing domain.

\ \ \N \N \N 22590 IPR004079

Reproduction is controlled in humans by the hypothalamic-pituitary-gonadal axis [MEDLINE:85012739]. A key molecule in this control circuit is the decapeptide \ luteinising hormone releasing hormone (LHRH), also termed gonadotropin-releasing hormone (GnRH). GnRH is produced by hypothalamic neurones, secreted in a pulsatile manner into the capillary plexus of the median eminence and mediates the release of luteinising hormone and follicle stimulating hormone from gonadotropic cells in the anterior pituitary. The peptide may have additional functions, as LHRH or LHRH-like immuno-reactivity has been found in gonadal tissue, placenta and the central nervous system, and exogenously administered LHRH affects behaviour [MEDLINE:85012739].

The GnRH decapeptide is processed from a larger precursor protein termed\ progonadoliberin I, which also contains prolactin release-inhibiting factor \ I.

\ \ luteinizing hormone-releasing factor activity ; GO:0005183 \N \N 22589 IPR004078

Interleukin-1 and interleukin-1 (IL-1 and IL-1 ) are cytokines that participate in the regulation of immune responses, inflammatory reactions, and hematopoiesis [MEDLINE:88290679]. Two types of IL-1 receptor, each with three extracellular immunoglobulin (Ig)-like domains, limited sequence similarity (28%) and different pharmacological characteristics have been cloned from mouse and human cell lines: these have been termed type I and type II receptors [MEDLINE:96355446]. The receptors both exist in transmembrane (TM) and soluble forms: the soluble IL-1 receptor is thought to be post-translationally derived from cleavage of the extracellular portion of the membrane receptors.

Both IL-1 receptors appear to be well conserved in evolution, and map to the\ same chromosomal location [MEDLINE:92007725]. The receptors can both bind all three forms of IL-1 (IL-1 , IL-1 and IL-1RA).

The vaccinia virus genes B15R and B18R each encode proteins with N-terminal \ hydrophobic sequences, possible sites for attachment of N-linked carbohydrate and a short C-terminal hydrophobic domain [MEDLINE:91170931] ]. These properties\ are consistent with the mature proteins being either virion, cell surface or secretory glycoproteins. Protein sequence comparisons reveal that the gene products are related to each other (20% identity) and to the Ig superfamily. The highest degree of similarity is to the human and murine interleukin-1 receptors, although both proteins are related to a wide range of Ig superfamily members, including the interleukin-6 receptor. A novel method for virus immune evasion has been proposed in which the product of one or both of these proteins may bind interleukin-1 and/or interleukin-6, preventing these cytokines reaching their natural receptors [MEDLINE:91170931] ]. A similar gene product from cowpox virus has also been shown to specifically bind murine IL-1 [MEDLINE:93008237].

\ \ interleukin-1 binding activity ; GO:0019966 \N virus-host interaction ; GO:0019048 22587 IPR004076

The crystal structure of the soluble extracellular part of type-I IL1R\ complexed with IL1RA has been determined to 2.7A resolution [MEDLINE:97215904] ]. The receptor structure is characterised by three Ig-like domains, of which\ domains 1 and 2 are tightly linked, while domain 3 is completely separate and connected by a flexible linker.

\ \ interleukin-1, Type I, activating receptor activity ; GO:0004909 \N \N 22588 IPR004077

The mature type II IL-1 receptor consists of (i) a ligand binding portion \ comprising three Ig-like domains; (ii) a single TM domain; and (iii) a short\ cytoplasmic domain of 29 amino acids [MEDLINE:92007725]. This contrasts with the ~215 amino acid cytoplasmic domain of the type I receptor, suggesting that the two IL-1 receptors may interact with different signal transduction pathways. The type II receptor is expressed in a number of different tissues, including both B and T lymphocytes, and can be induced in several cell types by treatment with phorbol ester. Both IL-1 receptors appear to be well conserved in evolution, and map to the same chromosomal location. Like the type I receptor, the human type II IL-1 receptor can bind all three forms of IL-1 (IL-1 , IL-1 and IL-1RA) [MEDLINE:92007725].

\ \ interleukin-1, Type II, blocking receptor activity ; GO:0004910 \N \N 22585 IPR004074

\ \ interleukin-1 receptor activity ; GO:0004908 \N \N 22586 IPR004075

Both IL-1 receptors appear to be well conserved in evolution, and map to the\ same chromosomal location. The receptors can both bind all three forms of IL-1 (IL-1 , IL-1 and IL-1RA) [MEDLINE:92007725]. The mature type I IL-1 \ receptor consists of (i) a ligand binding portion comprising three Ig-like\ domains; (ii) a single TM domain; and (iii) a large cytoplasmic domain of ~215 amino acids. This domain is shared by a number of other proteins, including the rat FIT-1M precursor, the murine ST2L protein precursor, human oligophrenin-4 and interleukin-18 receptor accessory protein, and Drosophila toll-like proteins.

\ \ interleukin-1, Type I, activating receptor activity ; GO:0004909 \N \N 22584 IPR004073

The metabotropic glutamate receptors are functionally and pharmacologically distinct from the ionotropic glutamate receptors. They are coupled to G-proteins and stimulate the inositol phosphate/Ca²⁺ intracellular signalling pathway [MEDLINE:91156047], [MEDLINE:92022526], [MEDLINE:92317054], [MEDLINE:92110002]. The amino acid sequences of the receptors contain high proportions of hydrophobic residues grouped into 7 domains, in a manner reminiscent of the rhodopsins and other receptors believed to interact with G-proteins. However, while a similar 3D framework has been proposed to account for this, there is no significant sequence identity between these and receptors of the rhodopsin-type family: the metabotropic glutamate receptors thus bear their own distinctive '7TM' signature. This 7TM signature is also shared by the calcium-sensing receptors, and GABA (gamma-amino-butyric acid) type B (GABA(B)) receptors.

Pheromones have evolved in all animal phyla, to signal sex and dominance\ status, and are responsible for stereotypical social and sexual behaviour among members of the same species. In mammals, these chemical signals are believed to be detected primarily by the vomeronasal organ (VNO), a chemosensory organ located at the base of the nasal septum [MEDLINE:21094488]. The VNO is present in most amphibia, reptiles and non-primate mammals but is absent in birds, adult catarrhine monkeys and apes [MEDLINE:20002969]. An active role for the human VNO in the detection of pheromones is disputed; the VNO is clearly present in the foetus but appears to be atrophied or absent in adults. Three distinct families of putative pheromone receptors have been identified in the vomeronasal organ (V1Rs, V2Rs and V3Rs). All are G protein-coupled receptors but are only distantly related to the receptors of the main olfactory system, highlighting their different role [MEDLINE:21094488].

The V2 receptors are members of the metabotropic glutamate receptor-like \ family of GPCRs and have close similarity to the extracellular Ca2+-sensing \ receptors [MEDLINE:97436753]. Rodents appear to have around 100 functional V2 receptors and many pseudogenes [MEDLINE:21094488]. These receptors are expressed in the basal regions of VNO, where they couple to Go proteins to mediate inositol trisphosphate responses [MEDLINE:20002969]. Homologues have also been identified in fish\ \ \ \ [MEDLINE:98226788], and the ligand specificity of one such receptor has been determined: a receptor from goldfish olfactory epithelium has been reported to bind basic amino acids, which are odorants for fish [MEDLINE:99360643].

\ \ metabotropic glutamate, GABA-B-like receptor activity ; GO:0008067 membrane ; GO:0016020 metabotropic glutamate receptor signaling pathway ; GO:0007216 22583 IPR004072

Pheromones have evolved in all animal phyla, to signal sex and dominance\ status, and are responsible for stereotypical social and sexual behaviour among members of the same species. In mammals, these chemical signals are believed to be detected primarily by the vomeronasal organ (VNO), a chemosensory organ located at the base of the nasal septum [MEDLINE:21094488]. The VNO is present in most amphibia, reptiles and non-primate mammals but is absent in birds, adult catarrhine monkeys and apes [MEDLINE:20002969] ]. An active role for the human VNO in the detection of pheromones is disputed; the VNO is clearly present in the foetus but appears to be atrophied or absent in adults. Three distinct families of putative pheromone receptors have been identified in the vomeronasal organ (V1Rs, V2Rs and V3Rs). All are G protein-coupled receptors but are only distantly related to the receptors of the main olfactory system, highlighting their different role [MEDLINE:21094488].

The V1 receptors share between 50 and 90% sequence identity but have little\ similarity to other families of G protein-coupled receptors. They appear to\ be distantly related to the mammalian T2R bitter taste receptors and the\ rhodopsin-like GPCRs [MEDLINE:20018185] ]. In rat, the family comprises 30-40 genes. These are expressed in the apical regions of the VNO, in neurons expressing Gi2. Coupling of the receptors to this protein mediates inositol trisphosphate signalling [MEDLINE:21094488]. A number of human V1 receptor homologues have also been found. The majority of these human sequences are pseudogenes [MEDLINE:20568487] but an apparently functional receptor has been identified that is expressed in the human olfactory system [MEDLINE:20428173].

\ \ pheromone receptor activity ; GO:0016503 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 22582 IPR004071

Leukotrienes (LT) are potent lipid mediators derived from arachidonic acid\ metabolism. They can be divided into two classes based on the presence or\ absence of a cysteinyl group. Leukotriene B4 (LTB4) does not contain such a\ group, whereas LTC4, LTD4, LTE4 and LTF4 are cysteinyl leukotrienes PUB00005890.

Cysteinyl leukotrienes (CysLTs), previously known as the "slow reacting\ substance of anaphylaxis", are produced predominantly by myeloid cells\ associated with inflammatory responses PUB00005890. They are the most potent bronchoconstrictors known and also have pro-inflammatory effects, making\ them important mediators in the pathophysiology of human asthma [MEDLINE:21127410]. CysLTs have also been implicated in a variety of other diseases, such as allergic rhinitis, inflammatory bowel disease and psoriasis [MEDLINE:20545741]. Pharmacological studies of the effects of CysLTs have provided evidence for the existence of at least 2 distinct receptor subtypes, belonging to the G protein-coupled receptor family, designated CysLT1 and CysLT2 [MEDLINE:99393629], [MEDLINE:21127410]. CysLT1 is thought to mediate bronchospasm, plasma exudation, vasoconstriction, mucus secretion and eosinophil recruitment [MEDLINE:21127410]. CysLT2 is less well defined, due to a lack of specific agonists and antagonists, but is thought to mediate some of the vascular effects attributed to CysLTs [MEDLINE:21127410], [MEDLINE:20545741]. Both receptor subtypes have now been cloned [MEDLINE:99393629], [MEDLINE:20459128].

\ \ leukotriene receptor activity ; GO:0004974 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 22581 IPR004070

The C-X-C chemokines IP10, Mig and I-TAC are upregulated in response to\ interferon-gamma and are potent chemoattractants for activated T cells [MEDLINE:98290735], [MEDLINE:98325037]. All three chemokines have been found to activate the type 3 C-X-C chemokine receptor (CXCR3) [MEDLINE:97188912], [MEDLINE:98290735]. CXCR3 is expressed in natural killer cells and activated T lymphocytes but not in resting T lymphocytes, B lymphocytes, monocytes or granulocytes [MEDLINE:97188912]. CXCR3 also appears to be constitutively expressed on endothelial cells of medium and large blood vessels [MEDLINE:21204751]. Upon binding to CXCR3, all three ligands cause mobilisation of intracellular calcium and chemotaxis. I-TAC, however, has a much higher affinity for the receptor and produces more potent effects than IP10 or Mig [MEDLINE:98290735]. I-TAC appears to bind to two distinct sites on CXCR3: when the receptor is in the active conformation, all three ligands can bind, but I-TAC binds at an allotropic site, distinct from that of IP10 and Mig. By contrast, only I-TAC can bind to the uncoupled conformation of the receptor [MEDLINE:21160231]. CXCR3 is also capable of binding a number of CC chemokines with moderate affinity. One of these, eotaxin, appears to act as a natural antagonist of the receptor [MEDLINE:98325037].

The main role of CXCR3 and its ligands appears to be the selective\ recruitment of effector T cells in both normal tissues and inflammation [MEDLINE:98290735]. CXCR3 may be involved in a number of T cell-mediated inflammatory diseases, such as autoimmune diseases, delayed-type hypersensitivity responses,\ certain viral diseases and transplant rejection. Upregulation of I-TAC in\ astrocytes and microglial cells by interferon suggests that it may also play\ a role in neuroinflammatory diseases, such as meningitis, encephalitis and\ multiple sclerosis [MEDLINE:98290735]. IP10 has also been suggested to be involved in recruitment of inflammatory cells into the brain following ischaemic injury\ [MEDLINE:20286573].

\ \ C-X-C chemokine receptor activity ; GO:0016494 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 22580 IPR004069

Chemokines are proteins that have important physiological and pathophysiological roles in a wide range of acute and chronic inflammatory\ processes . Their sequences are similar and are characterised by a\ 4-cysteine motif: the family can be divided according to whether the\ first 2 Cys residues are adjacent (the C-C family), or separated by an\ intervening residue (the C-x-C family). C-C chemokines are chemoattractant\ for monocytes but not for neutrophils. The C-C family includes human\ monocyte chemotactic protein-1 (MCP-1), regulated on activation, normal\ T cell expressed and secreted (RANTES) and macrophage inflammatory proteins\ (MIP-1a and MIP-1b) PUB00005876.

Human and mouse cDNAs encoding novel C-C chemokine receptors, designated CC\ chemokine receptor 8 (CC CKR8), have been isolated, which are expressed in the thymus. The receptors bind the human chemokine I-309 and its murine homologue TCA-3, respectively, with high affinity. Unlike most of the chemokine receptors, these receptors appear to bind only a single chemokine. In addition, like other C-C receptors, agonist binding elicits significant calcium mobilisation and subsequent transfectant cell migration that is sensitive to pertussis toxin inhibition [MEDLINE:98129363].

\ \ C-C chemokine receptor activity ; GO:0016493 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 22579 IPR004068

\ \ C-C chemokine receptor activity ; GO:0016493 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 22578 IPR004067

The novel C-C chemokine, Liver and Activation-Regulated Chemokine (LARC)\ functions as a chemoattractant for lymphocytes that express a class of receptor specifically binding to LARC with high affinity. This class of receptor has been identified as the orphan receptor GPR-CY4 and consequently renamed CC chemokine receptor 6 (CC CKR6). Like most other C-C chemokine receptors, agonist binding elicits an inward calcium flux and migration in cells transfected with the receptor. Unusually for a chemokine receptor, CC CKR6 appears to bind only LARC of the known chemokines [MEDLINE:97313465].

\ \ C-C chemokine receptor activity ; GO:0016493 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 22577 IPR004066

Lysophospholipids (LPs), such as lysophosphatidic acid (LPA), sphingosine\ 1-phosphate (S1P) and sphingosylphosphorylcholine (SPC), have long been known to act as signalling molecules in addition to their roles as intermediates in membrane biosynthesis [MEDLINE:21164675]. They have roles in the regulation of cell growth, differentiation, apoptosis and development, and have been implicated in a wide range of pathophysiological conditions, including: blood clotting, corneal wounding, subarachinoid haemorrhage, inflammation and colitis [MEDLINE:20072942]. A number of G protein-coupled receptors bind members of the lysophopholipid family - these include: the cannabinoid receptors; platelet activating factor receptor; OGR1, an SPC receptor identified in ovarian cancer cell lines; PSP24, an orphan receptor that has been proposed to bind LPA; and at least 8 closely related receptors, the EDG family, that bind LPA and S1P [MEDLINE:21164675].

LPA is found in all cell types in small quantities (associated with membrane\ biosynthesis) but is produced in significant quantities by some cellular\ sources, accounting for the levels of LPA in serum. LPA is also found in\ elevated levels in ovarian cancer ascites, and acts to stimulate proliferation and promote survival of the cancer cells [MEDLINE:20545693]. The effects of LPA on the proliferation and morphology of a number of other cell types have been well documented [MEDLINE:21164675], [MEDLINE:20545693]. However, identification of the mechanisms by which these effects are accomplished has been complicated by a number of factors, such as: a lack of antagonists, difficulty in ligand-binding experiments and the responsiveness of many cell types to LPA [MEDLINE:20545693]. The G protein-coupled receptors EDG-2, EDG-4 and EDG-7 have now been identified\ as high affinity receptors for LPA. It has been suggested that these receptors should now be referred to as lpA1, lpA2 and lpA3 respectively [MEDLINE:21164675], [MEDLINE:20072942].

EDG-4 is expressed at high levels in the testis and peripheral blood\ leukocytes of humans, and the testis, kidney and embryonic brain in mouse.\ Lower levels of expression are found in human pancreas, spleen, thymus and\ prostate, and mouse heart, lung, spleen, thymus, stomach and brain [MEDLINE:20545693]. Variant forms of the receptor are also expressed in cancer cells [MEDLINE:21164675]. Binding of LPA to EDG-4 results in increased calcium levels, inhibition of adenyly cylase, activation of MAP kinases and cell rounding, through coupling to Gi/o, Gq/11 and G12/13 proteins [MEDLINE:20545693].

\ \ lysosphingolipid and lysophosphatidic acid receptor activity ; GO:0001619 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 22576 IPR004065

\ \ lysosphingolipid and lysophosphatidic acid receptor activity ; GO:0001619 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 22575 IPR004064

S1P is released from activated platelets and is also produced by a number of other cell types in response to growth factors and cytokines [MEDLINE:20583949]. It is proposed to act both as an extracellular mediator and as an intracellular\ second messenger. The cellular effects of S1P include growth related effects, such as proliferation, differentiation, cell survival and apoptosis, and cytoskeletal effects, such as chemotaxis, aggregation, adhesion, morphological change and secretion. The molecule has been implicated in control of angiogenesis, inflammation, heart-rate and tumour progression, and may play an important role in a number of disease states, such as atherosclerosis, and breast and ovarian cancer [MEDLINE:20583949]. Recently, 5 G protein-coupled receptors have been identified that act as high affinity receptors for S1P, and also as low affinity receptors for the related lysophospholipid, SPC [MEDLINE:21164675]. EDG-1, EDG-3, EDG-5 and EDG-8 share a high degree of similarity, and are also referred to as lpB1, lpB3, lpB2 and lpB4, respectively. EDG-6 is referred to as lpC1, reflecting its more distant relationship to the other S1P receptors.

EDG-6 is expressed predominantly in lymphoid and haematopoietic tissues and\ in lung, a distribution that is quite restricted relative to other EDG\ family members [MEDLINE:99132320]. Binding of S1P to the receptor leads to activation of phospholipase C and MAP kinases in a pertussis toxin sensitive manner, through coupling to proteins of the Gi class. Whether EDG-6 can couple to any other G protein families is currently not known [MEDLINE:21164675].

\ \ lysosphingolipid and lysophosphatidic acid receptor activity ; GO:0001619 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 22574 IPR004063

EDG-5 is expressed abundantly in the heart and lung and at lower levels in\ the adult brain. It is also expressed strongly in the embryonic brain [MEDLINE:21164675], [MEDLINE:99132320]. Binding of S1P to EDG-5 activates G proteins of the Gi and Gq classes. G12 and G13 proteins are also constitutively activated by the receptor. These couplings produce a wide range of cellular effects, including: increased cyclic AMP and calcium levels, activation of MAP kinases and actin\ rearrangement [MEDLINE:21164675], [MEDLINE:20583949]. The receptor may have a role in neuronal development and, in zebrafish, has been found to be involved in the control of cell migration during development and organogenesis of the heart [MEDLINE:20365730].

\ \ lysosphingolipid and lysophosphatidic acid receptor activity ; GO:0001619 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 22573 IPR004062

EDG-3 is expressed at highest levels in the heart, kidney, placenta and\ liver of humans, with lower levels found in the lung [MEDLINE:21164675]. In mouse, highest levels are found in the heart, lung, kidney and spleen, with lower levels in the brain, thymus, muscle and testis [MEDLINE:99132320]. The receptor has also been found in rat Schwann cells, mouse embryonic brain and breast cancer cells [MEDLINE:21164675]. Binding of S1P to EDG-3 leads to activation of Gi and Gq classes of G proteins. G12 and G13 can also be constitutively activated by the receptor [MEDLINE:20583949]. These G proteins produce a range of effects, including: inhibition or activation or adenylyl cylase, MAP kinase activation, serum response element activation and phospholipase C activation, leading to cell proliferation and survival [MEDLINE:21164675], [MEDLINE:20583949].

\ \ lysosphingolipid and lysophosphatidic acid receptor activity ; GO:0001619 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 22572 IPR004061

\ \ lysosphingolipid and lysophosphatidic acid receptor activity ; GO:0001619 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 22571 IPR004060

The hypothalamus plays a central role in the integrated control of feeding\ and energy homeostasis [MEDLINE:98150861]. A new family of neuropeptides, orexins, have been identified that bind and activate two closely related (previously) orphan GPCRs [MEDLINE:98150861], [MEDLINE:98320882]. Orexins stimulate appetite and food consumption [MEDLINE:98320882]. Their genes are expressed bilaterally and symmetrically in the lateral hypothalamus, which has been shown to be the "feeding centre". By contrast, the "satiety centre" is expressed in the ventromedial hypothalamus and is dominated by the leptin-regulated neuropeptide network.

Both orexin receptors exhibit a similar pharmacology - the 2 orexin peptides, orexin-A and orexin-B, bind to both receptors and, in each case, agonist binding results in an increase in intracellular calcium levels. However, orexin-B shows a 10-fold selectivity for orexin receptor type 2, whilst orexin-A is equipotent at both receptors [MEDLINE:99430057].

\ \ orexin receptor activity ; GO:0016499 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 22569 IPR004058

Microtubules are polymers of tubulin, a dimer of two 55-kDa subunits, designated and [MEDLINE:85277991], [MEDLINE:90304955]. Within the microtubule lattice, - heterodimers associate in a head-to-tail fashion, giving rise to microtubule polarity. Fluorescent labelling studies have suggested that tubulin is oriented in microtubules with -tubulin toward the plus end [MEDLINE:93355288].

For maximal rate and extent of polymerisation into microtubules, tubulin \ requires GTP. Two molecules of GTP are bound at different sites, termed N \ and E. At the E (Exchangeable) site, GTP is hydrolysed during incorporation\ into the microtubule. Close to the E site is an invariant region rich in \ glycine residues, which is found in both chains and is thought to control\ access of the nucleotide to its binding site [MEDLINE:88058878].

Most species, excepting simple eukaryotes, express a variety of closely-\ related - and -isotypes. A third family member, gamma tubulin, has\ also been identified in a number of species. Gamma tubulin is found at \ microtubule-organising centres, such as the spindle poles or the centrosome, \ suggesting that it is involved in minus-end nucleation of microtubule \ assembly [MEDLINE:94099776]. More recently, zeta-tubulin has been identified in Trypanosoma brucei and Leishmania major\ \ \ \ [MEDLINE:20219670], and a partial sequence has also been identified in Xenopus laevis\ \ \ \ [MEDLINE:21094567].

\ \ structural molecule activity ; GO:0005198 microtubule ; GO:0005874 microtubule-based movement ; GO:0007018 22570 IPR004059

\ \ orexin receptor activity ; GO:0016499 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 22568 IPR004057

Most species, excepting simple eukaryotes, express a variety of closely-\ related - and -isotypes. A third family member, gamma tubulin, has\ also been identified in a number of species. Gamma tubulin is found at \ microtubule-organising centres, such as the spindle poles or the centrosome, \ suggesting that it is involved in minus-end nucleation of microtubule \ assembly [MEDLINE:94099776]. More recently, epsilon-tubulin has been identified in humans [MEDLINE:20089049] and Trypanosomes [MEDLINE:20219670]; in humans, it has been localised to centrosomes [MEDLINE:20089049].

\ \ structural molecule activity ; GO:0005198 microtubule ; GO:0005874 microtubule-based movement ; GO:0007018 22566 IPR004055

The first Shal (Kv4) sequence was found in Drosophila melanogaster. Several vertebrate\ K⁺ channels with similar amino acid sequences were subsequently found and,\ together with the Drosophila melanogaster Shal channel, now constitute the Shal (Kv4)\ family. These channels support outward K⁺-selective currents and are inhibited by free fatty acids PUB00009785. The Shal family can be further divided into 3 families, designated Kv4.1, Kv4.2 and Kv4.3.

Kv4.2 channels are the major contributors to somatodendritic A-type K⁺ channels in the basal ganglia and basal forebrain neurons PUB00009785. They are also expressed in the heart and CNS. In rodents, they are an important\ constituent of the cardiac transient outward current, Ito. In addition, they\ have a predicted role in regulating neuronal transmission at post-synaptic loci in defined brain regions. Kv4.2 channels contain a number of conserved sites for mitogen-activated protein kinase ERK phosphorylation, suggesting that ERK may regulate potassium channel function by direct phosphorylation [MEDLINE:20532639].

\ \ voltage-gated potassium channel activity ; GO:0005249 voltage-gated potassium channel complex ; GO:0008076 potassium ion transport ; GO:0006813 22564 IPR004053

The first Shaker (Kv1) sequence was found in Drosophila melanogaster. Several vertebrate\ K+ channels with similar amino acid sequences were subsequently found and,\ together with the Drosophila melanogaster Shaker channel, now constitute the Shaker (Kv1) \ family. These channels are mostly expressed in the brain, but can also be\ found in non-excitable cells, such as lymphocytes [MEDLINE:20256248], PUB00009778.

Kv1.6 is expressed in the heart, smooth muscle cells and brain, especially\ the midbrain areas and brainstem. The Kv1.6 -subunits can also coassemble with other Shaker subunits, for example, with Kv1.5 to form heteromultimeric K⁺ channels PUB00009778.

\ \ voltage-gated potassium channel activity ; GO:0005249 voltage-gated potassium channel complex ; GO:0008076 potassium ion transport ; GO:0006813 22567 IPR004056

Two isoforms of Kv4.3 have been cloned: one is full length and the other has\ a small amino acid deletion. Both forms are expressed in the brain, whereas\ in the heart only the longer isoform is found PUB00009785. Kv4.3 channels may have an important role in damping synaptic and excitatory membrane potentials. In the brain, they can also associate with Kv-beta2 subunits via the C-terminus, resulting in increased channel density and protein expression [MEDLINE:21265001].

\ \ voltage-gated potassium channel activity ; GO:0005249 voltage-gated potassium channel complex ; GO:0008076 potassium ion transport ; GO:0006813 22565 IPR004054

Kv4.1 channels are expressed in the heart, brain, liver, kidney and pancreas. Association with specific subunits increases their surface expression. Essential to their function are the N and C termini, which work together to control the inactivation of these channels PUB00009785.

\ \ voltage-gated potassium channel activity ; GO:0005249 voltage-gated potassium channel complex ; GO:0008076 potassium ion transport ; GO:0006813 22563 IPR004052

Kv1.5 channels are expressed in the heart and pancreatic -cells. The\ most studied is the human Kv1.5 channel (hKv1.5), which is thought to underlie the ultra-rapidly activating delayed rectifier K⁺ current Ikur found in human atrial myocytes PUB00009778. It is also expressed in the human ventricle where it is possible that it contributes to the K⁺ current through formation of heteromultimeric K⁺ channels with other Kv- subunits [MEDLINE:95340831]. Further experiments have shown that it is regulated by extracellular potassium and pH [MEDLINE:21099812].

\ \ voltage-gated potassium channel activity ; GO:0005249 voltage-gated potassium channel complex ; GO:0008076 potassium ion transport ; GO:0006813 22561 IPR004050

Kv1.3 subunits are expressed in T-lymphocytes, microglia and osteoclasts. \ In activated T-lymphocytes, they maintain the secretion of the lymphokine\ IL-2. They are also believed to be responsible for the decrease in regulatory volume in response to hypotonic shock, and a Kv1.3 homologue has predicted roles in renal medullary K⁺ transport PUB00009778.

\ \ voltage-gated potassium channel activity ; GO:0005249 voltage-gated potassium channel complex ; GO:0008076 potassium ion transport ; GO:0006813 22562 IPR004051

Kv1.4 channels are found in similar regions to Kv1.1 channels. They are\ particularly targeted to axons and possibly terminals, suggesting a pre-synaptic role in synaptic transmission PUB00009778.

\ \ voltage-gated potassium channel activity ; GO:0005249 voltage-gated potassium channel complex ; GO:0008076 potassium ion transport ; GO:0006813 22559 IPR004048

The Kv1.1 subfamily is expressed in the embryonic nervous system, brain and\ lymphoid thymocyte precursors PUB00009778. The Kv1.1 subunits can associate with Kv1.2 and Kv1.4 subunits, especially in the cerebellum. Point mutations in Kv1.1 result in the disruption of this association and episodic ataxia type I, a rare autosomal dominant neurological disorder characterised by brief episodes of ataxia [MEDLINE:99357714].

\ \ voltage-gated potassium channel activity ; GO:0005249 voltage-gated potassium channel complex ; GO:0008076 potassium ion transport ; GO:0006813 22560 IPR004049

Kv1.2 channels are uniformly distributed in the heart and brain. They play diverse functional roles in several neuronal compartments, especially in the regulation of pre- and post-synaptic membrane excitability. Kv1.2 subunits can co-localise with other Kv1 subunits. For example, Kv1.2 colocalises with Kv1.1 in the nodes of Ranvier in myelinated axons, and in the brain, in particular, the axons and nerve terminals; Kv1.2 coassembles with Kv1.4 subunits. In addition, Kv1.2 assembles with the Kv-beta2 subunit resulting in the promotion of Kv1.2 transport to the cell surface PUB00009778.

\ \ voltage-gated potassium channel activity ; GO:0005249 voltage-gated potassium channel complex ; GO:0008076 potassium ion transport ; GO:0006813 22558 IPR004047

Melanin-concentrating hormone (MCH) is a cyclic peptide originally identified in teleost fish\ \ \ \ [MEDLINE:94224751]. In fish, MCH is released from the\ pituitary and causes lightening of skin pigment cells through pigment\ aggregation [MEDLINE:94224751], [MEDLINE:90262152]. In mammals, MCH is predominantly expressed in the hypothalamus, and functions as a neurotransmitter in the control of a range of functions [MEDLINE:90262152]. A major role of MCH is thought to be in the regulation of\ feeding: injection of MCH into rat brains stimulates feeding; expression of MCH is upregulated in the hypothalamus of obese and fasting mice; and mice\ lacking MCH are lean and eat less [MEDLINE:94224751]. MCH and melanocyte-stimulating hormone (-MSH) have antagonistic effects on a number of physiological functions. Alpha-MSH darkens pigmentation in fish and reduces feeding in mammals, whereas MCH increases feeding [MEDLINE:94224751], [MEDLINE:90262152].

An orphan GPCR, previously known as SLC-1, has been identified as a\ receptor for MCH [MEDLINE:94224751]. Expression of the receptor has been found at highest levels in the brain, with moderate levels in the eye and skeletal muscle, and lower levels in the tongue and pituitary. In the brain, the receptor is expressed extensively in the hippocampus, olfactory regions and medial nucleus accumbens, a distribution that corresponds to connections between\ MCH-containing neurons and areas of the brain involved in taste and olfaction [MEDLINE:90262152]. This supports a role for the MCH receptor in olfactory learning and reinforcement mechanisms. The receptor is also found in parts of the hypothalamus, such as the ventromedial nucleus, that are known to\ regulate feeding and metabolism. The MCH receptor is expressed at moderate levels in the substantia nigra, ventral tegmental area and amygdala, suggesting that MCH may modulate the dopaminergic system. Expression has also been found in the locus coeruleus, indicating a possible role in the control of noradrenaline responses, including vigilance, attention, memory and sleep. Binding of MCH to the receptor results in inhibition of forskolin-stimulated cyclic AMP accumulation in a pertussis toxin sensitive manner, release of intracellular calcium in a partially pertussis toxin sensitive manner and activation of MAP kinase in a partially protein kinase C dependent manner [MEDLINE:88139292]. This indicates that the MCH receptor is capable of coupling to G proteins of the Gi, Go and Gq classes.

\ \ melanin-concentrating hormone receptor activity ; GO:0030273 integral to membrane ; GO:0016021 neuropeptide signaling pathway ; GO:0007218 22557 IPR004046

In eukaryotes, glutathione S-transferases (GSTs) participate in thedetoxification of reactive electrophilic compounds by catalysing their\ conjugation to glutathione. The GST domain is also found in S-crystallins from squid, and proteins with no known GST activity, such as eukaryotic elongation factors 1-gamma and the HSP26 family of stress-related proteins, which include auxin-regulated proteins in plants and stringent starvation proteins in E. coli. The major lens polypeptide of Cephalopoda is also a GST [MEDLINE:97228771], [MEDLINE:20387379], [MEDLINE:21264803], [MEDLINE:99344749].

Bacterial GSTs of known function often have a specific, growth-supporting role in biodegradative metabolism: epoxide ring opening and tetrachlorohydroquinone reductive dehalogenation are two examples of the reactions catalysed by these bacterial GSTs. Some regulatory proteins, like the stringent starvation proteins, also belong to the GST family [MEDLINE:21226181], [MEDLINE:97197501]. GST seems to be absent from Archaea in which gamma-glutamylcysteine substitute to glutathione as major thiol.

Glutathione S-transferases form homodimers, but in eukaryotes can also form heterodimers of the A1 and A2 or YC1 and YC2 subunits. The homodimeric enzymes display a conserved structural\ fold. Each monomer is composed of a distinct N-terminal sub-domain,\ which adopts the thioredoxin fold, and a C-terminal all-helical\ sub-domain. This entry is the C-terminal domain.

\ \ \N \N \N 22554 IPR004043

The LCCL domain has been named after the best characterized proteins that were found to contain it, namely Limulus factor C, Coch-5b2 and Lgl1. It is an about 100 amino acids domain whose C-terminal part contains a highly conserved histidine in a conserved motif YxxxSxxCxAAVHxGVI. The LCCL module is thought to be an autonomously folding domain that has been used for the construction of various modular proteins through exon-shuffling. It has been found in various metazoan proteins in association with complement B-type domains, C-type lectin domains, von Willebrand type A domains, CUB domains, discoidin lectin domains or CAP domains. It has been proposed that the LCCL domain could be involved in lipopolysaccharide (LPS) binding [MEDLINE:20428463], [MEDLINE:99021390]. Secondary structure prediction suggests that the LCCL domain contains six strands and two helices [MEDLINE:20428463].

Some proteins known to contain a LCCL domain include Limulus factor C, a LPS endotoxin-sensitive trypsin type serine protease which serves to protect the organism from bacterial infection; vertebrate cochlear protein cochlin or coch-5b2 (Cochlin is probably a secreted protein, mutations affecting the LCCL domain of coch-5b2 cause the deafness disorder DFNA9 in humans); and mammalian late gestation lung protein Lgl1, contains two tandem copies of the LCCL domain [MEDLINE:99292450].

\ \ \N \N \N 22555 IPR004044

\ \ nucleic acid binding activity ; GO:0003676 \N \N 22556 IPR004045

In eukaryotes, glutathione S-transferases (GSTs) participate in thedetoxification of reactive electrophilic compounds by catalysing their\ conjugation to glutathione. The GST domain is also found in S-crystallins from squid, and proteins with no known GST activity, such as eukaryotic elongation factors 1-gamma and the HSP26 family of stress-related proteins, which include auxin-regulated proteins in plants and stringent starvation proteins in Escherichia coli. The major lens polypeptide of Cephalopoda is also a GST [MEDLINE:97228771], [MEDLINE:20387379], [MEDLINE:21264803], [MEDLINE:99344749].

\ \ \N \N \N 22552 IPR004041

The NAF domain is a 24 amino acid domain that is found in a plant-specific subgroup of serine-threonine protein kinases (CIPKs), that interact with calcineurin B-like calcium sensor proteins (CBLs). Whereas the N-terminal part of CIPKs comprises a conserved catalytic domain typical of Ser-Thr kinases, the much less conserved C-terminal domain appears to be unique to this subgroup of kinases. The only exception is the NAF domain that forms an 'island of conservation' in this otherwise variable region. The NAF domain has been named after the prominent conserved amino acids Asn-Ala-Phe. It represents a minimum protein interaction module that is both necessary and sufficient to mediate the interaction with the CBL calcium sensor proteins [MEDLINE:21153204].

The secondary structure of the NAF domain is currently not known, but secondary structure computation of the C-terminal region of Arabidopsis thaliana CBL-interacting protein kinase 1 revealed a long helical structure [MEDLINE:21153204].

\ \ \N \N signal transduction ; GO:0007165 22553 IPR004042

Inteins (for INternal proTEINs) are in frame intervening sequences that disrupt the coding region of a host gene. They are post-translationallyexcised from a protein precursor by a self-catalytic protein splicing process\ [MEDLINE:21062355], [MEDLINE:97248673], [MEDLINE:20063303]. Most inteins are bifunctional proteins mediating both protein splicing and DNA clivage. The domain involved in splicing is formed by the two terminal splicing regions, which are separated by a small linker in mini-inteins or a 200- to 250-amino-acid homing endonuclease in larger inteins [MEDLINE:21062355], [MEDLINE:20063303]. Homing endonucleases are rare-cutting enzymes encoded by\ inteins and introns. By making a site-specific double-strand break in the\ intronless or inteinless alleles, these nucleases create recombinogenic ends\ which engage in a gene conversion process that duplicates the intron or intein\ [MEDLINE:97402526], [MEDLINE:99415130]. There are four families of homing endonucleases classified by conserved sequence motifs. Homing endonucleases found in inteins generally belong to the dodecapetide (DOD) family, but an HNH endonuclease is also found. Endonucleases of the DOD family contain one or two copies of a 10-residue sequence known as a dodecapeptide or LAGLIDADG motif. They recognize long, pseudopalindromic homing sites of 14-30 bp in length and cleave their homing site DNA to generate 4nt, 3' extensions. The DOD endonucleases found in inteins contain 2 dodecapeptide motifs and are active as monomers. Resolution of the 3D structure of PI-Sce revealed that the endonuclease domain consist of / motifs related by pseudo two-fold symmetry. The two -helices containing the dodecapeptide motifs form the axis of symmetry [MEDLINE:97402526], [MEDLINE:99415130].

This entry covers the conserved central intein Blocks C,\ D, E and H. Blocks C and E are the dodecapeptide motifs that are required for\ endonuclease activity and each contains an endonuclease active site Asp or Glu\ [MEDLINE:97248673].

\ \ endonuclease activity ; GO:0004519 \N \N 22551 IPR004039 Rubredoxin is a low molecular weight iron-containing bacterial protein involved in electron transfer [MEDLINE:91058526], [MEDLINE:91124457], sometimesreplacing ferredoxin as an electron carrier [MEDLINE:95243660].\ \

The 3-D structures of a number of rubredoxins have been solved [MEDLINE:93271899], [MEDLINE:88155649]. The fold belongs to the + class, with 2 -helices and 2-3 -strands. Its active site contains an iron ion which is co-ordinated by the sulphurs of four conserved cysteine residues forming an\ almost regular tetrahedron. The conserved cysteines reside on two loops, which are the most conserved regions of the protein. In addition, a ring of acidic residues in the proximity of the [Fe(Cys)4] centre is also well-conserved [MEDLINE:88155649]. \

\ \ heavy metal binding activity ; GO:0005505 \N electron transport ; GO:0006118 22549 IPR004037

\ \ \

The genomic structure and sequence of the human ribosomal protein L7a has been determined and shown to \ resemble other mammalian ribosomal protein genes [MEDLINE:92096469]. The sequence of a gene for ribosomal \ protein L4 of yeast has also been determined; its single open reading frame is highly similar\ to mammalian ribosomal protein L7a [MEDLINE:90221868], [MEDLINE:91260682]. Several other ribosomal proteins have \ been found to share sequence similarity with L7a, including Saccharomyces cerevisiae NHP2 [MEDLINE:91289691], B. subtilis \ hypothetical protein ylxQ, Haloarcula marismortui Hs6, and M. jannaschii MJ1203.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 22550 IPR004038

\ \ \

This family includes: Ribosomal L7A from metazoa, Ribosomal L8-A and L8-B from fungi, 30S ribosomal protein HS6 from archaebacteria, 40S ribosomal protein S12 from eukaryotes, Ribosomal protein L30 from eukaryotes and archaebacteria, Gadd45 and MyD118 [MEDLINE:97295598].

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 22548 IPR004036

Endonuclease III (EC: 4.2.99.18) is a DNA repair enzyme which removes a number of damaged pyrimidines from DNA via its glycosylase activity and also cleaves the phosphodiester backbone at apurinic / apyrimidinic sites via a -elimination mechanism [MEDLINE:95292058], [MEDLINE:97184707]. The structurally related DNA glycosylase MutYrecognises and excises the mutational intermediate 8-oxoguanine-adenine mispair [MEDLINE:93015679]. The 3-D structures of E. coli endonuclease III [MEDLINE:93030750] and catalytic domain of MutY [MEDLINE:99061333] have been determined. The\ structures contain two all- domains: a sequence-continuous, six-helix domain (residues 22-132) and a Greek-key,\ four-helix domain formed by one N-terminal and three C-terminal helices (residues 1-21 and 133-211) together with the\ [Fe4S4] cluster. The cluster is bound entirely within the C-terminal loop by four cysteine residues with a ligation pattern\ Cys-(Xaa)6-Cys-(Xaa)2-Cys-(Xaa)5-Cys which is distinct from all other known Fe4S4 proteins. This structural motif is\ referred to as a [Fe4S4] cluster loop (FCL) [MEDLINE:95393988]. Two DNA-binding motifs have been proposed, one at either end of the\ interdomain groove: the helix-hairpin-helix (HhH) (see IPR003265). The primary role of the iron-sulphur cluster appears to\ involve positioning conserved basic residues for interaction with the DNA phosphate backbone by forming the loop of\ the FCL motif [MEDLINE:95393988], [MEDLINE:20361758].

\ \ endonuclease activity ; GO:0004519 \N DNA repair ; GO:0006281 22543 IPR004031 Several vertebrate small integral membrane glycoproteins are evolutionary related [MEDLINE:96081949], [MEDLINE:96081962], [MEDLINE:97149281], including eye lens specific membrane protein 20 (MP20 or MP19); epithelial membrane protein-1 (EMP-1), which is also known as tumor-associated\ membrane protein (TMP) or as squamous cell-specific protein Cl-20; epithelial membrane protein-2 \ (EMP-2), which is also known as XMP; epithelial membrane protein-3 (EMP-3), also known as YMP;\ and peripheral myelin protein 22 (PMP-22), which is expressed in many tissues but mainly by \ Schwann cells as a component of myelin of the peripheral nervous system (PNS). PMP-22 probably \ plays a role both in myelinization and in cell proliferation. Mutations affecting PMP-22 are \ associated with hereditary motor and sensory neuropathies such as Charcot-Marie-Tooth disease \ type 1A (CMT-1A) in human or the trembler phenotype in mice. The proteins of this family are \ about 160 to 173 amino acid residues in size, and contain four transmembrane segments. PMP-22, \ EMP-1, -2 and -3 are highly similar, while MP20 is more distantly related. This family also includes the claudins, which are components of tight junctions.\ \ \N membrane ; GO:0016020 \N 22544 IPR004032 Several vertebrate small integral membrane glycoproteins are evolutionary related [MEDLINE:96081949], [MEDLINE:96081962], [MEDLINE:97149281], including eye lens specific membrane protein 20 (MP20 or MP19); epithelial membrane protein-1 (EMP-1), which is also known as tumor-associated\ membrane protein (TMP) or as squamous cell-specific protein Cl-20; epithelial membrane protein-2 \ (EMP-2), which is also known as XMP; epithelial membrane protein-3 (EMP-3), also known as YMP;\ and peripheral myelin protein 22 (PMP-22), which is expressed in many tissues but mainly by \ Schwann cells as a component of myelin of the peripheral nervous system (PNS). PMP-22 probably \ plays a role both in myelinization and in cell proliferation. Mutations affecting PMP-22 are \ associated with hereditary motor and sensory neuropathies such as Charcot-Marie-Tooth disease \ type 1A (CMT-1A) in human or the trembler phenotype in mice. The proteins of this family are \ about 160 to 173 amino acid residues in size, and contain four transmembrane segments. PMP-22, \ EMP-1, -2 and -3 are highly similar, while MP20 is more distantly related.\ \ \N membrane ; GO:0016020 \N 22545 IPR004033 A number of methyltransferases have been shown to share regions ofsimilarities [MEDLINE:97197541]. Apart from the ubiquinone/menaquinone biosynthesis methyltransferases (for example, the C-methyltransferase from the ubiE gene of Escherichia coli), the ubiquinone biosynthesis methyltransferases (for example, the C-methyltransferase from the COQ5 gene of Saccharomyces cerevisiae) and the menaquinone biosynthesis methyltransferases (for example, the C-methyltransferase from the MENH gene of Bacillus subtilis), this family also includes methyltransferases involved in biotin and sterol biosynthesis and in phosphatidylethanolamine methylation.\ \ methyltransferase activity ; GO:0008168 \N \N 22547 IPR004035

Endonuclease III (EC: 4.2.99.18) is a DNA repair enzyme which removes a number of damaged pyrimidines from DNA via its glycosylase activity and also cleaves the phosphodiester backbone at apurinic / apyrimidinic sites via a -elimination mechanism [MEDLINE:95292058], [MEDLINE:97184707]. The structurally related DNA glycosylase MutYrecognises and excises the mutational intermediate 8-oxoguanine-adenine mispair [MEDLINE:93015679]. The 3-D structures of Escherichia coli endonuclease III [MEDLINE:93030750] and catalytic domain of MutY [MEDLINE:99061333] have been determined. The\ structures contain two all- domains: a sequence-continuous, six-helix domain (residues 22-132) and a Greek-key,\ four-helix domain formed by one N-terminal and three C-terminal helices (residues 1-21 and 133-211) together with the\ [Fe4S4] cluster. The cluster is bound entirely within the C-terminal loop by four cysteine residues with a ligation pattern\ Cys-(Xaa)6-Cys-(Xaa)2-Cys-(Xaa)5-Cys which is distinct from all other known Fe4S4 proteins. This structural motif is\ referred to as a [Fe4S4] cluster loop (FCL) [MEDLINE:95393988]. Two DNA-binding motifs have been proposed, one at either end of the\ interdomain groove: the helix-hairpin-helix (HhH) region (see IPR003265) and FCL motif, described in this entry. The primary role of the iron-sulphur cluster appears to\ involve positioning conserved basic residues for interaction with the DNA phosphate backbone by forming the loop of\ the FCL motif [MEDLINE:95393988], [MEDLINE:20361758].

\ \ endonuclease activity ; GO:0004519 \N DNA repair ; GO:0006281 22546 IPR004034 Ubiquinone (coenzyme Q or Q) is a lipophilic metabolite that functions in the electron transport chain in the plasma membrane of prokaryotes and in the inner\ mitochondrial membrane of eukaryotes. Both the ubiE and COQ5 coding sequences contain sequence motifs common to a wide variety of\ S-adenosyl-L-methionine-dependent methyltransferases. \ The E. coli UbiE polypeptide (EC: 2.1.1.-) is required for the C methylation reactions in both ubiquinone and menaquinone biosynthesis [MEDLINE:97197541].\ \ methyltransferase activity ; GO:0008168 \N coenzyme biosynthesis ; GO:0009108 22536 IPR004024 This domain is found in several worm proteins. It contains 4 conserved cysteines. This domain is presumably extracellular and these cysteines form disulphide bridges.\ \N \N \N 22537 IPR004025 This enzyme hydrolyses 28S rRNA, and acts a protein synthesis inhibitor. Members of the ribonuclease U2 family include ribonuclease mitogillin, ribonuclease

-sarcin and ribonuclease clavin precursor proteins.\ ribonuclease activity ; GO:0004540 \N negative regulation of protein biosynthesis ; GO:0017148 22538 IPR004026 The Escherichia coli Ada protein repairs O6-methylguanine residues and methyl phosphotriesters in DNA by direct transfer of the methyl group to acysteine residue. This domain contains four conserved cysteines that form a\ zinc binding site [MEDLINE:92256385], [MEDLINE:93272965]. One of these cysteines is a methyl group acceptor. The methylated domain can then specifically bind to the ada box on a DNA duplex [MEDLINE:93272965].\ \ zinc ion binding activity ; GO:0008270 \N regulation of transcription, DNA-dependent ; GO:0006355 22539 IPR004027 The SEC-C motif found in the C-terminus of the SecA protein, in the middle of some SWI2 ATPases and also solo in several proteins. The motif is predicted to chelate zinc with the CXC and C[HC] pairs that constitute the most conserved feature of the motif. It is predicted to be a potential nucleic acid binding domain.\ \N \N \N 22540 IPR004028 Retroviruses contain a small protein, MA (matrix), which forms a proteinlining immediately beneath the phospholipid membrane of the mature virus\ particle. MA is located in the N-terminal region of the Gag precursor\ polyprotein. The N-terminal segment of MA proteins directs the Gag protein to the plasma membrane where budding takes place, and has been called the M domain. This domain forms an

helical bundle structure.\ \ \N \N \N 22541 IPR004029 UreE is a urease accessory protein. Urease IPR005848) of members of this family contains a His rich Nickel binding site.\ nickel ion binding activity ; GO:0016151 \N protein complex assembly ; GO:0006461 22542 IPR004030

Nitric oxide synthase (EC: 1.14.13.39) (NOS) enzymes produce nitric oxide (NO) by catalyzing a five-electron oxidation of a guanidino nitrogen of L-arginine (L-Arg). Oxidation of L-Arg to L-citrulline occurs via two successive monooxygenation reactions producing N(omega)-hydroxy-L-arginine as an intermediate. 2 mol of O(2) and 1.5 mol of NADPH are consumed per mole of NO formed [MEDLINE:96376725].

Arginine-derived NO synthesis has been identified in mammals, fish, birds, invertebrates, plants, and bacteria [MEDLINE:96376725]. Best studied are mammals, where three distinct genes encode NOS isozymes: neuronal (nNOS or NOS-1), cytokine-inducible (iNOS or NOS-2) and endothelial (eNOS or NOS-3) [MEDLINE:94183147]. iNOS and nNOS are soluble and found predominantly in the cytosol, while eNOS is membrane associated. The enzymes exist as homodimers, each monomer consisting of two major domains: an N-terminal oxygenase domain, which belongs to the class of heme-thiolate proteins, and a C-terminal reductase domain, which is homologous to NADPH:P450 reductase (EC: 1.6.2.4). The interdomain linker between the oxygenase and reductase domains contains a calmodulin (CaM)-binding sequence. NOSs are the only enzymes known to simultaneously require five bound cofactors/prosthetic groups: FAD, FMN, heme, tetrahydrobiopterin and Ca2+-CaM. The animal NOS isozymes are catalytically self-sufficient. The electron flow in the NO synthase reaction is: NADPH --> FAD --> FMN --> heme --> O(2).

eNOS localisation to endothelial membranes is mediated by cotranslational N-terminal myristoylation and post-translational palmitoylation [MEDLINE:97344274]. The subcellular localisation of nNOS in skeletal muscle is\ mediated by anchoring of nNOS to dystrophin. nNOS contains an additional \ N-terminal domain, the PDZ domain [MEDLINE:95224759]. Some bacteria, like Bacillus halodurans, Bacillus subtilis or Deinococcus radiodurans, contain homologs of NOS oxygenase domain. The pattern is directed against the N-terminal heme binding site.

\ \ nitric oxide synthase activity ; GO:0004517 \N nitric oxide biosynthesis ; GO:0006809 22535 IPR004023 This family was originally identified in Drosophila and called mago nashi, it is a strict maternal effect, grandchildless-like, gene [MEDLINE:92111401]. The human homologue has been shown to interact with an RNA binding protein, ribonucleoprotein rbm8 (Q9Y5S9.\ \N nucleus ; GO:0005634 sex determination ; GO:0007530 22533 IPR004021 This domain has no known function. It is found in one or two copies per protein, and is found associated with the PAAD/DAPIN domain IPR004020.\ \N \N \N 22534 IPR004022 This domain is predicted to be a DNA binding domain. The DDT domain is named after (DNA binding homeobox and Different Transcription factors). It is found in fetal Alzheimer antigen and several hypothetical and uncharacterised proteins.\ \N \N \N 22528 IPR004015 This domain is found in chromatin proteins, nuclear skip (SKI-interacting) protein, and some hypothetical proteins.\ \N nucleus ; GO:0005634 \N 22529 IPR004017 This domain is usually found in two copies per protein. It contains up to four conserved cysteines. The family includes a subunit from heterodisulfide reductase and a subunit from glycolate oxidase [MEDLINE:96178972] and glycerol-3-phosphate dehydrogenase.\ \N \N \N 22530 IPR004018 The RPEL repeat is named after four conserved amino acids it contains. The function of the RPEL repeat is unknown however it might be a DNA binding repeat based on the observation that Q9VZY2 contains a SAP domain that is also implicated in DNA binding.\ \N \N \N 22531 IPR004019 The YLP motif is found in several Drosophila proteins. Its function is unknown, however the presence of completely conserved tyrosine residues and its presence in the human erbb-4 receptor protein-tyrosine kinase precursor may suggest it could be a substrate for tyrosine kinases.\ \N \N \N 22532 IPR004020

Pyrin domain was identified as putative protein–protein interaction domain at the N-terminal region of several proteins thought to function in apoptotic and inflammatory signaling pathways. Using secondary structure prediction and potential-based fold recognition methods, the PYRIN domain is predicted to be a member of the six-helix bundle death domain-fold superfamily that includes death domains (DDs), death effector domains (DEDs), and caspase recruitment domains (CARDs). Members of the death domain-fold superfamily are well established mediators of protein–protein interactions found in many proteins involved in apoptosis and inflammation, indicating further that the PYRIN domains serve a similar function. Comparison of a circular dichroism spectrum of the PYRIN domain of CARD7/DEFCAP/NAC/NALP1 with spectra of several proteins known to adopt the death domain-fold provides experimental support for the structure prediction. [MEDLINE:21406150] It is found in interferon-inducible proteins, pyrin and myeloid cell nuclear differentiation antigen.

\ \N \N \N 22521 IPR004007 Dihydroxyacetone kinase (glycerone kinase) EC: 2.7.1.29 catalyses the phosphorylation of glycerone in the presence of ATP to glycerone phosphate in the glycerol utilization pathway. This is the predicted phosphatase domain of the dihydroxyacetone kinase family.\ glycerone kinase activity ; GO:0004371 \N glycerol metabolism ; GO:0006071 22522 IPR004009 This domain has an SH3-like fold. It is found at the N-terminus of many but not all myosins. The function of this domain is unknown.\ ATP binding activity ; GO:0005524 myosin ; GO:0016459 \N 22523 IPR004010 Cache is a signaling domain that is found in animal Calcium channel subunits and a certain class of prokaryotic chemotaxis receptors.\ \N membrane ; GO:0016020 \N 22524 IPR004011 The GYR motif is found in several Drosophila melanogaster proteins. Its function is unknown, however the presence of completely conserved tyrosine residues may suggest it could be a substrate for tyrosine kinases.\ \N \N \N 22525 IPR004012 This domain is present in several proteins that are linked to the functions of GTPases in the Rap and Rab families. They could therefore play important roles in multiple Ras-like GTPase signaling pathways.\ \N \N \N 22526 IPR004013 The PHP (Polymerase and Histidinol Phosphatase) domain is a putative phosphoesterase domain. This family is often associated with an N-terminal region IPR003141.\ \N \N \N 22527 IPR004014 The

chains of sodium/potassium-transporting ATPases (H⁺/K⁺ and Na⁺/K⁺-ATPase) catalyze the hydrolysis of ATP, coupled with the exchange of sodium and potassium ions across the plasma membrane. The proteins are located in the cell membrane [MEDLINE:90033318], the ion transport they mediate creating theelectro-chemical gradient that provides the energy for the active transport of various nutrients. H⁺/K⁺-transporting ATPases are also responsible for production of acid in the stomach [MEDLINE:87057383]. H⁺/K⁺ and Na⁺/K⁺-ATPase are members of the P-type (or E1-E2-type) cation-transporting ATPase superfamily, which has evolved from a common ancestral gene [MEDLINE:94202222]. The sequences contain 10 transmembrane (TM) helices, some of which are well conserved throughout the superfamily. They may thus all operate via a similar mechanism, with an aspartylphosphoryl enzyme intermediate [MEDLINE:87033715] being formed during the catalytic cycle. Members of these families are involved in Na+/K⁺, H+/K⁺, Ca²⁺ and Mg²⁺- transport.\ \ P-type ATPase activity ; GO:0015662 membrane ; GO:0016020 cation transport ; GO:0006812 22519 IPR004005 Caliciviruses are positive-stranded ssRNA viruses that cause gastroenteritis [MEDLINE:91361557]. The calicivirus genome contains two open reading frames, ORF1 and ORF2 [MEDLINE:97048080], [MEDLINE:96183913]. ORF1 encodes a non-structural polypeptide, which has RNA helicase, cysteine protease and RNA polymerase activity. The regions of the poly-protein in which these activities lie are similar to proteins produced by the picornaviruses\ \ \ [MEDLINE:97048080], [MEDLINE:92201399]. ORF2 encodes a structural protein [MEDLINE:97048080]. This signature finds ORF2, the structural coat protein. Two different families of caliciviruses can be distinguished on the basis of sequence similarity, namely those classified as small round structured viruses (SRSVs) and those classed as non-SRSVs.\ \ \N \N \N 22520 IPR004006 Dihydroxyacetone kinase (glycerone kinase) EC: 2.7.1.29 catalyses the phosphorylation of glycerone in the presence of ATP to glycerone phosphate in the glycerol utilization pathway. This is the kinase domain of the dihydroxyacetone kinase family.\ glycerone kinase activity ; GO:0004371 \N glycerol metabolism ; GO:0006071 22517 IPR004003 Alanine dehydrogenases (EC: 1.4.1.1) and pyridine nucleotide transhydrogenase (EC: 1.6.1.1) have beenshown to share regions of similarity [MEDLINE:93176150]. Alanine dehydrogenase catalyzes the NAD-dependent\ reversible reductive amination of pyruvate into alanine. Pyridine nucleotide transhydrogenase catalyzes\ the reduction of NADP⁺ to NADPH with the concomitant oxidation of NADH to NAD⁺. This enzyme is located\ in the plasma membrane of prokaryotes and in the inner membrane of the mitochondria of eukaryotes. The\ transhydrogenation between NADH and NADP is coupled with the translocation of a proton across the\ membrane. In prokaryotes the enzyme is composed of two different subunits, an

chain (gene pntA)\ and a

chain (gene pntB), while in eukaryotes it is a single chain protein. The sequence of alanine\ dehydrogenase from several bacterial species are related with those of the

subunit of bacterial\ pyridine nucleotide transhydrogenase and of the N-terminal half of the eukaryotic enzyme. The two most\ conserved regions correspond respectively to the N-terminal extremity of these proteins and to a central\ glycine-rich region which is part of the NAD(H)-binding site.\ \ NAD(P)+ transhydrogenase activity ; GO:0008746 \N electron transport ; GO:0006118 22518 IPR004004 Caliciviruses are positive-stranded ssRNA viruses that cause gastroenteritis [MEDLINE:91361557]. The calicivirus genome contains two open reading frames, ORF1 and ORF2 [MEDLINE:97048080], [MEDLINE:96183913]. ORF1 encodes a non-structural polypeptide, which has RNA helicase, cysteine protease and RNA polymerase activity. The regions of the poly-protein in which these activities lie are similar to proteins produced by the picornaviruses\ \ \ [MEDLINE:97048080], [MEDLINE:92201399]. ORF2 encodes a structural protein [MEDLINE:97048080]. This fingerprint includes the helicase and polymerase activities of ORF 1. Two different families of caliciviruses can be distinguished on the basis of sequence similarity, namely those classified as small round structured viruses (SRSVs) and those classed as non-SRSVs.\ \ ATP binding activity ; GO:0005524 \N \N 22516 IPR004001

Actin [MEDLINE:92399964], [MEDLINE:93192059] is a ubiquitous protein involved in the formation of filamentsthat are major components of the cytoskeleton. These filaments interact \ with myosin to produce a sliding effect, which is the basis of muscular\ contraction and many aspects of cell motility, including cytokinesis. Each\ actin protomer binds one molecule of ATP and has one high affinity site for\ either calcium or magnesium ions, as well as several low affinity sites.\ Actin exists as a monomer in low salt concentrations, but filaments form\ rapidly as salt concentration rises, with the consequent hydrolysis of ATP.\ Actin from many sources forms a tight complex with deoxyribonuclease\ (DNase I) although the significance of this is still unknown. The formation\ of this complex results in the inhibition of DNase I activity, and actin\ loses its ability to polymerise. It has been shown that an ATPase domain\ of actin shares similarity with ATPase domains of hexokinase and hsp70\ proteins [MEDLINE:91271327], [MEDLINE:92366447].

In vertebrates there are three groups of actin isoforms: , and gamma. The actins are found in muscle tissues and are a major constituent of the contractile apparatus. The and gamma actins co-exists in most cell types as components of the cytoskeleton and as mediators of internal cell motility. In plants there are many isoforms which are probably involved in a variety of functions such as cytoplasmic streaming, cell shape determination, tip growth, graviperception, cell wall deposition, etc.

\ \ structural constituent of cytoskeleton ; GO:0005200 actin filament ; GO:0005884 \N 22515 IPR004000

Recently some divergent actin-like proteins have been identified in several species. These proteins include centractin (actin-RPV) from mammals, fungi yeast ACT5, Neurospora crassa ro-4) and Pneumocystis carinii, which seems to be a component of a multi-subunit centrosomal complex involved in microtubule based vesicle motility (this subfamily is known as ARP1); ARP2 subfamily, which includes chicken ACTL, Saccharomyces cerevisiae ACT2, Drosophila melanogaster 14D and Caenorhabditis elegans actC; ARP3 subfamily, which includes actin 2 from mammals, Drosophila 66B, yeast ACT4 and Schizosaccharomyces pombe act2; and ARP4 subfamily, which includes yeast ACT3 and Drosophila 13E.

\ \ structural constituent of cytoskeleton ; GO:0005200 actin cytoskeleton ; GO:0015629 \N 22514 IPR003998

Translocation of proteins across the two membranes of Gram-negative bacteriacan be carried out via a number of routes. Most proteins marked for export \ carry a secretion signal at their N-terminus, and are secreted by the general secretory pathway. The signal peptide is cleaved as they pass through the outer membrane. Other secretion systems include the type III system found in a select group of Gram-negative plant and animal pathogens, and the CagA system of Helicobacter pylori\ \ \ \ [MEDLINE:98315056].

In some bacterial species, however, there exists a system that operates \ independently of the Sec pathway [MEDLINE:20117987]. It selectively translocates \ periplasmic-bound molecules that are synthesised with, or are in close \ association with, "partner" proteins bearing an (S/T)RRXFLK twin arginine \ motif at the N-terminus. The pathway is therefore termed the Twin-Arginine \ Translocation or TAT system. Surprisingly, the four components that make up \ the TAT system are structurally and mechanistically related to a pH-dependent import system in plant chloroplast thylakoid membranes [MEDLINE:20117987]. The\ gene products responsible for the Sec-independent pathway are called TatA,\ TatB, TatC and TatE.

TatB is essential for the secretion of these specific proteins, and forms a\ scaffold upon which TatC assembles in the membrane. Deletion studies have shown that it is crucial in the forming of the TAT complex, and is therefore necessary for the correct working of the system.

\ \ protein translocase activity ; GO:0015450 membrane ; GO:0016020 protein secretion ; GO:0009306 22513 IPR003997

Secretion of virulence factors in Gram-negative bacteria involves transportation of the protein across two membranes to reach the cell exterior [MEDLINE:92215588]. Four principal exotoxin secretion systems have been described. In the type II and IV secretion systems, toxins are first exported to the periplasm by way of a cleaved N-terminal signal sequence; a second set of proteins is used for extracellular transport (type II), or the C-terminus of the exotoxin itself is used (type IV). Type III secretion involves at least 20 molecules that assemble into a needle; effector proteins are then translocated through this without need of a signal sequence. In the Type I system, a complete channel is formed through both membranes, and the secretion signal is carried on the C-terminus of the exotoxin.

The RTX (repeats in toxin) family of cytolytic toxins belong to the Type I \ secretion system, and are important virulence factors in Gram-negative bacteria. As well as the C-terminal signal sequence, several glycine-rich\ repeats are also found. These are essential for binding calcium, and are critical for the biological activity of the secreted toxins [MEDLINE:96178390]. All RTX toxin operons exist in the order rtxCABD, RtxA protein being the structural\ component of the exotoxin, both RtxB and D being required for its export from the bacterial cell; RtxC is an acyl-carrier-protein-dependent acyl- modification enzyme, required to convert RtxA to its active form [MEDLINE:99400981].

Escherichia coli hemolysin (HlyA) is often quoted as the model for RTX \ toxins. Recent work on its relative rtxC gene product HlyC [MEDLINE:98190040] has revealed that it provides the acylation aspect for post-translational modification of two internal lysine residues in the HlyA protein. HlyD provides a cytoplasmic transport moiety for HlyA, and is situated in both the cytoplasm and periplasm, having a single transmembrane segment [MEDLINE:92357011].

\ \ type I protein secretor activity ; GO:0015428 membrane ; GO:0016020 protein secretion ; GO:0009306 22512 IPR003996

Escherichia coli hemolysin (HlyA) is often quoted as the model for RTX \ toxins. Recent work on its relative rtxC gene product HlyC [MEDLINE:98190040] has revealed that it provides the acylation aspect for post-translational modification of two internal lysine residues in the HlyA protein. Other residues, including His23 and two conserved tyrosine residues, also appear to be important [MEDLINE:99343572].

\ \ acyltransferase activity ; GO:0008415 cytoplasm ; GO:0005737 toxin metabolism ; GO:0009404 22510 IPR003994

The human Xp11 region is extremely gene rich and of great interestbiologically due to the large number of disease loci found there. Disease-\ related genes found in this region are involved in Norrie disease, retinitis pigmentosa, synovial sarcoma, syndromic and nonsyndromic mental retardation, Renpennning syndrome, Prieto syndrome and Sutherland-Hann syndrome. A number of oncogenes are also found here.

A novel gene was identified in the Xp11 region via exon-trapping experiments. Northern analysis revealed no apparent splice variants, and significant expression in all tissues tested. The gene was thus named ubiquitously expressed transcript (UXT). UXT does not share significant sequence similarity with any known genes. However, a search of dbEST indicated widespread expression in tumour tissue [MEDLINE:99189243].

\ \ \N \N \N 22511 IPR003995

Escherichia coli hemolysin (HlyA) is often quoted as the model for RTX \ toxins. Recent work on its relative rtxC gene product HlyC [MEDLINE:98190040] has revealed that it provides the acylation aspect for post-translational modification of two internal lysine residues in the HlyA protein. To cause pathogenicity, the HlyA toxin must first bind Ca2+ ions to the set of glycine-rich repeats and then be activated by HlyC [MEDLINE:96404790]. This has been demonstrated both in vitro and in vivo.

\ \ hemolysin activity ; GO:0015484 extracellular ; GO:0005576 pathogenesis ; GO:0009405 22508 IPR003992

Bordetella pertussis is a Gram-negative, aerobic coccobacillus that causes pertussis (whooping cough), especially in young children [MEDLINE:89264462]. Once present in the lungs, the bacterium attaches to ciliated pulmonary epithelial cells via a collection of outer membrane proteins, all of which are virulence \ factors.

\ \ \N \N cell adhesion ; GO:0007155 22509 IPR003993

Treacher Collins Syndrome (TCS) is an autosomal dominant disorder ofcraniofacial development, the features of which include conductive hearing \ loss and cleft palate [MEDLINE:97250498], [MEDLINE:97195537]; it is the most common of the human mandibulo-facial dysostosis disorders [MEDLINE:97250498]. The TCS locus has been mapped to human chromosome 5q31.3-32 and the mutated gene identified (TCOF1) [MEDLINE:97195537]. To date, 35 mutations have been reported in TCOF1, all but one of which result in the introduction of a premature-termination codon into the predicted protein, Treacle. The observed mutational spectrum supports the hypothesis that TCS results from haploinsufficiency.

Treacle is a low complexity protein of 1,411 amino acids whose predicted\ protein structure contains a set of highly polar repeated motifs [MEDLINE:97250498]. These motifs are common to nucleolar trafficking proteins in other species and are predicted to be phosphorylated by casein kinase. In concert with this observation, the full-length TCOF1 protein sequence also contains putative nuclear and nucleolar localisation signals [MEDLINE:97250498]. Throughout the open\ reading frame are found mutations in TCS families and several polymorphisms. It has thus been suggested that TCS results from defects in a nucleolar trafficking protein that is critically required during human craniofacial development.

\ \ \N \N \N 22507 IPR003991

The tcfA gene of Bordetella pertussis encodes a unique virulence-associated \ factor, Tcf (tracheal colonisation factor) [MEDLINE:96065692]. The derived amino acid sequence of tcfA predicts a 68kDa RGD-containing, proline-rich protein.\ Amino acid sequence analysis reveals that the C-terminal 30kDa of this protein shares ~50% identity with the 30kDa C-terminus of the Bordetella pertactin precursor.

The Bordetella resistance to killing, brk, locus has cloned and sequenced\ and found to encode two divergently transcribed open reading frames (ORFs),\ designated BrkA and BrkB [MEDLINE:95012680]. Both ORFs are necessary for serum resistance. BrkA shares ~29% identity with pertactin and contains two RGD motifs, in addition to a proteolytic processing site and an outer membrane targeting signal. BrkA, like pertactin, is involved in adherence and invasion. This entry is the C-terminal end of pertactin and is found associated with the N-terminal section IPR003992.

\ \ \N \N cell adhesion ; GO:0007155 22506 IPR003990

Pancreatitis-associated protein (PAP) is a lectin-related secretory proteinpresent in small amounts in normal pancreas and overexpressed during the \ acute phase of the pancreatitis [MEDLINE:94245143], [MEDLINE:93378971]. Conversely, PAP is constitutively expressed in the intestinal tract, but not in other tissues [MEDLINE:93378971]. PAP mRNA could not be evidenced in liver, stomach, salivary glands, brain, kidney or testis. Its pattern of expression during severe pancreatic aggression suggests that it might be a stress protein involved in the control of bacterial proliferation [MEDLINE:92105133].

The deduced amino acid sequence of PAP shows marked similarity to the\ carbohydrate-recognition domain (CRD) of animal lectins [MEDLINE:92105133]. Animal lectins display a wide variety of architectures, and are classified according to the CRD, of which there are two principal types: S-type and C-type. C-type lectins require Ca2+ for their activity. The CRD consists of 110-130 residues, which include four perfectly conserved cysteines that are involved in the formation of two disulphide bridges.

\ \ \N \N \N 22505 IPR003989

Intercellular adhesion molecules (ICAMs) and vascular cell adhesion molecule-1 (VCAM-1) are part of the immunoglobulin superfamily. They are\ important in inflammation, immune responses and in intracellular signalling\ events [MEDLINE:97296383]. The ICAM family consists of five members, designated ICAM-1 to ICAM-5. They are known to bind to leucocyte integrins CD11/CD18 during inflammation and in immune responses. In addition, ICAMs may exist in soluble forms in human plasma, due to activation and proteolysis mechanisms at cell surfaces.

ICAM-1 (CD54) contains five Ig-like domains. It is expressed on leucocytes, \ endothelial and epithelial cells, and is upregulated in response to bacterial invasion. The protein is a ligand for lymphocyte-function associated (LFA) antigens and also a receptor for CD11a,b/CD18, fibrinogen, human rhinoviruses and Plasmodium falciparum-infected erythrocytes. ICAM-1 binding sites for CD11a/CD18 and its other binding partners are located in the first domain and are overlapping. ICAM-1 domain 2 seems to play an important role in maintaining the conformation of domain 1 and particularly the structural integrity of the LFA-1 ligand-binding site [MEDLINE:21061404].

The 3-dimensional atomic structure of the tandem N-terminal Ig-like domains \ (D1 and D2) of ICAM-1 has been determined to 2.2A resolution and fitted into\ a cryoelectron microscopy reconstruction of a rhinovirus-ICAM-1 complex [MEDLINE:98208506]. Extensive charge interactions between ICAM-1 and human rhinoviruses are largely conserved in major and minor receptor groups of rhinoviruses. The interaction of ICAMs with LFA-1 is mediated by a divalent cation bound to the insertion (I)-domain on the chain of LFA-1 and the carboxyl group of a conserved glutamic acid residue on ICAMs.

VCAM-1 was first described as a cytokine-inducible endothelial adhesion molecule. It can bind to leucocyte integrin VL-4 (very late antigen-4) to recruit leucocytes to sites of inflammation [MEDLINE:21064999]. The predominant form of VCAM-1 in vivo has an N-terminal extracellular region comprising seven Ig-like domains [MEDLINE:95147978]. A conserved integrin-binding motif has been identified in domains 1 and 4, variants of which are present in the N-terminal domain of all members of the integrin-binding subgroup of the immunoglobulin superfamily. The structure of a VLA-4-binding fragment comprising the first two domains of VCAM-1 has been determined to 1.8A resolution. The integrin-binding motif is exposed and forms the N-terminal region of the loop between -strands C and D of domain 1 [MEDLINE:95147978]. VCAM-1 domains 1 and 2\ are structurally similar to ICAM-1 and ICAM-2 [MEDLINE:21064999].

\ \ \N membrane ; GO:0016020 cell-cell adhesion ; GO:0016337 22504 IPR003988

ICAM-2 (CD102) has two Ig-like domains. It is expressed on endothelial\ cells, leucocytes and platelets, and binds to CD11a,b/CD18. The protein is\ refractory to proinflammatory cytokines, and plays an important role in the\ adhesion of leucocytes to the uninduced endothelium [MEDLINE:99282946].

ICAM-3 (CD50) contains five Ig-like domains and binds to leucocyte integrins\ CD11a,d/CD18. The protein plays an important role in the immune response and\ perhaps in signal transduction [MEDLINE:20192041].

ICAM-4 (LW blood group Ag) is red blood cell (RBC) specific and binds to \ CD11a,b/CD18. It is associated with the RBC Rh antigens and could be \ important in retaining immature red cells in the bone marrow, or in the uptake of senescent cells into the spleen [MEDLINE:20408938].

ICAM-5 (telencephalin) has nine Ig-like domains and is confined to the \ telencephalon of the brain. The role of this CD11a/CD18 binding molecule \ is not yet known [MEDLINE:20203437].

\ \ \N membrane ; GO:0016020 cell-cell adhesion ; GO:0016337 22502 IPR003986

Neurotensin is a 13-residue peptide transmitter, sharing significant\ similarity in its 6 C-terminal amino acids with several other neuropeptides,\ including neuromedin N. This region is responsible for the biological activity, the N-terminal portion having a modulatory role. Neurotensin is distributed throughout the central nervous system, with highest levels in the hypothalamus, amygdala and nucleus accumbens. It induces a variety of effects, including: analgesia, hypothermia and increased locomotor activity. It is also involved in regulation of dopamine pathways. In the periphery, neurotensin is found in endocrine cells of the small intestine, where it leads to secretion and smooth muscle contraction PUB00005894.

The existence of 2 neurotensin receptor subtypes, with differing affinities\ for neurotensin and differing sensitivities to the antihistamine levocabastine, was originally demonstrated by binding studies in rodent brain. Two neurotensin receptors (NT1 and NT2) with such properties have since been cloned and have been found to be G-protein-coupled receptor family members PUB00005894.

The NT2 receptor was cloned from rat, mouse and human brains based on its\ similarity to the NT1 receptor. The receptor was found to be a low affinity,\ levocabastine sensitive receptor for neurotensin. Unlike the high affinity,\ NT1 receptor, NT2 is insensitive to guanosine triphosphate and has low sensitivity to sodium ions [MEDLINE:99322221]. Highest levels of expression of the receptor are found in the brain, in regions including: the olfactory system, cerebral and cerebellar cortices, hippocampus and hypothalamic nuclei. The distribution is distinct from that of the NT1 receptor, with only a few\ areas (diagonal band of Broca, medial septal nucleus and suprachiasmatic nuclei) expressing both receptor subtypes. The receptor has also been found at lower levels in the kidney, uterus, heart and lung [MEDLINE:99066919]. Activation\ of the NT2 receptor by non-peptide agonists suggests that the receptor can\ couple to phospholipase C, phospholipase A2 and MAP kinase. A functional\ response to neurotensin, however, is weak [MEDLINE:98288785] or absent, and neurotensin appears to act as an antagonist of the receptor [MEDLINE:99066919]. It has been suggested that a substance other than neurotensin may act as the natural ligand for this receptor.

\ \ neurotensin receptor activity, G-protein coupled ; GO:0016492 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 22503 IPR003987

ICAM-5 (telencephalin) has nine Ig-like domains and is confined to the \ telencephalon of the brain. The role of this CD11a/CD18 binding molecule \ is not yet known [MEDLINE:20203437].

\ \ \N membrane ; GO:0016020 cell-cell adhesion ; GO:0016337 22501 IPR003985

The NT1 receptor was cloned in 1990 from rat brain and found to act as a\ high affinity, levocabastine insensitive receptor for neurotensin [MEDLINE:90297956]. The affinity of neurotensin for the receptor could be decreased by both sodium ions and guanosine triphosphate (GTP) [MEDLINE:99322221]. The NT1 receptor is expressed predominantly in the brain and intestine. In the brain, expression has been found in the diagonal band of Broca, medial septal nucleus, nucleus basalis magnocellularis, suprachiasmatic nucleus, supramammillary area, substantia nigra and ventral tegmental area. The receptor is also expressed in the dorsal root ganglion neurones of the spinal cord. The predominant response upon activation of the receptor by neurotensin is activation of phospholipase C, causing an increase in intracellular calcium levels. The receptor can also stimulate cAMP formation, MAP kinase activation and the induction of growth related genes, such as krox-24 [MEDLINE:99322221].

\ \ neurotensin receptor activity, G-protein coupled ; GO:0016492 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 22500 IPR003984

\ \ neurotensin receptor activity, G-protein coupled ; GO:0016492 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 22499 IPR003983

Leukotrienes (LT) are potent lipid mediators derived from arachidonic acid\ metabolism. They can be divided into two classes, based on the presence or\ absence of a cysteinyl group. Leukotriene B4 (LTB4) does not contain such a\ group, whereas LTC4, LTD4, LTE4 and LTF4 are cysteinyl leukotrienes PUB00005667.

\ \

LTB4 is one of the most effective chemoattractant mediators known, and is\ produced predominantly by neutrophils and macrophages. It is involved in a\ number of events, including: stimulation of leukocyte migration from the\ bloodstream; activation of neutrophils; inflammatory pain; host defense\ against infection; increased interleukin production and transcription PUB00005667.\ It is found in elevated concentrations in a number of inflammatory and\ allergic conditions, such as asthma, psoriasis, rheumatoid arthritis and\ inflammatory bowel disease, and has been implicated in the pathogenesis of\ these diseases PUB00005667, PUB00005667.

Binding sites for LTB4 have been observed in membrane preparations from\ leukocytes, macrophages and spleen. Two receptors for LTB4 have since been\ cloned (BLT1 and BLT2); both are members of the rhodopsin-like G-protein-\ coupled receptor superfamily [MEDLINE:20399028].

The leukotriene B4 type 1 receptor (BLT1) has been cloned from human, mouse,\ rat and guinea pig, and was found to be identical to a previously cloned\ receptor, P2Y7 [MEDLINE:20399028], [MEDLINE:20180297]. This receptor was originally thought to be a\ purinoceptor but is now widely accepted to bind LTB4. BLT1 has also been\ reported to act as a coreceptor for macrophage-tropic HIV1 strains [MEDLINE:20180297]. BLT1\ is expressed primarily in peripheral leukocytes and peritoneal macrophages,\ with lower levels of expression detected in the spleen and thymus of humans\ [MEDLINE:20180297]. Activation of the receptor by LTB4 leads to the production of inositol\ trisphosphate and an increase in intracellular calcium levels. This response\ is sensitive to pertussis toxin in some cell types. The receptor also causes\ chemotaxis and inhibition of forskolin-stimulated adenylyl cyclase activity \ in a pertussis toxin sensitive manner. It has been demonstrated that BLT1\ can couple to Gi2 and G16 G-proteins, depending on the cell type in which\ it is expressed [MEDLINE:20399028].

\ \ leukotriene receptor activity ; GO:0004974 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 22498 IPR003982

\ \

The leukotriene B4 type 2 receptor gene (BLT2) has been located in both the\ human and mouse genomes, and is found in close proximity to BLT1 in both\ species [MEDLINE:20399028]. The receptor is expressed in most human tissues, with highest\ levels in the liver, spleen, ovary and leukocytes [MEDLINE:20418070]. Binding of LTB4 to\ the receptor produces increased levels of inositol trisphosphate and calcium,\ inhibition of forskolin-stimulated adenylyl cyclase activity and chemotaxis\ [MEDLINE:20576218]. These effects may be accomplished by coupling to G-proteins of the\ Gq, Gi and Gz classes [MEDLINE:20399028].

\ \ leukotriene receptor activity ; GO:0004974 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 22497 IPR003981

\ \

\ \ leukotriene receptor activity ; GO:0004974 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 22496 IPR003980

Histamine is distributed within mast cells in all peripheral tissues and \ is a well-characterised mediator of inflammation and allergy PUB00005667. It also\ regulates release of gastric acid from parietal cells in the gastric mucosa.\ H3 receptors function as presynaptic autoreceptors on histamine-containing\ neurones. They are expressed abundantly in the central nervous system, with\ highest levels found in the thalamus, caudate nucleus and cortex. High\ levels of expression are also found in the hypothalamus, hippocampus and\ olfactory tubercle. In the periphery, low levels of H3 have been detected in\ the human small intestine, testis and prostate but not in a number of other\ tissues tested, including the heart, lung and spleen PUB00005667. Binding of \ histamine to H3 receptors results in inhibition of forskolin-stimulated cAMP\ accumulation, suggesting coupling to a G-protein of the Gi class [MEDLINE:99278519].

\ \ histamine receptor activity ; GO:0004969 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 22493 IPR003977

Parkinson's disease (PD) is a common neurodegenerative disorder with complex clinical features and a poorly understood aetiology. PD is accompanied by a\ progressive loss of dopamine-containing neurons in the substantia nigra,\ with patients suffering from rigidity, slowness of movement, tremour and\ disturbances of balance. Autosomal recessive juvenile parkinsonism (AR-JP)\ is a rare form of familial PD mapped to chromosome 6 and linked strongly to\ a pair of markers. One of these markers has been cloned, yielding a sequence\ that encodes a protein, 465 amino acids long [MEDLINE:20298807]. The protein sequence,\ named parkin, shows moderate similarity with ubiquitin at the N-terminus and\ a ring-finger domain at the C-terminus.

In normal individuals, parkin binds to the E2 ubiquitin-conjugating human\ enzyme 8 (UbcH8) through the C-terminal ring-finger domain. In the presence\ of UbcH8, parkin has ubiquitin-protein ligase activity and even catalyses \ its own ubiquitination. Furthermore, parkin appears to target the synaptic\ vesicle-associated protein CDCrel-1 for ubiquitination and thus promotes its\ degradation. The mutated forms of parkin implicated in AR-JP appear to be\ defective in terms of UbcH8 binding, E3 ubiquitin protein-ligase activity,\ self-ubiquitination, and CDCrel-1 binding and ubiquitination [MEDLINE:20542129].

\ \ ubiquitin-protein ligase activity ; GO:0004842 \N ubiquitin cycle ; GO:0006512 22494 IPR003978

Megakaryocytes are large cells found in the bone marrow that, upon maturation, fragment into platelets. The term thrombopoietin (TPO) was\ coined in 1958 to describe a possible humoral entity that stimulates\ megakaryocyte development into platelets. The discovery of a novel\ haemopoietic cytokine receptor encoded by the proto-oncogene c-mpl raised\ speculation that this was the receptor for thrombopoietin, and prompted a\ search for the endogenous ligand [MEDLINE:99305660]. The ligand was cloned and in vivo-\ administration of the recombinant protein to mice produced a 4-fold increase\ in circulating platelets. These results suggested that the c-mpl ligand was\ in fact thrombopoietin [MEDLINE:94261207].

\ \

More recent studies have shown that TPO is expressed in hepatocytes, the\ renal proximal tubules, muscle cells and stromal cells in haemopoietic\ organs [MEDLINE:20049050]. TPO is a 332-residue protein with a 2-domain structure. The\ domain at the N-terminus is 153 amino acids long, shares similarity with\ erythropoietin and can itself stimulate megakaryopoiesis in vitro. A four- -helical structure is predicted, which is typical of many haemopoietic\ regulators. The C-terminal domain is 179 amino acids long, is highly \ variable across species and is not required for the binding of c-mpl [MEDLINE:98079053].

\ \ cytokine activity ; GO:0005125 extracellular ; GO:0005576 cell proliferation ; GO:0008283 22495 IPR003979

Tropoelastin is the precursor to the elastin molecule. Elastin aggregates are responsible for the stretch properties of skin, arterial walls and\ ligaments, and elastin is implicated in several hereditary diseases,\ including cutis laxa (where the elasticity of the skin is lost) and\ elastoderma (similar to cutis laxa but with grape-like accumulations of\ elastin in the dermis). The unusual and highly characteristic amino acid\ composition of this protein accounts for its great hydrophobicity. It contains one-third glycine amino acids and several lysine derivatives that serve as covalent\ cross-links between protein monomers. Elastin is thus a three-dimensional network with 60-70 amino acids between two cross-linking points. This molecular\ architecture is determinant for its elastic properties, insolubility and resistance to proteolysis.

\ \

Normally, the elastin gene contains 36 exons, and this structure allows the\ formation of stable isoforms by alternative splicing. The 3-dimensional\ structure of elastin is currently unknown and was originally thought to be\ an amorphous polymer. This is consistent with the theory of rubber\ elasticity, which requires the resting state of the protein to be of\ higher disorder (entropy) than the extended state [MEDLINE:99232605].

More recent studies show the presence of helical and other secondary\ structures [MEDLINE:69014683], and the elasticity theory has been amended to involve, in\ the resting state, secondary structure elements in chaotic motion. In the\ extended state of the protein, the secondary structures align to form an\ ordered structure together with neighbouring molecules [MEDLINE:99232605].\ \ Tropoelastin consists mainly of repetitive elements of four, five, six and\ nine hydrophobic residues [MEDLINE:91107187]. The five, six and nine residue repeats\ function as binding sites for fibroblasts during chemotaxis (the hexapeptide\ and nonapeptide repeats competing for the same receptor) [MEDLINE:88150092]. The\ hexapeptide repeat is also known to bind calcium ions.

The formation of the elastin fibre is a complicated process, involving the\ binding of a chaperone to the precursor to prevent aggregation in the cell,\ followed by migration out of the cell, whereupon the chaperone\ disassociates. The tropoelastin molecules then cross-link to each other\ using deaminated lysine residues, the microfibril structures functioning as\ a scaffold [MEDLINE:99232605].

\ \ extracellular matrix structural constituent ; GO:0005201 extracellular matrix ; GO:0005578 \N 22492 IPR003976

TREK is a member of the TWIK-related (2-pore domain) K+ channel family\ identifed in human tissues. It has two members, designate TREK-1 and TREK-2. \ TREK-1 is distributed in neuronal, cardiac and smooth muscle cells, whereas\ TREK-2 has been shown to be expressed in the cerebellum PUB00009384, [MEDLINE:20298807]. Both members\ are known as mechano-sensitive and unsaturated fatty acid-activated K+\ channels as they are opened by membrane stretch, cell swelling, shear\ stress and polyunsaturated fatty acids, such as arachidonic acid [MEDLINE:20298807].

\ \ potassium channel activity ; GO:0005267 membrane ; GO:0016020 potassium ion transport ; GO:0006813 22491 IPR003975

The first Shal (Kv4) sequence was found in Drosophila melanogaster. Several vertebrate\ K⁺ channels with similar amino acid sequences were subsequently found and,\ together with the Drosophila melanogaster Shal channel, now constitute the Shal (Kv4)\ family. These channels support outward K⁺-selective currents and are\ inhibited by free fatty acids PUB00009785. The Shal family can be further divided \ into 3 families, designated Kv4.1, Kv4.2 and Kv4.3.

\ \ voltage-gated potassium channel activity ; GO:0005249 voltage-gated potassium channel complex ; GO:0008076 potassium ion transport ; GO:0006813 22490 IPR003974

\ \ \ voltage-gated potassium channel activity ; GO:0005249 voltage-gated potassium channel complex ; GO:0008076 potassium ion transport ; GO:0006813 22488 IPR003972

The first Shaker (Kv1) sequence was found in Drosophila melanogaster. Several vertebrate\ K+ channels with similar amino acid sequences were subsequently found and,\ together with the Drosophila melanogaster Shaker channel, now constitute the Shaker (Kv1)\ family. These channels are mostly expressed in the brain, but can also be\ found in non-excitable cells, such as lymphocytes [MEDLINE:20256248], PUB00009778.

\ \ voltage-gated potassium channel activity ; GO:0005249 voltage-gated potassium channel complex ; GO:0008076 potassium ion transport ; GO:0006813 22489 IPR003973

\ \ voltage-gated potassium channel activity ; GO:0005249 voltage-gated potassium channel complex ; GO:0008076 potassium ion transport ; GO:0006813 22487 IPR003971

More recently, 4 new electrically-silent subunits have been cloned:\ Kv5 (KCNF), Kv6 (KCNG), Kv8 and Kv9 (KCNS). These subunits do not themselves\ possess any functional activity, but appear to form heteromeric channels\ with Kv2 subunits, and thus modulate Shab channel activity [MEDLINE:97450962]. When highly\ expressed, they inhibit channel activity, but at lower levels show more\ specific modulatory actions. Coexpression of Kv9 subunits with Shab subunits\ produces a shift in the voltage-dependence of channel inactivation toward\ more negative potentials [MEDLINE:97450962]. In addition, Shab channel deactivation and \ inactivation are slowed, and the single channel conductance is increased [MEDLINE:99413882].

\ \ voltage-gated potassium channel activity ; GO:0005249 voltage-gated potassium channel complex ; GO:0008076 potassium ion transport ; GO:0006813 22486 IPR003970

More recently, 4 new electrically-silent subunits have been cloned:\ Kv5 (KCNF), Kv6 (KCNG), Kv8 and Kv9 (KCNS). These subunits do not themselves\ possess any functional activity, but appear to form heteromeric channels\ with Kv2 subunits, and thus modulate Shab channel activity [MEDLINE:97450962]. When highly\ expressed, they inhibit channel activity, but at lower levels show more\ specific modulatory actions. Coexpression of Kv8 subunits with Shab subunits\ produces altered channel-activation kinetics that do not fit the standard\ model. In addition, channel inactivation shows a shift in voltage-dependence\ toward more negative potentials and a slower time course. TM domain 6 is\ thought to play a key role in these modulatory effects [MEDLINE:97236841].

\ \ voltage-gated potassium channel activity ; GO:0005249 voltage-gated potassium channel complex ; GO:0008076 potassium ion transport ; GO:0006813 22485 IPR003969

More recently, 4 new electrically-silent subunits have been cloned:\ Kv5 (KCNF), Kv6 (KCNG), Kv8 and Kv9 (KCNS). These subunits do not themselves\ possess any functional activity, but appear to form heteromeric channels\ with Kv2 subunits, and thus modulate Shab channel activity [MEDLINE:97450962]. When highly\ expressed, they inhibit channel activity, but at lower levels show more\ specific modulatory actions. Coexpression of Kv6 subunits with Shab subunits\ has a slowing effect on Shab channel inactivation at strong depolarising\ potentials, but has little effect on channel inactivation at intermediate\ potentials [MEDLINE:98359052].

\ \ voltage-gated potassium channel activity ; GO:0005249 voltage-gated potassium channel complex ; GO:0008076 potassium ion transport ; GO:0006813 22484 IPR003968

\ \ \ voltage-gated potassium channel activity ; GO:0005249 voltage-gated potassium channel complex ; GO:0008076 potassium ion transport ; GO:0006813 22482 IPR003966

The amino acid sequence of prothrombin has a modular architecture, comprising a series of N-terminal gamma-carboxyglutamate residues,\ activation peptides 1 and 2, thrombin light chains A and B, and two kringle \ domains. Modification of the glutamyl residues is necessary for calcium-\ dependent interaction of the protein with a negatively charged phospholipid \ surface, which is essential for the conversion of prothrombin to thrombin.

Prothrombin activation at the membrane surface is mediated by factors Va\ and Xa. Factor Xa removes the activation peptide and cleaves the remaining\ part into light and heavy chains. Activation is slow because factor V \ itself has to be activated by the initial small amounts of thrombin.

Thrombin is a member of the trypsin family of S1 peptidases. It catalyses\ the preferential cleavage of arginine-lysine bonds, converting fibrinogen \ to fibrin, and releasing fibrinopeptides A and B. Thrombin can itself cleave\ the N-terminal fragment (fragment 1) of prothrombin, prior to its activation\ by factor Xa. Its effects are mediated by the thrombin receptor.

\ \

The structure of the thrombin A-chain has been determined to 1.9A resolution [MEDLINE:90059942]. The A-chain, which is ordered only in its central part, is positioned\ along the molecular surface opposite to the active site. The B-chain \ exhibits the characteristic fold of trypsin-like proteases [MEDLINE:99162521].

\ \

The most conserved portions of the B chain are the active-site residues and\ adjacent amino acids, the B loop, and the primary substrate-binding region\ [MEDLINE:92212913]. The regions of poorest conservation in the B chain correspond to \ surface loops, including putative thrombomodulin-binding sites and a \ hirudin-binding region. The extent of sequence similarity between species\ and the conservation of many of the functional/structural motifs suggests\ that, in addition to their role in blood coagulation, vertebrate thrombins\ may play an important role in the general mechanisms of wound repair [MEDLINE:92212913].

\ \ calcium ion binding activity ; GO:0005509 \N blood coagulation ; GO:0007596 22483 IPR003967

The first EAG K+ channel was identified in Drosophila melanogaster, following a screen \ for mutations giving rise to behavioural abnormalities. Disruption of the\ Eag gene caused an ether-induced, leg-shaking behaviour. Subsequent studies\ have revealed a conserved multi-gene family of EAG-like K+ channels, which\ are present in humans and many other species. Based on the varying\ functional properties of the channels, the family has been divided into\ 3 subfamilies: EAG, ELK and ERG. Interestingly, Caenorhabditis elegans appears to lack\ the ELK type PUB00009384.

\ \

The human ether-a-go-go-related gene (HERG), cloned from hippocampus, shares\ 49% amino acid identity with EAG. It is also found in the heart, where it \ helps to control K+ efflux [MEDLINE:95327958]. Mutations in HERG result in the disruption\ of the repolarising current and the disease LQT2 syndrome, an inherited\ disorder of cardiac repolarisation that predisposes affected individuals to\ life-threatening arrhythmias [MEDLINE:99214568].

\ \ voltage-gated potassium channel activity ; GO:0005249 membrane ; GO:0016020 potassium ion transport ; GO:0006813 22479 IPR003963

Staphylococcus aureus is a Gram-positive coccus that grows in clusters or pairs, and is the major cause of nosocomial infections due to its multiple \ antibiotic resistant nature. Patients who are immunocompromised (e.g., \ those suffering from third degree burns or chronic illness) are at risk \ from deep staphylococcal infections, such as osteomyelitis and pneumonia.\ Most skin infections are also caused by this bacterium [MEDLINE:98011275].

Many virulence mechanisms are employed by Staphylococci to induce \ pathogenesis: these can include polysaccharide capsules and exotoxins [MEDLINE:98011275]. Examples of the latter are bi-component toxins, which involve the\ synergistic combination of an "S" and an "F" component [MEDLINE:99023796]. These undergo \ conformational changes in their protein structure and form oligomeric pores\ in the target cell membrane upon recognition of certain host receptors. The\ main cells targeted are polymorphonuclear cells, monocytes, erythrocytes \ and macrophages. Examples of this protein family include: leucocidin, gamma-\ hemolysin and -hemolysin.

\ \

Recently, the crystal structure of the Staphylococcus aureus leucocidin "F" \ component (LukF) has been determined to 1.9A resolution [MEDLINE:99140293]. This structure,\ which comprises a central 3-strand -sheet, with an N-terminal "latch",\ clarified the mechanism of virulence in the bi-component toxin. Further work\ using a different form of the leucocidin (LukF-PV) has suggested that it may\ be a representative fold for water-soluble transmembrane toxins [MEDLINE:99197293].

\ \ toxin activity ; GO:0015070 extracellular ; GO:0005576 pathogenesis ; GO:0009405 22480 IPR003964

The arginine dihydrolase (AD) pathway is found in many prokaryotes and some primitive eukaryotes. The three- \ enzyme anaerobic pathway breaks down L-arginine to form 1 mol of ATP, carbon \ dioxide and ammonia. In simpler bacteria, the first enzyme, arginine \ deiminase, can account for up to 10% of total cell protein [MEDLINE:98162867].

Carbamate kinase is involved in the last step of the AD pathway, converting\ carbamoyl phosphate and ADP into ammonia, carbon dioxide and ATP [MEDLINE:89137094]. The\ second step of the pathway involves the degradation of L-citrulline to \ carbamoyl phosphate and L-ornithine, using ornithine carbamoyltransferase [MEDLINE:99069319].

\ \

The crystal structure of Enterococcus faecium carbamate\ kinase has been determined to 2.8A resolution [MEDLINE:99226823]. The enzyme exists as a\ homodimer of two 33kDa subunits. The hallmark of the dimer is a 16-stranded -sheet, surrounded by -helices. Each subunit contains an active\ site within a large crevice.

\ \ carbamate kinase activity ; GO:0008804 \N arginine metabolism ; GO:0006525 22477 IPR003961

Fibronectins are multi-domain glycoproteins found in a soluble form in plasma, and in an insoluble form in loose connective tissue and basement membranes [MEDLINE:87054047]. They contain multiple copies of 3 repeat regions (types I, II and III), which bind to a variety of substances including heparin, collagen, DNA, actin, fibrin and fibronectin receptors on cell surfaces. The wide variety of these substances means that fibronectins are involved in a number of important functions: e.g., wound healing; cell adhesion; blood coagulation; cell differentiation and migration; maintenance of the cellular cytoskeleton; and tumour metastasis [MEDLINE:87175578]. The role of fibronectin in cell differentiation is demonstrated by the marked reduction in the expression of its gene when neoplastic transformation occurs. Cell attachment has been found to be mediated by the binding of the tetrapeptide RGDS to integrins on the cell surface [MEDLINE:89160821], although related sequences can also display cell adhesion activity.

Plasma fibronectin occurs as a dimer of 2 different subunits, linked together by 2 disulphide bonds near the C-terminus. The difference in the 2 chains occurs in the type III repeat region and is caused by alternative splicing of the mRNA from one gene [MEDLINE:87054047]. The observation that, in a given protein, an individual repeat of one of the 3 types (e.g., the first FnIII repeat) shows much less similarity to its subsequent tandem repeats within that protein than to its equivalent repeat between fibronectins from other species, has suggested that the repeating structure of fibronectin arose at an early stage of evolution. It also seems to suggest that the structure is subject to high selective pressure [MEDLINE:84082067].

The fibronectin type III repeat region is an approximately 100 amino acid domain, different tandem repeats of which contain binding sites for DNA, heparin and the cell surface [MEDLINE:87054047]. The superfamily of sequences believed to contain FnIII repeats represents 45 different families, the majority of which are involved in cell surface binding in some manner, or are receptor protein tyrosine kinases, or cytokine receptors.

\ \ \N \N \N 22478 IPR003962

\ \ \N \N \N 22481 IPR003965

The yeast fatty acid synthase (FAS) is a hexameric complex ( 6 6) of two multifunctional proteins, and [MEDLINE:87166038]. The subunit\ contains two of the seven enzymatic activities required for the synthesis\ of fatty acids, together with the site for attachment of the prosthetic\ group 4'-phosphopantetheine. The subunit contains the remaining\ five enzyme domains: acetyltransferase and malonyltransferase, s-acyl fatty\ acid synthase thioesterase, enoyl-[acyl-carrier protein] reductase, and\ 3-hydroxypalmitoyl-[acyl-carrier protein] dehydratase.

\ \

The sequential order of the five FAS1-encoded enzyme domains is co-linear \ in Yarrowia lipolytica and Saccharomyces cerevisiae, which observation \ is\ consistent with evidence that the functional organisation of FAS genes is\ similar in related organisms but differs between unrelated species [MEDLINE:91238709].

\ \

Sterigmatocystin (ST) and the aflatoxins (AFs) (related fungal secondary \ metabolites) are among the most toxic, mutagenic and carcinogenic natural\ products known [MEDLINE:96202293]. In Aspergillus nidulans, the ST biosynthetic pathway is \ believed to involve at least 15 enzymatic activities; some Aspergillus\ parasiticus, Aspergillus flavus and Aspergillus nomius strains \ contain\ additional activities that convert ST to AF.

\ \

A 60kb region of the A. nidulans genome has been characterised and found to contain virtually all of \ the genes needed for ST biosynthesis [MEDLINE:96202293]. The\ deduced polypeptide sequences of regions within this cluster share a high\ degree of similarity with enzymes that have activities predicted for ST/AF\ biosynthesis, including a polyketide synthase, a fatty acid synthase\ ( and subunits), five monooxygenases, four dehydrogenases, an\ esterase, an 0-methyltransferase, a reductase, an oxidase and a zinc\ cluster DNA binding protein [MEDLINE:96202293].

\ \ fatty-acid synthase activity ; GO:0004312 fatty-acid synthase complex ; GO:0005835 fatty acid biosynthesis ; GO:0006633 22475 IPR003959

A large family of ATPases has been described [MEDLINE:91317863], [MEDLINE:91121507], [MEDLINE:90269209], [MEDLINE:93283443], [MEDLINE:95374488] whose key feature is that they share a conserved region of about 220 amino acids that contains an ATP-binding site. This family is now called AAA, for 'A'TPases 'A'ssociated with diverse cellular 'A'ctivities. The proteins that belong to this family either contain one or two AAA domains.

It is proposed that, in general, the AAA domains in these proteins act as ATP-dependent protein clamps [MEDLINE:95374488].

In addition to the ATP-binding 'A' and 'B' motifs (see the relevant entry IPR001687), which are located in the N-terminal half of this domain, there is a highly conserved region located in the central part of the domain.

\ \ ATP binding activity ; GO:0005524 \N \N 22476 IPR003960

It is proposed that, in general, the AAA domains in these proteins act as ATP-dependent protein clamps [MEDLINE:95374488].

\ \ ATP binding activity ; GO:0005524 \N \N 22473 IPR003957

The CCAAT-binding factor (CBF) is a mammalian transcription factor that binds to a CCAAT motif in thepromoters of a wide variety of genes, including type I collagen and albumin. The factor is a heteromeric\ complex of A and B subunits, both of which are required for DNA-binding [MEDLINE:91093096], [MEDLINE:92195809]. The \ subunits can interact in the absence of DNA-binding, conserved regions in each being important in mediating \ this interaction.

The A subunit can be split into 3 domains on the basis of sequence similarity, a \ non-conserved N-terminal 'A domain'; a highly-conserved central 'B domain' involved in DNA-binding; and a \ C-terminal 'C domain', which contains a number of glutamine and acidic residues involved in protein-protein \ interactions [MEDLINE:92195809]. The A subunit shows striking similarity to the HAP3 subunit of the yeast \ CCAAT-binding heterotrimeric transcription factor [MEDLINE:92195809], [MEDLINE:95147853]. The Kluyveromyces lactis HAP3 protein \ has been predicted to contain a 4-cysteine zinc finger, which is thought to be present in similar HAP3\ and CBF subunit A proteins, in which the third cysteine is replaced by a serine [MEDLINE:95147853]. This family also includes DNA topoisomerase II, which controls the topology of DNA by transient breaking of the strands and rejoining.

\ \ DNA binding activity ; GO:0003677 nucleus ; GO:0005634 \N 22474 IPR003958

The A subunit can be split into 3 domains on the basis of sequence similarity, a \ non-conserved N-terminal 'A domain'; a highly-conserved central 'B domain' involved in DNA-binding; and a \ C-terminal 'C domain', which contains a number of glutamine and acidic residues involved in protein-protein \ interactions [MEDLINE:92195809]. The A subunit shows striking similarity to the HAP3 subunit of the yeast \ CCAAT-binding heterotrimeric transcription factor [MEDLINE:92195809], [MEDLINE:95147853]. The Kluyveromyces lactis HAP3 protein \ has been predicted to contain a 4-cysteine zinc finger, which is thought to be present in similar HAP3\ and CBF subunit A proteins, in which the third cysteine is replaced by a serine [MEDLINE:95147853]. This domain is found in the CCAAT transcription factor and archaeal histones.

\ \ DNA binding activity ; GO:0003677 \N \N 22470 IPR003953

In eukaryotes mitochondrial succinate dehydrogenase (ubiquinone) (EC: 1.3.5.1)\ is an enzyme composed of two subunits: a FAD flavoprotein and and iron-sulfur\ protein.

The flavoprotein subunit is a protein of about 60 to 70 Kd to which FAD is\ covalently bound to a histidine residue which is located in the N-terminal\ section of the protein [MEDLINE:89340438]. The sequence around that histidine is well\ conserved in Frd and Sdh from various bacterial and eukaryotic species [MEDLINE:92283874].

This family includes members that bind FAD such as the flavoprotein subunits from\ succinate and fumarate dehydrogenase, aspartate oxidase and the subunit of adenylylsulfate\ reductase.

\ \ oxidoreductase activity ; GO:0016491 \N electron transport ; GO:0006118 22471 IPR003954 Many eukaryotic proteins that are known or supposed to bind single-stranded RNA contain one or more copies of a putative RNA-binding domain of about 90 amino acids. This is known as the eukaryotic putative RNA-binding region RNP-1 signature [MEDLINE:89252819], [MEDLINE:89223025], or RNA recognition motif (RRM). RRMs are found in a variety of RNA binding proteins, including heterogeneous nuclear ribonucleoproteins (hnRNPs), proteins implicated in regulation of alternative splicing, and protein components of small nuclear ribonucleoproteins (snRNPs). The motif also appears in a few single stranded DNA binding proteins. The RRM structure consists of four strands and two helices arranged in an

\ \ DNA binding activity ; GO:0003677 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 22468 IPR003951 Secretion of virulence factors in Gram-negative bacteria involves transportation of the protein across two membranes to reach the cell exterior. There have been four secretion systems described in \ animal enteropathogens such as Salmonella and Yersinia, with further sequence homologies in plant pathogens like Ralstonia and Erwinia [MEDLINE:98284147]. \

The type III secretion system is of great interest, as it is used to \ transport virulence factors from the pathogen directly into the host cell \ and is only triggered when the bacterium comes into close contact with\ the host. The protein subunits of the system are very similar to those of \ bacterial flagellar biosynthesis. However, while the latter forms a\ ring structure to allow secretion of flagellin and is an integral part of\ the flagella itself, type III subunits in the outer membrane translocate \ secreted proteins through a channel-like structure [MEDLINE:98284147].

Exotoxins secreted by the type III system do not possess a secretion signal, and are considered unique because of this \ [MEDLINE:98284147]. Yersinia pestis secretes such a protein, as recently described [MEDLINE:98427122]. YopT \ is injected into the host cell upon contact, and is therefore considered to be a virulence factor. Haemophilus \ spp. express a similar toxin on their surface, a 76kDa\ antigen [MEDLINE:98427122].

\ \ \N \N \N 22469 IPR003952

In eukaryotes mitochondrial succinate dehydrogenase (ubiquinone) (EC: 1.3.5.1)\ is an enzyme composed of two subunits: a FAD flavoprotein and and iron-sulfur\ protein.

The flavoprotein subunit is a protein of about 60 to 70 Kd to which FAD is\ covalently bound to a histidine residue which is located in the N-terminal\ section of the protein [MEDLINE:89340438]. The sequence around that histidine is well\ conserved in Frd and Sdh from various bacterial and eukaryotic species [MEDLINE:92283874].

\ \ oxidoreductase activity ; GO:0016491 \N electron transport ; GO:0006118 22467 IPR003950

The first EAG K+ channel was identified in Drosophila melanogaster, following a screen \ for mutations giving rise to behavioural abnormalities. Disruption of the\ Eag gene caused an ether-induced, leg-shaking behaviour. Subsequent studies\ have revealed a conserved multi-gene family of EAG-like K+ channels, which\ are present in human and many other species. Based on the varying\ functional properties of the channels, the family has been divided into\ 3 subfamilies: EAG, ELK and ERG. Interestingly, Caenorhabditis elegans appears to lack\ the ELK type PUB00009384.

Little is known about the properties of channels of the ELK subfamily. \ However, when expressed in frog oocytes, they show properties between those\ of the EAG and ERG subtypes. Included in this family are Bec1 and Bec2,\ brain-specific genes found in the human telencephalon regions. It is thought\ that they are involved in cellular excitability of restricted neurons in the\ human central nervous system. Phylogenetic analysis reveals that these genes\ constitute a subfamily with Elk within the Eag family [MEDLINE:99386988]. Recently, a\ further Elk subfamily member has been identified in the mouse (Melk). On the\ basis of sequence similarity, this indicates a distinct subclass within \ this family [MEDLINE:99208772].

\ \ voltage-gated potassium channel activity ; GO:0005249 membrane ; GO:0016020 potassium ion transport ; GO:0006813 22466 IPR003949

The first EAG K+ channel was identified in Drosophila melanogaster, following a screen \ for mutations giving rise to behavioural abnormalities. Disruption of the\ Eag gene caused an ether-induced, leg-shaking behaviour. Subsequent studies\ have revealed a conserved multi-gene family of EAG-like K+ channels, which\ are present in human and many other species. Based on the varying\ functional properties of the channels, the family has been divided into\ 3 subfamilies: EAG, ELK and ERG. Interestingly, Caenorhabditis elegans appears to lack\ the ELK type PUB00009384.

The EAG subfamily has been expressed in heterologous systems to reveal their\ biophysical and pharmacological functions and to determine their currents in\ native tissues. All mammalian EAG subfamily K+ channels that have been \ identified have properties typical of delayed rectifiers, with no measurable\ inactivation [MEDLINE:98190099]. Only the Drosophila melanogaster Eag channel exhibits partial\ inactivation.

\ \ voltage-gated potassium channel activity ; GO:0005249 membrane ; GO:0016020 potassium ion transport ; GO:0006813 22465 IPR003948

KCNQ channels differ from other voltage-gated 6 TM helix channels, chiefly \ in that they possess no tetramerisation domain. Consequently, they rely on\ interaction with accessory subunits, or form heterotetramers with other\ members of the family PUB00009384. Currently, 5 members of the KCNQ family are \ known. These have been found to be widely distributed within the body,\ having been shown to be expressed in the heart, brain, pancreas, lung,\ placenta and ear. They were initially cloned as a result of a search for \ proteins involved in cardiac arhythmia. Subsequently, mutations in other \ KCNQ family members have been shown to be responsible for some forms of\ hereditary deafness [MEDLINE:96122034] and benign familial neonatal epilepsy [MEDLINE:98092527].

The KCNQ3 channel subunit is thought to form active channels by hetero-\ tetramerisation with KCNQ2, although some K+ channel activity does result\ from the expression of KCNQ3 alone [MEDLINE:99087323]. Channel function is modulated by\ phosphorylation; experiments have demonstrated that an increase in\ intracellular cAMP concentration can enhance channel activity.\ Frameshift mutations in both KCNQ2 and KCNQ3 are associated with benign\ familial neonatal epilepsy [MEDLINE:99087323], a disorder in which infants suffer\ convulsions within the first 3 days of life. These symptoms usually\ disappear after about 3 months, but affected individuals have a higher\ than average chance of subsequently developing epilepsy (10-15%) in later\ life [MEDLINE:98092527].

\ \ voltage-gated potassium channel activity ; GO:0005249 membrane ; GO:0016020 potassium ion transport ; GO:0006813 22463 IPR003945

NADH-plastoquinone oxidoreductase chain 5 is part of the NADH-ubiquinone oxidoreductase (complex I), which catalyses the transfer of two electrons from NADH to ubiquinone in a reaction that is associated with proton translocation across the membrane [MEDLINE:93110040]:

 NADH + ubiquinone = NAD(+) + ubiquinol

\ \ NADH dehydrogenase (ubiquinone) activity ; GO:0008137 \N oxidative phosphorylation, NADH to ubiquinone ; GO:0006120 22464 IPR003947

The KCNQ2 channel subunit is thought to form active channels by hetero-\ tetramerisation with KCNQ3, although some K+ channel activity does results\ from the expression of KCNQ2 alone [MEDLINE:99087323]. Channel function is modulated by\ phosphorylation, since experiments have demonstrated that an increase in\ intracellular cAMP concentration can enhance channel activity .\ Frameshift mutations in both KCNQ2 and KCNQ3 are associated with benign\ familial neonatal epilepsy [MEDLINE:99087323], a disorder where an infant begins to suffer\ convulsions, within the first three days of life. These symptoms usually\ disappear after approximately three months, but affected individuals have a\ higher than average chance of subsequently developing epilepsy (10-15%), in\ later life [MEDLINE:98092527].

\ \ voltage-gated potassium channel activity ; GO:0005249 membrane ; GO:0016020 potassium ion transport ; GO:0006813 22461 IPR003943

Thrombin is a coagulation protease that activates platelets, leukocytes, \ endothelial and mesenchymal cells at sites of vascular injury, acting partly\ through an unusual proteolytically activated GPCR [MEDLINE:97242411]. Gene knockout \ experiments have provided definitive evidence for a second thrombin receptor\ in mouse platelets and have suggested tissue-specific roles for different\ thrombin receptors. Because the physiological agonist at the receptor was\ originally unknown, it was provisionally named protease-activated receptor\ (PAR) [MEDLINE:95197620]. At least 4 PAR subtypes have now been characterised. Thus, the thrombin and PAR receptors constitute a fledgling receptor family that \ shares a novel proteolytic activation mechanism [MEDLINE:96379236].

The human thrombin receptor, designated protease-activated receptor 3 (PAR3),\ has been cloned and characterised [MEDLINE:97242411]. PAR3 can mediate thrombin-triggered phosphoinositide hydrolysis and is expressed in a variety of tissues, including human bone marrow and mouse megakaryocytes, making it a candidate for the sought-after second platelet thrombin receptor. PAR3 provides a new tool for understanding thrombin signalling and a possible target for therapeutics designed selectively to block thrombotic, inflammatory and\ proliferative responses to thrombin.

\ \ thrombin receptor activity ; GO:0015057 integral to membrane ; GO:0016021 blood coagulation ; GO:0007596 22462 IPR003944

The human thrombin receptor, designated protease-activated receptor 4 (PAR4),\ has been cloned and characterised [MEDLINE:98283984]. Northern blot analysis showed that PAR4 mRNA was expressed in a number of tissues, high levels being present\ in lung, pancreas, thyroid, testis and small intestine. Using fluorescence in situ hybridisation, the human PAR4 gene has been mapped to chromosome 19p12 [MEDLINE:97242411].

\ \ thrombin receptor activity ; GO:0015057 integral to membrane ; GO:0016021 blood coagulation ; GO:0007596 22460 IPR003942

Abnormal endometrial bleeding is a common manifestation of gynaecologicaldiseases. A human gene, termed endometrial bleeding associated factor (ebaf),\ which is expressed strongly in endometrium, has been shown to be associated\ with abnormal endometrial bleeding [MEDLINE:97298127]. The predicted protein product of ebaf shares similarity with members of TGF- superfamily. Thus ebaf is a novel member of the TGF- superfamily and an endometrial tissue factor whose expression is associated with normal menstrual and abnormal \ endometrial bleeding.

Examples of lateral asymmetry are often found in vertebrates (e.g., the \ heart being on the left side), but the molecular mechanisms governing \ establishment of left-right (L-R) handedness are unknown [MEDLINE:96202359]. It is now thought that the gene lefty, a member of the transforming growth factor- family, may encode a morphogen for L-R determination. Lefty protein, which contains the cysteine-knot motif characteristic of this superfamily, is expressed in the left half of gastrulating mouse embryos. This asymmetric\ expression is transient and occurs just before the first sign of lateral\ asymmetry appears]. Thus lefty may be involved in establishing L-R asymmetry in the organ systems of mammals.

\ \ transforming growth factor-beta receptor ligand activity ; GO:0005160 \N cell growth ; GO:0016049 22458 IPR003940

The transforming growth factors- (TGF- 1-5) constitute a family ofmulti-functional cytokines that regulate cell growth and differentiation [MEDLINE:93144319]. Many cells synthesise TGF-, and essentially all have specific receptors for this peptide [MEDLINE:87102890]. TGF- regulates the actions of many other peptide growth factors and determines a positive or negative direction of their effects. The protein functions as a disulphide-linked homodimer. Its sequence is characterised by the presence of several C-terminal cysteine residues, which form interlocking disulphide links arranged in a knot-like topology. A similar "cystine-knot" arrangement has been noted in the\ structures of some enzyme inhibitors and neurotoxins that bind to voltage-gated Ca2+ channels, although the precise topology differs.

The complete amino acid sequence of human 2 transforming growth factor\ (hTGF- 2) has been determined by automated Edman degradation [MEDLINE:87102890]. Human TGF- 2 consists of 2 identical disulphide-linked subunits that share a high degree of similarity with the functionally related TGF- 1, and reveal lower levels of similarity to porcine inhibins and activins, the \ C-terminal regions of human Mullerian inhibiting substance, and the putative\ decapentaplegic gene complex protein of Drosophila melanogaster.

The three-dimensional structures of several members of the TGF- super-family have been deduced. The crystal structure of the TGF- 2 monomer \ lacks a well-defined hydrophobic core and displays an unusual elongated \ non-globular fold [MEDLINE:92335881]. Eight cysteine residues form 4 intra-chain disulphide bonds, creating the characteristic knotted arrangement. The dimer is \ stabilised by a ninth cysteine, which forms an inter-chain disulphide bond,\ and by 2 identical hydrophobic interfaces. Other members of the TGF- superfamily, including activins, inhibins and various developmental factors,\ are also likely to adopt the TGF- fold.

\ \ transforming growth factor-beta receptor ligand activity ; GO:0005160 \N cell growth ; GO:0016049 22459 IPR003941

TGF- genes are expressed differentially, suggesting that the various TGF- species may have distinct physiological roles in vivo. Examination of\ TGF- 3 mRNA levels in adult murine tissues indicated that expression is \ predominant in brain, heart, adipose tissue and testis [MEDLINE:90190650]. TGF -3 mRNA is also observed in adult mouse lung and placenta. Research on rat foetal lung fibroblasts has shown that exposure to cortisol increases \ TGF- 3 mRNA expression in a time- and dose-dependent manner, suggesting that\ glucocorticoids may mediate their stimulatory effect on lung maturation by\ inducing TGF- 3 expression in foetal lung fibroblasts [MEDLINE:95155340].

The three-dimensional structures of several members of the TGF- super-family have been deduced. The crystal structure of TGF- 3 reveals a near identical central core to that of TGF- 2 [MEDLINE:96416253]. The principal differences are witnessed in the conformations of the N-terminal -helix and in the -sheet loops, which could account for the individual cellular\ responses, if these differences are recognised by the TGF- receptors.

\ \ transforming growth factor-beta receptor ligand activity ; GO:0005160 \N cell growth ; GO:0016049 22457 IPR003939

TGF- genes are expressed differentially, suggesting that the various TGF- species may have distinct physiological roles in vivo. Examination of\ TGF- 1 mRNA levels in adult murine tissues indicates that expression is\ predominant in spleen, lung and placenta [MEDLINE:90190650]. TGF- 1 is believed to play important roles in pathologic processes.

\ \ transforming growth factor-beta receptor ligand activity ; GO:0005160 \N cell growth ; GO:0016049 22456 IPR003938

The first EAG K+ channel was identified in Drosophila melanogaster, following a screen for mutations giving rise to behavioural abnormalities. Disruption of the Eag gene caused an ether-induced, leg-shaking behaviour. Subsequent studies have revealed a conserved multi-gene family of EAG-like K+ channels, which are present in human and many other species. Based on the varying functional properties of the channels, the family has been divided into 3 subfamilies: EAG, ELK and ERG. Interestingly, Caenorhabditis elegans appears to lack the ELK type PUB00009384.

\ \ voltage-gated potassium channel activity ; GO:0005249 membrane ; GO:0016020 potassium ion transport ; GO:0006813 22455 IPR003937

\ \ voltage-gated potassium channel activity ; GO:0005249 membrane ; GO:0016020 potassium ion transport ; GO:0006813 22453 IPR003935

The epithelial membrane proteins (EMP-1, -2 and -3), peripheral myelin protein 22 (PMP22), and lens fiber membrane intrinsic protein (LMIP) comprise a protein family on the basis of sequence and structural similarities [MEDLINE:96081949]. Each family member is a small hydrophobic membrane glycoprotein, ~160-170 amino acids in length, and shares a common predicted transmembrane (TM) topology of 4 TM domains, with intracellular N- and C-termini [MEDLINE:97038679].

LMIP, previously termed MP17, MP18, MP19 and MP20, is expressed at extremely high levels in the mammalian eye lens, where it is localised to the thicker (16-17nm) cell membrane junctions [MEDLINE:90062105]. Although its function has not been elucidated, it has been shown to co-localise with connexin-46, suggesting that it may be involved in the organisation of junctional plaques [MEDLINE:93055020]. A role for LMIP in signal transduction has also been proposed, as it is phosphorylated by cAMP-dependent kinase and binds calmodulin [MEDLINE:90062106].

\ \ structural constituent of eye lens ; GO:0005212 membrane ; GO:0016020 \N 22454 IPR003936

PMP22, also termed growth-arrest specific protein (GAS3), is a structural component of compact myelin in the peripheral nervous system. Aberrant expression of the PMP22 gene, and mutations in the protein, are associated with a variety of hereditary peripheral motor and sensory neuropathies [MEDLINE:93190363]. An intra-chromosomal duplication containing the PMP22 gene is found in the majority of patients suffering from the autosomal dominant demyelinating neuropathy Charcot-Marie-Tooth disease 1A (CMT1A) [MEDLINE:95328814]. In addition, rare point mutations in PMP22 have been found in non-duplication CMT1A patients and in the severe congenital peripheral neuropathy Dejerine-Sottas syndrome [MEDLINE:94100982].

\ \

PMP22 is also implicated in the control of cell proliferation. Its expression levels are up-regulated in cells undergoing growth arrest [MEDLINE:96081949], and it has been shown that modulating PMP22 levels in cultured Schwann cells exerts a profound effect on the length of the G1 phase of the cell cycle [MEDLINE:95237193]. It has also been demonstrated that over-expression of PMP22 in NIH 3T3 fibroblast cells induces apoptosis [MEDLINE:95377636].

\ \ \N membrane ; GO:0016020 \N 22451 IPR003933

A role for the EMP family members in the control of cell growth has been suggested [MEDLINE:96081949]. EMP-1 is expressed at high levels in proliferating cells, and at reduced levels in cells undergoing growth arrest [MEDLINE:97149281]. In contrast, PMP22, which is co-expressed with EMP-1 in a range of tissues, displays an inverse pattern of regulation, with high levels of expression in cultured cells undergoing growth arrest [MEDLINE:97149281]. It has therefore been proposed that these proteins may have reciprocal functions in the control of cell quiescence and proliferation.

\ \

EMP-2, previously termed XMP, was identified by expressed sequence tag (EST) database searching, pursuing sequences similar to EMP-1 [MEDLINE:97074659]. Mouse and human isoforms have been cloned. EMP-2 is expressed in a range of tissues, including ovary, heart, lung and intestine. Although its function has not been elucidated, it has been postulated that EMP-2 may be involved in the regulation of cell proliferation on the basis of its sequence similarity to EMP-1 [MEDLINE:97074659].

\ \ \N membrane ; GO:0016020 cell growth ; GO:0016049 22452 IPR003934

\ \

EMP-3, previously termed YMP, was identified by expressed sequence tag (EST) database searching, pursuing sequences similar to EMP-1 [MEDLINE:97074659]. Mouse, human and rat isoforms have been cloned. EMP-3 is expressed in a range of tissues, including peripheral blood leukocytes, ovary and intestine. Although its function has not been elucidated, it has been postulated that EMP-3 may be involved in the regulation of cell proliferation on the basis of its sequence similarity to EMP-1 [MEDLINE:97074659].

\ \ \N membrane ; GO:0016020 cell growth ; GO:0016049 22450 IPR003932

EMP-1, previously termed tumour-associated membrane protein (TMP), was originally isolated from a mouse brain tumour [MEDLINE:97149281]. Human, rat and rabbit isoforms have also been identified. EMP-1 is expressed in a wide range of tissues, including heart, placenta, lung, skeletal muscle, kidney and small intestine [MEDLINE:97271554]. A role for the protein in the control of cell growth has been suggested [MEDLINE:96081949]. EMP-1 is expressed at high levels in proliferating cells, and at reduced levels in cells undergoing growth arrest [MEDLINE:97149281]. In contrast, PMP22, which is co-expressed with EMP-1 in a range of tissues, displays an inverse pattern of regulation, with high levels of expression in cultured cells undergoing growth arrest [MEDLINE:97149281]. It has therefore been proposed that these proteins may have reciprocal functions in the control of cell quiescence and proliferation.

\ \ \N membrane ; GO:0016020 cell growth ; GO:0016049 22449 IPR003931

Ca2+-activated K+ channels are a diverse group of channels that are activated by an increase in intracellular Ca2+ concentration. They are found in the majority of nerve cells, where they modulate cell excitability and action potential. Three types of Ca2+-activated K+ channel have been characterised, termed small-conductance (SK), intermediate conductance (IK) and large conductance (BK) respectively PUB00009384.

\ \

SK channels are thought to play an important role in the functioning of all excitable tissues. To date, 3 subtypes (designated SK1-SK3) have been cloned, each of which possesses a different tissue expression profile: SK1 channels are expressed in the heart; SK2 channels are found in the adrenal gland; and SK3 channels are known to be present in skeletal muscle.

\ \

Although SK channels have been classified as belonging to the 6TM domain voltage-gated K+ channel family, they show little or no sequence similarity to other family members. The fourth TM domain resembles the S4 voltage sensor domain of Kv channels, since it contains 3 positively charged residues. However, despite similarity to the Kv voltage-sensory motif, SK channel activation is not voltage sensitive.

\ \ small conductance calcium-activated potassium channel activity ; GO:0016286 membrane ; GO:0016020 potassium ion transport ; GO:0006813 22448 IPR003930

\ \

Ca2+-activated K+ channels are a diverse group of channels that are\ activated by an increase in intracellular Ca2+ concentration. They are\ found in the majority of nerve cells, where they modulate cell excitability\ and action potential. Three types of Ca2+-activated K+ channel have been\ characterised, termed small-conductance (SK), intermediate conductance (IK)\ and large conductance (BK) respectively PUB00009384.

BK channels (also referred to as maxi-K channels) are widely expressed \ in the body, being found in glandular tissue, smooth and skeletal muscle, \ as well as in neural tissues. They have been demonstrated to regulate \ arteriolar and airway diameter, and also neurotransmitter release. Each\ channel complex is thought to be composed of 2 types of subunit: the pore-\ forming () subunits and smaller accessory () subunits.

\ \

The subunit of the BK channel was initially thought to share the\ characteristic 6TM organisation of the voltage-gated K+ channels. However,\ the molecule is now thought to possess an additional TM domain, with an \ extracellular N-terminus and intracellular C-terminus. This C-terminal \ region contains 4 predominantly hydrophobic domains, which are also thought\ to lie intracellularly. The extracellular N-terminus and the first TM region\ are required for modulation by the subunit. The precise location of the\ Ca2+-binding site that modulates channel activation remains unknown, but it\ is thought to lie within the C-terminal hydrophobic domains.

\ \

The subunit (which is thought to possess 2 TM domains) increases the\ Ca2+ sensitivity of the BK channel [MEDLINE:95209871]. It does this by enhancing the time\ spent by the channel in burst-like open states. However, it has little \ effect on the durations of closed intervals between bursts, or on the\ numbers of open and closed states entered during gating [MEDLINE:99162422].\

\ \ calcium-activated potassium channel activity ; GO:0015269 membrane ; GO:0016020 potassium ion transport ; GO:0006813 22447 IPR003929

\ \

BK channels (also referred to as maxi-K channels) are widely expressed in the body, being found in glandular tissue, smooth and skeletal muscle, as well as in neural tissues. They have been demonstrated to regulate arteriolar and airway diameter, and also neurotransmitter release. Each channel complex is thought to be composed of 2 types of subunit; the pore-forming () subunits and smaller accessory () subunits.

\ \

The subunit of the BK channel was initially thought to share the characteristic 6TM organisation of the voltage-gated K+ channels. However, the molecule is now thought to possess an additional TM domain, with an extracellular N-terminus and intracellular C-terminus. This C-terminal region contains 4 predominantly hydrophobic domains, which are also thought to lie intracellularly. The extracellular N-terminus and the first TM region are required for modulation by the subunit. The precise location of the Ca2+-binding site that modulates channel activation remains unknown, but it is thought to lie within the C-terminal hydrophobic domains.

\ \ calcium-activated potassium channel activity ; GO:0015269 membrane ; GO:0016020 potassium ion transport ; GO:0006813 22443 IPR003925

\ \ \

\ \

Claudin-6 was identified through searching expressed sequence tag (EST)\ databases for sequences similar to claudin-1 and -2 [MEDLINE:99110921]. It was subsequently cloned and expressed in cells, where it was shown to concentrate at tight junctions. Human and mouse isoforms have been identified. Claudin-6 shares ~25-70% overall similarity with other claudin family members at the amino acid level, displaying highest similarity to claudin-9.

\ \ structural molecule activity ; GO:0005198 membrane ; GO:0016020 \N 22444 IPR003926

Tight junctions (TJs) are specialised membrane domains found at the most apical region of polarised epithelial and endothelial cells. They create a \ primary barrier, preventing paracellular transport of solutes and restricting lateral diffusion of membrane lipids and proteins. They also act as diffusion barriers within plasma membranes, creating and maintaining apical and basolateral membrane domains.

\ \

Recently, the molecular architecture of tight junctions has begun to be elucidated. One group of proteins thought to be major components of TJs \ is the claudin family [MEDLINE:99299665]. Immunofluorescence studies have shown that claudins are targeted to and incorporated into tight junctions [MEDLINE:98311639]. Furthermore, when claudins are introduced into cells that lack tight junctions, networks of strands and grooves form at cell-cell contact sites that closely resemble native TJs [MEDLINE:99003297].

\ \

Hydropathy analysis suggests that all claudins share a common transmembrane\ (TM) topology. Each family member is predicted to possess four TM domains \ with intracellular N- and C-termini. Although their C-terminal cytoplasmic \ domain sequences vary, most claudin family members share a common motif of \ -Y-V in this region. This has been postulated as a possible binding motif \ for PDZ domains of other tight junction-associated membrane proteins, such as ZO-1.

\ \

Claudin-8 was identified through searching expressed sequence tag (EST)\ databases for sequences similar to claudin-1 and -2 [MEDLINE:99110921]. It was subsequently cloned and expressed in cells, where it was shown to concentrate at tight junctions. Human and mouse isoforms have been identified. Claudin-8 shares ~26-58% overall similarity with other claudin family members at the amino acid level, displaying highest similarity to claudin-17.

\ \ structural molecule activity ; GO:0005198 membrane ; GO:0016020 \N 22446 IPR003928

\ \ \

\ \

Human and mouse isoforms of claudin-18 have been cloned. Claudin-18 shares\ ~22-40% overall similarity with other claudin family members at the amino\ acid level, displaying highest similarity to claudin-1.

\ \ structural molecule activity ; GO:0005198 membrane ; GO:0016020 \N 22445 IPR003927

\ \ \

\ \

Claudin-16 was originally termed paracellin-1. It was re-classified as \ claudin-16 on the basis of its sequence similarity to the claudin family\ [MEDLINE:20272145] ]. Claudin-16 is involved in renal paracellular Mg2+ resorption and is required for selective paracellular conductance [MEDLINE:99322191]. Defects in the claudin-16 gene are associated with an autosomal recessive chronic interstitial nephritis with diffuse zonal fibrosis (CINF) [MEDLINE:20272145], [MEDLINE:99322191].

\ \ structural molecule activity ; GO:0005198 membrane ; GO:0016020 \N 22437 IPR003919

An operon encoding 4 proteins required for bacterial cellulose biosynthesis(bcs) in Acetobacter xylinum has been isolated via genetic complementation\ with strains lacking cellulose synthase activity [MEDLINE:91045951]. Nucleotide sequence analysis showed the cellulose synthase operon to consist of 4 genes, \ designated bcsA, bcsB, bcsC and bcsD, all of which are required for maximal bacterial cellulose synthesis in A. xylinum.

The calculated molecular mass of the protein encoded by bcsA is 84.4kDa [MEDLINE:91045951]. Sequence analysis suggests that the gene product is an integral membrane protein with several transmembrane (TM) domains [MEDLINE:91346705]. It is postulated that the protein is anchored in the membrane at the N-terminal end by a single hydrophobic helix. Two potential N-glycosylation sites are predicted from sequence analysis, consistent with earlier observations that BcsA is a glycoprotein. The function of BcsA is unknown. The sequence shares a high degree of similarity with Escherichia coli YhjO.

\ \ cellulose synthase activity ; GO:0016759 membrane ; GO:0016020 UDP-glucose metabolism ; GO:0006011 22438 IPR003920

The calculated molecular mass of the protein encoded by bcsB is 85.3kDa [MEDLINE:91045951]. BcsB encodes the catalytic subunit of cellulose synthase. The protein polymerises uridine 5'-diphosphate glucose to cellulose: UDP-glucose + (1,4--D-glucosyl)(N) = UDP + (1,4--D-glucosyl)(N+1). The enzyme is specifically activated by the nucleotide cyclic diguanylic acid. Sequence analysis suggests that BcsB contains several transmembrane (TM) domains, and shares a high degree of similarity with Escherichia coli YhjN.

\ \ \N membrane ; GO:0016020 UDP-glucose metabolism ; GO:0006011 22439 IPR003921

The calculated molecular mass of the protein encoded by bcsC is 141.0kDa [MEDLINE:91045951]. The function of BcsC is unknown. The sequence shares a high degree of similarity with Escherichia coli YhjL.

\ \ \N membrane ; GO:0016020 UDP-glucose metabolism ; GO:0006011 22440 IPR003922

The calculated molecular mass of the protein encoded by bcsD is 17.3kDa [MEDLINE:91045951]. The function of BcsD is unknown.

\ \ \N membrane ; GO:0016020 UDP-glucose metabolism ; GO:0006011 22441 IPR003923

Transcription initiation factor TFIID is a multimeric protein complex thatplays a central role in mediating promoter responses to various activators\ and repressors. The complex includes TATA binding protein (TBP) and various\ TBP-associated factors (TAFS). TFIID a bona fide RNA polymerase II-specific\ TATA-binding protein-associated factor (TAF) and is essential for viability [MEDLINE:96278804].

TFIID acts to nucleate the transcription complex, recruiting the rest of\ the factors through a direct interaction with TFIIB. The TBP subunit of TFIID is sufficient for TATA-element binding and TFIIB interaction, and can support basal transcription. The protein belongs to the TAF2H family.

\ \ transcription factor activity ; GO:0003700 nucleus ; GO:0005634 transcription initiation ; GO:0006352 22442 IPR003924

Latrophilins are a family of secretin-like GPCRs that can be subdivided\ into 3 subtypes: LPH1, LPH2 and LPH3. LPH1 is a brain-specific calcium\ independent receptor of -latrotoxin (LTX), a neurotoxin. It is the\ affinity of this form of the receptor for LTX that gives the family its name. LPH2 and LPH3, whilst sharing extensive sequence similarity to LPH1, do not bind LTX. LPH2 is distributed throughout most tissues, whereas LPH3 is also brain-specific [MEDLINE:99148828]. The endogenous ligand(s) for these receptors are at present unknown. Binding of LTX to LPH1 stimulates exocytosis and the\ subsequent release of large amounts of neurotransmitters from neuronal and\ endocrine cells. The latrophilins possess up to 7 sites of alternative splicing; the resulting number of possible splice variants leads to a highly variable family of proteins.

\ \ latrotoxin receptor activity ; GO:0016524 membrane ; GO:0016020 \N 22433 IPR003915

Polycystic kidney diseases (PKD) are disorders characterised by largenumbers of cysts distributed throughout grossly-enlarged kidneys. Cyst\ development is associated with impairment of kidney function, and ultimately\ kidney failure and death [MEDLINE:96202312]. Most cases of autosomal dominant PKD result from mutations in the PKD1 gene that cause premature protein termination. \

A second gene for autosomal dominant polycystic kidney disease has been\ identified by positional cloning [MEDLINE:96243133]. The predicted 968-amino acid sequence of the PKD2 gene product (polycystin-2) contains 6 transmembrane domains, with intracellular N- and C-termini. Polycystin-2 shares some similarity with the family of voltage-activated calcium (and sodium) channels, and contains a potential calcium-binding domain.

Polycystin-2 is strongly expressed in ovary, foetal and adult kidney, testis, and small intestine. Polycystin-1 requires the presence of this protein for stable expression and is believed to interact with it via its C-terminus. All mutations between exons 1 and 11 result in a truncated polycystin-2 that lacks a calcium-binding EF-hand domain and the cytoplasmic domains required for the interaction of polycystin-2 with polycystin-1 [MEDLINE:97465600]. PKD2, although clinically milder than PKD1, has a deleterious impact on life expectancy.

\ \ calcium ion binding activity ; GO:0005509 membrane ; GO:0016020 \N 22434 IPR003916

Mitochondrial NADH dehydrogenase subunit 5 (ND5) is an integral inner membrane protein. The protein is part of the NADH-ubiquinone oxidoreductase (complex I), which catalyses the transfer of two electrons from NADH to ubiquinone in a reaction that is associated with proton translocation across the membrane [MEDLINE:93110040]:

 NADH + ubiquinone = NAD(+) + ubiquinol

\ In chloroplasts, this reaction is:\

 NADH + plastoquinone = NAD(+) + plastoquinol.

\ \

Defects in the ND5 gene are one of the causes of Leber's hereditary optic neuropathy, a maternally inherited disease resulting in acute bilateral blindness due to retinal degeneration, predominantly in young men [MEDLINE:91144615], [MEDLINE:92120513]. Cardiac conduction defects and neurological defects have also been described, resulting in optic nerve degeneration and cardiac dysrhythmia [MEDLINE:89072713]. The clinical manifestations of this disease are thought to be the product of an overall decrease in mitochondrial energy production, rather than the result of a defect in a specific mitochondrial enzyme [MEDLINE:92120513].

\ \ NADH dehydrogenase (ubiquinone) activity ; GO:0008137 \N oxidative phosphorylation, NADH to ubiquinone ; GO:0006120 22435 IPR003917

Mitochondrial NADH dehydrogenase subunit 2 (ND2) is an integral inner membrane protein. The protein is part of the NADH-ubiquinone oxidoreductase (complex I), which catalyses the transfer of two electrons from NADH to ubiquinone in a reaction that is associated with proton translocation across the membrane [MEDLINE:93110040]:

 NADH + ubiquinone = NAD(+) + ubiquinol

\ In chloroplasts, this reaction is:\

 NADH + plastoquinone = NAD(+) + plastoquinol.

\ \

Defects in the ND2 gene are one of the causes of Leber's hereditary optic neuropathy, a maternally inherited disease resulting in acute bilateral blindness due to retinal degeneration, predominantly in young men [MEDLINE:91144615], [MEDLINE:92120513]. Cardiac conduction defects and neurological defects have also been described, resulting in optic nerve degeneration and cardiac dysrhythmia [MEDLINE:89072713]. The clinical manifestations of this disease are thought to be the product of an overall decrease in mitochondrial energy production, rather than the result of a defect in a specific mitochondrial enzyme [MEDLINE:92120513]. Further research has shown that a point mutation in ND2 is a potential risk factor for Alzheimer's disease [MEDLINE:92118019].

\ \ NADH dehydrogenase (ubiquinone) activity ; GO:0008137 \N oxidative phosphorylation, NADH to ubiquinone ; GO:0006120 22436 IPR003918

The protein is part of the NADH-ubiquinone oxidoreductase (complex I), which catalyses the transfer of two electrons from NADH to ubiquinone in a reaction that is associated with proton translocation across the membrane [MEDLINE:93110040]:

NADH + ubiquinone = NAD(+) + ubiquinol

\ In chloroplasts, this reaction is:\

NADH + plastoquinone = NAD(+) + plastoquinol

\ \

Leber's hereditary optic neuropathy is a maternally-inherited disease characterised by optic nerve degeneration and cardiac dysrhythmia [MEDLINE:89072713]. A mitochondrial DNA replacement mutation that correlates with this disease in multiple families has been identified - the mutation converts a conserved arginine to a histidine at codon 340 in the NADH dehydrogenase subunit 4 gene. This finding demonstrates that a nucleotide change in a mitochondrial DNA energy production gene can result in a neurological disease [MEDLINE:89072713].

\ \ NADH dehydrogenase (ubiquinone) activity ; GO:0008137 \N oxidative phosphorylation, NADH to ubiquinone ; GO:0006120 22430 IPR003912

\ \ thrombin receptor activity ; GO:0015057 integral to membrane ; GO:0016021 blood coagulation ; GO:0007596 22431 IPR003913

Tuberous sclerosis (TSC) is an autosomal dominant disorder caused by a mutation in either the TSC1 or TSC2 tumour suppressor genes. The disease is\ characterised by hamartomas in one or more organs (including brain, skin,\ heart and kidney) giving rise to a broad phenotypic spectrum (including \ seizures, mental retardation, renal dysfunction and dermatological abnormalities [MEDLINE:98248432]. TSC2 encodes tuberin, a putative GTPase activating protein for rap1 and rab5. The TSC1 gene was recently identified and codes for hamartin, a novel protein with no significant similarity to tuberin or any other known vertebrate protein. Hamartin and tuberin have been shown to associate physically in vivo, their interaction being mediated by predicted coiled-coil domains. It is thought that hamartin and tuberin function in the same complex, rather than in separate pathways. Moreover, because oligomerisation of the hamartin C-terminal coiled coil domain is inhibited by the presence of tuberin, it is possible that tuberin acts as a chaperone, preventing hamartin self-aggregation. \

Tuberin, is a widely expressed 1784-amino-acid protein [MEDLINE:96047333]. Expression of the wild-type gene in TSC2 mutant tumour cells inhibits proliferation and tumorigenicity. This "suppressor" activity is encoded by a functional domain in the C-terminus that shares similarity with the GTPase activating protein Rap1GAP. Using a yeast two-hybrid assay, the cytosolic factor, rabaptin-5, was found to associate with a distinct domain lying adjacent\ to the TSC2 GAP similarity region. Rabaptin-5 also binds the active form\ of GTPase Rab5. It is thought that tuberin may function as a Rab5GAP in vivo \ to negatively regulate Rab5-GTP activity in endocytosis [MEDLINE:97197768].

\ \ GTPase activator activity ; GO:0005096 \N cell growth and/or maintenance ; GO:0008151 22432 IPR003914

Regeneration of injured axons at neuromuscular junctions has been assumedto be regulated by extra-cellular factors that promote neurite outgrowth.\ A novel neurite outgrowth factor from chick denervated skeletal muscle has \ been cloned and characterised. The protein, termed neurocrescin (rabaptin),\ has been shown to be secreted in an activity-dependent fashion [MEDLINE:98087215].

Rabaptin is a 100kDa coiled-coil protein that interacts with the GTP form of the small GTPase Rab5, a potent regulator of endocytic transport [MEDLINE:96067640]. It is mainly cytosolic, but a fraction co-localises with Rab5 to early endosomes. Rab5 recruits rabaptin-5 to purified early endosomes in a\ GTP-dependent manner, demonstrating functional similarities with other members of the Ras superfamily. Immunodepletion of rabaptin-5 from cytosol strongly inhibits Rab5-dependent early endosome fusion. Thus, rabaptin-5 is a Rab effector required for membrane docking and fusion.

\ \ growth factor activity ; GO:0008083 \N \N 22428 IPR003910

Several 7TM receptors have been cloned but their endogenous ligands are\ unknown; these have been termed orphan receptors. GPR56 was isolated from a\ human heart cDNA library using oligonucleotide primers corresponding to TM domains 4 and 7 of the secretin-like receptor family. The mRNA transcript\ is widely distributed throughout most tissues, the highest levels being found in thyroid, brain and heart. Within the brain, the hippocampus and hypothalamic nuclei express GPR56 in particularly high levels.

\ \ \N \N \N 22429 IPR003911

The three-dimensional structures of several members of the TGF- super-family have been deduced [MEDLINE:96416253], [MEDLINE:96266150], [MEDLINE:92335881]. The solution structure of human TGF- 1 was determined using multinuclear magnetic resonance spectroscopy with hybrid distance geometry/simulated annealing [MEDLINE:96266150]. The structure shows a high degree of similarity to that of TGF- 2, but with notable differences in structure and flexibility. The crystal structure of the TGF- 2 monomer lacks a well-defined hydrophobic core and displays an unusual elongated non-globular fold [MEDLINE:92335881]. Eight cysteine residues form 4 intra-chain disulphide bonds, creating the characteristic knotted arrangement. The dimer is stabilised by a ninth cysteine, which forms an inter-chain disulphide bond, and by 2 identical hydrophobic interfaces. Other members of the TGF- superfamily, including activins, inhibins and various developmental factors, are also likely to adopt the TGF- fold. The crystal structure of TGF- 3 reveals a near identical central core to that of TGF- 2 [MEDLINE:96416253]. The principal differences are witnessed in the conformations of the N-terminal -helix and in the -sheet loops, which could account for the individual cellular responses, if these differences are recognised by the TGF- receptors.

\ \ transforming growth factor-beta receptor ligand activity ; GO:0005160 \N cell growth ; GO:0016049 22424 IPR003906

G-protein-coupled receptors (GPCRs) constitute a vast protein family that \ encompasses a wide range of functions (including various autocrine, paracrine and endocrine processes). They show considerable diversity at the sequence level, on the basis of which they can be separated into distinct groups. We use the term clan to describe the GPCRs, as they embrace a group of families for which there are indications of evolutionary relationship, but between which there is no statistically significant similarity in sequence [MEDLINE:94224751]. The currently known clan members include the rhodopsin-like \ GPCRs, the secretin-like GPCRs, the cAMP receptors, the fungal mating\ pheromone receptors, and the metabotropic glutamate receptor family.

The rhodopsin-like GPCRs themselves represent a widespread protein family \ that includes hormone, neurotransmitter and light receptors, all of which transduce extracellular signals through interaction with guanine\ nucleotide-binding (G) proteins. Although their activating ligands vary \ widely in structure and character, the amino acid sequences of the receptors are very similar and are believed to adopt a common structural framework comprising 7 transmembrane (TM) helices [MEDLINE:90262152], [MEDLINE:88139292], [MEDLINE:93234436].

Galanin is a neurotransmitter in the peripheral and central nervous systems\ with a wide spectrum of activity. In the periphery, galanin inhibits\ glucose-induced insulin release and may be the sympathetic mediator of this\ effect during stress. In the CNS, it inhibits firing of locus coeruleus\ cells, is synergistic with opiates in inducing analgesia at the level of\ the spinal cord, and stimulates feeding behaviour and release of growth\ hormone PUB00005882. Its ability to inhibit acetylcholine release in the hippocampus has led to the suggestion that galanin antagonists may be of use in the treatment of Alzheimer's disease.

Galanin receptors are expressed abundantly in a wide range of CNS and\ peripheral tissues, mirroring the distribution of galanin. Three receptor\ subtypes have been identified, differing from one another in terms of their\ expression patterns, affinity for various peptide analogues and G-protein-\ coupling specificity PUB00005882. All are capable of activating K+ channels by coupling to G-proteins of the Gi/Go class [MEDLINE:20156794].

The galanin 1 receptor subtype is expressed at significant levels in regions\ of the brain and spinal cord including the hypothalamus, amygdala,\ hippocampus, thalamus and brainstem. It has also been detected throughout\ the length of the human gastro-intestinal tract [MEDLINE:20156794]. Activation of the receptor by galanin leads to decreased cAMP levels, opening of inwardly\ rectifying K+ channels and stimulation of MAP kinase activity, indicating\ coupling to a Gi-protein. The receptor does not appear to couple to Go-, Gq-\ or Gs-proteins [MEDLINE:98244848].

\ \ galanin receptor activity ; GO:0004966 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 22425 IPR003907

The galanin 2 receptor subtype is expressed abundantly in both central and\ peripheral systems. In the brain, it has been found in the hypothalamus,\ amygdala, hippocampus, pyriform cortex, dendate gyrus, mammillary nuclei and\ cerebellar cortex. Peripheral regions expressing the receptor include the\ prostate, uterus, ovary, vas deferens, stomach, intestine, dorsal root,\ pancreas, liver, heart and retina [MEDLINE:20156794]. Activation of the receptor by galanin leads to inhibition of forskolin-stimulated increase in cAMP levels,\ activation of MAP kinase, and increased inositol phosphate production,\ indicating that the receptor can couple to Gi, Go and Gq type G-proteins. The receptor does not appear to couple to Gs [MEDLINE:98244848].

\ \ galanin receptor activity ; GO:0004966 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 22423 IPR003905

Growth hormone (GH) release is thought to occur under the reciprocal\ regulation of two hypothalamic peptides (GH releasing hormone (GHRH) and\ somatostatin) via their engagement with specific cell surface receptors on\ the anterior pituitary somatotroph [MEDLINE:97246555], [MEDLINE:96337998]. GH-releasing peptides (such as GHRP-6, and the nonpeptide mimetics, L-692, 429 and MK-0677) stimulate GH release through their activation of a distinct receptor, the GH secretagogue receptor (GHSR). This receptor couples to G--11 proteins.

\ \ growth hormone-releasing hormone receptor activity ; GO:0016520 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 22427 IPR003909

Several 7TM receptors have been cloned but their endogenous ligands are\ unknown; these have been termed orphan receptors. GPR37 was isolated from a\ set of human brain frontal lobe expressed sequence tags. The GPR37 genomic\ sequence was subsequently mapped to chromosome 7. A putative orthologue, 83%\ identical to the human form in terms of predicted amino acid sequence, has\ since been identified in the mouse genome and mapped to chromosome 6. Northern blot analyses revealed a highly expressed 3.8kb mRNA and a less abundant 8kb mRNA in both human and mouse brain. The 3.8kb mRNA was also less abundantly expressed in human liver and placenta, and a further 3kb mRNA was found in mouse testis [MEDLINE:99017968].

\ \ G-protein coupled receptor activity, unknown ligand ; GO:0016526 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 22426 IPR003908

The galanin 3 receptor subtype is expressed abundantly in the periphery and\ at lower levels in the CNS. In the brain, the highest levels have been found\ in the hypothalamus and pituitary. Expression has also been detected in \ peripheral tissues, including the pancreas, liver, kidney, stomach, adrenal \ gland, lung and spleen [MEDLINE:98389766]. Activation of the receptor by galanin leads to opening of inwardly rectifying K+ channels, indicating a coupling to Gi type G-proteins [MEDLINE:20156794].

\ \ galanin receptor activity ; GO:0004966 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 22421 IPR003903 The Ubiquitin Interacting Motif (UIM) was first described in the 26S proteasome subunit PSD4/RPN-10 [MEDLINE:98157934]. It is known to bind multiple ubiquitin and was also found in many proteins involved in the endocytic pathway, includingthe PSD4/RPN-10/S5a multiubiquitin binding subunit of the 26S proteasome; the VPS27 vacuolar sorting protein; and ataxin-3, a protein involved in ataxia disease.\ \ \N \N \N 22422 IPR003904

The human APJ gene was originally cloned in 1993 using a set of primers\ based on the 7 conserved TM domains. The putative sequence is closest in\ terms of identity (40-50% in the TM regions) to the angiotensin receptor\ (AT1); however, angiotensin II shows no affinity for the receptor [MEDLINE:94124031]. The endogenous ligand has recently been isolated from bovine stomach and characterised as a 77 amino acid peptide, which was named apelin [MEDLINE:99011403]. The mature transcript encodes a preproprotein that yields a 13 amino acid active peptide from the C-terminal end. Apelin has a similar mRNA distribution to angiotensin II and the active peptides share some similarity. In vivo administration of apelin to rats results in acute hypotensive and thirst \ promoting effects [MEDLINE:20083393].

\ \ G-protein coupled receptor activity ; GO:0004930 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 22417 IPR003899

A large group of bacterial exotoxins are referred to as "A/B toxins", essentially because they are formed from two subunits [MEDLINE:94041637]. The "A" subunit\ possesses enzyme activity, and is transferred to the host cell following a conformational change in the membrane-bound transport "B" subunit [MEDLINE:94041637].

Bordetella pertussis is the causative agent of whooping cough, and is a \ Gram-negative aerobic coccus. Its major virulence factor is the pertussis \ toxin, an A/B exotoxin that mediates both colonisation and toxaemic stages\ of the the disease [MEDLINE:86208173], [MEDLINE:86259651]. Recombinant, inactive forms of the 5 subunits that make up the toxin have proven to be good vaccines. The S2 and S3 subunits of the toxin form part of the "B" moiety. They are responsible for binding the whole toxin to host cells prior to invasion, and are classed as adhesins [MEDLINE:86259651]. S2 attaches to a host receptor called lactosylceramide. It has also been speculated that the S3 unit may preferentially bind phagocytes.

The crystal structure of pertussis toxin has been determined to 2.9A \ resolution [MEDLINE:94356444]. The catalytic A-subunit (S1) shares structural similarity with other ADP-ribosylating bacterial toxins, although differences in the C-terminal portion explain its unique activation mechanism. Despite its\ heterogeneous subunit composition, the structure of the cell-binding\ B-oligomer (S2, S3, two copies of S4, and S5) resembles the symmetrical\ B-pentamers of the cholera and Shiga toxin families, but it interacts\ differently with the A-subunit and there is virtually no sequence similarity between B-subunits of the different toxins. Two peripheral domains that are unique to the pertussis toxin B-oligomer share structural similarity with a calcium-dependent eukaryotic lectin, and reveal possible receptor-binding sites.

\ \ toxin activity ; GO:0015070 extracellular ; GO:0005576 pathogenesis ; GO:0009405 22415 IPR003897

Clostridial species are one of the major causes of food poisoning/gastro-intestinal illnesses. They are Gram-positive, spore-forming rods that occur naturally in the soil [MEDLINE:93328302]. Among the family are: Clostridium botulinum, which produces one of the most potent toxins in existence; Clostridium tetani, causative agent of tetanus; and Clostridium perfringens, commonly found in wound infections and diarrhoea cases. The use of toxins to damage the host is a method deployed by many bacterial pathogens.

The major virulence factor of C. perfringens is the CPE enterotoxin,\ which is secreted upon invasion of the host gut, and contributes to food \ poisoning and other gastrointestinal illnesses [MEDLINE:93328302]. It has a molecular weight of 35.3kDa, and is responsible for the disintegration of tight \ junctions between endothelial cells in the gut [MEDLINE:97242441]. This mechanism is mediated by host claudins-3 and -4, situated at the tight junctions.

Recently, two more host receptors have been characterised and expressed in \ vivo [MEDLINE:97476271]. Named CPE-R and RVP1, these may be utilised in the passage of Clostridial species through the gut wall, although the regulatory mechanisms\ have not been elucidated.

\ \ toxin activity ; GO:0015070 extracellular ; GO:0005576 pathogenesis ; GO:0009405 22418 IPR003900 This group of proteins contains the KID repeat as found in Borrelia and spirochete RepA / Rep+ proteins. The function of these proteins is unknown. RepA and related Borrelia proteins have been suggested to play an important genus-wide role in the biology of the Borrelia [MEDLINE:98406056].\ \N \N \N 22419 IPR003901 Methyl coenzyme M reductase (MCR) catalyses the final step in methanogenesis. MCR is composed of three subunits,

and gamma [MEDLINE:97016827]. Genes encoding the

(mcrB) and gamma (mcrG) subunits are separated by two open reading frames coding for two proteins C and D [MEDLINE:89008091]. The function of proteins C and D (this family) is unknown.\ \N \N methanogenesis ; GO:0015948 22420 IPR003902 The GCM motif is an around 150 amino acid residues domain that has beenidentified in the N-terminal part of proteins belonging to a family of\ transcriptional regulators which comprise Drosophila melanogaster GCM and its mammalian\ homologs [MEDLINE:97121489], [MEDLINE:97272295]. The GCM motif has been shown to be a DNA binding domain that recognizes preferentially the nonpalindromic octamer 5'-ATGCGGGT-3' [MEDLINE:97121489], [MEDLINE:97272295], [MEDLINE:98248577]. The GCM motif contains many conserved basic amino acid residues, seven cysteine residues, and four histidine residues [MEDLINE:97121489]. The conserved cysteines are involved in shaping the overall conformation of the domain, in the process of DNA binding and in the redox regulation of DNA binding [MEDLINE:98248577]. Proteins known to contain a GCM motif include Drosophila glial cell missing (GCM) protein, which functions as an important switch during early neurogenesis by committing cells to the glial cell fate [MEDLINE:97121489], [MEDLINE:97272295]; mammalian GCMa (or GCM1) protein,which may be involved in the expression of multiple placenta-specific genes [MEDLINE:20138214], [MEDLINE:20011432]; and mammalian GCMb (or GCM2) protein, the function of which is not yet known [MEDLINE:20138214]. The profile covers the entire GCM motif.\ \ DNA binding activity ; GO:0003677 \N regulation of transcription, DNA-dependent ; GO:0006355 22416 IPR003898

Bordetella pertussis is the causative agent of whooping cough, and is a \ Gram-negative aerobic coccus. Its major virulence factor is the pertussis \ toxin, an A/B exotoxin that mediates both colonisation and toxaemic stages\ of the the disease [MEDLINE:86208173], [MEDLINE:86259651]. Recombinant, inactive forms of the 5 subunits that make up the toxin have proven to be good vaccines.\ The S1 ("A") subunit of pertussis toxin causes the characteristic sound of \ the "whoop" in whooping cough. It achieves this through ADP-ribosylation of \ host Gi -units, an adenylate cyclase inhibitor [MEDLINE:86208173], [MEDLINE:86259651]. Uninhibited, this enzyme produces elevated levels of cAMP, leading to increased cell exudate and inflammation in the lungs [MEDLINE:89290006].

\ \ toxin activity ; GO:0015070 extracellular ; GO:0005576 pathogenesis ; GO:0009405 22413 IPR003895

Secretion of virulence factors in Gram-negative bacteria involves transportation of the protein across two membranes to reach the cell exterior [MEDLINE:95332200]. There have been four secretion systems described in animal enteropathogens, such as Salmonella and Yersinia, with further \ sequence similarities in plant pathogens like Ralstonia and Erwinia.

The type III secretion system is of great interest, as it is used to \ transport virulence factors from the pathogen directly into the host cell \ [MEDLINE:98284147] and is only triggered when the bacterium comes into close contact with the host. The protein subunits of the system are very similar to those of bacterial flagellar biosynthesis. However, while the latter forms a\ ring structure to allow secretion of flagellin and is an integral part of\ the flagellum itself [MEDLINE:20032050], type III subunits in the outer membrane\ translocate secreted proteins through a channel-like structure.

Exotoxins secreted by the type III system do not possess a secretion signal,\ and are considered unique for this reason [MEDLINE:98284147]. Salmonella and Shigella spp. secrete an invasive protein, named SipB and IpaB respectively. These proteins are required for internalisation of the bacterium within the host\ cell [MEDLINE:95332200]. Induction of apoptosis is then carried out, by the binding of IL-1 converting enzyme to the exotoxin.

\ \ \N membrane ; GO:0016020 \N 22414 IPR003896

A large group of bacterial exotoxins are referred to as "A/B toxins", essentially because they are formed from two subunits [MEDLINE:94041637]. The "A" subunit possesses enzyme activity, and is transferred to the host cell following\ a conformational change in the membrane-bound transport "B" subunit. Clostridial species are one of the major causes of food \ poisoning/gastro-intestinal illnesses. They are Gram-positive, spore-forming rods that occur naturally in the soil [MEDLINE:94041637]. Among the toxins produced by certain Clostridium spp. are the binary exotoxins. These proteins consist of two independent polypeptides, which correspond to the A/B subunit moieties. The enzyme component (A) enters the cell through endosomes produced by the oligomeric binding/translocation protein (B), and prevents actin polymerisation through ADP-ribosylation of monomeric G-actin [MEDLINE:94041637], [MEDLINE:98323874], [MEDLINE:20263779].

Members of the "B" binary toxin family also include the Bacillus anthracis protective antigen (PA) protein [MEDLINE:94041637], most likely due to a common evolutionary ancestor. B. anthracis, a large Gram-positive spore-forming rod, is the causative agent of anthrax. Its two virulence factors are the \ poly-D-glutamate polypeptide capsule, and the actual anthrax exotoxin PUB00010540. The toxin comprises three factors: the protective antigen (PA); the oedema factor (EF); and the lethal factor (LF). Each is a thermolabile \ protein of ~80kDa. PA forms the "B" part of the exotoxin and allows passage\ of the "A" moiety (consisting of EF and LF) into target cells. PA protein forms the central part of the complete anthrax toxin, and translocates the B moiety into host cells after assembling as a heptamer in the membrane PUB00010540, [MEDLINE:89172073].

\ \ toxin activity ; GO:0015070 extracellular ; GO:0005576 pathogenesis ; GO:0009405 22398 IPR003879

Several proteins that contain RING fingers also contain a well-conserved40-residue cysteine-rich domain termed a B-box zinc finger. Often, one or \ two copies of the B-box are associated with a coiled coil domain in addition\ to the ring finger, forming a tripartite motif. The tripartite motif is \ found in transcription factors, ribonucleoproteins and proto-oncoproteins,\ but no function has yet been ascribed to the domain [MEDLINE:99120579].

The solution structure of the B-box motif has been determined by NMR. \ The protein is a monomer, with 2 -strands, 2 helical turns and 3\ extended loop regions packed in a novel topology [MEDLINE:96112809]. Of 7 potential zinc\ ligands, only 4 are used, binding a single zinc atom in a C2-H2 tetrahedral \ arrangement. The B-box structure differs in tertiary fold from all\ other known zinc-binding motifs.

A group of proteins that contain the B-box motif also host a well conserved\ domain of unknown function (DUF). Proteins that include this domain are,\ e.g.: butyrophilin, the RET finger protein, the 52kDa Ro protein and the\ Xenopus nuclear factor protein. The C-terminal portion of this region has\ been termed the SPRY domain (after SPla and the RYanodine Receptor) [MEDLINE:99120579].

\ \ \N \N \N 22399 IPR003881

Iron is essential for growth in both bacteria and mammals. Controlling theamount of free iron in solution is often used as a tactic by hosts to limit\ invasion of pathogenic microbes; binding iron tightly within protein\ molecules can accomplish this. Such iron-protein complexes include haem in\ blood, lactoferrin in tears/saliva and transferrin in blood plasma. Some\ bacteria express surface receptors to capture eukaryotic iron-binding compounds, while others have evolved siderophores to scavenge iron from iron-binding host proteins [MEDLINE:94335702].

The absence of free iron molecules in the surrounding environment triggers \ transcription of gene clusters that encode both siderophore-synthesis \ enzymes, and receptors that recognise iron-bound siderophores [MEDLINE:89123154]. Classic examples are the enterobactin/enterochelin clusters found in Escherichia\ coli and Salmonella spp., although similar moieties in other pathogens have \ been identified. The enzymic machinery that produces vibrionectin in Vibrio\ cholera is such a homologue [MEDLINE:98037504].

EntB, an isochorismate enzyme, is involved in the second stage of \ enterobactin biosynthesis. It has a molecular weight of 35kDa, and is \ believed to possess bifunctional activity. Deletion studies involving EntB- \ mutants have shown that it is essential for virulence [MEDLINE:89123155].

\ \ isochorismatase activity ; GO:0008908 \N biosynthesis ; GO:0009058 22395 IPR003875 This family consists of the polymerase accessory protein C from members of the paramyxoviridae.\ \N \N \N 22396 IPR003876 This is a family of arginine deiminases, EC: 3.5.3.6. The aligned region corresponds to the C-terminal of the protein. These enzymes catalyse the conversion of arginine + H2O to citrulline + NH3. Also found in this family is the Streptococcus anti tumor glycoprotein [MEDLINE:88114832].\ \ arginine deiminase activity ; GO:0016990 \N arginine catabolism ; GO:0006527 22397 IPR003877 The SPRY domain is of unknown function. Distant homologues are domains inbutyrophilin/marenostrin/pyrin [MEDLINE:97348747].\ Ca²⁺-release from the sarcoplasmic or endoplasmic reticulum, the intracellular\ Ca²⁺ store, is mediated by the ryanodine receptor (RyR) and/or the inositol\ trisphosphate receptor (IP3R).\ \ \N \N \N 22412 IPR003894 This domain is found in drosophila nervy, CBFA2T1, human TAF105, human TAF130, and drosophila TAF110. The TAF proteins are transcription factors of the TFIID type, which are multimeric protein complexes that play a central role in mediating promoter responses to various activators and repressors. The domain is also known as the nervy homology region 1 (NHR1).\ transcription factor activity ; GO:0003700 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 22410 IPR003892 This domain may be involved in binding ubiquitin-conjugating enzymes (UBCs). CUE domains also occur in two protein of the IL-1 signal transduction pathway, tollip and TAB2.\ \N \N \N 22411 IPR003893 This is a motif found only in Iroquois-class homeodomain proteins. It has unknown function. Examples include iroquois-class homeodomain protein IRX-4, and homeobox proteins caupolican and araucan, which control proneural and vein forming genesand are positive transcriptional controllers of achaete-scute. They may act as activators that interact with the transcriptional initiation complex assembled on the achaete and scute promoters.\ DNA binding activity ; GO:0003677 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 22409 IPR003891 This domain is found in DAP-5, eIF4G, MA-3 and other proteins. DAP-5 and MA-3 are involved in cell death or apoptosis. The domain is highly

-helical, and may contain repeats and/or regions similar to MIF4G domains.\ \N \N \N 22408 IPR003890 This is the middle domain of eukaryotic initiation factor 4G (eIF4G). It also occurs in the nonsense-mediated mRNA decay protein 2 (NMD2p), which is involved in nonsense-mediated decay of mRNAs containing premature stop codons, and nuclear cap-binding protein (CBP80). The domain is rich in

-helices and may contain multiple

-helical repeats. In eIF4G, this domain binds eIF4A, eIF3, RNA and DNA.\ RNA binding activity ; GO:0003723 \N protein biosynthesis ; GO:0006412 22406 IPR003888 The "FY-rich" domain N-terminal region is sometimes closely juxtaposed with the C-terminal region (IPR003889), but sometimes is far distant. It is of unknown function, but occurs frequently in chromatin-associated proteins like trithorax and its homologues.\ DNA binding activity ; GO:0003677 nucleus ; GO:0005634 \N 22407 IPR003889 The "FY-rich" domain C-terminal region is sometimes closely juxtaposed with the N-terminal region (IPR003888), but sometimes is far distant. It is of unknown function, but occurs frequently in chromatin-associated proteins like trithorax and its homologues.\ DNA binding activity ; GO:0003677 nucleus ; GO:0005634 \N 22405 IPR003887 The LEM domain is found in nuclear membrane-associated proteins, including lamino-associated polypeptide 2 and emerin. Defects in the emerin gene are a cause of Emery-Dreifuss muscular dystrophy, an X-linked disorder characterised by early contractures, muscle wasting, weakness and cardiomyopathy.\ \N nuclear membrane ; GO:0005635 \N 22404 IPR003886 This is an extracellular domain of unknown function in nidogen (entactin) and hypothetical proteins. Nidogen is a sulfated glycoprotein which is widely distributed in basement membranes and is tightly associated with laminin. It also binds to collagen IV. Nidogen probably plays a role in cell adhesion and cell-extracellular matrix intercations.\ \N \N cell-matrix adhesion ; GO:0007160 22403 IPR003885 Leucine-rich repeats (LRRs) are relatively short motifs (22-28 residues in length) found in a variety of cytoplasmic, membrane and extracellular proteins [MEDLINE:91099665]. Although these proteins are associated with widely different functions, a common property involves protein-protein interaction. Little is known about the 3D structure of LRRs, although it is believed that they can form amphipathic structures with hydrophobic surfaces capable of interacting with membranes [MEDLINE:88135762]. This is the SDS22-like subfamily of leucine-rich repeats.\ \N \N \N 22402 IPR003884 This domain is found in complement component proteins, complement component factor 1 and agrin. Factor I is responsible for cleving

chains of C4B and C3B in the presence of the cofactors C4-binding protein and factor H respectively. Agrin is a component of the basal lamina that causes the aggregation of acetylcholine receptors and acetylcholine-esterase on the surface of muscle fibres of the neuromuscular junction.\ \N \N \N 22400 IPR003882 Extensins are plant cell-wall proteins; they can account for up to 20% ofthe dry weight of the cell wall. They are highly-glycosylated, possibly\ reflecting their interactions with cell-wall carbohydrates. Amongst their \ functions is cell wall strengthening in response to mechanical stress (e.g.,\ during attack by pests, plant-bending in the wind, etc.).\ By contrast with extensin genes, pistil-specific extensin-like genes are\ not induced under stress conditions. Gene expression is organ-specific \ and temporally regulated during pistil development. After pollination, \ transcript levels of pistil-specific extensin-like genes change relative to\ levels in unpollinated pistils [MEDLINE:93005740]. The protein sequence is characterised\ by multiple tandem ser-pro-pro-pro-pro pentapeptide repeats.\ \ structural constituent of cell wall ; GO:0005199 \N \N 22401 IPR003883 Extensins are plant cell-wall proteins; they can account for up to 20% of the dry weight of the cell wall. They are highly-glycosylated, possibly reflecting their interactions with cell-wall carbohydrates. Amongst their functions is cellwall strengthening in response to mechanical stress (e.g., during attack by pests, plant-bending in the wind, etc.). This family includes extensin-like proteins.\ \ structural constituent of cell wall ; GO:0005199 \N \N 22391 IPR003871

This domain (DUF223) found in eukaryotic proteins is of unknown function.

\ \N \N \N 22392 IPR003872 This is a family of spirochete major outer sheath protein C-terminal regions. These proteins are present on the bacterial cell surface. In Treponema denticola the major outer sheath protein (Msp) binds immobilized laminin and fibronectin supporting the hypothesis that Msp mediates the extracellular matrix binding activity of T. denticola [MEDLINE:97175532].\ structural molecule activity ; GO:0005198 \N \N 22393 IPR003873 This is a family of small nonstructural proteins, well conserved among Coronavirus strains. This protein is also found in murine hepatitis virus as small envelope protein E.\ \N membrane ; GO:0016020 \N 22394 IPR003874 CDC45 is an essential gene required for initiation of DNA replication in Saccharomyces cerevisiae (cell division control protein 45), forming a complex with MCM5/CDC46. Homologs of CDC45 have been identified in human [MEDLINE:98325026], mouse and the smut fungus, Melampsora spp., (tsd2 protein) among others.\ \N \N DNA replication initiation ; GO:0006270 22382 IPR003860 This is a family of hemagglutinin esterases from influenza C and Coronaviruses. Hemagglutinin esterases are membrane glycoproteins present on the surface of the virus and are involved with the cell infection process.\ hydrolase activity, acting on ester bonds ; GO:0016788 \N initiation of viral infection ; GO:0019059 22390 IPR003870 This domain is found in a family of hypothetical proteins, mostly from Mycobacterium tuberculosis, which includes a putative transposase.\ \N \N \N 22388 IPR003868 This is a family of Herpesvirus proteins including UL31, UL53, and the product of ORF 69 in some strains. The proteins in this family have no known function.\ \N \N \N 22389 IPR003869 This is a family of diverse bacterial polysaccharide biosynthesis proteins including the CapD protein from Staphylococcus aureus\ \ \ [MEDLINE:95050273], the WalL protein, mannosyl-transferase [MEDLINE:97234624], and several putative epimerases. The CapD protein is required for biosynthesis of type 1 capsular polysaccharide.\ \ \N \N biosynthesis ; GO:0009058 22387 IPR003867 This is a family of poxvirus proteins including Vaccinia virus proteins B15 and C6, and Capripoxvirus T3A protein. Members of this family are approximately 150 residues long and have no known function.\ \N \N \N 22386 IPR003866 This is a family of isoflavone reductases from plants. Isoflavone reductase enzymes EC: 1.3.1.45 catalyse the penultimate step in the synthesis of the phytoalexin medicarpin [MEDLINE:96158112]. They reduce achiral isoflavones to chiral isoflavones during the biosynthesis of chiral pterocarpanphytoalexins. The reduction product is a third isomer, which is the penultimate intermediate.\ \ enzyme activity ; GO:0003824 \N \N 22384 IPR003863 This domain is a region found in several Arabidopsis thaliana hypothetical proteins none of which have any known function. The aligned region contains two cysteine residues.\ \N \N \N 22385 IPR003864 This domain is found in a family of hypothetical transmembrane proteins none of which have any known function, the aligned region is at 538 residues at maximum length.\ \N membrane ; GO:0016020 \N 22383 IPR003861 This is is a family of Papillomavirus proteins, E4, coded for by ORF4. A splice variant, E1--E4, exists but the function of neither E4 nor E1--E4 is known [MEDLINE:98118447].\ \N \N \N 22369 IPR003846

This entry describes proteins of unknown function.

\ \N \N \N 22370 IPR003847

This entry describes proteins of unknown function.

\ \N \N \N 22371 IPR003848

This domain of unknown function is found in several uncharacterized proteins.

\ \N \N \N 22372 IPR003849

This entry describes proteins of unknown function.

\ \N \N \N 22373 IPR003850 Several uncharacterized proteins have similarities, and can be grouped into the ACR, YexA/UPF0062 family.\ \N \N \N 22374 IPR003851 The Dof domain is a zinc finger DNA-binding domain, that shows resemblance to the Cys2 zinc finger, although it has a longer putative loop where an extra Cys residue is conserved [MEDLINE:98351835]. AOBP, a DNA-binding protein in pumpkin (Cucurbita maxima), contains a 52 amino acid Dof domain, which is highly conserved in severalDNA-binding proteins of higher plants.\ \ DNA binding activity ; GO:0003677 \N \N 22375 IPR003852 This is a family of KdpD sensor kinase proteins that regulate the kdpFABC operon responsible for potassium transport [MEDLINE:97369818]. The aligned region corresponds to the N-terminal cytoplasmic part of the protein which may be the sensor domain responsible for sensing turgor pressure [MEDLINE:92202141].\ two-component sensor molecule activity ; GO:0000155 membrane ; GO:0016020 signal transduction ; GO:0007165 22376 IPR003853 This is a family of adenoviral early E1A proteins. The E1A protein is 32 kDa it can however be cleaved to yield the 28 kDa protein. The E1A protein is responsible for the transcriptional activation of the early genes with in the viral genome at the start of the infection process as well as some cellular genes [MEDLINE:92052288].\ \N \N regulation of transcription, DNA-dependent ; GO:0006355 22377 IPR003854 This is the GASA gibberellin regulated cysteine rich protein family. The expression of these proteins is up-regulated by the plant hormone gibberellin, most of these proteins have some role in plant development. There are 12 cysteine residues conserved within the alignment giving the potential for these proteins to posses 6 disulphide bonds.\ \N \N \N 22378 IPR003855 This is a family of K+ potassium transporters that are conserved across phyla, having both bacterial (KUP) [MEDLINE:94042856], yeast (HAK) [MEDLINE:95347328], and plant (AtKT) [MEDLINE:98010480] sequences as members.\ potassium ion transporter activity ; GO:0015079 membrane ; GO:0016020 potassium ion transport ; GO:0006813 22381 IPR003859 This is a family of galactosyltransferases from a wide range of metazoa with three related galactosyltransferase activities; all three of which are possessed by one sequence in some cases. The three functions are N-acetyllactosamine synthase (EC: 2.4.1.90);

-N-acetylglucosaminyl-glycopeptide

-1,4-galactosyltransferase (EC: 2.4.1.38); and lactose synthase (EC: 2.4.1.22). Note that N-acetyllactosamine synthase is a component of lactose synthase along with

-lactalbumin, in the absence of

-lactalbumin N-acetyllactosamine synthase is used.\ \N \N \N 22380 IPR003857 This is a family of spirochete major outer sheath protein N-terminal regions. These proteins are present on the bacterial cell surface. In Treponema denticola the major outer sheath protein (Msp) binds immobilized laminin and fibronectin supporting the hypothesis that Msp mediates the extracellular matrix binding activity of T. denticola [MEDLINE:97175532].\ structural molecule activity ; GO:0005198 \N \N 22379 IPR003856

A number of related proteins are involved in the synthesis of lipopolysaccharide, O-antigen polysaccharide, capsule polysaccharide and exopolysaccharides. Chain length determinant protein (or wzz protein) is involved in lipopolysaccharide (lps) biosynthesis, conferring a modal distribution of chain length on the O-antigen component of lps [MEDLINE:98241528]. It gives rise to a reduced number of short chain molecules and increases in numbers of longer molecules, with a modal value of 20. The MPA/MPA2 proteins function in CPS and EPS polymerization and export [MEDLINE:20121732].

\ \N membrane ; GO:0016020 lipopolysaccharide biosynthesis ; GO:0009103 22367 IPR003844

This entry describes integral membrane proteins of unknown function.

\ \N membrane ; GO:0016020 \N 22368 IPR003845 This domain is found in a family of hypothetical worm (Caenorhabditis elegans) proteins, none of which have any known function. The aligned region is repeated two or three times in many of the sequences in this family.\ \N \N \N 22365 IPR003841 This family includes the mammalian type II renal Na+/Pi-cotransporters and other proteins from lower eukaryotes and bacteria some of which are also Na+/Pi-cotransporters. In the kidney these proteins may be involved in actively transporting phosphate into cells via Na+ cotransport in the renal brush border membrane [MEDLINE:93317607].\ sodium-dependent phosphate transporter activity ; GO:0015321 membrane ; GO:0016020 phosphate transport ; GO:0006817 22366 IPR003842

Helicobacter pylori is a micro-aerophilic bacterium with the extraordinary ability to establish infections in human stomachs that can last for years or \ decades, despite immune and inflammatory responses and normal turnover of \ the gastric epithelium and overlying mucin layer in which it resides. Most H.pylori strains secrete a toxin (VacA) that induces multiple \ structural and functional alterations in eukaryotic cells. The most \ prominent effect of VacA is its capacity to induce the formation of large \ cytoplasmic vacuoles in eukaryotic cells. In addition, VacA interferes with \ the process of antigen presentation, increases permeability of polarised \ epithelial cell monolayers, and forms anion-selective membrane channels. \ Formation of channels in endosomal membranes of cells may be an important \ feature of the mechanism by which VacA induces cell vacuolation. H.pylori \ vacA encodes a ~139kDa protoxin, which undergoes cleavage of a 33-residue \ N-terminal signal sequence and C-terminal proteolytic processing to \ yield a mature secreted toxin. Purified VacA degrades during prolonged \ storage into two fragments (of ~34 and 58kDa), which are derived from the\ N- and the C-terminus of the toxin respectively. The mass of the\ experimentally intact toxin (~88.2kDa) corresponds closely to the sum of \ the masses of the two proteolytic fragments [MEDLINE:21101073].\

\ Secondary structure predictions suggest that a 35kDa portion of the VacA \ C-terminal domain is rich in amphipathic -sheets, and this region \ exhibits low-level similarity to members of the family of autotransporter \ proteins. In addition, at the C-terminus of VacA, there is a phenylalanine-\ containing motif that is commonly found in autotransporter proteins, as well\ as in numerous Gram-negative bacterial outer membrane proteins. An intact \ N-terminal portion of VacA is not required for proteolytic processing of the\ protoxin. However, the N-terminal 32 amino acids of the mature VacA are \ predicted to form the only contiguous hydrophobic region in the protein that\ is long enough to span the membrane. What is more, isogenic H.pylori mutant\ strains in which the C-terminal VacA domain is disrupted, fail to express or\ secrete any detectable VacA, which is probably attributable to the \ degradation of export-incompetent toxin precursors within the periplasm. It \ is speculated that the VacA protoxin may undergo proteolytic cleavage at\ multiple sites downstream from amino acid 854 of the protoxin, which would\ yield a 33kDa cell-associated domain, as well as a fragment of ~15kDa [MEDLINE:21101073].\ \

\ \ toxin activity ; GO:0015070 \N \N 22363 IPR003839 This is an uncharacterized domain found in proteins of unknown function. It is present in a large family of Caenorhabditis elegans proteins.\ \N \N \N 22364 IPR003840 Helicases from the herpes viruses are responsible for the unwinding of DNA and are essential for replication and completion of the viral life cycle.\ \ ATP binding activity ; GO:0005524 \N viral genome replication ; GO:0019079 22355 IPR003831

This entry describes proteins of unknown function.

\ \N \N \N 22356 IPR003832

This entry describes proteins of unknown function.

\ \N \N \N 22357 IPR003833 Uncharacterized domain in proteins of unknown function.\ \N \N \N 22358 IPR003834 DsbA and DsbC, periplasmic proteins of Escherichia coli, are two key players involved in disulfide bond formation. DsbD generates a reducing source in the periplasm, which is required for maintaining proper redox conditions [MEDLINE:95354659]. DipZ is essential for maintaining cytochrome c apoproteins in the correct conformations for the covalent attachment of haem groups to the appropriate pairs of cysteine residues [MEDLINE:95349398].\ \N membrane ; GO:0016020 cytochrome biogenesis ; GO:0017004 22359 IPR003835

These enzymes belong to the glycosyltransferase family 19 CAZY:GT_19. These enzymes catalyse the first disaccharide step in the synthesis of lipid-A-disaccharide.

\ \ lipid-A-disaccharide synthase activity ; GO:0008915 \N lipid A biosynthesis ; GO:0009245 22360 IPR003836 Glucokinases EC: 2.7.1.2 are found in invertebrates and microorganisms and are highly specific for glucose. These enzymes phosphorylate glucose using ATP as a donor to give glucose-6-phosphate and ADP [MEDLINE:97175560].\ ATP binding activity ; GO:0005524 \N glycolysis ; GO:0006096 22361 IPR003837

Glu-tRNAGln amidotransferase is a heterotrimeric enzyme that is required for correct decoding of glutamine codons during translation. The Glu-tRNA Gln amidotransferase enzyme is an important translational fidelity mechanism replacing incorrectly charged Glu-tRNAGln with the correct Gln-tRANGln via transmidation of the misacylated Glu-tRNAGln [MEDLINE:98004482]. This activity supplements the lack of glutaminyl-tRNA synthetase activity in gram-positive eubacteria, cyanobacteria, archaea, and organelles [MEDLINE:98004482].

\ \N \N regulation of translational fidelity ; GO:0006450 22362 IPR003838 Uncharacterized domain in proteins of unknown function. Proteins that contain this domain are often predicted permeases and hypothetical transmembrane proteins.\ \N membrane ; GO:0016020 \N 22347 IPR003823 This entry represents an uncharacterized domain in proteins of unknown function. This domain is found associated with CBS domains in some proteins IPR000644.\ \ \N \N \N 22348 IPR003824 Bacitracin resistance protein (BacA) may confer resistance to bacitracin by phosphorylation of undecaprenol [MEDLINE:93285992].\ \N membrane ; GO:0016020 \N 22349 IPR003825 Colicin V production protein is required in E. Coli for colicin V production from plasmid pColV-K30 [MEDLINE:89255077]. This protein is coded for in the purF operon.\ \ \N membrane ; GO:0016020 toxin biosynthesis ; GO:0009403 22350 IPR003826 Members of this family are related to the amino terminus of Eshcerichia coli S-adenosylmethionine decarboxylase EC: 4.1.1.50.\ \N \N \N 22351 IPR003827

This entry describes proteins of unknown function.

\ \N \N \N 22352 IPR003828

This entry describes proteins of unknown function.

\ \N \N \N 22353 IPR003829

This entry describes proteins of unknown function.

\ \N \N \N 22354 IPR003830

This entry describes proteins of unknown function.

\ \N \N \N 22343 IPR003819 This family consists of TauD/TfdA taurine catabolism dioxygenases. The Escherichia coli tauD gene is required for the utilization of taurine (2-aminoethanesulfonic acid) as a sulfur source and is expressed only under conditions of sulfate starvation. TauD is an

-ketoglutarate-dependent dioxygenase catalyzing the oxygenolytic release of sulfite from taurine [MEDLINE:97435261]. The 2,4-dichlorophenoxyacetic acid/

-ketoglutarate dioxygenase from Burkholderia sp. strain RASC also belongs to this family [MEDLINE:96271695]. TfdA from Alcaligenes eutrophus is a 2,4-D monooxygenase [MEDLINE:87250253].\ oxidoreductase activity ; GO:0016491 \N electron transport ; GO:0006118 22345 IPR003821 1-deoxy-D-xylulose 5-phosphate reductoisomerase synthesizes 2-C-methyl-D-erythritol 4-phosphate from 1-deoxy-D-xylulose 5-phosphate in a single step by intramolecular rearrangement and reduction and is responsible for terpenoid biosynthesis in some organisms [MEDLINE:98374274]. In Arabidopsis thaliana 1-deoxy-D-xylulose 5-phosphate reductoisomerase is the first committed enzyme of the non-mevalonate pathway for isoprenoid biosynthesis.\ enzyme activity ; GO:0003824 \N isoprenoid biosynthesis ; GO:0008299 22346 IPR003822 The four paired amphipathic helix motifs has been identified in the myc family of helix-loop-helix DNA-binding proteins and in the TPR family of regulatory proteins. The SIN3 gene (also known as SDI1) is a negative regulator of the yeast HO gene [MEDLINE:91042523].\ \N nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 22344 IPR003820

Kdp, the high affinity ATP-driven K+-transport system of Escherichia coli, is a complex of the membrane-bound subunits KdpA, KdpB, KdpC and the small peptide KdpF. KdpC forms strong interactions with the KdpA subunit, serving to assemble and stabilize the Kdp complex [MEDLINE:99077600]. It has been suggested that KdpC could be one of the connecting links between the energy providing subunit KdpB and the K+- transporting subunit KdpA [MEDLINE:99077600]. The K+ transport system actively transports K+ ions via ATP hydrolysis.

\ potassium-transporting ATPase activity ; GO:0008556 membrane ; GO:0016020 potassium ion transport ; GO:0006813 22332 IPR003806

This entry describes proteins of unknown function.

\ \N \N \N 22333 IPR003807

This entry describes proteins of unknown function.

\ \N \N \N 22334 IPR003808

This entry describes proteins of unknown function.

\ \N \N \N 22335 IPR003810 Uncharacterized domain in proteins of unknown function.\ \N \N \N 22336 IPR003811

This entry describes proteins of unknown function.

\ \N \N \N 22337 IPR003812 cAMP may be a regulation factor in cell division of some bacteria.The Fic (filamentation induced by cAMP) protein is involved in the synthesis of PAB or folate. It would appear that the Fic protein and cAMP are involved in a regulatory mechanism of cell division via folate metabolism and in these organisims cell division could be controlled by coordination of cAMP, Fic and Fts proteins [MEDLINE:92021789].\ \ \N \N regulation of cell cycle ; GO:0000074 22338 IPR003813 Methyl-viologen-reducing hydrogenase (MVH) is one of the enzymes involved in methanogenesis and coded in the mth-flp-mvh-mrt cluster of methane genes in Methanobacterium thermoautotrophicum\ \ \ [MEDLINE:95247681]. No specific\ functions have been assigned to the delta subunit.\ \ \N \N methanogenesis ; GO:0015948 22339 IPR003814 Formylmethanofuran dehydrogenase (EC: 1.2.99.5) found in methanogenic Archaea, are molybdenum or tungsten iron-sulfur proteins containing a pterin cofactor [MEDLINE:94170797]. The enzyme from Methanosarcina barkeri is a molybdenum iron-sulfur protein involved in methanogenesis. Subunit E protein is co-expressed with the enzyme but fails to co-purify and thus its function is unknown [MEDLINE:96184912].\ enzyme activity ; GO:0003824 \N methanogenesis ; GO:0015948 22340 IPR003815

In bacteria, the regulation of gene expression in response to changes in cell density is called quorum sensing. Quorum-sensing bacteria produce, release, and respond to hormone-like molecules (autoinducers) that accumulate in the external environment as the cell population grows. The LuxS protein is involved in quorum sensing and is a autoinducer-production protein [MEDLINE:99145603].

\ \N \N quorum sensing ; GO:0009372 22341 IPR003816

The nitrate reductase enzyme (EC: 1.7.99.4) is composed of three subunits; an , a and two gamma. It is the second nitrate reductase enzyme which it can substitute for the NRA enzyme in Escherichia coli allowing it to use nitrate as an electron acceptor during anoerobic respiration [MEDLINE:91042410].

Nitrate reductase gamma subunit resembles cytochrome b and transfers electrons from quinones to the subunit [MEDLINE:98409266].

\ \ nitrate reductase activity ; GO:0008940 nitrate reductase complex ; GO:0009325 electron transport ; GO:0006118 22342 IPR003817 Phosphatidylserine decarboxylase plays a pivotal role in the synthesis of phospholipid by the mitochondria. The substrate phosphatidylserine is synthesized extramitochondrially and must be translocated to the mitochondria prior to decarboxylation [MEDLINE:94012701]. Phosphatidylserine decarboxylases EC: 4.1.1.65 is responsible for conversion of phosphatidylserine to phosphatidylethanolamine and plays a central role in the biosynthesis of aminophospholipids [MEDLINE:95197637].\ \ phosphatidylserine decarboxylase activity ; GO:0004609 \N phospholipid biosynthesis ; GO:0008654 22316 IPR003787 Four small, soluble proteins (DsrE, DsrF, DsrH and DsrC) are encoded in the dsr gene region of the phototrophic sulfur bacterium Chromatium vinosum D. The dsrAB genes encoding dissimilatory sulfite reductase are part of the gene cluster, dsrABEFHCMK. The remaining proteins that are encoded are a transmembrane protein (DsrM) with similarity to haem-b-binding polypeptides and a soluble protein (DsrK) resembling [4Fe-4S]-cluster-containing heterodisulfide reductase from methanogenic archaea. \ DsrE is a small soluble protein involved in intracellular sulfur reduction [MEDLINE:98361034].\ \ \N \N \N 22317 IPR003788

This entry describes proteins of unknown function.

\ \N \N \N 22318 IPR003789 This domain is found in GatB and proteins related to bacterial Yqey. It is about 140 amino acid residues long. This domain is found at the C terminus of GatB which transamidates Glu-tRNA to Gln-tRNA. The function of this domain is uncertain. It does however suggest that Yqey and its relatives\ have a role in tRNA metabolism.\ \ \N \N \N 22319 IPR003790

This entry describes proteins of unknown function.

\ \N \N \N 22320 IPR003791

This entry describes proteins of unknown function.

\ \N \N \N 22321 IPR003793 This is an uncharacterised domain found in proteins of unknown function.\ \N \N \N 22322 IPR003794

This entry describes proteins of unknown function.

\ \N \N \N 22323 IPR003795

This entry describes proteins of unknown function.

\ \N \N \N 22324 IPR003796 Uncharacterized domain in proteins of unknown function.\ \N \N \N 22325 IPR003797 This family of proteins is related to DegV of Bacillus subtilis and includes paralogous sets in several species (B. subtilis, Deinococcus radiodurans, Mycoplasma pneumoniae) that\ are closer in percent identity to each than to most homologs from other species. This\ suggests both recent paralogy and diversity of function.\ \ \N \N \N 22312 IPR003783 RecX is a putative bacterial regulatory protein [MEDLINE:20327581]. The gene encoding RecX is found downstream of recA, and it is suggested that the RecX protein might be regulator of RecA activity by interaction with the RecA protein or filament [MEDLINE:20327581].\ \N \N regulation of DNA repair ; GO:0006282 22313 IPR003784 The BioY protein is involved in bioconversion of pimelate into dethiobiotin [MEDLINE:90236299] although the exact function of the protein is unknown.\ \N \N \N 22314 IPR003785 Creatininase (EC: 3.5.2.10) catalyses the hydrolysis of creatinine to creatine [MEDLINE:95400012].\ \N \N \N 22315 IPR003786 Formate dehydrogenase is required for nitrate inducable formate dehydrogenase activity. In Wolinella succinogenes it is a membraneous molybdo-enzyme which is involved in phosphorylative electron transport. The functional formate dehydrogenase may be made up of three or four different subunits [MEDLINE:92143671]. In E. coli, FdhD is required for the formation of active formate dehydrogenases.\ formate dehydrogenase activity ; GO:0008863 formate dehydrogenase complex ; GO:0009326 electron transport ; GO:0006118 22331 IPR003805 Some bacteria synthesize cobalamin (vitamin B12) de novo under anaerobic conditions. \ The CobU, CobS, CobT, and CobC proteins have been proposed to catalyze the late steps in adenosylcobalamin biosynthesis, which define the nucleotide loop assembly pathway [MEDLINE:99449762]. CobS is the cobalamin(-5'-phosphate) synthase enzyme.\ \ cobalamin [5'-phosphate] synthase activity ; GO:0008818 \N vitamin B12 biosynthesis ; GO:0009236 22326 IPR003798 Uncharacterized domain in proteins of unknown function.\ \N \N \N 22327 IPR003799

This entry describes proteins of unknown function.

\ \N \N \N 22328 IPR003801

This entry describes proteins of unknown function.

\ \N \N \N 22329 IPR003802

This entry describes proteins of unknown function.

\ \N \N \N 22330 IPR003804 L-lactate permease is an integral membrane protein probably involved in L-lactate transport.\ lactate transporter activity ; GO:0015129 \N lactate transport ; GO:0015727 22297 IPR003767

The malate dehydrogenase (MDH) of some extremophilies is more similar to the L-lactate dehydrogenases (L-LDH) EC: 1.1.1.27 from various sources than to other MDHs [MEDLINE:93237239].

This family consists of bacterial and archaeal malate/L-lactate dehydrogenases. The archaebacterial malate dehydrogenase EC: 1.1.1.37, EC: 1.1.1.82 deviates from the eubacterial and eukaryotic enzymes having a low selectivity for the coenzyme (NAD(H) or NADP(H)) and catalyzing the reduction of oxalacetate to malate more efficiently than the reverse reaction [MEDLINE:90235834].

\ \ oxidoreductase activity ; GO:0016491 \N metabolism ; GO:0008152 22298 IPR003768

This entry describes proteins of unknown function.

\ \N \N \N 22299 IPR003769

This entry describes proteins of unknown function.

\ \N \N \N 22300 IPR003770

This entry describes proteins of unknown function.

\ \N \N \N 22301 IPR003772

This entry describes proteins of unknown function.

\ \N \N \N 22302 IPR003773

This entry describes proteins of unknown function.

\ \N \N \N 22303 IPR003774

This entry describes proteins of unknown function.

\ \N \N \N 22304 IPR003775

This entry describes proteins of unknown function.

\ \N \N \N 22305 IPR003776

This is a family of proteins of unknown function.

\ \N \N \N 22306 IPR003777

This entry describes proteins of unknown function.

\ \N \N \N 22307 IPR003778 Uncharacterized domain in proteins of unknown function. This domain is found in a multifunctional enzyme, urea amidolyase, from yeast.\ \N \N \N 22308 IPR003779 The catechol and protocatechuate branches of the 3-oxoadipate pathway, which areimportant for the bacterial degradation of aromatic compounds, converge at the common intermediate 3-oxoadipate enol-lactone. \ Carboxymuconolactone decarboxylase (CMD) EC: 4.1.1.44 is involved in protocatechuate catabolism. In some\ bacteria a gene fusion event leads to expression of CMD with a hydrolase involved in the same pathway [MEDLINE:98155132].\ \ enzyme activity ; GO:0003824 \N aromatic compound metabolism ; GO:0006725 22309 IPR003780 Cytochrome aa3 is one of two terminal oxidase complexes in the Bacillus subtiliselectron transport chain. CtaA is required for cytochrome aa3 biosynthesis and sporulation in Bacillus subtilis\ \ \ \ [MEDLINE:89359135]. In yeast the COX15 protein is required for cytochrome c oxidase assembly.\ \ \N membrane ; GO:0016020 protein complex assembly ; GO:0006461 22310 IPR003781 This domain has a Rossmann fold and is found in a number of proteins including succinyl CoA synthetases, malate and ATP-citrate ligases. \ \ \N \N \N 22311 IPR003782 This family is involved in biogenesis of respiratory and photosynthetic systems. In yeast the SCO1 protein is specifically required for a post-translational step in the accumulation of subunits 1 and 2 of cytochrome c oxidase (COXI and COX-II)[MEDLINE:92049241]. It is a mitochondrion-associated cytochrome c oxidase assembly factor.\

The purple nonsulfur photosynthetic eubacterium Rhodobacter capsulatus is a versatile organism that can obtain cellular energy by several means, including the capture of light energy for photosynthesis as well as the use of light-independent respiration, in which molecular oxygen serves as a terminal electron acceptor. The SENC protein is required for optimal cytochrome c oxidase activity in aerobically grown R. capsulatus cells and is involved in the induction of structural polypeptides of the light-harvesting and reaction center complexes [MEDLINE:96074328].

\ \ \N \N electron transport ; GO:0006118 22291 IPR003761

Exonuclease VII EC: 3.1.11.6 is composed of two non-identical subunits; one large subunit and 4 small ones [MEDLINE:82239360]. Exonuclease VII catalyses exonucleolytic cleavage in either 5'-3' or 3'-5' direction to yield 5'-phosphomononucleotides.

\ \ exodeoxyribonuclease VII activity ; GO:0008855 exodeoxyribonuclease VII complex ; GO:0009318 DNA catabolism ; GO:0006308 22292 IPR003762 The Escherichia coli araBAD operon consists of three genes encoding three enzymes that convert L-arabinose to D-xylulose-5 phosphate.L-arabinose isomerase (araA) EC: 5.3.1.4 catalyses the coversion of L-arabinose to L-ribulose as the first step in the pathway of L-arabinose utilization as a carbon source [MEDLINE:97237725].\ \ L-arabinose isomerase activity ; GO:0008733 \N metabolism ; GO:0008152 22295 IPR003765 The nitrate-reducing system, nitrate reductase EC: 1.7.99.4, is stimulated by anaerobiosis, nitrate, and nitrite. The delta subunit is not part of the nitrate reductase enzyme but is most likely needed for assembly of the multisubunit enzyme complex. In the absence of the delta subunit the core

enzyme complex is unstable [MEDLINE:98409266]. The delta subunit is essential for enzyme activity in vivo\ and in vitro.\ \ nitrate reductase activity ; GO:0008940 nitrate reductase complex ; GO:0009325 electron transport ; GO:0006118 22296 IPR003766 Glucuronate isomerase EC: 5.3.1.12 catalyses the reaction D-glucuronate to D-fructuronate and also converts D-galacturonate to D-tagaturonate [MEDLINE:99102204].\ glucuronate isomerase activity ; GO:0008880 \N glucuronate catabolism ; GO:0006064 22294 IPR003764 Three enzymes are required for N-acetylglucosamine (NAG) utilization in Escherichia coli: enzyme IInag (gene nagE), N-acetylglucosamine-6-phosphate deacetylase (gene nagA), and glucosamine-6-phosphate isomerase (gene nagB) [MEDLINE:90274974]. This is family of N-acetylglucosamine-6-phosphate deacetylases, EC: 3.5.1.25\ \ \ \ [MEDLINE:97446530].\ \ N-acetylglucosamine-6-phosphate deacetylase activity ; GO:0008448 \N N-acetylglucosamine metabolism ; GO:0006044 22293 IPR003763 The CDP-diacylglycerol pyrophosphatases EC: 3.6.1.26 play a role in the regulation of phospholipid metabolism by inositol, as well as regulating the cellular levels of phosphatidylinositol [MEDLINE:20576243].\ \ CDP-diacylglycerol pyrophosphatase activity ; GO:0008715 membrane ; GO:0016020 phospholipid biosynthesis ; GO:0008654 22290 IPR003760 This is a family of basic membrane lipoproteins from Borrelia and various putative lipoproteins from other bacteria. All of these proteins are outer membrane proteins and are thus antigenic in nature when possessed by the pathogenic\ members of the family [MEDLINE:98010210]. \

The Bacillus subtilis degR, a positive regulator of the production of degradative enzymes, is also a member of this group [MEDLINE:97474245].

\ \ lipid binding activity ; GO:0008289 \N \N 22289 IPR003759 Cobalamin-dependent methionine synthase EC: 2.1.1.13 is a large enzyme composed of structurally and functionally distinct regions. The B12 binding domain is where cobalamin (B12), the prosthetic group binds. Cobalamin-dependent methionine synthase catalyzes methyl transfer from methyltetrahydrofolate (CH3-H4folate) to homocysteine. The B12 (cobalamin) cofactor plays an essential role in this reaction, accepting the methyl group from CH3-H4folate to form methylcob(III)alamin and in turn donating the methyl group to homocysteine to generate methionine and cob(I)alamin.The domain is also present in other shorter proteins (mutases and\ methionine synthases) that bind to B12 [MEDLINE:95227826].

The domain structure is a 4 helix bundle. Many of the conserved residues in this domain are involved in B12 binding, such as\ those in the MXXVG motif [MEDLINE:95084154].

\ \ \ 5-methyltetrahydrofolate-homocysteine S-methyltransferase activity ; GO:0008705\ \N \N methionine biosynthesis ; GO:0009086 22288 IPR003758 Tetraacyldisaccharide 4'-kinase EC: 2.7.1.130 phosphorylates the 4'-position of a tetraacyldisaccharide 1-phosphate precursor (DS-1-P) of lipid A, but the enzyme has not yet been purified because of instability [MEDLINE:98241618]. This enzyme is involved in the synthesis of lipid A portion of the bacterial lipopolysaccharide layer (LPS).\ \ tetraacyldisaccharide 4'-kinase activity ; GO:0009029 \N lipid A biosynthesis ; GO:0009245 22283 IPR003753

Exonuclease VII EC: 3.1.11.6 is composed of two nonidentical subunits; one large subunit and 4 small ones [MEDLINE:82239360].Exonuclease VII catalyses exonucleolytic cleavage in\ either 5'-3' or 3'-5' direction to yield 5'-phosphomononucleotides. The large subunit also contains the OB-fold domains (IPR004365) that bind to nucleic acids at the N-terminus.

\ \ exodeoxyribonuclease VII activity ; GO:0008855 exodeoxyribonuclease VII complex ; GO:0009318 DNA catabolism ; GO:0006308 22284 IPR003754 Uroporphyrinogen III synthase (HEM4) EC: 4.2.1.75 catalyses the fourth step in the heme biosynthetic pathway in eukaryotes, bacteria and archaea [MEDLINE:95321013].

Congenital erythropoietic porphyria (CEP) is an autosomal recessive inborn error of metabolism that results from the markedly deficient activity of HEM4 [MEDLINE:96271980].

\ \ uroporphyrinogen-III synthase activity ; GO:0004852 \N heme biosynthesis ; GO:0006783 22285 IPR003755 HPr(Ser) kinase is the sensor in a multicomponent phosphorelay system that controls catabolite repression, sugar transport and carbon metabolism in gram-positive bacteria. These are all phosphorylation-dependent carbon control mechanisms. This kinase in unusual in that it recognizes the tertiary structure of its target protein, HPr, a phosphocarrier protein of the bacterial phosphotransferase system and a transcriptional cofactor controlling the phenomenon of catabolite repression [MEDLINE:98230327]\ \ ATP binding activity ; GO:0005524 \N regulation of carbohydrate metabolism ; GO:0006109 22286 IPR003756

This entry describes proteins of unknown function.

\ \N \N \N 22287 IPR003757 The trimeric photosystem I of the cyanobacterium Synechococcus elongatus recomprises 11 protein subunits. Subunit XI, PsaL, from plants and bacteria is one of the smaller subunits with only two transmembrane

helices. PsaL interacts closely with PsaI [MEDLINE:97057537].\ \N photosystem I reaction center ; GO:0009538 photosynthesis ; GO:0015979 22265 IPR003734

This entry describes proteins of unknown function.

\ \N \N \N 22266 IPR003735

This entry describes proteins of unknown function.

\ \N \N \N 22267 IPR003736

This domain is found in the PAAI protein from Escherichia coli that may be involved in phenylacetic acid degradation and in a few others that may be transcription regulators [MEDLINE:90008771].

\ \N \N \N 22268 IPR003737

Although most of the proteins in this group are of unknown function one, from Schizosaccharomyces pombe, has been characterised as a probable N-acetylglucosaminyl-phosphatidylinositol de-N-acetylase.

\ \ \ \N \N \N 22269 IPR003738

This entry describes proteins of unknown function.

\ \N \N \N 22270 IPR003739

This is a family of proteins of unknown function. It shows similarity to molybdenum cofactor biosynthesis protein MoaA and related proteins.

\ \ \N \N \N 22271 IPR003740

This entry describes proteins of unknown function.

\ \N \N \N 22272 IPR003741

This entry describes proteins of unknown function.

\ \N \N \N 22273 IPR003742 Family of uncharacterized proteins of unknown function. The protein from Streptococcus pneumoniae may be a sensor regulator [MEDLINE:97206147].\ \N \N \N 22274 IPR003743

This entry describes proteins of unknown function.

\ \N \N \N 22275 IPR003744 This is a family of uncharacterized proteins. Conserved regions of hydrophobicity suggest that all members of the family may be integral membrane proteins. \ \ \N \N \N 22276 IPR003745

This entry describes proteins of unknown function.

\ \N \N \N 22277 IPR003746

This entry describes proteins of unknown function.

\ \N \N \N 22278 IPR003748

This entry describes proteins of unknown function.

\ \N \N \N 22279 IPR003749 ThiS (thiaminS) is a 66 aa protein involved in sulphur transfer. ThiS is coded in the thiCEFSGH operon in E. coli. This family of proteins have two conserved Glycines at the COOH terminus. Thiocarboxylate is formed at the last G in the activation process. Sulphur is transferred from ThiI to ThiS in a reaction catalysed by IscS [MEDLINE:20347927]. MoaD, a protein involved in sulphur transfer during molybdopterin synthesis, is about the same length and shows limited sequence similarity to ThiS. Both have the conserved GG at the COOH end. \ \N \N sulfur metabolism ; GO:0006790 22280 IPR003750

This entry describes proteins of unknown function.

\ \N \N \N 22281 IPR003751

The RNA-binding protein CsrA (carbon storage regulator) is a new kind of global regulator, which facilitates specific mRNA decay [MEDLINE:97362239]. CsrA is entirely contained within a globular complex of approximately 18 CsrA-H6 subunits and a single RNA, CsrB. CsrA binds to the CsrB RNA molecule to form the Csr regulatory system which has a strong negative regulatory effect on glycogen biosynthesis, glyconeogenesis and glycogen catabolism and a positive regulatory effect on glycolysis [MEDLINE:97362239].

\ RNA binding activity ; GO:0003723 \N mRNA metabolism ; GO:0016071 22258 IPR003726 S-methylmethionine: homocysteine methyltransferase EC: 2.1.1.10 from Escherichia coli accepts selenohomocysteine as a substrate. S-methylmethionine is an abundant plant product that can be utilized for methionine biosynthesis [MEDLINE:99102233]. Human methionine synthase (5-methyltetrahydrofolate:L-homocysteine S-transmethylase; EC: 2.1.1.13) shares 53 and 63% identity with the E. coli and the presumptive Caenorhabditis elegans proteins, respectively, and contains all residues implicated in B12 binding to the E. coli protein [MEDLINE:97166216]. Betaine--homocysteine S-methyltransferase (EC: 2.1.1.5) converts betaine and homocysteine to dimethylglycine and methionine, respectively. This reaction is also required for the irreversible oxidation of choline [MEDLINE:96394355].\ \ homocysteine S-methyltransferase activity ; GO:0008898 \N \N 22282 IPR003752 DsbB is a protein component of the pathway that leads to disulfide bond formation in periplasmic proteins of Escherichia coli and other bacteria.The DsbB protein oxidizes the\ periplasmic protein DsbA which in turn oxidizes cysteines in other periplasmic proteins in order to make disulfide\ bonds [MEDLINE:93157338]. DsbB acts as a redox potential transducer across the cytoplasmic membrane. It is a membrane protein which spans the membrane four times with both the N- and C-termini of the protein are in the cytoplasm. Each of the periplasmic domains of the protein has two essential cysteines. The two\ cysteines in the first periplasmic domain are in a Cys-X-Y-Cys configuration that is\ characteristic of the active site of other proteins involved in disulfide bond formation,\ including DsbA and protein disulfide isomerase [MEDLINE:95045404].\ \ protein disulfide oxidoreductase activity ; GO:0015035 membrane ; GO:0016020 electron transport ; GO:0006118 22245 IPR003713 The fliD operon of several bacteria consists of three flagellar genes, fliD, fliS, and fliT, and is transcribed in this order [MEDLINE:96146544]. In Bacillus subtilis the operon encoding the flagellar proteins FliD, FliS, and FliT is sigma D-dependent [MEDLINE:94252974].\ \N flagellum (sensu Bacteria) ; GO:0009288 flagella biogenesis ; GO:0009296 22246 IPR003714 PhoH is a cytoplasmic protein and predicted ATPase that is induced by phosphate starvation and belongings to the phosphate regulon (pho) in Escherichia coli\ \ \ [MEDLINE:93186698].\ \ ATP binding activity ; GO:0005524 \N cellular response to phosphate starvation ; GO:0016036 22247 IPR003715 The extracellular polysaccharide colanic acid (CA) is produced by species of the family Enterobacteriaceae. In Escherichia coli K12 the CA cluster comprises 19 genes. The wzx gene encodes a protein with multiple transmembrane segments that may function in export of the CA repeat unit from the cytoplasm into the periplasm in a process analogous to O-unit export. The CA gene clusters may be involved in the export of polysaccharide from the cell [MEDLINE:96326333].\ polysaccharide transporter activity ; GO:0015159 membrane ; GO:0016020 polysaccharide transport ; GO:0015774 22264 IPR003733

Thiamine monophosphate synthase (TMP) (EC: 2.5.1.3) catalyzes the substitution of the pyrophosphate of 2-methyl-4-amino-5- hydroxymethylpyrimidine pyrophosphate by 4-methyl-5- (-hydroxyethyl)thiazole phosphate to yield thiamine phosphate in the thiamine biosynthesis pathway [MEDLINE:97284509].

TENI, a protein from Bacillus subtilis that regulates the production of several extracellular enzymes by reducing alkaline protease production belongs to this group [MEDLINE:91100316].

\ \ thiamin-phosphate pyrophosphorylase activity ; GO:0004789 \N thiamin biosynthesis ; GO:0009228 22259 IPR003728

This entry describes proteins of unknown function.

\ \N \N \N 22260 IPR003729

This entry describes proteins of unknown function.

\ \N \N \N 22261 IPR003730

This entry describes proteins of unknown function.

\ \N \N \N 22262 IPR003731

This family includes MTH1175 for which there is a known structure. SCOP analysis of MTH1175 reveals that it is most similar to structures within the ribonuclease H superfamily. While MTH1175 lacks the key catalytic residues of RNase H, an RNA binding capability is suggested by a Gly and Arg-rich region in the flexible C-terminus. However the biochemical function of this protein remains to be determined [MEDLINE:20473232].

\ \N \N \N 22263 IPR003732

This homodimeric enzyme appears able to cleave any D-amino acid (and glycine, which does not have distinct D/L forms) from charged tRNA. The name reflects characterization with respect to D-Tyr on tRNA(Tyr) as established in the literature, but substrate specificity seems much broader.

\ hydrolase activity, acting on ester bonds ; GO:0016788 cytoplasm ; GO:0005737 D-amino acid catabolism ; GO:0019478 22250 IPR003718 Osmotically inducible protein C (OsmC)) is a stress -induced protein found in E. Coli. The transcription of the osmC gene of Escherichia coli is regulated as a function of the phase of growth and is induced during the decelerating phase, before entry into stationary phase. The transcription is initiated by two overlapping promoters, osmCp1 and osmCp2 [MEDLINE:96417852].

An organic hydroperoxide detoxification protein (OHR) from Xanthomonas campestris pv. phaseoli is highly induced by organic hydroperoxides, weakly induced by H2O2, and not induced at all by a superoxide generator. Ohr may be a new type of organic hydroperoxide detoxification protein [MEDLINE:98241524].

\ \ \N \N response to stress ; GO:0006950 22251 IPR003719

Five genes, phzF, phzA, phzB, phzC and phzD, encode enzymes for phenazine biosynthesis in the biological control bacterium Pseudomonas aureofaciens. Protein PhzF is similar to 3-deoxy-D-arabino-heptulosonate-7-phosphate synthases of solanaceous plants. PhzC is responsible for the conversion of phenazine-I-carboxylic acid to 2-hydroxy-phenazine-I-carboxylic acid [MEDLINE:96102876].

\ enzyme activity ; GO:0003824 \N biosynthesis ; GO:0009058 22252 IPR003720 Thiamine pyrophosphate (TPP) is synthesized de novo in many bacteria and is a required cofactor for many enzymes in the cell. ThiI is required for thiazole synthesis in the thiamine biosynthesis pathway [MEDLINE:97352701]. Almost all the proteins in this group have an N-terminal THUMP domain (see IPR004114).\ \ \N \N thiamin biosynthesis ; GO:0009228 22253 IPR003721 D-Pantothenate is synthesized via four enzymes from ketoisovalerate, which is an intermediate of branched-chain amino acid synthesis [MEDLINE:99240418].\ Pantoate-

-alanine ligase, also know as pantothenate synthase, (EC: 6.3.2.1) catalyzes the formation of\ pantothenate from pantoate and alanine in the pantothenate biosynthesis pathway [MEDLINE:96349105].\ \ pantoate-beta-alanine ligase activity ; GO:0004592 \N pantothenate biosynthesis ; GO:0015940 22254 IPR003722

A number of bacteria synthesize cobalamin (vitamin B12) by an anaerobic pathway, in which cobalt is added at an early stage and molecular oxygen is not required [MEDLINE:98416126]. Of the 30 cobalamin synthetic genes, 25 are clustered in one operon, cob, and are arranged in three groups, each group encoding enzymes for a biochemically distinct portion of the biosynthetic pathway [MEDLINE:93273696]. Precorrin-8X methylmutase (also known as precorrin isomerase), CbiC/CobH, EC: 5.4.1.2 catalyses a methyl rearrangement.

\ precorrin-8X methylmutase activity ; GO:0016993 \N vitamin B12 biosynthesis ; GO:0009236 22256 IPR003724

The BtuR, CobO, CobP proteins are Cob(I)alamin adenosyltransferases EC: 2.5.1.17 involved with cobalamin biosynthesis (vitamin B12). They synthesize cobalamin by an anaerobic pathway, in which cobalt is added at an early stage and molecular oxygen is not required [MEDLINE:98416126].

\ \ cob(I)alamin adenosyltransferase activity ; GO:0008817 \N vitamin B12 biosynthesis ; GO:0009236 22257 IPR003725 Molybdenum-dependent repression of transcription of the Escherichia coli modABCDoperon, which encodes the high-affinity molybdate transporter, is mediated by the ModE protein. When molybdate or tungstate bind to ModE there is little change in its

-helical content, but a major change in the environment of tryptophan and tyrosine residues occurs [MEDLINE:97354179]. \ This is the N-terminal domain of molybdenum-binding proteins ModE, ModA, MopA and MopB. These proteins\ are involved in molybdenum transport. ModE acts both as a repressor and activator of the mod and moa operons, respectively, depending on the properties of the binding site [MEDLINE:97197196].\ \ molybdate ion transporter activity ; GO:0015098 \N molybdate ion transport ; GO:0015689 22240 IPR003708

Secretion across the inner membrane in some Gram-negative bacteria occurs via the preprotein translocase pathway. Proteins are produced in the \ cytoplasm as precursors, and require a chaperone subunit to direct them to \ the translocase component. [MEDLINE:90361702]. From there, the mature proteins are either \ targeted to the outer membrane, or remain as periplasmic proteins. The \ translocase protein subunits are encoded on the bacterial chromosome.

\ The translocase itself comprises 7 proteins, including a chaperone protein\ (SecB), an ATPase (SecA), an integral membrane complex (SecCY, SecE and \ SecG), and two additional membrane proteins that promote the release of \ the mature peptide into the periplasm (SecD and SecF) [MEDLINE:90361702]. The chaperone \ protein SecB [MEDLINE:21235707] is a highly acidic homotetrameric protein that exists\ as a "dimer of dimers" in the bacterial cytoplasm. SecB maintains \ preproteins in an unfolded state after translation, and targets these to \ the peripheral membrane protein ATPase SecA for secretion [MEDLINE:99346703].

\ Recently, the tertiary structure of Haemophilus influenzae SecB (P44853) was resolved\ by means of X-ray crystallography to 2.5A [MEDLINE:20553716]. The chaperone comprises four\ chains, forming a tetramer, each chain of which has a simple + fold\ arrangement. While one binding site on the homotetramer recognises unfolded\ polypeptides by hydrophobic interactions, the second binds to SecA through\ the latter's C-terminal 22 residues.

\ \ chaperone activity ; GO:0003754 \N protein transport ; GO:0015031 22255 IPR003723

A number of bacteria synthesize cobalamin (vitamin B12) by an anaerobic pathway, in which cobalt is added at an early stage and molecular oxygen is not required [MEDLINE:98416126]. Of the 30 cobalamin synthetic genes, 25 are clustered in one operon, cob, and are arranged in three groups, each group encoding enzymes for a biochemically distinct portion of the biosynthetic pathway [MEDLINE:93273696].Precorrin-6x reductase EC: 1.3.1.54, CbiJ/CobK, catalyses the reduction of macrocycle of precorrin-6Y to precorrin-6X.

\ \ precorrin-6X reductase activity ; GO:0016994 \N vitamin B12 biosynthesis ; GO:0009236 22248 IPR003716 In some bacteria RNA polymerase contains a small subunit termed omega. The omega protein may not be necessary for the operation of the stringent RNA control response [MEDLINE:91267958].\ DNA-directed RNA polymerase activity ; GO:0003899 \N transcription ; GO:0006350 22249 IPR003717 The damage avoidance-tolerance pathway(s) requires functional recA, recF, recO, and recR genes, suggesting the mechanism to be daughter strand gap repair. The ruvABC genes or the recG gene is also required. The RecG pathway appears to be more active than the RuvABC pathway [MEDLINE:20528307]. RecO may contain a mononucleotide-binding fold [MEDLINE:89291705].\ \N \N DNA recombination ; GO:0006310 22244 IPR003712 Some bacteria can overcome the toxicity of environmental cyanate by hydrolysis of cyanate. This reaction is catalyzed by cyanate lyase (also known as cyanase) EC: 4.2.1.104\ \ \ [MEDLINE:89008347]. Cyanate lyase is found in bacteria and plants and catalyzes the reaction of cyanate with bicarbonate to produce ammonia and carbon dioxide. \

The cyanate lyase monomer is composed of two domains. The N-terminal domain shows structural similarity to the DNA-binding -helix bundle motif. The C-terminal domain has an 'open fold' with no structural homology to other proteins. The dimer structure reveals the C-terminal domains to be intertwined, and the decamer is formed by a pentamer of these dimers. The active site of the enzyme is located between dimers and is comprised of residues from four adjacent subunits of the homodecamer [MEDLINE:20264317].

\ \ cyanate lyase activity ; GO:0008824 \N cyanate metabolism ; GO:0009439 22243 IPR003711

The bacterium Myxococcus xanthus responds to blue light by producing carotenoids. It also responds to starvation conditions by developing fruiting bodies, where the cells differentiate into myxospores. Each response entails the transcriptional activation of a separate set of genes. A single gene, carD, is required for the activation of both light- and starvation-inducible genes [MEDLINE:96293442].

The predicted protein contains four repeats of a DNA-binding domain present in mammalian high mobility group I(Y) proteins and other nuclear proteins from animals and plants. Other peptide stretches on CarD also resemble functional domains typical of eukaryotic transcription factors, including a very acidic region and a leucine zipper. High mobility group yI(Y) proteins are known to bind the minor groove of A+T-rich DNA [MEDLINE:96293442].

\ \ transcription factor activity ; GO:0003700 \N regulation of transcription, DNA-dependent ; GO:0006355 22242 IPR003710

ApbA, the ketopantoate reductase enzyme EC: 1.1.1.169 of Salmonella typhimurium is required for the synthesis of thiamine via the alternative pyrimidine biosynthetic pathway [MEDLINE:98157949]. Precursors to the pyrimidine moiety of thiamine are synthesized de novo by the purine biosynthetic pathway or the alternative pyrimidine biosynthetic (APB) pathway. The ApbA protein catalyzes the NADPH-specific reduction of ketopantoic acid to pantoic acid. This activity had previously been associated with the pantothenate biosynthetic gene panE [MEDLINE:98389700]. ApbA and PanE are allelic [MEDLINE:98389700].

\ \ 2-dehydropantoate 2-reductase activity ; GO:0008677\ \N \N pyrimidine base metabolism ; GO:0006206 22241 IPR003709 Acquired VanA- and VanB-type glycopeptide resistance in enterococci is due to synthesis of modified peptidoglycan precursors terminating in D-lactate. As opposed to VanA-type strains which are resistant to both vancomycin and teicoplanin, VanB-type strains remain teicoplanin susceptible [MEDLINE:96200099]. The vanY gene was necessary for synthesis of the vancomycin-inducible D,D-carboxypeptidase EC: 3.4.16.4 activity previously proposed to be responsible for glycopeptide resistance. However, this activity was not required for peptidoglycan synthesis in the presence of glycopeptides [MEDLINE:93013009].\ \ serine-type D-Ala-D-Ala carboxypeptidase activity ; GO:0009002 \N \N 22233 IPR003700 The panB gene from Escherichia coli encodes the first enzyme of the pantothenate biosynthesis pathway, ketopantoate hydroxymethyltransferase (KPHMT) EC: 2.1.2.11. Fungal ketopantoate hydroxymethyltransferase is essential for the biosynthesis of coenzyme A, while the pathway intermediate 4'-phosphopantetheine is required for penicillin production [MEDLINE:99430867].\ \ 3-methyl-2-oxobutanoate hydroxymethyltransferase activity ; GO:0003864\ \N \N pantothenate biosynthesis ; GO:0015940 22234 IPR003701

Mre11 and Rad50 are two proteins required for DNA repair and meiosis-specific double-strand break formation in Saccharomyces cerevisiae. Mre11 by itself has 3' to 5' exonuclease activity that is increased when Mre11 is in a complex with Rad50 [MEDLINE:98315380].

\ \ exonuclease activity ; GO:0004527 \N DNA metabolism ; GO:0006259 22235 IPR003702 This family contains several enzymes which take part in pathways involving acetyl-CoA. Acetyl-CoA hydrolase EC: 3.1.2.1 from yeast catalyses the formation of acetate from acetyl-CoA, CoA transferase (CAT1)EC: 2.8.3.- produces succinyl-CoA, and acetate-CoA transferase EC: 2.8.3.8 utilizes\ acyl-CoA and acetate to form acetyl-CoA.\ \ enzyme activity ; GO:0003824 \N acetyl-CoA metabolism ; GO:0006084 22236 IPR003703 This is a family of acyl-CoA thioesterases of unknown function that hydrolyse a range of acyl-CoA thioesters [MEDLINE:91250410].\ acyl-CoA thioesterase activity ; GO:0016291 \N acyl-CoA metabolism ; GO:0006637 22237 IPR003704 Carbon monoxide dehydrogenase (Cdh) from Methanosarcina frisia Go1 is a Ni2+-, Fe2+-, and S2-containing alpha2beta2 heterotetramer [MEDLINE:96278885]. The CO dehydrogenase enzyme complex from Methanosarcina thermophila contains a corrinoid/iron-sulfur enzyme composed of two subunits (delta and gamma) [MEDLINE:96134964]. This family consists of carbon monoxide dehydrogenase I/II

subunit EC: 1.2.99.2 and CO dehydrogenase (acetyl-CoA synthase\ epsilon subunit).\ \ enzyme activity ; GO:0003824 \N metabolism ; GO:0008152 22238 IPR003705

The cobalt transport protein CbiN is part of the active cobalt transport system involved in uptake of cobalt in to the cell involved with cobalamin biosynthesis (vitamin B12). It has been suggested that CbiN may function asthe periplasmic binding protein component of the active cobalt transport system [MEDLINE:93273696].

\ \ cobalt ion transporter activity ; GO:0015087 membrane ; GO:0016020 vitamin B12 biosynthesis ; GO:0009236 22239 IPR003706 Escherichia coli induces the synthesis of at least 30 proteins at the onset of carbon starvation, two-thirds of which are positively regulated by the cyclic AMP (cAMP) and cAMP receptor protein (CRP) complex. This family consists of carbon starvation protein CstA a predicted membrane protein. It has been suggested that\ CstA is involved in peptide utilization [MEDLINE:91162636].\ \ \N membrane ; GO:0016020 cellular response to starvation ; GO:0009267 22218 IPR003684 This family consists of porins from the

subdivision of proteobacteria the members of this family are related to Gram-ve_porins [MEDLINE:92104965]. The porins form large aqueous channels in the cell membrane allowing the selective entry of\ hydrophilic compounds this so called 'molecular sieve' is found in the cell walls of gram negative bacteria.\ \ porin activity ; GO:0015288 membrane ; GO:0016020 transport ; GO:0006810 22219 IPR003685

PsaD is a small, extrinsic polypeptide located on the stromal side (cytoplasmic side in cyanobacteria) of the photosystem I reaction centre complex. It is required for native assembly of PSI reaction clusters and is implicated in the electrostatic binding of ferredoxin within the reaction center [MEDLINE:98355682]. PsaD forms a dimer in solution which is bound by PsaE however PsaD is monomeric in its native complexed PSI environment [MEDLINE:98355682].

\ \N photosystem I reaction center ; GO:0009538 photosynthesis ; GO:0015979 22220 IPR003686

A subcore complex of photosystem II (PSII), a pigment-protein complex in cyanobacteria, algae and higher plants, contains the chlorophyll-binding protein, CP47,\ and the reaction center components, D1, D2, and cytochrome b559. The photosystem II\ reaction center is responsible for catalysing the core photosynthesis reaction the\ light-induced splitting of water and the consequential release of dioxygen. Proteins\ PsbTc, PsbI and PsbW are identified as being intimately associated with the D1 and\ D2 proteins [MEDLINE:98298118].

PsbI is a small, integral membrane component of PSII\ the role of which is not clear. Synechocystis mutants lacking PsbI have 20-30% loss of\ PSII activity however the PSII complex is not destabilized [MEDLINE:96132547].

\ \ \N photosystem II reaction center ; GO:0009539 photosynthesis ; GO:0015979 22221 IPR003687

A subcore complex of photosystem II (PSII), a pigment-protein complex in cyanobacteria, algae and higher plants, contains thechlorophyll-binding protein, CP47, and the reaction center components, D1, D2, and cytochrome b559. The photosystem II reaction center is responsible for catalysing the core photosynthesis reaction the light-induced splitting of water and the consequential release of dioxygen. Proteins PsbTc, PsbI and PsbW are identified as being intimately associated with the D1 and D2 proteins [MEDLINE:98298118]. In the case of the dimer, importance is placed on the PsbL and PsbK proteins in sustaining plastoquinone binding and maintenance of the dimeric organization [MEDLINE:98298118], [MEDLINE:94250840].

\ \ \N photosystem I reaction center ; GO:0009538 photosynthesis ; GO:0015979 22222 IPR003688 The TRAG family are bacterial conjugation proteins. These proteins aid the transfer of DNA from the plasmid into the host bacterial chromosome although the exact mechanism of action is unknown.\ \ \N membrane ; GO:0016020 unidirectional conjugation ; GO:0009291 22223 IPR003689 These ZIP zinc transporter proteins define a family of metal ion transporters that are found in plants, protozoa, fungi, invertebrates, and vertebrates, making it now possible to address questions of metal ion accumulation and homeostasis in diverse organisms [MEDLINE:98284085].\ heavy metal ion transporter activity ; GO:0015076 membrane ; GO:0016020 heavy metal ion transport ; GO:0006823 22224 IPR003690

This family currently contains one sequence of known function human mitochondrial transcription termination factor (mTERF), a multizipper protein but binds to DNA as a monomer, with evidence pointing to intramolecular leucine zipper interactions [MEDLINE:97224133]. The precursors contain a mitochondrial targeting sequence, and the mature mTERF exhibits three leucine zippers, of which one is bipartite, and two widely spaced basic domains. Both basic domains and the three leucine zipper motifs are necessary for DNA binding. The leucine zippers are not implicated in a dimerisation role as in other leucine zippers [MEDLINE:97224133].

The rest of the family consists of hypothetical proteins none of which have any functional information.

\ \ \N \N \N 22225 IPR003691

Three genes, crcA, cspE and crcB when present in high copy confer camphor resistance on a cell and suppress mutations in the chromosomal partition gene mukB in Escherichia coli. The cspE gene has been previously identified as a cold shock-like protein with homologues in all organisms tested [MEDLINE:97001112].

Camphor and mukB mutations may interfere with chromosome condensation and high copy crcA, cspE and crcB have been implicated as promoting or protecting chromosome folding [MEDLINE:97001112].

\ \ \N membrane ; GO:0016020 \N 22226 IPR003692 An appreciable fraction of the sulphur present in the mammal occurs in the form of glutathione. The synthesis of glutathione and its utilization take place by the reactions of the gamma-glutamyl cycle, which include those catalysed by gamma-glutamylcysteine and glutathione synthetases, gamma-glutamyl transpeptidase, cysteinylglycinase, gamma-glutamyl cyclotransferease, and 5-oxoprolinase [MEDLINE:80245596].

This family includes N-methylhydantoinase B which converts hydantoin to N-carbamyl-amino acids, and\ 5-oxoprolinase EC: 3.5.2.9 which catalyses the formation of L-glutamate from 5-oxo-L-proline.\ These enzymes are part of the oxoprolinase family and are related to hydantoinase_A.

\ \ enzyme activity ; GO:0003824 \N \N 22227 IPR003694 NAD+ synthase (EC: 6.3.5.1) catalyzes the last step in the biosynthesis of nicotinamide adenine dinucleotide and is induced by stress factors such as heat shock and glucose limitation. The three-dimensional structure of NH3-dependent NAD+ synthetase from Bacillus subtilis, in its free form and in complex with ATP shows that the enzyme consists of a tight homodimer with

subunit topology [MEDLINE:97050817].\ ATP binding activity ; GO:0005524 \N nicotinamide adenine dinucleotide biosynthesis ; GO:0009435 22228 IPR003695 Exopolyphosphate phosphatase (Ppx) EC: 3.6.1.11 and guanosine pentaphosphate phosphatase (GppA) EC: 3.6.1.40 belong to the sugar kinase/actin/hsp70 superfamily [MEDLINE:94025037].\ \N \N \N 22216 IPR003682 This is a family of bacterial glucose inhibited division proteins that are probably involved in the regulation of cell division [MEDLINE:99014240].\ \N \N cell cycle ; GO:0007049 22217 IPR003683

This family consists of cytochrome b6/f complex subunit 5 (PetG). The cytochrome bf complex found in green plants, eukaryotic algae and cyanobacteria, connects photosystem I to photosystem II in the electron transport chain, functioning as a plastoquinol:plastocyanin/cytochrome c6 oxidoreductase [MEDLINE:96094322]. The purified complex from the unicellular alga Chlamydomonas reinhardtii contains seven subunits; namely four high molecular weight subunits (cytochrome f, Rieske iron-sulfur protein, cytochrome b6, and subunit IV) and three approximately miniproteins (PetG, PetL, and PetX) [MEDLINE:96094329]. Stoichiometry measurements are consistent with every subunit being present as two copies per b6/f dimer. The absence of PetG affects either the assembly or stability of the cytochrome bf complex in Chlamydomonas reinhardtii\ \ \ [MEDLINE:96094322].

\ \ \N cytochrome b6f complex ; GO:0009512 electron transport ; GO:0006118 22232 IPR003699 Queuosine is a hypermodified nucleoside that usually occurs in the first position of the anticodon of tRNAs specifying the amino acids asparagine, aspartate, histidine, and tyrosine. The hypermodified nucleoside is found in eubacteria and eucaryotes. [MEDLINE:93349860]. Queuosine is synthesized de novo exclusively in eubacteria; for eucaryotes the compound is a nutrient factor. Queuosine biosynthesis protein, or S-adenosylmethionine:tRNA -ribosyltransferase-isomerase, is required for the synthesis of the queuosine precursor (oQ).\ \ enzyme activity ; GO:0003824 \N queuosine biosynthesis ; GO:0008616 22230 IPR003697 Maf is a putative inhibitor of septum formation in eukaryotes, bacteria, and archaea. The Maf protein shares substantial\ amino acid sequence identity with the E. coli OrfE protein [MEDLINE:93259962].\ \ \N \N \N 22231 IPR003698 Lipoic acid is a covalently bound disulfide-containing cofactor required for function of the pyruvate dehydrogenase,

-ketoglutarate dehydrogenase, and glycine cleavage enzyme complexes of Escherichia coli. Two genes, lipA and lipB, are involved in lipoic acid biosynthesis or metabolism. LipA is required for the insertion of the first sulfur into the octanoic acid backbone. LipB functions downstream of LipA, but its role\ in lipoic acid metabolism remains unclear [MEDLINE:93186699].\ Lipoate synthase (or lipoic acid synthetase) catalyses the formation of

-(+)-lipoic acid, required for lipoate\ biosynthesis.\ \ lipoate synthase activity ; GO:0016992 \N lipoate biosynthesis ; GO:0009107 22229 IPR003696 The putative O-carbamoyltransferases (O-Cases) encoded by the nodU genes of Rhizobium fredii and Bradyrhizobium japonicum are involved in the synthesis of nodulation factors [MEDLINE:96032729]. The cmcH genes of Nocardia lactamdurans and Streptomyces clavuligerus encode a functional 3'-hydroxymethylcephem O-carbamoyltransferase EC: 2.1.3.7 for cephamycin biosynthesis that shows significant similarity to the O-carbamoyltransferases [MEDLINE:96009872].\ enzyme activity ; GO:0003824 \N biosynthesis ; GO:0009058 22212 IPR003678 Helicobacter pylori is a causative agent of gastritis and peptic ulceration in humans. As the first step towards development of a vaccine against H. pylori infection, many attempts have been made to identify protective antigens. A potential target of vaccine development would be a H. pylori specific proteins that are surface-exposed and highly antigenic.

This family consists of putative outer membrane proteins from Helicobacter pylori.

\ \ \N external outer membrane (sensu Gram-negative Bacteria) ; GO:0009279 \N 22213 IPR003679 This family consists of bacterial aminoglycoside 3-N-acetyltransferases (EC: 2.3.1.81) that catalyse the reaction [MEDLINE:92104494]:

Acetyl-Co + a 2-deoxystreptamine antibiotic = CoA + N3'-acetyl-2-deoxystreptamine antibiotic

The enzyme\ can use a range of antibiotics with 2-deoxystreptamine rings as acceptor for its acetyltransferase activity, this\ inactivates and confers resistance to gentamicin, kanamycin, tobramycin, neomycin and apramycin amongst others. For the kanamycin group antibiotics acetylation occurred at the 3"-amino group in arbekacin and amikacin, and at the 3-amino group in dibekacin as in the case of kanamycin reflecting the effect of the (S)-4-amino-2-hydroxybutyryl side chain which is present in arbekacin and amikacin, but absent in dibekacin and kanamycin [MEDLINE:98437855].\ \ gentamicin 3'-N-acetyltransferase activity ; GO:0016991 \N \N 22214 IPR003680

This family consists of bacterial and eukaryotic NAD(P)H dehydrogenase (quinone) EC: 1.6.99.2 that catalyses the NAD(P)H-dependent two-electron reductions of quinones and protect cells against damage by free radicals and reactive oxygen species [MEDLINE:96004635]. This enzyme uses a FAD co-factor. These two-electron reductions participate in the reductive bioactivation of cancer chemotherapeutic agents such as mitomycin C in tumor cells. Thus the same enzymatic reaction that protects normal cells activates cytotoxic drugs used in cancer chemotherapy. [MEDLINE:96004635].

The crystal structure of rat liver quinone reductase reveals that the folding of a portion of each monomer is similar to that of flavodoxin, a bacterial FMN-containing protein [MEDLINE:96004635].

\ \ NAD(P)H dehydrogenase (quinone) activity ; GO:0003955 \N electron transport ; GO:0006118 22215 IPR003681 The glycophorin-binding protein contains a tandem repeat. The repeated sequence determines the binding domain for an erythrocyte receptor binding protein of P. falciparum , the malarial parasite [MEDLINE:86133561]. Erythrocyte invasion by the malarial merozoite is a receptor-mediated process, an obligatory step in the development of the parasite. The Plasmodium falciparum protein binds to the erythrocyte receptor glycophorin.\ \N \N \N 22202 IPR003668

Rotavirus non-structural protein 35 (Ns35) is a basic protein which possesses RNA-binding activity and is essential for genome replication [MEDLINE:93134787]. It may also be important for viral RNA packaging.

\ \ RNA binding activity ; GO:0003723 \N viral genome replication ; GO:0019079 22203 IPR003669 Thymidylate synthase complementing protein (Thy1) complements the thymidine growth requirement of the organisms in which it is found, but shows no homology to thymidylate synthase [MEDLINE:98332770].\ \ \N \N \N 22204 IPR003670 The UK protein is an African swine fever virus (ASFV) protein that is highly conserved amongst strains. Data indicates that the highly conserved UK gene of ASFV, while being nonessential for growth in\ macrophages in vitro, is an important viral virulence determinant for domestic pigs [MEDLINE:98105741].\ \ \N \N \N 22205 IPR003671 Spindlin (Spin) is a novel maternal transcript present in the unfertilized egg and early embryo. Spin exhibits high homology to a multicopy gene, Y-linked spermiogenesis-specific transcript (Ssty), and together they form a new gene family expressed during gametogenesis [MEDLINE:97178984]. Spindlin may play a role in cell-cycle regulation during the transition from gamete to embryo.\ \ \N \N gametogenesis ; GO:0007276 22206 IPR003672 This family contains a domain common to the cobN protein and to magnesium protoporphyrin chelatase. CobN may play a role in cobalt insertion reactions and is implicated in the conversion of precorrin-2 to cobyrinic acid in cobalamin biosynthesis [MEDLINE:92011366]. Magnesium protoporphyrin chelatase is involved in chlorophyll biosynthesis as the third subunit of light-independent protochlorophyllide reductase in bacteria and plants\ \ \ \ [MEDLINE:93224465].\ \ \N \N biosynthesis ; GO:0009058 22207 IPR003673

This is a family of enzymes with diverse function, including fatty-acid CoA racemase enzymes such as arylpropionyl-CoA epimerase a key enzyme in the inversion metabolism of ibuprofen, carnitine dehydratase (CAIB) (EC: 4.2.1.89) and bile acid-inducible operon protein F (BAIF) [MEDLINE:89008068].

The 2-arylpropionic acid derivatives, including ibuprofen, are the most widely used anti-inflammatory analgesic cyclooxygenase inhibitors. The (-)-R-enantiomer, which is inactive in terms of cyclooxygenase inhibition, is epimerized in vivo via 2-arylpropionyl-coenzyme A (CoA) epimerase to the cyclooxygenase-inhibiting (+)-S-enantiomer. In addition to its obvious importance in drug metabolism, the homology of the epimerase with carnitine dehydratases from several species suggests that this protein, which up to now has only been characterized as having a role in drug transformation, has a function in lipid metabolism [MEDLINE:97260501].\ Carnitine dehydratase catalyzes the dehydration of L-(-)-carnitine to crotonobetaine [MEDLINE:94245624].

\ \ \N \N metabolism ; GO:0008152 22211 IPR003677 This domain has no known function. An immunodominant hypodermal antigen present in adult and larval Onchocerca volvulus parasites possesses this domain [MEDLINE:94074642].\ \N \N \N 22210 IPR003676 This family consists of the protein products of a gene cluster that encodes a group of auxin-regulated RNAs (small auxin up RNAs, SAURs) [MEDLINE:92404712]. Proteins from this ARG7 auxin responsive genes family have no identified functional role [MEDLINE:99452391].\ \N \N \N 22209 IPR003675

This family consists of various hypothetical protein sequences for which the function is unknown.One of the proteins is an abortive infection protein that confers resistance to the bacteriophage Phi 712\ \ \ [MEDLINE:96387723]. AbiG is an abortive infection (Abi) mechanism encoded by the conjugative plasmid pCI750 originally isolated from Lactococcus lactis subsp. cremoris UC653. The resistance mechanism acts at neither the phage adsorption or phage DNA restriction level [MEDLINE:96387723].

\ \

Also in this family is a series of bacteriocin-like peptides PlnP, PlnI, PlnT, PlnP and PlnU from Lactobacillus plantarum C11. Lactobacillus plantarum C11 secretes a small cationic peptide, plantaricin A, that serves as an induction signal for bacteriocin production as well as transcription of plnABCD. The plnABCD operon encodes the plantaricin A precursor (PlnA) itself and determinants (PlnBCD) for a signal transducing pathway [MEDLINE:96345611].

\ \ \N \N \N 22208 IPR003674

N-linked glycosylation is a ubiquitous protein modification, and is essential for viability in eukaryotic cells. A lipid-linked core-oligosaccharide is assembled at the membrane of the endoplasmic reticulum and transferred to selected asparagine residues of nascent polypeptide chains by the oligosaccharyl transferase (OTase) complex [MEDLINE:96067124].

This family consists of the oligsacharyl transferase STT3 subunit and related proteins. The STT3 subunit is part of the oligosccharyl transferase (OTase) complex of proteins and is required for its activity [MEDLINE:96067124].

\ \ oligosaccharyl transferase activity ; GO:0004576 membrane ; GO:0016020 protein amino acid glycosylation ; GO:0006486 22197 IPR003663

\ \

This family includes just the sugar transporters.

\ \ sugar porter activity ; GO:0005351 membrane ; GO:0016020 carbohydrate transport ; GO:0008643 22198 IPR003664 The plsX gene is part of the bacterial fab gene cluster which encodes several key fatty acid biosynthetic enzymes [MEDLINE:98317265]. The plsX gene encodes a poorly understood enzyme of phospholipid\ metabolism [MEDLINE:99395062].\ \ enzyme activity ; GO:0003824 \N fatty acid biosynthesis ; GO:0006633 22199 IPR003665 Restriction-modification (R-M) systems protect a bacterial cell against invasion of foreign DNA by endonucleolytic cleavage of DNA that lacks a site specific modification. The R-M system is a complex containing three polypeptide subunits:\ M (this family), S (Methylase_S), and R [MEDLINE:98101482].\ \ site-specific DNA-methyltransferase (adenine-specific) activity ; GO:0009007 \N DNA modification ; GO:0006304 22200 IPR003666 Photosystem I (PSI) is an integral membrane protein complex that uses light energy to mediate electron transfer from plastocyanin to ferredoxin. Subunit III (or PsaF) is one of at least 14 different subunits that compose the photosystem I reaction center (PSI-RC) [MEDLINE:93184215].\ \ \N photosystem I reaction center ; GO:0009538 photosynthesis ; GO:0015979 22201 IPR003667 The rnf genes of Rhodobacter capsulatus, essential for nitrogen fixation, are thought to encode a system for electron transport to nitrogenase. The rnfABCDGEH operon comprises seven genes that show similarities in gene arrangement and deduced protein sequences to homologous regions in the genomes of Haemophilus influenzae and E. coli. Four of the rnf gene products were found to be similar in sequence to components of an Na+-dependent NADH:ubiquinone oxidoreductase from Vibrio alginolyticus\ \ \ \ [MEDLINE:98151232].\ \ \N membrane ; GO:0016020 electron transport ; GO:0006118 22192 IPR003657 The WRKY domain is a 60 amino acid region that is defined by the conservedamino acid sequence WRKYGQK at its N-terminal end, together with a novel\ zinc-finger- like motif. The WRKY domain is found in one or two copies in a\ superfamily of plant transcription factors involved in the regulation of\ various physiological programs that are unique to plants, including pathogen\ defense, senescence, trichome development and the biosynthesis of secondary\ metabolites. The WRKY domain binds specifically to the DNA sequence motif\ (T)(T)TGAC(C/T), which is known as the W box. The invariant TGAC core of the W\ box is essential for function and WRKY binding [MEDLINE:20249261]. Some proteins known to contain a WRKY domain include Arabidopsis thaliana ZAP1 (Zinc-dependent Activator Protein-1) and AtWRKY44/TTG2, a protein involved in trichome\ development and anthocyanin pigmentation; and wild oat ABF1-2, two proteins involved in the gibberelic acid-induced expression of the

-Amy2 gene.\ \ DNA binding activity ; GO:0003677 \N \N 22193 IPR003658 An anti-sigma factor antagonist is an anti-anti-sigma factor, which relieves inhibition of sigma factor activity by the anti-sigma factor. Examples include the Bacillus subtilis SpoIIAA protein, which, in its phosphorylated form, acts as an anti-anti-sigma factor to relieve SpoIIAB inhibition of sigma F; and the anti-sigma B factor antagonist, RsbV, which counteracts the RsbW-mediated inhibition of sigma B by binding to RsbW.\ \N \N \N 22194 IPR003659 This is a domain that has been found in plexins, semaphorins and integrins. Plexin is involved in the development of neural and epithelial tissues; semaphorins induce the collapse and paralysis of neuronal growth cones; and integrins may mediate adhesive or migratory functions of epithelial cells.\ \N \N development ; GO:0007275 22195 IPR003660 This domain is known as the HAMP domain for histidine kinases, adenylyl cyclases, methyl binding proteins and phosphatases.\ It is found in bacterial sensor and chemotaxis proteins and in eukaryotic histidine kinases. The bacterial proteins are usually integral membrane proteins and part of a two-component signal transduction pathway.\ \ signal transducer activity ; GO:0004871 membrane ; GO:0016020 signal transduction ; GO:0007165 22196 IPR003661 The histidine kinase A (phosphoacceptor) N-terminal domain is a dimerisation and phosphoacceptor domain of histidine kinases. It has been found in bacterial sensor protein/histidine kinases.\ two-component sensor molecule activity ; GO:0000155 membrane ; GO:0016020 signal transduction ; GO:0007165 22189 IPR003654 This 14 amino acid motif has been identified within the C-terminal region ofseveral Paired-like homeodomain (HD) containing proteins [MEDLINE:97099449],\ [MEDLINE:98133920]. It was named OAR domain after the initials of otp, aristaless, and rax [MEDLINE:97250494]. Although it has been proposed that this domain could be important for transactivation and be involved in protein-protein interactions or DNA binding [MEDLINE:97250494], [MEDLINE:97285122], is function is not yet known. Some proteins known to contain a OAR domain include human RIEG, defects in which are the cause of Rieger syndrome [MEDLINE:97099449]; human OG12X and murine Og12x, whose function is not yet known [MEDLINE:98133920]; vertebrate Rax, which plays a role in the proliferation and/or differentiation of retinal cells [MEDLINE:97250494]; Drosophila DRX, which appears to be important in brain development [MEDLINE:98151514]; and human SHOX, encoded by the short stature homeobox-containing gene. Defects or lack of this protein are the cause of short stature associated with the Turner syndrome [MEDLINE:97285122].\ \ DNA binding activity ; GO:0003677 nucleus ; GO:0005634 development ; GO:0007275 22187 IPR003652

Spinocerebellar ataxia type 1 (SCA1) is a neurodegenerative disorder caused by expansion of a CAG trinucleotide repeat. The encoded protein, ataxin-1, is widely expressed throughout the body. This domain is of unknown function but is sometimes found along with the HMG_12_box domain IPR000910.

\ \N \N \N 22188 IPR003653

Deubiquitinating enzymes (DUB) form a large family of cysteine protease that can deconjugate ubiquitin or ubiquitin-like proteins from ubiquitin-conjugated proteins. They can be classified in 3 families according to sequence homology [MEDLINE:20072557], [MEDLINE:97137083]: Ubiquitin carboxyl-terminal hydrolase (UCH) (see PDOC00127), and ubiquitin-like protease (ULP) specific for deconjugating ubiquitin-like proteins. In contrast to the UBP pathway, which is very redundant (16 UBP enzymes in yeast), there are few ubiquitin-like proteases (only one in yeast, Ulp1).

Ulp1 catalyses two critical functions in the SUMO/Smt3 pathway via its\ cysteine protease activity. Ulp1 processes the Smt3 C-terminal sequence\ (-GGATY) to its mature form (-GG), and it deconjugates Smt3 from the lysine\ epsilon-amino group of the target protein [MEDLINE:99191836].

Crystal structure of yeast Ulp1 bound to Smt3 [MEDLINE:20337970] revealed that the catalytic and interaction interface is situated in a shallow and narrow cleft where conserved residues recognize the Gly-Gly motif at the C-terminal extremity of Smt3 protein. Ulp1 adopts a novel architecture despite some structural similarity with other cysteine protease. The secondary structure is composed of seven helices and seven strands. The catalytic domain includes the central helix, -strands 4 to 6, and the catalytic triad (Cys-His-Asp). This profile is directed against the C-terminal part of ULP proteins that displays full proteolytic activity [MEDLINE:20337970].

\ \ peptidase activity ; GO:0008233 \N \N 22191 IPR003656 The BED finger which was named after the Drosophila proteins BEAF and DREF, isfound in one or more copies in cellular regulatory factors and transposases\ from plants, animals and fungi. The BED finger is an about 50 to 60 amino acid\ residues domain that contains a characteristic motif with two highly conserved\ aromatic positions, as well as a shared pattern of cysteines and histidines\ that is predicted to form a zinc finger. As diverse BED fingers are able to\ bind DNA, it has been suggested that DNA-binding is the general function of\ this domain [MEDLINE:20446300]. Some proteins known to contain a BED domain include animal, plant and fungi AC1 and Hobo-like transposases; C. elegans Dpy-20 protein, a predicted cuticular gene transcriptional regulator; Drosophila BEAF (boundary element-associated factor), thought to be involved in chromatin insulation; Drosophila DREF, a transcriptional regulator for S-phase genes; and tobacco 3AF1 and tomato E4/E8-BP1, light- and ethylene-regulated DNA binding proteins that contain two BED fingers.\ \ DNA binding activity ; GO:0003677 \N \N 22190 IPR003655

This domain of about 63 amino acid residues is related to the KRAB domain and has been identified in the N-terminal ends of proteinsbelonging to the SSX family [MEDLINE:95292974], [MEDLINE:96302330], [MEDLINE:98021352]. Proteins of the SSX family lack the C2H2-type zinc finger which is invariably found in proteins containing the KRAB domain. The KRAB-related domains show greatest homology to the KRAB A subdomain and contain a high proportion of the amino acids which are usually conserved between the KRAB A subdomains of zinc finger proteins [MEDLINE:95292974].

Although the KRAB-related domains of SSX1 and SSX2 contribute to the repressive activity of these proteins, transcriptional repression is mainly mediated by a region located in their C-terminus. Hence, unlike the KRAB domain, the KRAB-related domain is only a weak transcriptional repression domain. In addition the KRAB-related domain is unable to interact with the KAP-1/TIF1- protein which appears to function as a universal corepressor for KRAB domain proteins [MEDLINE:99002495].

\ \ \N \N regulation of transcription, DNA-dependent ; GO:0006355 22181 IPR003646 A homologue of the SH3 domain has been found in a number of different bacterial proteins including glycyl-glycine endopeptidase, bacteriocin and some hypothetical proteins.\ \N \N \N 22182 IPR003647 This is a repeat of unknown function, but possibly involved in DNA-binding via a helix-turn-helix motif.\ \N \N \N 22183 IPR003648 The splicing factor motif is present in splicing factors including Prp18 and Pr04. In yeast, Pr04 is a U4/U6 small nuclear ribonucleoprotein involved in RNA splicing. It is required for the association of U4/U6 snRNP with U5 snRNP in an early step of spliceosome assembly.\ \N \N RNA splicing ; GO:0008380 22184 IPR003649 The B-box C-terminal domain is a coiled coil region C-terminal to (some) B-Box domains. It is found in transcription intermediary factor 1-

, which associates with DNA-bound estrogen receptors; ring finger protein, a putative transcriptional regulator; and the GTP-binding protein Ard-1.\ \N intracellular ; GO:0005622 \N 22185 IPR003650 This domain confers specificity among members of the Hairy/E(SPL) family. HES-2 (hairy and enhancer of split 2) is a transcription factor, and the hairy protein is a pair-rule protein that regulates embryonic segmentation and adult bristle patterning. These proteins are transcriptional repressors of genes that require the BHLH protein for their transcription.\ DNA binding activity ; GO:0003677 \N regulation of transcription, DNA-dependent ; GO:0006355 22186 IPR003651

Endonuclease III (EC: 4.2.99.18) is a DNA repair enzyme which removes a number of damaged pyrimidines from DNA via its glycosylase activity and also cleaves the phosphodiester backbone at apurinic / apyrimidinic sites via a -elimination mechanism [MEDLINE:95292058], [MEDLINE:97184707]. The structurally related DNA glycosylase MutYrecognises and excises the mutational intermediate 8-oxoguanine-adenine mispair [MEDLINE:93015679]. The 3-D structures of Escherichia coli endonuclease III [MEDLINE:93030750] and catalytic domain of MutY [MEDLINE:99061333] have been determined. The\ structures contain two all- domains: a sequence-continuous, six-helix domain (residues 22-132) and a Greek-key,\ four-helix domain formed by one N-terminal and three C-terminal helices (residues 1-21 and 133-211) together with the\ [Fe4S4] cluster. The cluster is bound entirely within the C-terminal loop by four cysteine residues with a ligation pattern\ Cys-(Xaa)6-Cys-(Xaa)2-Cys-(Xaa)5-Cys which is distinct from all other known Fe4S4 proteins. This structural motif is\ referred to as a [Fe4S4] cluster loop (FCL) [MEDLINE:95393988]. Two DNA-binding motifs have been proposed, one at either end of the\ interdomain groove: the helix-hairpin-helix (HhH) and FCL motifs. The primary role of the iron-sulphur cluster appears to\ involve positioning conserved basic residues for interaction with the DNA phosphate backbone by forming the loop of\ the FCL motif [MEDLINE:95393988], [MEDLINE:20361758].

\ \ \

The iron-sulfur cluster loop (FCL) is also found in DNA-(apurinic or apyrimidinic site) lyase, a subfamily of endonuclease III. The enzyme has both apurinic and apyrimidinic endonuclease activity and a DNA N-glycosylase activity. It cuts damaged DNA at cytosines, thymines and guanines, and acts on the damaged strand 5' of the damaged site. The enzyme binds a 4Fe-4S cluster which is not important for the catalytic activity, but is probably involved in the alignment of the enzyme along the DNA strand.

\ \ iron ion binding activity ; GO:0005506 \N \N 22172 IPR003637

Cytokines can be grouped into a family on the basis ofsequence, functional and structural similarities [MEDLINE:93200072], [MEDLINE:92310561], PUB00001027. Tumor necrosis factor (TNF) (also known as TNF- or cachectin) is a monocyte-derived cytotoxin\ that has been implicated in tumour regression, septic shock and cachexia\ PUB00001027, [MEDLINE:88165056]. The protein is synthesised as a prohormone with an unusually long and atypical signal sequence, which is absent from the mature secreted cytokine [MEDLINE:91097531]. A short hydrophobic stretch of amino acids serves to anchor the prohormone in lipid bilayers [MEDLINE:89380231]. Both the mature protein and a \ partially-processed form of the hormone are secreted after cleavage of the\ propeptide [MEDLINE:89380231].

There are a number of different families of TNF, but all these cytokines seem to form homotrimeric (or heterotrimeric in the case of LT-/) complexes that are recognized by their specific receptors.

Tumor necrosis factor ligand superfamily member 7 (CD27 ligand) (CD27- L) (CD70 antigen). These are tumor necrosis factors.Family members are similar to tumor necrosis factor-related proteins. Family members are ligands for the receptor CD27 (TNFRSF7); they contain a type II transmembrane domain and they induce activated T lymphocytes to proliferate and become cytolytic.

\ \ \ tumor necrosis factor receptor ligand activity ; GO:0005164 membrane ; GO:0016020 immune response ; GO:0006955 22173 IPR003638

There are a number of different families of TNF, but all these cytokines seem to form homotrimeric (or heterotrimeric in the case of LT-/) complexes that are recognized by their specific receptors.

This family is similar to tumor necrosis factor-related proteins; enhances CD3-activated T lymphocyte proliferation; and contains a type II transmembrane domain.

\ \ tumor necrosis factor receptor ligand activity ; GO:0005164 membrane ; GO:0016020 immune response ; GO:0006955 22178 IPR003643 These are putative serine/threonine specific protein phosphatases, a group of enzymes removing the serine- or threonine-bound phosphate group from a wide range of phosphoproteins, including a number of enzymes which have been phosphorylated under the action of a kinase. Although some of the proteins are hypothetical, they all have a protein phosphatase 2C domain.\ \N \N \N 22179 IPR003644 This domain has been found in Na-Ca exchangers and integrin subunit beta4, as well as some cyanobacterial proteins.\ \N \N \N 22180 IPR003645 This EGF-like domain resembles the follistatin-N-terminal domain, and is distinct from the kazal-like sequence. Follistatin binds to activin and is a specific inhibotor of the biosynthesis and secretion of pituitary follicle stimulating hormone. This domain is also found in prespore vesicle protein and agrin.\ \N \N \N 22177 IPR003642 Sarafotoxin and bibrotoxin are related to endothelins (ET's), which are the most potent vasoconstrictors known [MEDLINE:90101102], [MEDLINE:90367885], [MEDLINE:92008946]. Sarafotoxin and bibrotoxin, also vasoconstrictors, cause cardiac arrest probably as a result of coronary vasoplasm.\ toxin activity ; GO:0015070 \N pathogenesis ; GO:0009405 22176 IPR003641

Endothelins (ET's) are the most potent vasoconstrictors known [MEDLINE:90101102], [MEDLINE:90367885], [MEDLINE:92008946]. They stimulate cardiac contraction, regulate release of vasoactive substances, and stimulate mitogenesis in blood vessels in primary culture. They also stimulate contraction in almost all other smooth muscles (e.g., uterus, bronchus, vas deferensa and stomach) and stimulate secretion in several tissues (e.g., kidney, liver and adrenals). Endothelin receptors have also been found in the brain, e.g. cerebral cortex, cerebellum and glial cells. Endothelins have been implicated in a variety of pathophysiological conditions associated with stress, including hypertension, myocardial infarction, subarachnoid haemorrhage and renal failure.

Endothelins are synthesised by proteolysis of large preproendothelins, which are cleaved to 'big endothelins' before being processed to the mature peptide.

\ \ toxin activity ; GO:0015070 \N pathogenesis ; GO:0009405 22174 IPR003639 Mov34 proteins act as the regulatory subunit of the 26 proteasome, which is involved in the ATP-dependent degradation of ubiquitinated proteins. The function of this domain is unclear, but it is found in the N-terminus of the proteasome regulatory subunits, eukaryotic initiation factor 3 (eIF3) subunits and regulators of transcription factors.\ \ \N \N \N 22175 IPR003640 Mov34 proteins act as the regulatory subunit of the 26 proteasome, which is involved in the ATP-dependent degradation of ubiquitinated proteins. The function of this domain is unclear, but it is found in the N-terminus of the proteasome regulatory subunits, eukaryotic initiation factor 3 (eIF3) subunits and regulators of transcription factors. This subtype includes the 26S proteasome regulatory subunit and translation initiation factor 3.\ \ translation initiation factor activity ; GO:0003743 \N translational initiation ; GO:0006413 22167 IPR003632 A number of GPI-linked cell-surface glycoproteins are related. These include prostate stem cell antigen, lymphocyte antigen LY-6H and CD59 glycoprotein, also known as MAC-inhibitory protein.\ \N \N \N 22168 IPR003633 Variant-surface-glycoprotein phospholipase C (EC: 3.1.4.47), by hydrolysis of the attached glycolipid, releases soluble variant surface glycoprotein containing phosphoinositol from the cell wall after lysis. It catalyses the conversion of variant-surface-glycoprotein 1,2 didecanoyl-SN-phosphatidylinositol and water to 1,2-didecanoylglycerol and the soluble variant-surface-glycoprotein. It also cleaves similar membrane anchors on some mammalian proteins.\ phospholipase C activity ; GO:0004629 \N \N 22169 IPR003634 Interleukin-13 (IL-13) is a pleiotropic cytokine which may be important in the regulation of the inflammatory and immune responses [MEDLINE:93211479]. It inhibits inflammatory cytokine production and synergises with IL-2 in regulating interferon-gamma synthesis. The sequences of IL-4 and IL-13 are distantly related.\ interleukin-13 receptor ligand activity ; GO:0005144 extracellular ; GO:0005576 immune response ; GO:0006955 22170 IPR003635 Tachykinins [MEDLINE:88208276], [MEDLINE:90201634], [MEDLINE:92375028] are a group of biologically active peptides which exciteneurons, evoke behavioral responses, are potent vasodilatators and contract\ (directly or indirectly) many smooth muscles. This family includes neurokinins, as well as many other peptides. Like other tachykinins, neurokinins are synthesized as larger protein precursors that are enzymatically converted to their mature forms.\ \ \N \N tachykinin signaling pathway ; GO:0007217 22171 IPR003636

There are a number of different families of TNF, but all these cytokines seem to form homotrimeric (or heterotrimeric in the case of LT-/) complexes that are recognized by their specific receptors.

The structure of human TNF has been determined to 2.9 A using X-ray crystallography. The protein is trimeric, each subunit consisting of an anti-parallel -sandwich. The subunits trimerise via a novel edge-to-face packing of -sheets [MEDLINE:89159409]. It is believed that each TNF molecule has three receptor-interaction sites (between the three subunits), thus allowing\ signal transmission by receptor clustering [MEDLINE:91184128]. Lymphotoxin- (LT- or TNF-) and lymphotoxin- (LT-) are related cytokines produced by lymphocytes. The proteins are cytotoxic for a wide range of tumour cells in vitro and in vivo.

\ \ tumor necrosis factor receptor ligand activity ; GO:0005164 membrane ; GO:0016020 immune response ; GO:0006955 22162 IPR003627 Mammaglobin and prostatein are members of the uteroglobin family. Mammaglobin may bind androgens and other steroids, and may be under transcriptional regulation of steroid hormones. Prostatein is also a steroid-binding protein, which can bind non-polar steroids, cholesterol and a group of small, proline-rich peptides. Prostatein is composed of three different peptides called C1, C2 and C3. These form covalent C1:C3 (F) and C2:C3 (S) heterodimers whose non-covalent association forms tetrameric (C1:C3/C3:C2) prostatein molecules.\ steroid binding activity ; GO:0005496 \N \N 22163 IPR003628 Uteroglobin [MEDLINE:89199637] is a protein that seems specific to lagomorphes (rabbit, hare, and pica) and which binds progesterone specifically and with high affinity. Itmay regulate progesterone concentrations reaching the blastocyst. Uteroglobin\ is also a potent inhibitor of phospholipase A2. It is a protein of 70 amino\ acids that form antiparallel disulfide-linked dimers. The progesterone-\ binding site is formed by a cavity between the monomeric subunits. This subfamily also includes lipophilin A and some prostateins.\ \ steroid binding activity ; GO:0005496 \N \N 22164 IPR003629

Members of this family include granulocyte colony-stimulating factor (GCSF) and myelomonocytic growth factor (MGF). GCSF acts in hematopoiesis by affecting the production, differentiation and function of 2 related white cell groups in the blood [MEDLINE:89286115]. MGF also acts in hematopoiesis, stimulating proliferation and colony formation of normal and transformed avian cells of the myeloid lineage.

Cytokines of the IL6/GCSF/MGF family are glycoproteins of about 170 to 180 amino acid residues that contains four conserved cysteine residues involved in two disulfide bonds [MEDLINE:89286115]. They have a compact, globular fold (similar to other interleukins), stabilised by the 2 disulphide bonds. One half of the structure is dominated by a 4 -helix bundle with a left-handed twist [MEDLINE:93015916]: the helices are anti-parallel, with 2 overhand connections, which fall into a 2-stranded anti-parallel -sheet. The fourth -helix is important to the biological activity of the molecule [MEDLINE:91243808].

\ \ growth factor activity ; GO:0008083 \N immune response ; GO:0006955 22157 IPR003621 Diuretic hormones are involved in the regulation of fluid secretion. They stimulate primary urine secretion by malpighian tubules and cause a dose-dependent stimulation of cAMP levels in the tubules.\ diuretic hormone activity ; GO:0008613 extracellular ; GO:0005576 fluid secretion ; GO:0007589 22158 IPR003623 Oncostatin is a growth regulator, which inhits the proliferation of a number of tumour cell lines. It regulates cytokine production, including IL-6, G-CSF and GM-CSF from endothelial cells. Oncostatin belongs to the same family as the cytokine leukemia inhibitory factor.\ oncostatin-M receptor ligand activity ; GO:0005147 \N regulation of cell growth ; GO:0001558 22165 IPR003630 Interleukin-9 (IL-9)is a cytokine that supports IL-2 independent and IL-4 independent growth of helper T-cells.\ interleukin-9 receptor ligand activity ; GO:0005140 extracellular ; GO:0005576 immune response ; GO:0006955 22166 IPR003631 A variety of GPI-linked cell-surface glycoproteins are composed of one or more copies of a conserved domain of about 100 amino-acid residues [MEDLINE:91210310], [MEDLINE:93352546]. Among these proteins, Urokinase plasminogen activator surface receptor (U-PAR) contains three tandem copies of the domain, while all the others are made up of a single domain. U-PAR acts as a receptor for urokinase plasminogen activator and plays a role in localising and promoting plasmin formation. It mediates the proteolysis-independent signal transduction activation effects of urokinase plasminogen activator.\ U-plasminogen activator receptor activity ; GO:0030377 \N cell surface receptor linked signal transduction ; GO:0007166 22156 IPR003620

Corticotropin-releasing factor (CRF), urotensin-I, urocortin and sauvagine form a family of related neuropeptides in vertebrates. The family can be\ grouped into 2 separate paralogous lineages, with urotensin-I, urocortin and\ sauvagine in one group and CRF forming the other group. Urocortin and\ sauvagine appear to represent orthologues of fish urotensin-I in mammals and\ amphibians, respectively. The peptides have a variety of physiological\ effects on stress and anxiety, vasoregulation, thermoregulation, growth and\ metabolism, metamorphosis and reproduction in various species, and are all\ released as preprohormones [MEDLINE:99307121].

\ CRF [MEDLINE:90341332] is a hormone found mainly in the paraventricular nucleus of the mammalian hypothalamus that regulates the release of corticotropin (ACTH) from the pituitary gland. From here, CRF\ is transported to the anterior pituitary, stimulating adrenocorticotropic\ hormone (ACTH) release via CRF type 1 receptors, thereby activating the\ hypothalamo-pituitary-adrenocortical axis (HPA) and thus glucocorticoid\ release.

\ CRF is evolutionary related to a number of other active peptides. Urocortin acts in vitro to stimulate the secretion of adrenocorticotropic hormone. Urotensin is found in the teleost caudal neurosecretory system and may play a role in osmoregulation and as a corticotropin-releasing factor. Urotensin-I is released\ from the urophysis of fish, and produces ACTH and subsequent cortisol \ release in vivo. The nonhormonal portion of the prohormone is thought to be\ the urotensin binding protein (urophysin).

\ \ hormone activity ; GO:0005179 extracellular ; GO:0005576 \N 22161 IPR003626 Parathyroid hormone (PTH) is a polypeptidic hormone that elevates calciumlevel by dissolving the salts in bone and preventing their renal excretion.\ The 'parathyroid hormone-related protein' (PTH-rP) is structurally related to PTH [MEDLINE:90048075] and seems to play a physiological role in lactation, possibly as a hormone for the mobilization and/or transfer of calcium to the milk. PTH and PTH-rP bind to the same G-protein coupled receptor.\ \ hormone activity ; GO:0005179 extracellular ; GO:0005576 lactation ; GO:0007595 22160 IPR003625 Parathyroid hormone (PTH) is a polypeptidic hormone that elevates calciumlevel by dissolving the salts in bone and preventing their renal excretion. Defects in PTH are a cause of familial isolated hypoparathyroidism.\ \ hormone activity ; GO:0005179 extracellular ; GO:0005576 \N 22159 IPR003624 Leukemia inhibitory factor is a small cytokine that has the capacity to induce terminal differentiation in leukemic cells. It also induces hematopoietic differentiation in normal and myeloid leukemia cells, and neuronal cell differentiation, as well as stimulating acute-phase protein synthesis in hepatocytes.\ leukemia inhibitory factor receptor ligand activity ; GO:0005146 extracellular ; GO:0005576 \N 22144 IPR003608 This is a domain found in ryanodine, inositol trisphosphate receptor and protein O-mannosyltransferase. Inositol 1,4,5-trisphosphate (InsP3) is an intracellular second messenger that transduces growth factor and neurotransmitter signals. InsP3 mediates the release of Ca²⁺ from intracellular stores by binding to specific Ca²⁺ channel-coupled receptors. Ryanodine receptors are involved in communication between transverse-tubules and the sarcoplamic reticulum of cardiac and skeletal muscle. The proteins function as a Ca²⁺-release channels following depolarisation of transverse-tubules [MEDLINE:91250425]. The function is modulated by Ca²⁺, Mg2+, ATP and calmodulin. Deficiency in the ryanodine receptor may be the cause of malignant hyperthermia (MH) and of central core disease of muscle (CCD) [MEDLINE:95130087]. protein O-mannosyltransferases transfer mannose from DOL-P-mannose to ser or thr residues on proteins.\ \N membrane ; GO:0016020 \N 22145 IPR003609 The apple domain, IPR000177) and S-receptor kinases. The domain is predicted to possess protein- and/or carbohydrate-binding functions.\ \N \N \N 22146 IPR003610

This short domain is found in many different glycosyl hydrolase enzymes and is presumed to have a carbohydrate binding function. The domain has six aromatic groups that may be important for binding.

\ \ carbohydrate binding activity ; GO:0030246 extracellular ; GO:0005576 carbohydrate metabolism ; GO:0005975 22147 IPR003611 This is a short helical motif of unknown function found in intron-associated nuclease 2, which is involved in intron homing.\ endonuclease activity ; GO:0004519 \N \N 22148 IPR003612 This domain is found is several proteins, including plant lipid transfer protein, seed storage protein and trypsin-

amylase inhibitor. The domain forms a four-helical bundle with an internal cavity.\ \N \N \N 22149 IPR003613 The modified RING finger domain is without the full complement of Zn2+-binding ligands. It is found in pre-mRNA splicing factor, several hypothetical proteins, and ubiquitin fusion degradation protein 2, where it may be involved in E2-dependent ubiquitination.\ \N \N \N 22150 IPR003614 The knottin family includes plant lectins or antimicrobial peptides, plant proteinase/amylase inhibitors, plant gamma-thionins and arthropod defensins.\ defense/immunity protein activity ; GO:0003793 \N \N 22151 IPR003615 This domain is found in HNH family of nucleases that includes yeast intron 1 protein, MutS, and bacterial colicins and pyocins. They are found in bacteria, viruses and eukaryotes.\ \N \N \N 22152 IPR003616 This is a cysteine-rich motif following a subset of SET domains. Deletion of this region of SUV39H1 impairs its histone methyltransferase function.\ \N \N \N 22153 IPR003617 This domain is found in the N-terminal region of transcription elongation factor S-II and in several hypothetical proteins.\ \N \N transcription ; GO:0006350 22154 IPR003618 This domain is found in the central region of transcription elongation factor S-II and in several hypothetical proteins.\ \N \N transcription ; GO:0006350 22155 IPR003619 Mammalian dwarfins are phosphorylated in response to transforming growth factor

and are implicated in control of cell growth [MEDLINE:96392344]. The dwarfin family also includes the Drosophila protein MAD that is required for the function of decapentaplegic (DPP) and may play a role in DPP signaling. Drosophila Mad binds to DNA and directly mediates activation of vestigial by Dpp [MEDLINE:97373960]. This domain is also found in nuclear factor I (NF-I) or CCAAT box-binding transcription factor (CTF).\ \ \N intracellular ; GO:0005622 regulation of transcription, DNA-dependent ; GO:0006355 22138 IPR003602 Prokaryotic topoisomerase I (EC: 5.99.1.2) [MEDLINE:95292060], PUB00001074, PUB00001074, otherwise known as relaxing enzyme, untwisting enzyme or swivelase, catalyses the ATP-independent breakage of single-stranded DNA, followed by passage and rejoining of another single-stranded DNA region [MEDLINE:94159070]. This reaction brings about the conversion of one topological isomer of DNA into another: e.g., relaxation of superhelical turns; interconversion of simple and knotted rings of single-stranded DNA; and\ intertwisting of single-stranded rings of complementary sequences [MEDLINE:94159070], [MEDLINE:90036864].\ Prokaryotic topoisomerase I folds in an unusual way to give 4 distinct\ domains, enclosing a hole large enough to accommodate a double-stranded DNA\ segment [MEDLINE:94159070]. A tyrosine at the active site, which lies at the interface of\ 2 domains, is involved in transient breakage of a DNA strand, and formation\ of a covalent protein-DNA intermediate [MEDLINE:94159070]. The structure reveals a\ plausible mechanism by which this and related enzymes could catalyse the \ passage of one DNA strand through a transient break in another strand [MEDLINE:94159070].\ E.coli contains 2 type I topoisomerases: topoisomerases I and III [MEDLINE:90036864].\ Topoisomerase III can be purified as a potent concatenase, but its role in\ DNA metabolism is still unclear [MEDLINE:90036864]. Eukaryotes, also contains topoisomerases, which may be similar in sequence and function to the prokaryotic type I topoisomerases [MEDLINE:89324087]. This domain is found in a variety of prokaryotic and eukaryotic topoisomerases.\ \ DNA topoisomerase activity ; GO:0003916 \N DNA unwinding ; GO:0006268 22139 IPR003603 This motif occurs C-terminal to leucine-rich repeats in "sds22-like" and "typical" LRR-containing proteins.\ \N \N \N 22140 IPR003604

U1-like zinc fingers are a family of C2H2-type zinc fingers present in matrin, U1 small nuclear ribonucleoprotein C and other RNA-binding proteins.

\ \ RNA binding activity ; GO:0003723 nucleus ; GO:0005634 \N 22141 IPR003605 This approximately 30 amino acid motif precedes the kinase domain in types I and II TGF

receptors. Mutation of two or more of the serines or threonines in the TTSGSGSG of TGF-

type I receptor impairs phosphorylation and signaling activity.\ ATP binding activity ; GO:0005524 membrane ; GO:0016020 protein amino acid phosphorylation ; GO:0006468 22142 IPR003606 This is a Cys-rich putative Zn2+-binding domain that occurs N-terminal to some SET domains. The function of this domain is unknown.\ \N \N \N 22143 IPR003607 The HD domain is found in a superfamily of enzymes with a predicted or known phosphohydrolase activity. These enzymes appear to be involved in the nucleic acid metabolism, signal transduction and possibly other functions in bacteria, archaea and eukaryotes.The fact that all the highly conserved redisues in the HD superfamily are histidines or aspartates suggests that coordination of divalent cations is essential for the activity of these proteins [MEDLINE:99085258]. This domain is also found in eukaryotic 3',5'-cGMP phosphodiesterase (EC: 3.1.4.17) (PDE), which is located in photoreceptor outer segments PUB00005667 and it is light activated, playing a pivotal role in\ signal transduction. This profile/HMM does not detect HD homologues in bacterial glycine aminoacyl-tRNA synthetases (

subunit).\ \ enzyme activity ; GO:0003824 \N \N 22135 IPR003598

This subfamily is the C-2-type and includes glycoproteins and other unrelated proteins with immunoglobin domains eg.carcinoembryonic antigens and fibroblast growth factor receptors.

\ \ \N \N \N 22136 IPR003599

This subfamily includes killer cell inhibitory receptor, as well as other cell surface receptors containing an immunoglobin domain.

\ \ \N \N \N 22137 IPR003601 Prokaryotic topoisomerase I (EC: 5.99.1.2) [MEDLINE:95292060], PUB00001074, PUB00001074, otherwise known as relaxing enzyme, untwisting enzyme or swivelase, catalyses the ATP-independent breakage of single-stranded DNA, followed by passage and rejoining of another single-stranded DNA region [MEDLINE:94159070]. This reaction brings about the conversion of one topological isomer of DNA into another: e.g., relaxation of superhelical turns; interconversion of simple and knotted rings of single-stranded DNA; and\ intertwisting of single-stranded rings of complementary sequences [MEDLINE:94159070], [MEDLINE:90036864].\ Prokaryotic topoisomerase I folds in an unusual way to give 4 distinct\ domains, enclosing a hole large enough to accommodate a double-stranded DNA\ segment [MEDLINE:94159070]. A tyrosine at the active site, which lies at the interface of\ 2 domains, is involved in transient breakage of a DNA strand, and formation\ of a covalent protein-DNA intermediate [MEDLINE:94159070]. The structure reveals a\ plausible mechanism by which this and related enzymes could catalyse the \ passage of one DNA strand through a transient break in another strand [MEDLINE:94159070].\ E.coli contains 2 type I topoisomerases: topoisomerases I and III [MEDLINE:90036864].\ Topoisomerase III can be purified as a potent concatenase, but its role in\ DNA metabolism is still unclear [MEDLINE:90036864]. Eukaryotes, also contains topoisomerases, which may be similar in sequence and function to the prokaryotic type I topoisomerases [MEDLINE:89324087]. This domain is found in a variety of prokaryotic and eukaryotic topoisomerases.\ \ DNA topoisomerase activity ; GO:0003916 \N DNA unwinding ; GO:0006268 22125 IPR003585 The putative band 4.1 homologues' binding motif is found in neurexins,syndecans and glycophorin C intracellular C-termini. Syndecans are cell surface proteoglycans and glycophorin C is a minor sialoglycoprotein in human erythrocyte membranes, which play an important role in regulating the stability of red cells.\

\ \ \N \N \N 22126 IPR003586 Hedgehog proteins are involved in intracellular signalling required for a variety of patterning events during development. The hint domain is found in these proteins, as well as several proteins which contain inteins and undergo protein splicing. These include the V-type ATP synthase

chain from Pyrococcus and the Guillardia replicative DNA helicase DNAB.The Hedgehog/Intein domain has been split to accommodate large insertions of\ endonucleases. This entry is the C-terminal region.\ \ \N \N \N 22127 IPR003587 Hedgehog proteins are involved in intracellular signalling required for a variety of patterning events during development. The hint domain is found in these proteins, as well as several proteins which contain inteins and undergo protein splicing. These include the V-type ATP synthase

chain from Pyrococcus and the Guillardia replicative DNA helicase DNAB.The Hedgehog/Intein domain has been split to accommodate large insertions of\ endonucleases. This entry is the N-terminal region.\ \ \N \N \N 22128 IPR003590 Leucine-rich repeats (LRRs) are relatively short motifs (22-28 residues in length) found in a variety of cytoplasmic, membrane and extracellular proteins [MEDLINE:91099665]. Although these proteins are associated with widely different functions, a common property involves protein-protein interaction. Little is known about the 3D structure of LRRs, although it is believed that they can form amphipathic structures with hydrophobic surfaces capable of interacting with membranes [MEDLINE:88135762]. In vitro studies of a synthetic LRR from Drosophila Toll protein have indicated that the peptides form gels by adopting

-sheet structures that form extended filaments. These results are consistent with the idea that LRRs mediate protein-protein interactions and cellular adhesion [MEDLINE:92038020]. Other functions of LRR-containing proteins include, for example, binding to enzymes [MEDLINE:90094386] and vascular repair [MEDLINE:89367331]. The 3-D structure of ribonuclease inhibitor, a protein containing 15 LRRs, has been determined [MEDLINE:94088748], revealing LRRs to be a new class of

fold. LRRs form elongated non-globular structures and are often flanked by cysteine rich domains. This subtype is found in ribonuclease inhibitors.\ \N \N \N 22129 IPR003591 Leucine-rich repeats (LRRs) are relatively short motifs (22-28 residues in length) found in a variety of cytoplasmic, membrane and extracellular proteins [MEDLINE:91099665]. Although these proteins are associated with widely different functions, a common property involves protein-protein interaction. Little is known about the 3D structure of LRRs, although it is believed that they can form amphipathic structures with hydrophobic surfaces capable of interacting with membranes [MEDLINE:88135762]. In vitro studies of a synthetic LRR from Drosophila Toll protein have indicated that the peptides form gels by adopting

fold. LRRs form elongated non-globular structures and are often flanked by cysteine rich domains.\ \N \N \N 22130 IPR003593 A large family of ATPases has been described [MEDLINE:91317863], [MEDLINE:91121507], [MEDLINE:90269209], [MEDLINE:93283443], [MEDLINE:95374488] whose key feature is that they share a conserved region of about 220 amino acids that contains an ATP-binding site. This family is now called AAA, for 'A'TPases 'A'ssociated with diverse cellular 'A'ctivities. The proteins that belong to this family either contain one or two AAA domains.\ It is proposed that, in general, the AAA domains in these proteins act as ATP-dependent protein clamps [MEDLINE:95374488]. This profile/alignment only detects a fraction of this vast family. The poorly conserved N-terminal helix is missing from the alignment.\ \ \ nucleotide binding activity ; GO:0000166 \N \N 22133 IPR003596

This subfamily includes the V-type immunoglobins, and hits the V regions of the molecule.

\ \ \N \N \N 22134 IPR003597

This subfamily is the C-type, and includes MHC class II antigen and chains.

\ \ \N \N \N 22131 IPR003594 This domain is found in several ATP-binding proteins for example: histidine kinase, DNA gyrase B, topoisomerases, heat shock protein HSP90, phytochrome-like ATPases and DNA mismatch repair proteins.\ ATP binding activity ; GO:0005524 \N \N 22132 IPR003595

Tyrosine specific protein phosphatases (EC: 3.1.3.48) (PTPase) [MEDLINE:91320111], [MEDLINE:93119746], [MEDLINE:92084630], [MEDLINE:90162933], [MEDLINE:89376550] areenzymes that catalyze the removal of a phosphate group attached to a tyrosine\ residue. These enzymes are very important in the control of cell growth,\ proliferation, differentiation and transformation. Multiple forms of PTPase\ have been characterized and can be classified into two categories: soluble\ PTPases and transmembrane receptor proteins that contain PTPase domain(s). This motif encompasses only part of the PTP domain structure.

\ \ protein tyrosine phosphatase activity ; GO:0004725 \N \N 22117 IPR003574

Interleukin-6 (IL6), also refered to as B-cell stimulatory factor-2 (BSF-2) and interferon -2, is a cytokine involved in a wide variety of biological functions [MEDLINE:87065033]. It plays an essential role in the finaldifferentiation of B-cells into IG-secreting cells, as well as inducing myeloma/plasmacytoma growth, nerve cell differentiation and, in hepatocytes, acute phase reactants [MEDLINE:87065033], [MEDLINE:91243808].

\ \ interleukin-6 receptor ligand activity ; GO:0005138 extracellular ; GO:0005576 immune response ; GO:0006955 22118 IPR003577 The Ras branch of the Ras superfamily consists of small GTPases most closely related to Ras and include the R-Ras, Rap, Ral, Rheb, Rin and Rit proteins. Although our understanding of Ras signaling and biology is now considerable, recent observations suggest that Ras function is more complex than previously believed. This family is similar in fold and function to the bacterial EF-Tu GTPase. p21Ras couples receptor Tyr kinases and G protein receptors to protein kinase cascades.\ GTP binding activity ; GO:0005525 \N small GTPase mediated signal transduction ; GO:0007264 22119 IPR003578 Small GTPases are involved in intracellular cell signalling processes. The Ras family includes a large number of small GTPases. Members of the Rho subfamily of Ras-like small GTPases include Cdc42 and Rac, as well as Rho isoforms.\ GTP binding activity ; GO:0005525 \N small GTPase mediated signal transduction ; GO:0007264 22120 IPR003579 Small GTPases are involved in intracellular cell signalling processes. The Ras family includes a large number of small GTPases. Members of the Rab GTPases subfamily have been implicated in vesicle trafficking.\ GTP binding activity ; GO:0005525 \N protein transport ; GO:0015031 22121 IPR003581 The tail specific protease domain is found in several proteases including tricorn protease homologue and carboxy-terminal processing protease. It is also found in the interphotoreceptor retinoid-binding protein, IRBP, which shuttles 11-cis and all trans retinoids between the retinol isomerase in the pigment epithelium and the visual pigments in the photoreceptor cells of the retina. This domain sometimes occurs downstream of the PDZ domain (IPR001478).\ \ peptidase activity ; GO:0008233 \N \N 22122 IPR003582 The ShK toxin domain is found in metridin, a toxin from sea anemone, and several hypothetical proteins from C. elegans.\ \N \N \N 22123 IPR003583 The HhH motif is an around 20 amino acids domain present in prokaryotic andeukaryotic non-sequence-specific DNA binding proteins [MEDLINE:95393988], [MEDLINE:99141217], [MEDLINE:99141601]. \ The HhH motif is similar to, but distinct from, the HtH motif. Both of these\ motifs have two helices connected by a short turn. In the HtH motif the second\ helix binds to DNA with the helix in the major groove. This allow the contact\ between specific base and residues throughout the protein. In the HhH motif\ the second helix does not protrude from the surface of the protein and\ therefore cannot lie in the major groove of the DNA. Crystallographic studies\ suggest that the interaction of the HhH domain with DNA is mediated by amino\ acids located in the strongly conserved loop (L-P-G-V) and at the N-terminal\ end of the second helix [MEDLINE:95393988]. This interaction could involve the formation of\ hydrogen bonds between protein backbone nitrogens and DNA phosphate groups\ [MEDLINE:96292250]. \ The structural difference between the HtH and HhH domains is reflected at the\ functional level: whereas the HtH domain, found primarily in gene regulatory\ proteins, binds DNA in a sequence specific manner, the HhH domain is rather\ found in proteins involved in enzymatic activities and binds DNA with no\ sequence specificity [MEDLINE:96292250].\ \ DNA binding activity ; GO:0003677 intracellular ; GO:0005622 \N 22124 IPR003584 The HhH motif is an around 20 amino acids domain present in prokaryotic andeukaryotic non-sequence-specific DNA binding proteins [MEDLINE:95393988], [MEDLINE:99141217], [MEDLINE:99141601]. \ The HhH motif is similar to, but distinct from, the HtH motif. Both of these\ motifs have two helices connected by a short turn. In the HtH motif the second\ helix binds to DNA with the helix in the major groove. This allow the contact\ between specific base and residues throughout the protein. In the HhH motif\ the second helix does not protrude from the surface of the protein and\ therefore cannot lie in the major groove of the DNA. Crystallographic studies\ suggest that the interaction of the HhH domain with DNA is mediated by amino\ acids located in the strongly conserved loop (L-P-G-V) and at the N-terminal\ end of the second helix [MEDLINE:95393988]. This interaction could involve the formation of\ hydrogen bonds between protein backbone nitrogens and DNA phosphate groups\ [MEDLINE:96292250]. \ The structural difference between the HtH and HhH domains is reflected at the\ functional level: whereas the HtH domain, found primarily in gene regulatory\ proteins, binds DNA in a sequence specific manner, the HhH domain is rather\ found in proteins involved in enzymatic activities and binds DNA with no\ sequence specificity [MEDLINE:96292250].\ \ DNA binding activity ; GO:0003677 intracellular ; GO:0005622 \N 22113 IPR003570 Within mitochondria and bacteria, a family of related proteins is involved in the assembly of periplasmic c-type cytochromes: these include CycK [MEDLINE:95394794],\ CcmF [MEDLINE:95362656],[MEDLINE:97195802], NrfE [MEDLINE:94335626] and CcbS [MEDLINE:93288005]. These proteins may play a role in \ guidance of apocytochromes and haem groups for their covalent linkage \ by the cytochrome-c-haem lyase. Members of the family are probably integral\ membrane proteins, with up to 16 predicted transmembrane (TM) helices.\

A seven-gene operon, designated nrf, has been shown to be essential for \ formate-dependent nitrite reduction to ammonia by enteric bacteria [MEDLINE:93288005].\ Expression of lac fused to nrfA, nrfE or nrfG is regulated by oxygen\ repression, FNR-dependent anaerobic induction, nitrite induction and\ nitrate repression during anaerobic growth. NrfE is a hydrophobic, \ integral membrane protein that shares a high degree of similarity with the\ CdI1 protein of Rhodobacter capsulatus implicated in the assembly of\ periplasmic c-type cytochromes [MEDLINE:93288005]. Hydropathy analysis reveals up to 16\ putative TM domains.

\ \ \ heme transporter activity ; GO:0015232 membrane ; GO:0016020 cytochrome biogenesis ; GO:0017004 22114 IPR003571

Snake toxins belong to a family of proteins [MEDLINE:84292329], PUB00005927, PUB00005927 which groups short andlong neurotoxins, cytotoxins and short toxins, as well as a other miscellaneous\ venom peptides. Most of these toxins act by binding to the nicotinic\ acetylcholine receptors in the postsynaptic membrane of skeletal muscles and\ prevent the binding of acetylcholine, thereby blocking the excitation of\ muscles.

Snake toxins are proteins that consist of sixty to seventy five amino acids.\ Among the invariant residues are eight cysteines all involved in disulfide\ bonds. The structure is small, disulfide-rich, nearly all sheet.

\ \ toxin activity ; GO:0015070 extracellular ; GO:0005576 pathogenesis ; GO:0009405 22115 IPR003572

Snake toxins belong to a family of proteins [MEDLINE:84292329], PUB00005927, PUB00005927 which groups short andlong neurotoxins, cytotoxins and short toxins, as well as a other miscellanous\ venom peptides. Most of these toxins act by binding to the nicotinic\ acetylcholine receptors in the postsynaptic membrane of skeletal muscles and\ prevent the binding of acetylcholine, thereby blocking the excitation of\ muscles.

\ \ toxin activity ; GO:0015070 extracellular ; GO:0005576 pathogenesis ; GO:0009405 22116 IPR003573

A number of other cytokines may be grouped with IL6 on the basis of sequence similarity [MEDLINE:87065033], [MEDLINE:91243808], [MEDLINE:89286115]: these include granulocyte colony-stimulating factor (GCSF) and myelomonocytic growth factor (MGF). GCSF acts in hematopoiesis by affecting the production, differentiation and function of 2 related white cell groups in the blood [MEDLINE:89286115]. MGF also acts in hematopoiesis, stimulating proliferation and colony formation of normal and transformed avian cells of the myeloid lineage.

It has been said [MEDLINE:92020908] that this family can be extended by the adjunction of LIF and OSM (see the relevant entry IPR001581) which seem to be structurally related.

\ \ cytokine activity ; GO:0005125 extracellular ; GO:0005576 immune response ; GO:0006955 22110 IPR003567 Within mitochondria and bacteria, a family of related proteins is involved in the assembly of periplasmic c-type cytochromes: these include CycK [MEDLINE:95394794],\ CcmF [MEDLINE:95362656],[MEDLINE:97195802], NrfE [MEDLINE:94335626] and CcbS [MEDLINE:93288005]. These proteins may play a role in \ guidance of apocytochromes and haem groups for their covalent linkage \ by the cytochrome-c-haem lyase. Members of the family are probably integral\ membrane proteins, with up to 16 predicted transmembrane (TM) helices.\ \ \ heme transporter activity ; GO:0015232 membrane ; GO:0016020 cytochrome biogenesis ; GO:0017004 22111 IPR003568 Within mitochondria and bacteria, a family of related proteins is involved in the assembly of periplasmic c-type cytochromes: these include CycK [MEDLINE:95394794],\ CcmF [MEDLINE:95362656],[MEDLINE:97195802], NrfE [MEDLINE:94335626] and CcbS [MEDLINE:93288005]. These proteins may play a role in \ guidance of apocytochromes and haem groups for their covalent linkage \ by the cytochrome-c-haem lyase. Members of the family are probably integral\ membrane proteins, with up to 16 predicted transmembrane (TM) helices.\

The gene products of the hel and ccl loci have been shown to be required\ specifically for the biogenesis of c-type cytochromes in the Gram-negative\ photosynthetic bacterium Rhodobacter capsulatus. The ccl locus contains\ two genes, ccl1 and ccl2, each of which possesses typical signal sequences\ to direct them to the periplasm [MEDLINE:92146961]. Ccl1 is similar to proteins encoded\ by chloroplast and mitochondrial genes, suggesting analogous functions in \ these organelles. It is believed that the hel-encoded proteins are required \ for the export of haem to the periplasm, where it is subsequently ligated\ to the c-type apocytochromes [MEDLINE:92146961].

\ \

The CycK and CycL proteins of Bradyrhizobium japonicum share up to 53% \ amino acid sequence identity with Rhodobacter capsulatus proteins Cc11 and\ Cc12 proteins, respectively. CycK and CycL proteins, which are encoded\ by the cycHJKL-cluster, may form part of a cytochrome c-haem lyase complex\ whose active site faces the periplasm [MEDLINE:95231513].

\ \ \ heme transporter activity ; GO:0015232 membrane ; GO:0016020 cytochrome biogenesis ; GO:0017004 22112 IPR003569 Within mitochondria and bacteria, a family of related proteins is involved in the assembly of periplasmic c-type cytochromes: these include CycK [MEDLINE:95394794],\ CcmF [MEDLINE:95362656],[MEDLINE:97195802], NrfE [MEDLINE:94335626] and CcbS [MEDLINE:93288005]. These proteins may play a role in \ guidance of apocytochromes and haem groups for their covalent linkage \ by the cytochrome-c-haem lyase. Members of the family are probably integral\ membrane proteins, with up to 16 predicted transmembrane (TM) helices.\

Analysis of a transcribed region in the mitochondrial genome of Oenothera \ revealed an open reading frame (ORF) that is also conserved in carrot\ \ \ \ [MEDLINE:93288005]. \ Extensive RNA editing (46 C to U transitions) alters the Oenothera mRNA\ sequence, yielding a sequence with high similarity to the homologous gene\ product in Marchantia. The deduced polypeptides share significant\ similarity with the ccl1-encoded protein involved in cytochrome c biogenesis\ in the photosynthetic bacterium Rhodobacter capsulatus. A highly \ conserved domain is also found in plastid ORFs, suggesting that these\ bacterial, chloroplast and mitochondrial genes encode polypeptides with\ analogous functions in assembly and maturation of cytochromes c [MEDLINE:93288005].

\ \ \ heme transporter activity ; GO:0015232 membrane ; GO:0016020 cytochrome biogenesis ; GO:0017004 22105 IPR003562 MutT is a small bacterial protein (~12-15kDa) involved in the GO system [MEDLINE:93015679] responsible for removing an oxidatively damaged form of guanine (8-hydroxy-\ guanine or 7,8-dihydro-8-oxoguanine) from DNA and the nucleotide pool.\ 8-oxo-dGTP is inserted opposite dA and dC residues of template DNA with\ near equal efficiency, leading to A.T to G.C transversions. MutT\ specifically degrades 8-oxo-dGTP to the monophosphate, with the concomitant\ release of pyrophosphate. A short conserved N-terminal region of mutT \ (designated the MutT domain) is also found in a variety of other\ prokaryotic, viral, and eukaryotic proteins [MEDLINE:94051617], [MEDLINE:94224150], [MEDLINE:94043152], [MEDLINE:99303955]. Recently, the generic\ name 'NUDIX hydrolases' (NUcleoside DIphosphate linked to some other moeity\ X) has been coined for this domain family [MEDLINE:96411704].\ \

Like MutT, the pure MutX protein hydrolyses all canonical nucleoside \ triphosphates at different rates, with a preference for dGTP, yielding \ nucleoside monophosphates and inorganic pyrophosphate [MEDLINE:94216358]. Despite the\ similarity in enzymatic activity, the two proteins have distinct primary\ and quaternary structures. Their sequences share only a small region \ of similarity (the MutT domain), and under the same conditions in which \ MutT exists as a monomer in solution, MutX behaves as a trimer [MEDLINE:94216358].

\ \ \ 7,8-dihydro-8-oxoguanine-triphosphatase activity ; GO:0008413\ \N \N DNA repair ; GO:0006281 22106 IPR003563 The enzyme 8-oxo-7,8-dihydrodeoxyguanosine triphosphatase (8-oxo-dGTPase) is present in a variety of organisms, where it plays an important role in\ the control of spontaneous mutagenesis [MEDLINE:96033912]. The enzyme degrades 8-oxoguanine-\ containing deoxyribonucleoside triphosphate, a potentially mutagenic\ substrate for DNA synthesis, to the corresponding monophosphate, thereby\ preventing misincorporation of 8-oxo-dGTP into DNA [MEDLINE:96033912]. \ \

8-oxo-dGTPase is an 18kDa protein containing 156 amino acid residues. The\ amino acid sequence shares a degree of similarity with the MutT domain of \ the Escherichia coli MutT protein, which has a distinct 8-oxo-dGTPase \ activity [MEDLINE:94043152]. When human cDNA is expressed in E.coli mutT- mutant cells,\ there is a significant amount of 8-oxo-dGTPase activity and a reduced \ frequency of spontaneous mutation. Human 8-oxo-dGTPase is thought to \ protect genetic information from the untoward effects of endogenous oxygen\ radicals [MEDLINE:94043152].

\ \ \ 7,8-dihydro-8-oxoguanine-triphosphatase activity ; GO:0008413\ \N \N DNA repair ; GO:0006281 22107 IPR003564 MutT is a small bacterial protein (~12-15kDa) involved in the GO system [MEDLINE:93015679] responsible for removing an oxidatively damaged form of guanine (8-hydroxy-\ guanine or 7,8-dihydro-8-oxoguanine) from DNA and the nucleotide pool.\ 8-oxo-dGTP is inserted opposite dA and dC residues of template DNA with\ near equal efficiency, leading to A.T to G.C transversions. MutT\ specifically degrades 8-oxo-dGTP to the monophosphate, with the concomitant\ release of pyrophosphate. A short conserved N-terminal region of mutT \ (designated the MutT domain) is also found in a variety of other\ prokaryotic, viral, and eukaryotic proteins [MEDLINE:94051617], [MEDLINE:94224150], [MEDLINE:94043152], [MEDLINE:99303955]. Recently, the generic\ name 'NUDIX hydrolases' (NUcleoside DIphosphate linked to some other moeity\ X) has been coined for this domain family [MEDLINE:96411704].\

DATP pyrophosphohydrolase hydrolyses nucleoside triphosphates with a\ preference for DATP. The protein sequence shares significant similarity\ to proteins with a core MutT domain.

\ \ dATP pyrophosphohydrolase activity ; GO:0008828 \N DNA repair ; GO:0006281 22108 IPR003565 MutT is a small bacterial protein (~12-15kDa) involved in the GO system [MEDLINE:93015679] responsible for removing an oxidatively damaged form of guanine (8-hydroxy-\ guanine or 7,8-dihydro-8-oxoguanine) from DNA and the nucleotide pool.\ 8-oxo-dGTP is inserted opposite dA and dC residues of template DNA with\ near equal efficiency, leading to A.T to G.C transversions. MutT\ specifically degrades 8-oxo-dGTP to the monophosphate, with the concomitant\ release of pyrophosphate. A short conserved N-terminal region of mutT \ (designated the MutT domain) is also found in a variety of other\ prokaryotic, viral, and eukaryotic proteins [MEDLINE:94051617], [MEDLINE:94224150], [MEDLINE:94043152], [MEDLINE:99303955]. Recently, the generic\ name 'NUDIX hydrolases' (NUcleoside DIphosphate linked to some other moeity\ X) has been coined for this domain family [MEDLINE:96411704].\

The enzyme diadenosine 5',5''-P1,P4-tetraphosphate pyrophosphohydrolase \ asymmetrically hydrolyses AP4A to yield AMP and ATP. The catalysed reaction\ is as follows:\

        P(1),P(4)-bis(5'-adenosyl)tetraphosphate + H(2)O = ATP + AMP.

\ \

The cDNA and derived amino acid sequence of human diadenosine 5',5"'- \ P1,P4-tetraphosphate pyrophosphohydrolase have been determined by means of\ EST analysis [MEDLINE:96067583]. The protein possesses a modification of the MutT domain \ found in certain nucleotide pyrophosphatases.

\ \ bis(5'-nucleosyl)-tetraphosphatase activity ; GO:0008796 \N \N 22103 IPR003560 Iron is essential for growth in both bacteria and mammals. Controlling the amount of free iron in solution is often used as a tactic by hosts to limit\ invasion of pathogenic microbes; binding iron tightly within protein\ molecules can accomplish this. Such iron-protein complexes include haem in\ blood, lactoferrin in tears/saliva and transferrin in blood plasma. Some\ bacteria express surface receptors to capture eukaryotic iron-binding\ compounds, while others have evolved siderophores to scavenge iron from\ iron-binding host proteins [MEDLINE:94335702].\ \

The absence of free iron molecules in the surrounding environment triggers \ transcription of gene clusters that encode both siderophore-synthesis \ enzymes, and receptors that recognise iron-bound siderophores [MEDLINE:89123154]. Classic\ examples are the enterobactin/enterochelin clusters found in Escherichia\ coli and Salmonella, although similar moieties in other pathogens have \ been identified. The enzymic machinery that produces vibrionectin in Vibrio\ cholera is such a homologue [MEDLINE:98037504].

EntA, a 2,3-dihydro-2,3-dihydroxybenzoate dehydrogenase enzyme, is involved\ in the third stage of enterobactin biosynthesis and converts isochorismate \ to 2,3-dihydroxybenzoic acid (DHBA). Deletion studies involving EntA- \ mutants have shown that it is essential for virulence [MEDLINE:89123155].\

\ \ \ 2,3-dihydro-2,3-dihydroxybenzoate dehydrogenase activity ; GO:0008667\ \N \N enterobactin biosynthesis ; GO:0009239 22104 IPR003561 MutT is a small bacterial protein (~12-15kDa) involved in the GO system [MEDLINE:93015679] responsible for removing an oxidatively damaged form of guanine (8-hydroxy-\ guanine or 7,8-dihydro-8-oxoguanine) from DNA and the nucleotide pool.\ 8-oxo-dGTP is inserted opposite dA and dC residues of template DNA with\ near equal efficiency, leading to A.T to G.C transversions. MutT\ specifically degrades 8-oxo-dGTP to the monophosphate, with the concomitant\ release of pyrophosphate. A short conserved N-terminal region of mutT \ (designated the MutT domain) is also found in a variety of other\ prokaryotic, viral, and eukaryotic proteins [MEDLINE:94051617], [MEDLINE:94224150], [MEDLINE:94043152], [MEDLINE:99303955]. Recently, the generic\ name 'NUDIX hydrolases' (NUcleoside DIphosphate linked to some other moeity\ X) has been coined for this domain family [MEDLINE:96411704].\ \

The solution structure of the MutT enzyme has been solved by NMR [MEDLINE:96072737]. The\ structure is globular and compact, and contains a five-stranded mixed -sheet. The parallel portion of the sheet is sandwiched between two -helices, forming an + fold.

\ \ \ 7,8-dihydro-8-oxoguanine-triphosphatase activity ; GO:0008413\ \N \N DNA repair ; GO:0006281 22109 IPR003566 The egg peptide speract receptor is a transmembrane glycoprotein of about 500 amino acids [MEDLINE:89184581]. Topologically, it comprises a large extracellular\ domain of about 450 residues, followed by a transmembrane domain and a\ short cytoplasmic region of about 12 amino acids. The extracellular\ domain contains 4 repeats of a well-conserved region, which spans 115\ amino acids and contains 6 conserved cysteines. A similar domain is also\ found towards the C-terminus of macrophage scavenger receptor type I [MEDLINE:91062370],\ a membrane glycoprotein implicated in the pathologic deposition of\ cholesterol in arterial walls during artherogenesis, and in the CD5\ glycoprotein, which acts as a receptor in regulating T-cell proliferation.\

The T1/Leu-1/CD5 glycoprotein is expressed at the surface membrane of all\ mature T cells. It has been implicated both in the proliferative \ response of activated T cells and in T-cell helper function [MEDLINE:87014786]. The\ complete amino-acid sequence of the T1 precursor has been deduced from cDNA\ clones. The protein contains a classical signal peptide; a 347-residue \ extracellular segment; a transmembrane region; and a 93-residue intra-\ cellular segment [MEDLINE:87014786]. The extracellular region contains several cysteine\ residues and comprises 2 speract receptor domains separated by a proline/\ threonine-rich region [MEDLINE:87014786]. CD5 has been shown to function as a receptor,\ delivering co-stimulatory signals to T-cells, interacting specifically with\ the cell-surface protein CD72 (Lyb-2 in mice) exclusive to B-cells [MEDLINE:91270374].

\ \ \N membrane ; GO:0016020 \N 22098 IPR003555

\ \ \

\ \

Claudin-11 was originally termed oligodendrocyte-specific protein (OSP).\ It was reclassified as claudin-11 due to its sequence similarity to \ claudins and its ability to form TJ strands in transfected fibroblasts.\ Claudin-11 expression is highly regulated during development and it has \ been postulated that it may play an important role in the growth and \ differentiation of oligodendrocytes and other cells outside the CNS [MEDLINE:21206015].

\ \ structural molecule activity ; GO:0005198 tight junction ; GO:0005923 \N 22099 IPR003556

\ \ \

\ \

Claudin-14 was identified through cDNA database searching, pursuing\ sequences similar to other claudin family members [MEDLINE:99299665]. Human and mouse\ isoforms have been cloned. Claudin-14 shares ~25-45% overall similarity with\ other claudin family members at the amino acid level, displaying highest\ similarity to claudin-4.

\ \ \ structural molecule activity ; GO:0005198 tight junction ; GO:0005923 \N 22100 IPR003557 Within mitochondria and bacteria, a family of related proteins is involved in the assembly of periplasmic c-type cytochromes: these include CycK [MEDLINE:95394794], CcmF [MEDLINE:95362656],[MEDLINE:97195802], NrfE [MEDLINE:94335626] and CcbS [MEDLINE:93288005]. These proteins may play a role in \ guidance of apocytochromes and haem groups for their covalent linkage \ by the cytochrome-c-haem lyase. Members of the family are probably integral\ membrane proteins, with up to 16 predicted transmembrane (TM) helices. \ \

The gene products of the hel and ccl loci have been shown to be required\ specifically for the biogenesis of c-type cytochromes in the Gram-negative\ photosynthetic bacterium Rhodobacter capsulatus\ \ \ \ [MEDLINE:92146961]. Genetic and molecular\ analyses show that the hel locus contains at least 4 genes, helA, helB, helC\ and orf52. HelA is similar to the ABC transporters and helA, helB, and\ helC are proposed to encode an export complex [MEDLINE:94335626]. It is believed that the\ hel-encoded proteins are required for the export of haem to the periplasm,\ where it is subsequently ligated to the c-type apocytochromes [MEDLINE:92146961]. However,\ while CcmB and CcmC have the potential to interact with CcmA, the 3 gene \ products probably associating to form a complex with (CcmA)2-CcmB-CcmC\ stoichiometry, the substrate for the putative CcmABC-transporter is probably\ neither haem nor c-type apocytochromes [MEDLINE:97195802]. Hydropathy analysis suggests\ the presence of 6 TM domains.

\ \ heme transporter activity ; GO:0015232 membrane ; GO:0016020 cytochrome biogenesis ; GO:0017004 22101 IPR003558 Escherichia coli, Haemophilus spp and Campylobacter spp. all produce a toxin that is seen to cause distension in certain cell lines [MEDLINE:94156453], [MEDLINE:99221815], \ which eventually disintegrate and die. This novel toxin, termed cytolethal \ distending toxin (cdt), has three subunits: A, B and C. Their sizes are \ approx. 27.7, 29.5 and 19.9kDa respectively [MEDLINE:94156453], and they appear to be \ entirely novel [MEDLINE:99221815]. \ \

Further research on the complete toxin has revealed that it blocks the cell\ cycle at stage G2, through inactivation of the cyclin-dependent kinase Cdk1, and without induction of DNA breaks. This leads to multipolar abortive \ mitosis and micronucleation, associated with centrosomal amplification [MEDLINE:20236869].\ The roles of each subunit are unclear, but it is believed that they have\ separate roles in pathogenicity.

\ \ toxin activity ; GO:0015070 \N pathogenesis ; GO:0009405 22102 IPR003559 Escherichia coli, Haemophilus spp. and Campylobacter spp. all produce a toxin that is seen to cause distension in certain cell lines [MEDLINE:94156453], [MEDLINE:99221815], \ which eventually disintegrate and die. This novel toxin, termed cytolethal \ distending toxin (cdt), has three subunits: A, B and C. Their sizes are \ approx. 27.7, 29.5 and 19.9kDa respectively [MEDLINE:94156453], and they appear to be \ entirely novel [MEDLINE:99221815]. \ \

\ \ toxin activity ; GO:0015070 \N pathogenesis ; GO:0009405 22095 IPR003552

\ \ \

\ \

Claudin-7 was identified through searching expressed sequence tag (EST)\ databases for sequences similar to claudin-1 and -2. It was \ subsequently cloned and expressed in cells, where it was shown to\ concentrate at tight junctions [MEDLINE:99110921].

\ \ \ structural molecule activity ; GO:0005198 tight junction ; GO:0005923 \N 22096 IPR003553

\ \ \

\ \

Claudin-9 was identified through cDNA database searching, pursuing sequences\ similar to other claudin family members [MEDLINE:99299665]. Human and mouse isoforms have\ been cloned. Claudin-9 shares ~25-70% overall similarity with other claudin\ family members at the amino acid level, displaying highest similarity to\ claudin-6.

\ \ \ structural molecule activity ; GO:0005198 tight junction ; GO:0005923 \N 22097 IPR003554

\ \ \

\ \

Claudin-10 was identified through cDNA database searching, pursuing\ sequences similar to other claudin family members [MEDLINE:99299665]. Human and mouse\ isoforms have been cloned. Claudin-10 shares ~20-45% overall similarity with\ other claudin family members at the amino acid level, displaying highest\ similarity to claudin-15.

\ \ \ structural molecule activity ; GO:0005198 tight junction ; GO:0005923 \N 22090 IPR003547 Secretion of virulence factors in Gram-negative bacteria involves transportation of the protein across two membranes to reach the cell \ exterior [MEDLINE:98284147]. There have been four secretion systems described in \ animal enteropathogens, such as Salmonella and Yersinia, with further \ sequence similarities in plant pathogens like Ralstonia and Erwinia [MEDLINE:98284147].\ \

The type III secretion system is of great interest, as it is used to \ transport virulence factors from the pathogen directly into the host cell \ and is only triggered when the bacterium comes into close contact with\ the host. The protein subunits of the system are very similar to those of \ bacterial flagellar biosynthesis [MEDLINE:98284147]. However, while the latter forms a\ ring structure to allow secretion of flagellin and is an integral part of\ the flagellum itself, type III subunits in the outer membrane\ translocate secreted proteins through a channel-like structure.

\ \

Exotoxins secreted by the type III system do not possess a secretion signal,\ and are considered unique for this reason [MEDLINE:98284147]. Yersinia spp. secrete a \ serine/threonine kinase, YpkA, [MEDLINE:93180911], [MEDLINE:94321324] that causes autophosphorylation of host \ cell components, although the exact targets are unknown at present. It \ has also been suggested that the YpkA protein is involved in interference\ of signal transduction in the target cell [MEDLINE:96347131].

\ \ protein serine/threonine kinase activity ; GO:0004674 \N protein amino acid phosphorylation ; GO:0006468 22091 IPR003548

\ \ \

\ \

Claudin-1 was the first member of the claudin family to be identified as\ a tight junction component [MEDLINE:98311639]. The human isoform of claudin-1 was \ originally termed senescence-associated epithelial membrane protein 1 \ (SEMP1) [MEDLINE:99132301], but has since been reclassified.

\ \ structural molecule activity ; GO:0005198 tight junction ; GO:0005923 \N 22092 IPR003549

\ \ \

\ \

Claudin-3 was originally termed rat ventral prostate 1 protein (RVP1), and\ Clostridium perfringens enterotoxin receptor 2 (CPETR2). It was \ reclassified as claudin-3 on the basis of cDNA similarity with claudins-1 and\ -2, and antibody studies that showed it to be expressed at tight junctions\ [MEDLINE:99110921].

\ \ \ structural molecule activity ; GO:0005198 tight junction ; GO:0005923 \N 22093 IPR003550

\ \ \

\ \

Claudin-4 was originally termed Clostridium perfringens enterotoxin \ receptor (CPE-R). It was reclassified as claudin-4 on the basis of cDNA \ sequence similarity with claudins-1 and -2, and antibody studies that\ showed it to be expressed at tight junctions [MEDLINE:99110921].

\ \ \ structural molecule activity ; GO:0005198 tight junction ; GO:0005923 \N 22094 IPR003551

\ \ \

\ \

Claudin-5 was originally termed lung-specific membrane protein, brain\ endothelial cell clone 1 protein (BEC1), and transmembrane protein deleted\ in velo-cardio-facial syndrome (TMVCF). It was reclassified as claudin-5\ on the basis of cDNA sequence similarity with claudins-1 and -2, and \ antibody studies that showed it to be expressed at tight junctions [MEDLINE:99110921]. \ Claudin-5 may play an important role in development, since the gene is \ frequently deleted in velo-cardio-facial/DiGeorge syndrome patients [MEDLINE:97336049].

\ \ \ structural molecule activity ; GO:0005198 tight junction ; GO:0005923 \N 22089 IPR003546 Secretion of virulence factors in Gram-negative bacteria involves transportation of the protein across two membranes to reach the cell \ exterior [MEDLINE:98284147]. There have been four secretion systems described in \ animal enteropathogens, such as Salmonella and Yersinia , with further sequence similarities in plant pathogens like Ralstonia and Erwinia [MEDLINE:98284147].\

The type III secretion system is of great interest, as it is used to \ transport virulence factors from the pathogen directly into the host cell \ and is only triggered when the bacterium comes into close contact with\ the host. The protein subunits of the system are very similar to those of \ bacterial flagellar biosynthesis [MEDLINE:98284147]. However, while the latter forms a\ ring structure to allow secretion of flagellin and is an integral part of\ the flagellum itself, type III subunits in the outer membrane\ translocate secreted proteins through a channel-like structure.

\ \

Exotoxins secreted by the type III system do not possess a secretion signal,\ and are considered unique for this reason [MEDLINE:98284147]. Salmonella/Yersinia spp.\ secrete a protein, SptP, with tyrosine phosphatase activity [MEDLINE:97020031], [MEDLINE:94137987]. SptP \ exerts its function by acting as a GTPase-activating protein, and \ counteracts the effects of SopE [MEDLINE:99427936]. This is similar to the Yersinia \ exotoxin YopH, which degrades host cell signal transduction [MEDLINE:98284147].

\ \

X-ray crystal structures of the Yersinia tyrosine phosphatase (PTPase) in \ complex with tungstate and nitrate have been solved to 2.4A resolution [MEDLINE:96324959].\ The fold belongs to the - class. The crystal structure reveals\ that the nucleophilic cysteine (Cys 403) is positioned at the centre of a\ distinctive phosphate-binding loop. This loop is at the hub of\ several hydrogen-bond arrays that not only stabilise a bound oxyanion, but\ may activate Cys 403 as a reactive thiolate. Binding of tungstate\ triggers a conformational change that traps the oxyanion and swings Asp 356,\ an important catalytic residue that resides in a flexible loop, by ~6A into\ the active site [MEDLINE:96324959].

\ \ protein tyrosine phosphatase activity ; GO:0004725 \N \N 22086 IPR003543 The egg peptide speract receptor is a transmembrane glycoprotein of about 500 amino acids [MEDLINE:89184581]. Topologically, it comprises a large extracellular domain of about 450 residues, followed by a transmembrane domain and a short cytoplasmic region of about 12 amino acids. The extracellular\ domain contains 4 repeats of a well-conserved region, which spans 115\ amino acids and contains 6 conserved cysteines. A similar domain is also\ found towards the C-terminus of macrophage scavenger receptor type I [MEDLINE:91062370], a membrane glycoprotein implicated in the pathologic deposition of\ cholesterol in arterial walls during artherogenesis, and in the CD5\ glycoprotein, which acts as a receptor in regulating T-cell proliferation.\ \

The type I and type II human scavenger receptors are similar to their \ bovine, rabbit and murine counterparts. They consist of 6 domains:\ cytoplasmic (I); membrane-spanning (II); spacer (III); -helical coiled-\ coil (IV); collagen-like (V); and a type-specific C-terminal (VI) [MEDLINE:91067661]. Immunohistochemical studies have indicated the presence of scavenger\ receptors in the macrophages of lipid-rich atherosclerotic lesions, suggesting the involvement of these receptors in atherogenesis [MEDLINE:91067661].

\ \

The macrophage scavenger receptor is trimeric and has unusual ligand-binding\ properties [MEDLINE:90136965]. The trimeric structure of the bovine type I scavenger \ receptor contains 3 extracellular C-terminal cysteine-rich domains connected\ to the transmembrane domain by a long fibrous stalk. The stalk structure,\ which consists of an -helical coiled coil and a collagen-like triple\ helix, has not previously been observed in an integral membrane protein [MEDLINE:90136965].

\ \ scavenger receptor activity ; GO:0005044 membrane ; GO:0016020 receptor mediated endocytosis ; GO:0006898 22087 IPR003544 Within mitochondria and bacteria, a family of related proteins is involved in the assembly of periplasmic c-type cytochromes: these include CycK [MEDLINE:95394794], CcmF [MEDLINE:95362656],[MEDLINE:97195802], NrfE [MEDLINE:94335626] and CcbS [MEDLINE:93288005]. These proteins may play a role in \ guidance of apocytochromes and haem groups for their covalent linkage \ by the cytochrome-c-haem lyase. Members of the family are probably integral\ membrane proteins, with up to 16 predicted transmembrane (TM) helices. \ \

The gene products of the hel and ccl loci have been shown to be required\ specifically for the biogenesis of c-type cytochromes in the Gram-negative\ photosynthetic bacterium Rhodobacter capsulatus\ \ \ \ [MEDLINE:92146961]. Genetic and molecular\ analyses show that the hel locus contains at least 4 genes, helA, helB, helC\ and orf52. HelA is similar to the ABC transporters and helA, helB, and\ helC are proposed to encode an export complex [MEDLINE:94335626]. It is believed that the\ hel-encoded proteins are required for the export of haem to the periplasm,\ where it is subsequently ligated to the c-type apocytochromes [MEDLINE:92146961]. However,\ while CcmB and CcmC have the potential to interact with CcmA, the 3 gene \ products probably associating to form a complex with (CcmA)2-CcmB-CcmC\ stoichiometry, the substrate for the putative CcmABC-transporter is probably\ neither haem nor c-type apocytochromes [MEDLINE:97195802]. Hydropathy analysis suggests\ the presence of 6 TM domains.

\ \ heme transporter activity ; GO:0015232 membrane ; GO:0016020 cytochrome biogenesis ; GO:0017004 22088 IPR003545 Telomerase is an enzyme that, in certain cells, maintains the physical ends of chromosomes (telomeres) during replication. In somatic cells, replication\ of the lagging strand requires the continual presence of an RNA primer\ approximately 200 nucleotides upstream, which is complementary to the\ template strand. Since there is a region of DNA less than 200 base pairs\ from the end of the chromosome where this is not possible, the chromosome is\ continually shortened. However, there is a surplus of repetitive DNA at the \ ends, the telomeres, that protects against the erosion of gene-encoding DNA.\ \

Telomerase is a ribonucleoprotein (RNP) that synthesises the telomeric DNA\ repeats. The telomerase RNA subunit provides the template for synthesis of\ these repeats. There are 2 protein components of the RNP: the catalytic\ subunit is known as telomerase reverse transcriptase (TERT). The reverse\ transcriptase domain is located in the C-terminal region of the TERT\ polypeptide and single amino acid substitutions in this region lead to\ telomere shortening and senescence [MEDLINE:97274210].

\ \

Telomerase is not normally expressed in somatic cells and it has been\ suggested that exogenous TERT may extend the lifespan of, or even\ immortalise, the cell. However, recent studies have shown that telomerase\ activity can be induced by a number of oncogenes [MEDLINE:20359924]. Conversely, the\ oncogene c-myc can be activated in human TERT immortalised cells [MEDLINE:20322556].

\ \ telomeric template RNA reverse transcriptase activity ; GO:0003721 nucleus ; GO:0005634 \N 22083 IPR003540 A large group of bacterial exotoxins are referred to as "A/B toxins", essentially because they are formed from two subunits. The "A" subunit\ possesses enzyme activity, and is transferred to the host cell following\ a conformational change in the membrane-bound transport "B" subunit [MEDLINE:94041637].\ \

Clostridial species are one of the major causes of food poisoning/gastro-\ intestinal illnesses. They are Gram-positive, spore-forming rods that occur\ naturally in the soil [MEDLINE:94041637]. Included in the family are: Clostridium botulinum, which produces one of the most potent toxins in existence; Clostridium tetani, causative agent of tetanus; and Clostridium perfringens, commonly found in wound infections and diarrhoea cases.

\ \

Among the toxins produced by certain Clostridium spp. are the binary \ exotoxins. These proteins consist of two independent polypeptides, which\ correspond to the A/B subunit moieties. The enzyme component (A) enters \ the cell through endosomes produced by the oligomeric binding/translocation\ protein (B), and prevents actin polymerisation through ADP-ribosylation of \ monomeric G-actin [MEDLINE:94041637], [MEDLINE:96184657], [MEDLINE:20263779].

\ \

Members of the "A" binary toxin family include C.perfringens iota toxin Ia\ [MEDLINE:94041637], C.botulinum C2 toxin CI [MEDLINE:96184657], and Clostridium difficile ADP-ribosyltransferase \ [MEDLINE:20263779]. Other homologous proteins have been found in Clostridium spiroforme\ \ \ \ [MEDLINE:96184657], [MEDLINE:20263779].

\ \ toxin activity ; GO:0015070 extracellular ; GO:0005576 pathogenesis ; GO:0009405 22084 IPR003541 A large group of bacterial exotoxins are referred to as "A/B toxins", essentially because they are formed from two subunits. The "A" subunit\ possesses enzyme activity, and is transferred to the host cell following\ a conformational change in the membrane-bound transport "B" subunit [MEDLINE:94041637].\

Bacillus anthracis, a large Gram-positive spore-forming rod, is the \ causative agent of anthrax [MEDLINE:89211974]. Its two virulence factors are the \ poly-D-glutamate polypeptide capsule, and the actual anthrax exotoxin [MEDLINE:91372952]. The toxin comprises three factors: the protective antigen (PA); the oedema factor (EF) [MEDLINE:89211974]; and the lethal factor (LF) [MEDLINE:90034185]. Each is a thermolabile protein of ~80kDa. PA forms the "B" part of the exotoxin and allows passage of the "A" moiety (consisting of EF and LF) into target cells.

\ \

EF is necessary for the oedema-producing activity of the toxin, and is \ known to be an inherent adenylate cyclase. It causes dysregulation of intracellular signalling [MEDLINE:89211974], [MEDLINE:91372952]. Uptake of the lethal factor LF occurs via activated heptameric PA. Once inside the host lymphocytes/macrophages, the zinc metalloprotease of LF [MEDLINE:95154669] cleaves MAP kinases, inhibits cell proliferation, and leads to cell death [MEDLINE:91372952], [MEDLINE:90034185].

\ \ toxin activity ; GO:0015070 extracellular ; GO:0005576 pathogenesis ; GO:0009405 22085 IPR003542 Iron is essential for growth in both bacteria and mammals. Controlling the amount of free iron in solution is often used as a tactic by hosts to limit\ invasion of pathogenic microbes; binding iron tightly within protein\ molecules can accomplish this. Such iron-protein complexes include haem in\ blood, lactoferrin in tears/saliva and transferrin in blood plasma. Some\ bacteria express surface receptors to capture eukaryotic iron-binding\ compounds, while others have evolved siderophores to scavenge iron from\ iron-binding host proteins [MEDLINE:94335702].\ \

The absence of free iron molecules in the surrounding environment triggers \ transcription of gene clusters that encode both siderophore-synthesis \ enzymes, and receptors that recognise iron-bound siderophores [MEDLINE:89123154]. Classic\ examples are the enterobactin/enterochelin clusters found in Escherichia\ coli and Salmonella , although similar moieties in other pathogens have \ been identified. The enzymic machinery that produces vibrionectin in Vibrio\ cholera is such a homologue [MEDLINE:98037504].

\ \

EntD forms part of the enterobactin-synthetase enzyme complex. It is \ involved in the final stage of enterobactin biosynthesis, converting\ 2,3-dihydroxybenzoic acid (DHBA) and L-serine to enterobactin. Deletion\ studies involving EntD- mutants have shown that it is essential for\ virulence [MEDLINE:89123155].

\ \ \N enterobactin synthetase complex ; GO:0009366 enterobactin biosynthesis ; GO:0009239 22082 IPR003539 Escherichia coli, Haemophilus spp. and Campylobacter spp. all produce a toxin that is seen to cause distension in certain cell lines [MEDLINE:94156453], [MEDLINE:99221815], which eventually disintegrate and die. This novel toxin, termed cytolethal distending toxin (cdt), has three subunits: A, B, and C. Their sizes are approx. 27.7, 29.5 and 19.9kDa respectively [MEDLINE:94156453], and they appear to be entirely novel [MEDLINE:99221815]. \

Further research on the complete toxin has revealed that it blocks the cell\ cycle at stage G2, through inactivation of the cyclin-dependent kinase Cdk1, and without induction of DNA breaks. This leads to multipolar abortive\ mitosis and micronucleation, associated with centrosomal amplification [MEDLINE:20236869].\ The roles of each subunit are unclear, but it is believed that they have\ separate roles in pathogenicity.

\ \ toxin activity ; GO:0015070 \N pathogenesis ; GO:0009405 22079 IPR003536 Secretion of virulence factors in Gram-negative bacteria involves transportation of the protein across two membranes to reach the cell \ exterior. There have been four secretion systems described in \ animal enteropathogens, such as Salmonella and Yersinia, with further \ sequence similarities in plant pathogens like Ralstonia and Erwinia [MEDLINE:98284147].\ \

The type III secretion system is of great interest, as it is used to \ transport virulence factors from the pathogen directly into the host cell \ and is only triggered when the bacterium comes into close contact with\ the host. The protein subunits of the system are very similar to those of \ bacterial flagellar biosynthesis. However, while the latter forms a\ ring structure to allow secretion of flagellin and is an integral part of\ the flagellum itself [MEDLINE:98284147], type III subunits in the outer membrane \ translocate secreted proteins through a channel-like structure.

\ \

Exotoxins secreted by the type III system do not possess a secretion signal,\ and are considered unique for this reason [MEDLINE:98284147]. Enteropathogenic and entero-\ haemorrhagic Escherichia coli secrete the bacterial adhesion mediation\ molecule intimin [MEDLINE:20296671], which targets the translocated intimin receptor, Tir. Tir is secreted by the bacteria and is embedded in the target cell's plasma membrane [MEDLINE:20296671]. This facilitates bacterial cell attachment to the host.

\ \ receptor activity ; GO:0004872 \N cell adhesion ; GO:0007155 22080 IPR003537 Secretion of virulence factors in Gram-negative bacteria involves transportation of the protein across two membranes to reach the cell \ exterior. There have been four secretion systems described in \ animal enteropathogens, such as Salmonella and Yersinia, with further \ sequence similarities in plant pathogens like Ralstonia and Erwinia [MEDLINE:98284147].\ \

The type III secretion system is of great interest, as it is used to \ transport virulence factors from the pathogen directly into the host cell \ and is only triggered when the bacterium comes into close contact with\ the host. The protein subunits of the system are very similar to those of \ bacterial flagellar biosynthesis. However, while the latter forms a\ ring structure to allow secretion of flagellin and is an integral part of\ the flagellum itself [MEDLINE:98284147], type III subunits in the outer membrane \ translocate secreted proteins through a channel-like structure.

\ \

Exotoxins secreted by the type III system do not possess a secretion signal,\ and are considered unique for this reason [MEDLINE:98284147]. Yersinia secrete a Rho GTPase-activating protein, YopE [MEDLINE:90170873], [MEDLINE:90279509], that disrupts the host cell actin cytoskeleton. YopE is regulated by another bacterial gene, SycE [MEDLINE:99348356], that enables the exotoxin to remain soluble in the bacterial cytoplasm. A similar protein, exoenzyme S from Pseudomonas aeruginosa, has both ADP-ribosylation and GTPase activity [MEDLINE:90279509], [MEDLINE:99348356].

\ \ GTPase activator activity ; GO:0005096 membrane ; GO:0016020 \N 22081 IPR003538 Iron is essential for growth in both bacteria and mammals. Controlling the amount of free iron in solution is often used as a tactic by hosts to limit\ invasion of pathogenic microbes; binding iron tightly within protein\ molecules can accomplish this. Such iron-protein complexes include haem in\ blood, lactoferrin in tears/saliva and transferrin in blood plasma. Some\ bacteria express surface receptors to capture eukaryotic iron-binding\ compounds, while others have evolved siderophores to scavenge iron from\ iron-binding host proteins [MEDLINE:94335702].\ \

The absence of free iron molecules in the surrounding environment triggers \ transcription of gene clusters that encode both siderophore-synthesis \ enzymes, and receptors that recognise iron-bound siderophores [MEDLINE:89123154]. An \ example of the latter is Escherichia coli fepA, which resides in the outer \ envelope and captures iron-bound enterobactin [MEDLINE:99101384].

\ \

To complete transport of bound iron across the inner membrane, a second \ receptor complex is needed. The major component of this is tonB, a 27kDa\ protein that facilitates energy transfer from the proton motive force to\ outer receptors [MEDLINE:98305689]. B-12 and colicin receptors also make use of the tonB\ system to drive active transport at the outer membrane.

\ \ iron ion transporter activity ; GO:0005381 periplasmic space (sensu Gram-negative Bacteria) ; GO:0030288 iron ion transport ; GO:0006826 22077 IPR003534 The major royal jelly proteins (MRJPs) comprise 12.5% of the mass , and 82-90% of the protein content [MEDLINE:99007754], of honeybee (Apis mellifera) royal jelly. Royal jelly is a substance secreted by the cephalic glands of nurse bees [MEDLINE:99373663] and it is used to trigger development of a queen bee from a bee larva. The biological function of the MRJPs is unknown, but they are believed to play a major role in nutrition due to their high essential amino acid content [MEDLINE:99309773].\

Two royal jelly proteins, MRJP3 and MRJP5, contain a tandem repeat that\ results from a high genetic variablility. This polymorphism may be useful \ for genotyping individual bees [MEDLINE:99309773].

\ \ \N \N \N 22078 IPR003535 Secretion of virulence factors in Gram-negative bacteria involves transportation of the protein across two membranes to reach the cell \ exterior. There have been four secretion systems described in \ animal enteropathogens, such as Salmonella and Yersinia, with further \ sequence similarities in plant pathogens like Ralstonia and Erwinia [MEDLINE:98284147].\ \

The type III secretion system is of great interest, as it is used to \ transport virulence factors from the pathogen directly into the host cell \ and is only triggered when the bacterium comes into close contact with\ the host. The protein subunits of the system are very similar to those of \ bacterial flagellar biosynthesis. However, while the latter forms a\ ring structure to allow secretion of flagellin and is an integral part of\ the flagellum itself [MEDLINE:98284147], type III subunits in the outer membrane \ translocate secreted proteins through a channel-like structure.

\ \

The crystal structure of an enteropathogenic Escherichia coli intimin\ C-terminal fragment has been determined to 1.9A resolution. The \ structure has also been resolved in complex with the Tir intimin-binding\ domain, giving insight into the molecular mechanisms of adhesion in\ attaching and effacing pathogens [MEDLINE:20346505].

\ \ \N \N cell adhesion ; GO:0007155 22076 IPR003533

X-linked lissencephaly is a severe brain malformation affecting males.Recently it has been demonstrated that the doublecortin gene is implicated in\ this disorder [MEDLINE:98149343]. Doublecortin was found to bind to the microtubule\ cytoskeleton. In vivo and in vitro assays show that Doublecortin stabilizes\ microtubules and causes bundling [MEDLINE:99371766]. Doublecortin is a basic protein with an\ iso-electric point of 10, typical of microtubule-binding proteins. However,\ its sequence contains no known microtubule-binding domain(s).

\ \

The detailed sequence analysis of Doublecortin and Doublecortin-like proteins\ allowed the identification of an evolutionarily conserved Doublecortin (DC)\ domain. This domain is found in the N-terminus of proteins and consists of one\ or two tandemly repeated copies of an around 80 amino acids region. It has\ been suggested that the first DC domain of Doublecortin binds tubulin and\ enhances microtubule polymerization [MEDLINE:20215298].

\ \ \N \N intracellular signaling cascade ; GO:0007242 22072 IPR003529

A number of receptors for lymphokines, hematopoietic growth factors andgrowth hormone-related molecules have been found to share a common binding\ domain. These receptors are designated as hematopoietin receptors [MEDLINE:93015939] and\ the corresponding ligands as hematopoietins. Further, hematopoietins have been\ subdivided into two major structural groups: Large/long and small/short\ hematopoietins.

\ One subset of individual receptor chains that are part of receptor complexes\ for large hematopoietins contain common structural elements in their\ extracellular parts: an immunoglobin-like domain, an hematopoietin-receptor\ domain, and 3 fibronectin type-III domains (2 in the leptin receptor). This\ subgroup was designated as "gp130 family of receptors" [MEDLINE:97115791] and contains the\ following chains: Leptin receptor (LPTR), Granulocyte colony stimulating factor receptor (GCSFR), Interleukin-6/-11/LIF/OSM/CNTF common chain (GP130), Leukemia inhibiting factor receptor (LIFR), Oncostatin-M receptor chain (OSMR), Interleukin-12 receptor -1 chain (IL12RB1), Interleukin-12 receptor -2 chain (IL12RB2).

\ \

A schematic representation of the structure of these receptors is shown below:

 \
+-------+-------------------------+-----------------xxxxxxx-----------------+\
|Ig-like| C C  C  C Extracellular |    FnIII (x3)   XXXXXXX   Cytoplasmic   |\
+-------+-|-|--|--|---------------+-----------------xxxxxxx-----------------+\
          | |  |  |                              Transmembrane\
          +-+  +--+\

\ \

These receptor chains homodimerize (GCSFR, GP130, LPTR) or heterodimerize\ (GP130 with LIFR or OSMR, IL12RB1 with IL12RB2) upon binding of the cognate\ cytokine: G-CSF, LIF, OSM, LPT, or the cytokine/ chain complex:\ IL-6/IL6RA, IL-11/IL11RA, CNTF/CNTFRA, IL-12 (p35/p40) [MEDLINE:94123333],[MEDLINE:97098510].

\ \ hematopoietin/interferon-class (D200-domain) cytokine receptor activity ; GO:0004896 membrane ; GO:0016020 \N 22073 IPR003530

\ \

One subset of individual receptor chains that are part of receptor complexes\ for large hematopoietins contain common structural elements in their\ extracellular parts: an immunoglobulin-like domain at the N-terminal end of\ the hematopoietin receptor domain (except for the EBCV-induced interleukin-12 chain) and a short (or no) cytoplasmic domain. They define a structural \ subgroup containing the following chains: Interleukin-6 receptor chain (IL6RA). Interleukin-11 receptor chain (IL11RA), Ciliary neurotrophic factor receptor chain (CNTFRA), Interleukin-12 chain p40 (IL12BC),\ Interleukin-12 chain induced by Epstein-Barr Virus (EBI3).

A schematic representation of the structure of these receptors is shown below:

 \
+-----------+--------------------------------------------+\
|  Ig-like  |  C C     C  C         Extracellular        |\
+-----------+--|-|-----|--|------------------------------+\
               | |     |  |\
               +-+     +--+\

Members of this subgroup bind to their cognate cytokines with low affinity\ and possess transmembrane and short cytoplasmic domains (IL6RA and IL11RA),\ or are GPi-linked membrane proteins (CNTFRA). Truncated soluble forms of\ IL-6 and CNTF receptors chains are physiologically active [MEDLINE:94123333]. IL-12\ is an heterodimeric cytokine made of an chain (p35) and a chain\ (p40). p40 (IL12BC) can be regarded as an chain receptor devoid of\ cytoplasmic domain [MEDLINE:91300556]. Members of this family have the ability to bind\ corresponding cytokines with no signalling function.

\ \ hematopoietin/interferon-class (D200-domain) cytokine receptor activity ; GO:0004896 membrane ; GO:0016020 \N 22074 IPR003531

One subset of individual receptor chains that are part of receptor complexes for small hematopoietins are structurally related such that their extracellular parts strictly contain the 200 amino-acids hematopoietin domain (duplicated in IL-3/-5/GM-CSF chain receptors KH97/AIC2B and AIC2A). They define a structural subgroup containing the following chains: Interleukin-2 receptor chain (IL2RB), Interleukin-2 receptor common gamma chain (IL2RG), Interleukin-3 receptor chain (AIC2A), Interleukin-3/-5/GM-CSF receptor common chain (KH97/AIC2B), Interleukin-4 receptor chain (IL4RA), Interleukin-7 receptor chain (IL7RA), Interleukin-9 receptor chain (IL9RA).

A schematic representation of the structure of these receptors is shown below:

 \
 +----------------------------------------xxxxxxx---------------------------+\
 | C C       C  C  Extracellular          XXXXXXX   Cytoplasmic             |\
 +-|-|-------|--|-------------------------xxxxxxx---------------------------+\
   | |       |  |                      Transmembrane\
   +-+       +--+\

IL4RA, IL7RA and IL9RA are specific chain receptors for IL-4, IL-7\ and IL-9 respectively, whereas IL2RB is common to IL-2 and IL-15 (IL2RA and\ IL15RA are not members of the hematopoietin receptor superfamily). IL2RG is\ part of IL-2, IL-15, IL-7, IL-9 and IL-4 form I receptor complexes [MEDLINE:95032867].\ KH97/AIC2B chain is part of GM-CSF, IL-3 and IL-5 receptor complexes and in\ the mouse, AIC2B can be substituted by AIC2A, an IL-3 specific chain\ receptor [MEDLINE:92005681]. Together with either IL13RA1 or IL13RA2, IL4RA is also part\ of the IL-13 receptor complex for which IL-4 can compete with IL-13 (IL-4\ receptor complex form II) [MEDLINE:96133964].\

\ \ hematopoietin/interferon-class (D200-domain) cytokine receptor activity ; GO:0004896 membrane ; GO:0016020 \N 22075 IPR003532

\ \

One subset of individual receptor chains that are part of receptor complexes\ for small hematopoietins contain common structural elements in their\ extracellular parts: an immunoglobulin-like domain at the N-terminal end of\ the hematopoietin receptor domain and a rather short cytoplasmic domain. They\ define a structural subgroup containing the following chains: Granulocyte/macrophage colony stimulating factor receptor (GMCSFRA), \ Interleukin-3 receptor chain (IL3RA), Interleukin-5 receptor chain (IL5RA), Interleukin-13 receptor -1 chain (IL13RA1), Interleukin-13 receptor -2 chain (IL13RA2).

A schematic representation of the structure of these receptors is shown below:

 \
+-----------+-------------------------------------------xxxxxxx-------------+\
|  Ig-like  |  C C     C  C         Extracellular       XXXXXXX Cytoplasmic |\
+-----------+--|-|-----|--|-----------------------------xxxxxxx-------------+\
               | |     |  |                          Transmembrane\
               +-+     +--+\

GMCSFRA, IL3RA or IL5RA chains of this subgroup bind to their cognate\ cytokines: GM-CSF, IL-3 and IL-5, with a common chain, KH97/AIC2B [MEDLINE:92005681].

\ \

Either IL13RA1 chain or IL13RA2 chain form the IL13R complex together with\ IL4RA chain. IL-4 can compete with IL-13 to bind to either IL13R form [MEDLINE:96133964].

\ \ hematopoietin/interferon-class (D200-domain) cytokine receptor activity ; GO:0004896 membrane ; GO:0016020 \N 22068 IPR003524

Phospho-N-acetylmuramoyl-pentapeptide-transferase (EC: 2.7.8.13) (mraY) is a bacterial enzyme responsible for the formation of the first lipidintermediate of the cell wall peptidoglycan synthesis. It catalyzes the\ formation of undecaprenyl-pyrophosphoryl-N-acetylmuramoyl-pentapeptide from\ UDP-MurNAc-pentapeptide and undecaprenyl-phosphate.

\ \

It is an integral membrane protein with probably ten transmembrane domains. It belongs to family 4 of glycosyl transferases. Homologs of mraY have been found in the archaebacteria Methanobacterium thermoautotrophicum and in Arabidopsis thaliana.

\ \ phospho-N-acetylmuramoyl-pentapeptide-transferase activity ; GO:0008963 membrane ; GO:0016020 peptidoglycan biosynthesis ; GO:0009252 22069 IPR003526 The ygbB protein is a putative enzyme of deoxy-xylulose pathway (terpenoid biosynthesis) [MEDLINE:20183914]. A number of proteins from eukaryotes and prokaryotes share this common N-terminal signature and have been shown to play a role in terpenoid biosynthesis.\ \ 2C-methyl-D-erythritol 2,4-cyclodiphosphate synthase activity ; GO:0008685\ \N \N terpenoid biosynthesis ; GO:0016114 22070 IPR003527

Eukaryotic serine-threonine mitogen-activated protein (MAP) kinases are key regulators of cellular signal transduction systems and are conserved from baker's yeast to human beings. MAPK pathways are signalling cascades differentially regulated by growth factors, mitogens, hormones and stress which mediate cell growth, differentiation and survival. MAPK activity is regulated through a (usually) three-tiered cascade composed of a MAPK, a MAPK kinase (MAPKK, MEK) and a MAPK kinase kinase (MAPKK, MEKK). Substrates for the MAPKs include other kinases and transcription factors [MEDLINE:21133147].

\ \

Mammals express at least four distinctly related groups of MAPKs, extracellularly-regulated kinases (ERKs), c-jun N-terminal kinases (JNKs), p38 proteins and ERK5. Plant MAPK pathways have\ attracted increasing interest, resulting in the isolation of a large number of different components of MAPK cascades. MAPKs play important roles in the signaling of most plant hormones and in developmental processes [MEDLINE:20509515]. In the budding yeast, Saccharomyces cerevisiae, four separate but structurally related mitogen-activated protein kinase (MAPK)\ activation pathways are known, regulating mating, cell integrity and osmosity [MEDLINE:96192967].

\ \ \ \

Enzymes in this family are characterised by two domains separated by a deep channel where potential substrates might bind. The N-terminal domain creates a binding pocket for the adenine ring of ATP, and the C-terminal domain contains the catalytic base, magnesium binding sites and phosphorylation lip [MEDLINE:97066959]. Almost all MAPKs possess a conserved TXY motif in which both the threonine and\ tyrosine residues are phosphorylated during activation of the enzyme by\ upstream dual-specificity MAP kinase kinases (MAPKKs).

\ \ ATP binding activity ; GO:0005524 \N protein amino acid phosphorylation ; GO:0006468 22071 IPR003528

\ \

Several receptor chains for large hematopoietins are structurally related\ such that their extracellular parts strictly contain the 200 amino-acids\ hematopoietin domain, duplicated in the thrombopoietin receptor and in\ avian prolactin receptors. This subgroup of receptor chains contains: Growth hormone receptor (GHR), Prolactin receptor (PRLR), Erythropoietin receptor (EPOR), Thrombopoietin receptor (TPOR).

\ \

A schematic representation of the structure of these receptors is shown below:

\ \

\
 +----------------------------------------xxxxxxx-------------------------+\
 | C C       C  C  Extracellular          XXXXXXX       Cytoplasmic       |\
 +-|-|-------|--|-------------------------xxxxxxx-------------------------+\
   | |       |  |                      Transmembrane\
   +-+       +--+\

\ \

These receptor chains are single components of receptors that homodimerize\ upon binding of the cognate cytokine, following the structural model\ described for the growth hormone-receptor complex [MEDLINE:92196577].\

\ \ hematopoietin/interferon-class (D200-domain) cytokine receptor activity ; GO:0004896 membrane ; GO:0016020 \N 22064 IPR003520

Secretion of virulence factors in Gram-negative bacteria involves transportation of the protein across two membranes to reach the cell \ exterior. There have been four secretion systems described in \ sequence similarities in plant pathogens like Ralstonia and Erwinia [MEDLINE:97125927].

The type III secretion system is of great interest, as it is used to \ transport virulence factors from the pathogen directly into the host cell \ [MEDLINE:99269264] and is only triggered when the bacterium comes into close contact with\ the host. The protein subunits of the system are very similar to those of \ bacterial flagellar biosynthesis. However, while the latter forms a\ ring structure to allow secretion of flagellin and is an integral part of\ the flagellum itself [MEDLINE:20032050], type III subunits in the outer membrane\ translocate secreted proteins through a channel-like structure.

The Salmonella/Shigella invasion protein E gene (InvE) is one such type\ III secretion protein subunit, and is localised to the outer membrane of \ the SPI I pathogenicity island, and is involved in the surface presentation.

\ \ type III protein (virulence-related) secretor activity ; GO:0015448 \N protein secretion ; GO:0009306 22065 IPR003521 The nucleotide-sensitive chloride conductance regulatory protein (ICln) isfound ubiquitously in mammalian (and other) cell types and is postulated to\ play a critical role in cell volume regulation. Initial studies proposed\ that ICln was itself a swelling-activated anion channel; however, further\ studies demonstrated that it is localised primarily to the cell cytoplasm.\ It has therefore been postulated that activation of cell volume regulation\ may involve reversible translocation of ICln from the cytoplasm, and its\ insertion into the plasma membrane. It is not resolved whether the anionic channel involved in cell volume regulation after cell-swelling comprises one or more subunits, and if it does, whether ICln is in fact one of them [MEDLINE:98359057].\ \ \N \N regulation of cell volume ; GO:0006884 22066 IPR003522

Secretion of virulence factors in Gram-negative bacteria involves transportation of the protein across two membranes to reach the cell \ exterior. There have been four secretion systems described in \ animal enteropathogens such as Salmonella and Yersinia, with further sequence similarities in plant pathogens like Ralstonia and Erwinia [MEDLINE:97125927].

The type III secretion system is of great interest, as it is used to \ transport virulence factors from the pathogen directly into the host cell \ [MEDLINE:99269264] and is only triggered when the bacterium comes into close contact with\ the host. The protein subunits of the system are very similar to those of \ bacterial flagellar biosynthesis [MEDLINE:20032050]. However, while the latter forms a\ ring structure to allow secretion of flagellin and is an integral part of\ the flagellum itself [MEDLINE:20032050], type III subunits in the outer membrane\ translocate secreted proteins through a channel-like structure.

One of the outer membrane protein subunit families, termed "G" here for \ nomenclature purposes, aids in the structural assembly of the invasion \ complex [MEDLINE:96310365]. Another characteristic of this family is its ability to form a \ channel through the outer bacterial membrane, allowing secretion to take \ place. Members include the Salmonella InvG and SpiA gene, the Shigella MxiD, \ and the Yersinia Kim5 and YscC proteins. Plant pathogen members include the \ Hypersensitivity Response (HR) genes of Burkholderia and Erwinia.

\ \ type III protein (virulence-related) secretor activity ; GO:0015448 \N protein secretion ; GO:0009306 22067 IPR003523

The independent cloning of rodent EBF/Olf-1 and Drosophila melanogaster Collier has defineda family of transcription factors, the Collier or COE family [MEDLINE:99406633]. COE proteins\ have various functions in different organisms.

In mouse, COE1 has a role in B-cell differentiation, and could also perform a\ role in neuronal differentiation. All three COE are expressed in immature\ olfactory neuronal precursors and mature olfactory neurons as well as in\ developping nervous system during embryogenesis.

\ \

In Drosophila, Collier is involved in the formation of the embryonic somatic\ muscle DA3, in the patterning of the wing by mediating Hedgehog activity.\ It could also act as a second-level regulator in the patterning of embryonic\ head.

\ \ DNA binding activity ; GO:0003677 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 22062 IPR003518

Salmonella typhimurium contains a 90kb plasmid that is associated withvirulence. This plasmid encodes at least 6 genes needed by the\ bacterium for invading host macrophages during infection. These include\ the 70kDa mkaA protein [MEDLINE:90316693], a recognised virulence factor, and more recently described, four spv genes under the control of a regulator [MEDLINE:93247482].

Deletion studies on the virulence plasmid have shown that an open reading \ frame encoding a 28kDa protein was needed for successful invasion of the \ host. This protein, designated mkfA [MEDLINE:90316693], VRP4 [MEDLINE:90161559] or VirA [MEDLINE:92041614] by different\ groups, is utilised by the microbe upon entry into macrophages, although the \ exact mechanism is unclear.

\ \ \N \N \N 22057 IPR003513 This is a family of proteins from single-stranded DNA bacteriophages. Scaffold proteins B and D are required for procapsid formation. Sixty copies of the internal scaffold protein B are found in the procapsid.\ \ \N viral procapsid ; GO:0046729 viral capsid assembly ; GO:0019069 22058 IPR003514 This is a family of proteins from single-stranded DNA bacteriophages. Protein F is the major capsid component, sixty copies of which are found in the virion. The virion is also composed of 60 copies of each of the G and J proteins, and 12 copies of the H protein.\ \ structural molecule activity ; GO:0005198 viral capsid ; GO:0019028 \N 22059 IPR003515 This is a family of proteins from single-stranded DNA bacteriophages. The G protein is a major spike protein involved in attachment to the bacterial host cell. The virion is composed of sixty copies of each of the F, G and J proteins, and 12 copies of the H protein. There are twelve spikes formed by five G proteins, each a tight

barrel, and one H protein.\ \N \N virus-host interaction ; GO:0019048 22060 IPR003516 Fanconi anaemia (FA) [MEDLINE:92350288], [MEDLINE:93258346], [MEDLINE:95015009] is a recessive inherited disease characterised bydefective DNA repair. FA cells are sensitive to DNA cross-linking agents\ that cause chromosomal instability and cell death. The disease is manifested\ clinically by progressive pancytopenia, variable physical anomalies, and\ predisposition to malignancy [MEDLINE:95015009]. Four complementation groups have been\ identified, designated A to D. The FA group A gene (FAA) has been\ cloned [MEDLINE:97312685], but its function remains to be elucidated.\ \ \N \N \N 22061 IPR003517

Three cysteine-rich proteins (also believed to be lipoproteins) make up theextracellular matrix of the Chlamydial outer membrane [MEDLINE:91141306]. They are involved \ in the essential structural integrity of both the elementary body (EB) and \ recticulate body (RB) phase. As these bacteria lack the peptidoglycan layer\ common to most Gram-negative microbes, such proteins are highly important \ in the pathogenicity of the organism.

The largest of these is the major outer membrane protein (MOMP), and \ constitutes around 60% of the total protein for the membrane [MEDLINE:93238877]. OMP2\ is the second largest, with a molecular mass of 58kDa, while the OMP3\ protein is ~15kDa [MEDLINE:91141306]. MOMP is believed to elicit the strongest immune \ response, and has recently been linked to heart disease through its sequence\ similarity to a murine heart-muscle specific myosin [MEDLINE:99157122].

The OMP3 family plays a structural role in the outer membrane during \ the EB stage of the Chlamydial cell, and different biovars show a small, yet \ highly significant, change at peptide charge level [MEDLINE:91141306]. Members of this \ family include Chlamydia trachomatis, Chlamydia pneumoniae, and Chlamydia psittaci.

\ \ extracellular matrix structural constituent ; GO:0005201 extracellular matrix ; GO:0005578 \N 22063 IPR003519

Salmonella typhimurium contains a 90kb plasmid that is associated withvirulence. This plasmid encodes at least 6 genes needed by the \ bacterium for invading host macrophages during infection. These include \ the 70kDa mkaA protein [MEDLINE:90316693], a recognised virulence factor.

Deletion studies into the virulence plasmid have shown that an open reading\ frame encoding a 28kDa protein was needed for successful invasion of the \ host. This protein, designated mkfA [MEDLINE:90316693], VRP4 [MEDLINE:90161559] or VirA [MEDLINE:92041614] by different\ groups, is utilised by the microbe upon entry into macrophages, although the\ exact mechanism is unclear.

\ \ \N \N \N 22049 IPR003505

Glial cell line-derived neurotrophic factor (GDNF) and its related factorsneurturin (NTN), artemin (ART) and persephin (PSP), are members of the GDNF\ family of neurotrophic factors. They form a sub-group in the transforming \ growth factor- (TGF-) superfamily. These factors are involved in\ the promotion of neurone survival, exerting their effects through specific \ receptors.

The GDNF family receptors (GFRs) are glycosyl-phosphatidylinositol-linked,\ cell surface receptors [MEDLINE:99286308]. Four receptor subtypes, termed GFRalpha-1 to 4, are currently recognised. GFRalpha-3 has been cloned from mammalian tissue [MEDLINE:98245162]. It represents the least conserved member of the GFR family in terms of amino acid sequence, and is activated by artemin [MEDLINE:99098192].

Activation of GFR family members triggers their interaction with the membrane-bound receptor kinase Ret. This induces Ret homo-dimerisation, \ triggering a cascade of intracellular signalling events such as the \ activation of the Ras-mitogen-activated protein kinase (MAPK), phosphoinositol-3-kinase (PI3K), Jun N-terminal kinase (JNK) and \ phospholipase C gamma (PLC gamma) dependent pathways [MEDLINE:99286308].

\ \ receptor activity ; GO:0004872 \N \N 22050 IPR003506

Three cysteine-rich proteins (also believed to be lipoproteins) make up theextracellular matrix of the Chlamydial outer membrane [MEDLINE:91141306]. They are involved in the essential structural integrity of both the elementary body (EB) and recticulate body (RB) phase. As these bacteria lack the peptidoglycan layer common to most Gram-negative microbes, such proteins are highly important \ in the pathogenicity of the organism.

The largest of these is the major outer membrane protein (MOMP), and \ constitutes around 60% of the total protein for the membrane [MEDLINE:93238877]. OMP6 is the second largest, with a molecular mass of 58kDa, while the OMP3 protein is ~15kDa [MEDLINE:91141306]. MOMP is believed to elicit the strongest immune response, and has recently been linked to heart disease through its sequence similarity to a murine heart-muscle specific myosin [MEDLINE:99157122].

The OMP6 family plays a structural role in the outer membrane during \ the EB stage of the Chlamydial cell, and different biovars show a small, yet \ highly significant, change at peptide charge level [MEDLINE:91141306]. Members of this family include Chlamydia trachomatis, Chlamydia pneumoniae and Chlamydia psittaci.

\ \ extracellular matrix structural constituent ; GO:0005201 extracellular matrix ; GO:0005578 \N 22056 IPR003512 This family contains the bacteriophage helix-destabilizing protein, or single-stranded DNA binding protein, required for DNA synthesis. The protein binds to DNA in a highly cooperative manner without pronounced sequence specificity. In the presence of single-stranded DNA it binds cooperatively to form a helical protein-DNA complex. It prevents the conversion during synthesis of the single-stranded (progeny) viral DNA back into the double-stranded replicative form.\ single-stranded DNA binding activity ; GO:0003697 \N DNA replication ; GO:0006260 22053 IPR003509 The function of this family is unknown. Members include several bacterial hypothetical proteins.\ \N \N \N 22054 IPR003510 Fumarate reductase is a membrane-bound flavoenzyme consisting of four subunits, A-B. A and B comprise the membrane-extrinsic catalytic domain and C and D link the catalytic centers to the electron-transport chain. This family consists of the 15kDa hydrophobic subunit C.\ \N membrane ; GO:0016020 electron transport ; GO:0006118 22055 IPR003511 The HORMA (for Hop1p, Rev7p and MAD2) domain has been suggested to recognise chromatin states that result from DNA adducts, double stranded breaks or non-attachment to the spindle and acts as an adaptor that recruits other proteins. Hop1 is a meiosis-specific protein, Rev7 is required for DNA damage induced mutagenesis, and MAD2 is a spindle checkpoint protein which prevents progression of the cell cycle upon detection of a defect in mitotic spindle integrity.\ \N \N \N 22051 IPR003507 This signature is found in the Escherichia coli microcin C7 self-immunity protein MCCF and a set of uncharacterised proteins including hypothetical proteins from various bacteria.\ \N \N \N 22052 IPR003508 This domain is found in caspase-activated (CAD) nuclease, which induces DNA fragmentation and chromatin condensation during apoptosis, and in the cell death activator proteins CIDE-A and CIDE-B, which are inhibitors of CAD nuclease. The two proteins interact through this domain.\ apoptosis regulator activity ; GO:0016329 intracellular ; GO:0005622 apoptosis ; GO:0006915 22043 IPR003499 This family includes proteins that are probably involved in DNA packing in herpesvirus. This domain is normally found at the N-terminus of the protein.\ \ \N \N DNA packaging ; GO:0006323 22044 IPR003500 This family of proteins contains the sugar isomerase enzymes ribose 5-phosphate isomerase B (rpiB), galactose isomerase subunit A (LacA) and galactose isomerase subunit B (LacB). Ribose 5-phosphate isomerase B forms a homodimer and catalyses the conversion of D-ribose 5-phosphate to D-ribulose 5-phosphate in the nonoxidative branch of the pentose phosphate pathway. Galactose-6-phosphate isomerase is a heteromultimeric protein consisting of subunits LacA and LacB, and catalyses the conversion of D-galactose 6-phosphate to D-tagatose and 6-phosphate in the tagatose 6-phosphate pathway of lactose catabolism. The enzyme is induced by galactose or lactose.\ \N \N carbohydrate metabolism ; GO:0005975 22045 IPR003501 The bacterial phosphoenolpyruvate: sugar phosphotransferase system (PTS) is a multi-protein system involved in the regulation of a variety of metabolic and transcriptional processes. The lactose/cellobiose-specific family are one of four\ structurally and functionally distinct group IIB PTS system cytoplasmic enzymes. The fold of IIB cellobiose shows similar\ structure to mammalian tyrosine phosphatases. This signature is often found downstream of IPR003352.\ \ sugar porter activity ; GO:0005351 \N phosphoenolpyruvate-dependent sugar phosphotransferase system ; GO:0009401 22046 IPR003502 Over a hundred cytokines have now been identified, including several putative new members of the IL-1 family. The IL-1 family consists of 2 main classes, designated

(IL1A) and

(IL1B), as well as the more recently discovered IL-1 receptor antagonist (IL1RA). Sequence similarity is high within the IL1A and IL1B subfamilies (about 60-70%) but low between them (less than 30%). IL1Asand IL1Bs are synthesised as larger precursors, which are processed to give mature carboxy fragments. IL1B requires this cleavage to become biologically active, but IL1A precursor is already active. Both IL1A and IL1B bind to the same IL1-specific receptor on the target cell, which is then internalised to initiate the relevant effects (which appear to be similar or identical). The N terminal approx. 115 amino acids form a propeptide that is cleaved off to release the active interleukin-1. This signature is for the propeptide.\ \ interleukin-1 receptor ligand activity ; GO:0005149 \N immune response ; GO:0006955 22047 IPR003503

The GDNF family receptors (GFRs) are glycosyl-phosphatidylinositol-linked,\ cell surface receptors [MEDLINE:99286308]. Four receptor subtypes, termed GFRalpha-1 to 4, are currently recognised. Homologues for the GFRalpha-1 receptor subtype have been cloned from mammalian and avian tissue. The receptor is activated by GDNF [Pubmed:8954626], although there is evidence it can also bind neurturin, the principal ligand for GFRalpha-2 [MEDLINE:97338137].

Activation of GFRalpha-1 triggers its interaction with the membrane-bound receptor kinase Ret. This induces Ret homo-dimerisation, \ triggering a cascade of intracellular signalling events such as the \ activation of the Ras-mitogen-activated protein kinase (MAPK), phosphoinositol-3-kinase (PI3K), Jun N-terminal kinase (JNK) and \ phospholipase C gamma (PLC gamma) dependent pathways [MEDLINE:99286308].

\ \ receptor activity ; GO:0004872 \N \N 22037 IPR003493 Herpesvirus glycoprotein H (gH) is a virion associated envelope glycoprotein [MEDLINE:98187294]. Complex formation between gH and gL has been demonstrated in both virions and infected cells [MEDLINE:97410287].\ \N \N \N 22038 IPR003494 FtsA is essential for bacterial cell division, and co-localizes to the septal ring with FtsZ. It has been suggested that the interaction of FtsA-FtsZ has arisen through coevolution in different bacterial strains [MEDLINE:98012980].\ \ \N \N cell cycle ; GO:0007049 22039 IPR003495 This family of proteins contains P47K, a Pseudomonas chlororaphis protein needed for nitrile hydratase expression, and the cobW gene product, which may be involved in cobalamin biosynthesis in Pseudomonas denitrificans\ \ \ [MEDLINE:92011366].\ \ \N \N \N 22040 IPR003496 This is a family of plant proteins induced by water deficit stress (WDS) [MEDLINE:98088006], or abscisic acid (ABA) stress and ripening [MEDLINE:95357432].\ \N \N response to stress ; GO:0006950 22041 IPR003497 This family includes the N-terminus of baculovirus BRO and ALI motif proteins. The function of BRO proteins is unknown. It has been suggested that BRO-A and BRO-C are DNA binding proteins that influence host DNA replication and/or transcription\ [MEDLINE:20347340]. This Pfam domain does not include the characteristic invariant alanine, leucine, isoleucine motif of the ALI proteins [MEDLINE:99102612].\ \ \N \N \N 22042 IPR003498 This family includes proteins that are probably involved in DNA packing in herpesvirus. This domain is found at the C-terminus of the protein.\ \ \N \N DNA packaging ; GO:0006323 22048 IPR003504

The GDNF family receptors (GFRs) are glycosyl-phosphatidylinositol-linked,\ cell surface receptors [MEDLINE:99286308]. Four receptor subtypes, termed GFRalpha-1 to 4, are currently recognised. Homologues for the GFRalpha-2 receptor subtype have been cloned from mammalian and avian tissue. The receptor is preferentially activated by neurturin, although there is evidence that \ GFRalpha-2 can also bind GDNF if pre-coupled to its effector molecule [MEDLINE:97322356].

Activation of GFRalpha-2 triggers its interaction with the membrane-bound receptor kinase Ret. This induces Ret homo-dimerisation, \ triggering a cascade of intracellular signalling events such as the \ activation of the Ras-mitogen-activated protein kinase (MAPK), phosphoinositol-3-kinase (PI3K), Jun N-terminal kinase (JNK) and \ phospholipase C gamma (PLC gamma) dependent pathways [MEDLINE:99286308].

\ \ receptor activity ; GO:0004872 \N \N 22034 IPR003490 Infectious hematopoietic necrosis virus (IHNV) is a member of the family Rhabdoviridae. The non-virion protein (NV) is coded for by one of the six genes of the IHNV genome [MEDLINE:96118173], but is absent in vesiculovirus -like rhabdovirus [MEDLINE:97163473].\ \ \N \N \N 22036 IPR003492

Batten's disease, the juvenile variant of neuronal ceroid lipofuscionosis(NCL), is a recessively inherited disorder affecting children of 5-10\ years of age. The disease is characterised by progressive loss of vision,\ seizures and psychomotor disturbances. Biochemically, the disease is\ characterised by lysosomal accumulation of hydrophobic material, mainly ATP\ synthase subunit C, largely in the brain but also in other tissues. The disease is fatal within a decade [MEDLINE:96016090].

Mutations in the CLN3 gene are believed to cause Batten's disease [MEDLINE:96016090]. The\ CLN3 gene, with a predicted 438-residue product, maps to chromosome p16p12.1. The gene contains at least 15 exons spanning 15kb and is highly conserved in mammals [MEDLINE:90307738]. A 1.02kb deletion in the CLN3 gene, occurring in either one or both alleles, is found in 85% of Batten disease chromosomes causing a frameshift generating a predicted translated product of 181 amino acid residues [MEDLINE:96016090], [MEDLINE:99208853]. 22 other mutations, including deletions, insertions and point mutations, have been\ reported. It has been suggested that such mutations result in severely\ truncated CLN3 proteins, or affect its structure/conformation [MEDLINE:96016090], [MEDLINE:97456421].

CLN3 proteins, which are believed to associate in complexes, are heavily\ glycosylated lysosomal membrane proteins [MEDLINE:99208853], containing complex Asn-linked\ oligosaccharides [MEDLINE:90307738]. Extensive glycosylation is important for the stability\ of these lysosomal proteins in the highly hydrolytic lysosomal lumen. Lysosomal\ sequestration of active lysosomal enzymes, transport of degraded molecules\ from the lysosomes, and fusion and fission between lysosomes and other\ organelles. The CLN3 protein is a 43kDa, highly hydrophobic, multi-transmembrane (TM),\ phosphorylated protein [MEDLINE:99208853]. Hydrophobicity analysis predicts 6-9 TM\ segments, suggesting that CLN3 is a TM protein that may function as a\ chaperone or signal transducer. The majority of putative phosphorylation\ sites are found in the N-terminal domain, encompassing 150 residues [MEDLINE:99208852].\ Phosphorylation is believed to be important for membrane compartment \ interaction, in the formation of functional complexes, and in regulation \ and interactions with other proteins [MEDLINE:93128844].

CLN3 contains several motifs that may undergo lipid post-translational\ modifications (PTMs). PTMs contribute to targeting and anchoring of modified\ proteins to distinct biological membranes [MEDLINE:95232494]. There are three general \ classes of lipid modification: N-terminal myristoylation, C-terminal \ prenylation, and palmitoylation of cysteine residues. Such modifications \ are believed to be a common form of PTM occurring in 0.5% of all cellular\ proteins, including brain tissue [MEDLINE:99208850]. The C terminus of the CLN3 contains\ various lipid modification sites: C435, target for prenylation; G419, \ target for myristoylation; and C414, target for palmitoylation [MEDLINE:98046010].\ Prenylation results in protein hydrophobicity, influences interaction with\ upstream regulatory proteins and downstream effectors, facilitates protein-protein interaction (multisubunit assembly) and promotes anchoring to\ membrane lipids. The prenylation motif, Cys-A-A-X, is highly conserved\ within CLN3 protein sequences of different species [MEDLINE:99208850].\ Species with known CLN3 protein homologues include: Homo sapiens, Canis \ familiaris, Mus musculus, Saccharomyces cerevisiae and Drosophila\ melanogaster.

\ \ \ \N membrane ; GO:0016020 \N 22035 IPR003491 Plasmid replication is initiated by the replication initiation factor (REP). This family represents a probable topoisomerase that makes a sequence-specific single-stranded nick in the plasmid DNA at the origin of replication. Human proteins also belong to\ this family, including myelin transcription factor 2 and cerebrin-50 [MEDLINE:95253026].\ \ DNA topoisomerase activity ; GO:0003916 \N DNA replication initiation ; GO:0006270 22025 IPR003481 The flagellar hook-associated protein 2 (HAP2 or FliD) is the capping protein for the flagella and forms the distal end of the flagella. The protein plays a role in mucin specific adhesion of the bacteria [MEDLINE:98147712].\ \N flagellum (sensu Bacteria) ; GO:0009288 flagella biogenesis ; GO:0009296 22026 IPR003482 WhiB is a putative transcription factor in Actinobacteria, required for differentiation and sporulation. The process of mycelium formation in Streptomyces, which occurs in response to nutrient limitation, is controlled by a number of whi genes, named for the white colour of aerial hyphae when mutations occur in these genes. The normal colour is grey. The exact role of WhiB is not clear, but a mutation in the gene results in white, tightly coiled aerial hyphae.\ transcription factor activity ; GO:0003700 \N regulation of transcription, DNA-dependent ; GO:0006355 22027 IPR003483 This is a family of outer surface proteins (Osp) from the Borrelia spp. spirochete [MEDLINE:97136624]. The family includes OspE, OspF, and OspEF-related proteins (Erp) [MEDLINE:96256604]. These proteins are coded for on different circular plasmids in the Borrelia genome.\ \N \N \N 22028 IPR003484 Rhizobia nodulation (nod) genes control the biosynthesis of Nod factors required for infection and nodulation of their legume hosts. Nodulation protein A (NodA) is a N-acetyltransferase involved in production of Nod factors that stimulate mitosis in various plant protoplasts.\ acyltransferase activity ; GO:0008415 \N \N 22029 IPR003485

This is a family of unique short (US) region proteins from herpesvirus strains. The US2 family has no known function.

\ \N \N \N 22030 IPR003486 The nucleoprotein of the ssRNA negative-strand Nairovirus is an internal part of the virus particle.\ \N viral nucleocapsid ; GO:0019013 \N 22031 IPR003487 This family represents the phosphoprotein of Paramyxoviridae, a putative RNA polymerase

subunit that may function in template binding.\ RNA-directed RNA polymerase activity ; GO:0003968 \N \N 22032 IPR003488 The SMF family (DNA processing chain A, dprA) are a group of bacterial proteins. In Helicobacter pylori, dprA is required for natural chromosomal and plasmid transformation [MEDLINE:20108718].\ \N \N DNA mediated transformation ; GO:0009294 22033 IPR003489

\ \ \

This family contains the sigma-54 modulation protein family and the S30AE family of ribosomal proteins which includes the light-repressed protein (lrtA) [MEDLINE:94342247].

\ \ \N \N \N 22018 IPR003474 This is a family of integral membrane permeases that are involved in gluconate uptake. Escherichia coli contains several members of this family including GntU, a low affinity transporter [MEDLINE:97280784] and GntT, a high affinity transporter [MEDLINE:97197521].\ gluconate transporter activity ; GO:0015128 membrane ; GO:0016020 gluconate transport ; GO:0015725 22019 IPR003475 This family of insect proteins are each about 100 amino acids long and have 6 conserved cysteine residues. They all have a predicted signal peptide and are probably excreted. The function of the proteins is unknown [MEDLINE:96152797].\ \N \N \N 22020 IPR003476

\ This group of

-galactosidase enzymes (EC: 3.2.1.23) belong to the glycosyl hydrolase 42 family CAZY:GH_42. The enzyme catalyses the hydrolysis of terminal, non-reducing terminal

-D-galactosidase residues.\ \ beta-galactosidase activity ; GO:0004565 beta-galactosidase complex ; GO:0009341 carbohydrate metabolism ; GO:0005975 22014 IPR003470 Early region 3 (E3) of human adenoviruses (Ads) codes for proteins that appear to control viral interactions with the host [MEDLINE:96186708]. This region called CR1 (conserved region 1) [MEDLINE:96186708] is found three times in Adenovirus type 19 (a subgroup D virus) 49 Kd protein in the E3 region. CR1 is also found in the 20.1 Kd protein of subgroup B adenoviruses. The function of this 80 amino acid region is unknown. This region is probably a divergent immunoglobulin domain.\ \N \N \N 22023 IPR003479 The major capsid protein of the adenovirus strain is also known as a hexon. This is a family of hexon-associated proteins (protein IIIa).\ \N \N \N 22024 IPR003480 This family includes a number of transferase enzymes. These include anthranilate N-hydroxycinnamoyl/benzoyltransferase that catalyzes the first committed reaction of phytoalexin biosynthesis [MEDLINE:98088004]. Deacetylvindoline 4-O-acetyltransferase (EC: 2.3.1.107) catalyzes the last step in vindoline biosynthesis is also a member of this family [MEDLINE:98346012]. The motif HXXXD is probably part of the active site. The family also includes trichothecene 3-O-acetyltransferase.\ \N \N \N 22022 IPR003478 The reoviral gene S1 encodes for haemagglutinin (sigma 1 protein), an outer capsid protein and a major factor in determining virus-host cell interactions. Sigma 1s is one of two translation products of the S1 gene.\ \N \N virus-host interaction ; GO:0019048 22021 IPR003477 PemK is a growth inhibitor in Escherichia coli known to bind to the promoter region of the Pem operon, auto-regulating synthesis. This family consists of the PemK protein in addition to ChpA, ChpB and other PemK-like proteins.\ DNA binding activity ; GO:0003677 \N \N 22016 IPR003472 This protein family is found in pox viruses, the function of the protein is unknown.\ \N \N \N 22017 IPR003473 Quinolinate synthetase catalyzes the second step of the de novo biosynthetic pathway of pyridine nucleotide formation. In particular, quinolinate synthetase is involved in the condensation of dihydroxyacetone phosphate and iminoaspartate to form quinolinic acid [MEDLINE:20115266]. This synthesis requires two enzymes, an FAD-containing "B protein" and an "A protein".\ quinolinate synthetase A activity ; GO:0008987 \N nicotinamide adenine dinucleotide biosynthesis ; GO:0009435 22015 IPR003471 Early region 3 (E3) of human adenoviruses (Ads) codes for proteins that appear to control viral interactions with the host [MEDLINE:96186708]. This region called CR1 (conserved region 1) [MEDLINE:96186708] is found three times in Adenovirus type 19 (a subgroup D virus) 49 Kd protein in the E3 region. CR1 is also found in the 20.1 Kd protein of subgroup B adenoviruses. The function of this 80 amino acid region is unknown. This region is probably a divergent immunoglobulin domain.\ \N \N \N 22010 IPR003466 Chalcone-flavanone isomerase (EC: 5.5.1.6) is a plant enzyme responsible for the isomerisation of chalcone to naringenin, a key step in the biosynthesis of flavonoids. The Petunia hybrida genome contains two genes coding for very similar enzymes, ChiA and ChiB, but only the first seems to encode a functional chalcone-flavanone isomerase.\ \N \N \N 22011 IPR003467 Fimbriae (also know as pili) are polar filaments radiating from the surface of the bacterium to a length of 0.5-1.5 micrometers, that enable bacteria to colonize the epithelium of specific host organs. This family consists of the minor and major fimbrial subunits.\ \N fimbria ; GO:0009289 cell adhesion ; GO:0007155 22012 IPR003468 The bacterial oxidase complex, fixNOPQ or cytochrome cbb3, is thought to be required for respiration in endosymbiosis. FixO is a membrane bound mono-heme constituent of the fixNOPQ complex.\ cytochrome c oxidase activity ; GO:0004129 \N electron transport ; GO:0006118 22013 IPR003469

\ This family consists of the glycosyl hydrolase 68 family (CAZY:GH_68), catalyses the hydrolysis of terminal non-reducing

-D-fructofuranoside residues in

-D-fructofuranosides.\ \ hydrolase activity, hydrolyzing O-glycosyl compounds ; GO:0004553 \N sugar utilization ; GO:0007587 22000 IPR003455 This domain found in mycobacteria and Streptomyces coelicolor has no known function nor do any of the proteins that possess it. The aligned region is approximately 120 amino acids long.\ \N \N \N 22001 IPR003457 MerT is an mercuric transport integral membrane protein and is responsible for transport of the Hg2+ iron from periplasmic MerP (also part of the transport system) to mercuric reductase (MerA).\ mercury ion transporter activity ; GO:0015097 membrane ; GO:0016020 mercury ion transport ; GO:0015694 22002 IPR003458 This family contains bacterial and phage proteins. The function of these proteins is uncertain, however the phage proteins, have been suggested to be involved in tail fiber assembly ([MEDLINE:92165720]). Escherichia coli contains several members of this family.\ \N \N \N 22003 IPR003459 This protein is encoded by an open reading frame in plasmid borne DNA repeats of Borrelia spp species. This protein is known as ORF-A [MEDLINE:96218697]. The function of this putative protein is unknown.\ \N \N \N 22004 IPR003460 This family of extracellular proteins is involved in stopping the formation of ice crystals at low temperatures. The proteins are composed of a 12 residue repeat that forms a structural repeat. The structure of the repeats is a

helix. Each repeat contains two cys residues that form a disulphide bridge.\ \N \N \N 22005 IPR003461 Keratins are a well known group of intermediate filament proteins. Like actin filaments, keratins are flexible but provide a firm cell skeleton. Unlike actin, however, no known keratins are associated with motor functions. This family represents avian keratin proteins [MEDLINE:84158528], found in feathers, scale and claw. The avian keratins (F-ker, S-ker, C-ker and B-ker) are a complex mixture of very similar polypeptides.\ structural constituent of cytoskeleton ; GO:0005200 intermediate filament ; GO:0005882 \N 21998 IPR003453 This domain has no known function nor do any of the proteins that possess it. The aligned region is approximately 150 amino acids long.\ \N \N \N 21999 IPR003454 This family consists of monooxygenase components such as MmoB methane monooxygenase (EC: 1.14.13.25) regulatory protein B. When MmoB is present at low concentration it converts methane monooxygenase from an oxidase to a hydroxylase and stabilizes intermediates required for the activation of dioxygen [MEDLINE:99324156]. Also found in this family is DmpM or Phenol hydroxylase (EC: 1.14.13.7) protein component P2, this protein lacks redox co-factors and is required for optimal turnover of Phenolhydroxylase [MEDLINE:97164903]. Phenol hydroxylase catabolises phenol and some of its methylated derivatives in the first step of phenol biodegradation, and is required for growth on phenol. The multicomponent enzyme is made up of P0, P1, P2, P3, P4 and P5 polypeptides.\ \ monooxygenase activity ; GO:0004497 \N aromatic compound metabolism ; GO:0006725 22009 IPR003465 Members of this family are proteinase inhibitors that contain eight cysteines that form four disulphide bridges. They function in the prevention of damage to the plant. The structure of the proteinase-inhibitor complex is known [MEDLINE:89178636].\ serine protease inhibitor activity ; GO:0004867 \N \N 22008 IPR003464 This small enzyme forms a homodecameric complex, that catalyses the third step in the catabolism of catechol to succinate- and acetyl-coa in the

-ketoadipate pathway (EC: 5.3.3.4). The protein has a ferredoxin-like fold according to SCOP.\ \N \N aromatic compound metabolism ; GO:0006725 22007 IPR003463 This family includes insect peptides that are short (23 amino acids) and contain 1 disulphide bridge. The family includes growth-blocking peptide (GBP) of Pseudaletia separata and the paralytic peptides from Manduca sexta, Heliothis virescens, and Spodoptera exigua\ \ \ [MEDLINE:91302298] as well as plasmatocyte-spreading peptide (PSP1) [MEDLINE:99143099]. These peptides function to halt metamorphosis from larvae to pupae.\ \ \N \N \N 22006 IPR003462

This family contains the bacterial Ornithine cyclodeaminase enzyme (EC: 4.3.1.12), which catalyses the deamination of ornithine to proline [MEDLINE:89123162]. This family also contains mu-crystallin the major component of the eye lens in several Australian marsupials, mRNA for this protein has also been found in human retina [MEDLINE:93028450].

\ \N \N \N 21986 IPR003441 This is a family of no apical meristem (NAM) proteins that are plant development proteins. Mutations in NAM result in the failure to develop a shoot apical meristem in Petunia hybrida embryos. NAM is indicated as having a role in determining positions of meristems and primordia [MEDLINE:96200768]. One member of this family NAP (NAC-like, activated by AP3/PI) is encoded by the target genes of the AP3/PI transcriptional activators and functions in the transition between growth by cell division and cell expansion in stamens and petals [MEDLINE:98149347].\ \N \N \N 21987 IPR003442 This signature is found in a family of bacterial proteins, which contain a P-loop.\ \N \N \N 21988 IPR003443 Interleukin-15 (IL-15) is a cytokine that possesses a variety of biological functions, including stimulation and maintenance of cellular immune responses [MEDLINE:20329080]. IL-15 stimulates the proliferation of T-lymphocytes, which requires interaction of IL-15 with components of IL-2R, including IL-2R

and probably IL-2R gamma, but not IL-2R

.\ hematopoietin/interferon-class (D200-domain) cytokine receptor ligand activity ; GO:0005126 extracellular ; GO:0005576 immune response ; GO:0006955 21989 IPR003444

This family is characterized by a 70 amino acid region. Its members are probably enzymes containing a conserved DXXXR motif that probably forms part of the active site.

\ \N \N \N 21990 IPR003445 This family consists of various potassium transport proteins (Trk) and V-type sodium ATP synthase subunit J or translocating ATPase J (EC: 3.6.1.34). These proteins are involved in active sodium up-take utilizing ATP in the process. TrkH from Escherichia coli is a hydrophobic membrane protein and determines the specificity and kinetics of cation transport by the TrK system in this organism [MEDLINE:95204366]. This protein interacts with TrkA and requires TrkE for transport activity.\ cation transporter activity ; GO:0008324 \N cation transport ; GO:0006812 21991 IPR003446 This protein is plasmid encoded and found to be essential for plasmid replication, and is involved in copy control functions [MEDLINE:88289416].\ \N \N plasmid maintenance ; GO:0006276 21992 IPR003447 The femAB operon codes for two nearly identical approximately 50-kDa proteins involved in the formation of the Staphylococcal pentaglycine interpeptide bridge in peptidoglycan [MEDLINE:98053874]. These proteins are also considered as a factor influencing the level of methicillin resistance [MEDLINE:99226243].\ \N \N peptidoglycan biosynthesis ; GO:0009252 21993 IPR003448

This family contains the MoaE protein that is involvedin biosynthesis of molybdopterin [MEDLINE:93293873]. Molybdopterin, the universal\ component of the pterin molybdenum cofactors, contains a dithiolene\ group serving to bind Mo. Addition of the dithiolene sulfurs to a\ molybdopterin precursor requires the activity of the converting factor.\ Converting factor contains the MoaE and MoaD proteins.

\ \ \ \N \N Mo-molybdopterin cofactor biosynthesis ; GO:0006777 21994 IPR003449 This is a family of proteins from coronavirus which may function in the formation of membrane-bound replication complexes or in viral assembly.\ \N \N \N 21995 IPR003450 This family represents the herpesvirus origin of replication binding protein, probably involved in DNA replication.\ ATP binding activity ; GO:0005524 \N DNA replication ; GO:0006260 21996 IPR003451

Terpenes are among the largest groups of natural products and include compounds such as vitamins, cholesterol and carotenoids. The biosynthesis of all terpenoids begins with one orboth of the two C5 precursors of the pathway: isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). In\ animals, fungi, and certain bacteria, the synthesis of IPP and DMAPP occurs via the well-known mevalonate pathway, however, a second, nonmevalonate terpenoid pathway has been identified in many eubacteria, algae and the chloroplasts of higher plants [MEDLINE:20461233].

LytB(IspH) catalyses the conversion of 1-hydroy-2-methyl-2-(E)-butenyl 4-diphosphate into IPP and DMAPP in this second pathway The enzyme appears to be responsible for a branch-step in the nonmevalonate pathway, in that IPP and DMAPP are produced in parallel from a single precursor although the exact mechanism of this is not currently fully understood [MEDLINE:21819424].

\ \ \N \N isopentenyl diphosphate biosynthesis, mevalonate independent ; GO:0019288 21997 IPR003452 Stem cell factor (SCF) is a homodimer involved in hematopoiesis. SCF binds to and activates the SCF receptor (SCFR), a receptor tyrosine kinase. SCF stimulates the proliferation of mast cells and is able to augment the proliferation of both myeloid and lymphoid hematopoietic progenitors in bone marrow culture. It also mediates cell-cell adhesion and acts synergistically with other cytokines. SCF is a type I membrane protein, but is also found in a secretable, soluble form. The crystal structure of human SCF has been resolved and a potential receptor-binding site identified [MEDLINE:20345055].\ stem cell factor receptor binding activity ; GO:0005173 membrane ; GO:0016020 cell adhesion ; GO:0007155 21982 IPR003437

This family consists of glycine cleavage system P-proteins (EC: 1.4.4.2) from bacterial, mammalian and plant sources. The P protein is part of the glycine decarboxylase multienzyme complex (EC: 2.1.2.10 (GDC) also annotated as glycine cleavage system or glycine synthase. The P protein binds the -amino group of glycine through its pyridoxal phosphate cofactor, carbon dioxide is released and the remaining methylamin moiety is then transferred to the lipoamide cofactor of the H protein. GDC consists of four proteins P, H, L and T [MEDLINE:94237484]. The reaction catalysed by this protein is:

Glycine + lipoylprotein = S-aminomethyldihydrolipoylprotein + CO2

\ \ glycine dehydrogenase (decarboxylating) activity ; GO:0004375 glycine dehydrogenase complex (decarboxylating) ; GO:0005961 glycine metabolism ; GO:0006544 21983 IPR003438

The GDNF family receptors (GFRs) are glycosyl-phosphatidylinositol-linked,\ cell surface receptors [MEDLINE:99286308]. Four receptor subtypes, termed GFRalpha-1 to 4, are currently recognised. GFRalpha-1 and 2 are activated by GDNF and NTN respectively, although some degree of ligand promiscuity is thought to occur [MEDLINE:97338137]. Homologues for these receptor subtypes have been cloned from mammalian and avian tissue. The principal ligand for GFRalpha-3 is artemin. This receptor subtype is currently described only in mammals [MEDLINE:98245162]. GFRalpha-4 is activated by persephin and has so far only been found in chicken [MEDLINE:98313402]. This entry is general for types 1 to 3.

\ \ receptor activity ; GO:0004872 \N \N 21981 IPR003436 This is a family of viral fusion proteins from the chordopoxviruses. A 14-kDa Vaccinia Virus protein has been demonstrated to function as a viral fusion protein mediating cell fusion at endosmomal (low) pH [MEDLINE:90357795]. The protein, found in the envelope fraction of the virions, is required for fusing the outermost of the two golgi-derived membranes enveloping the virus with the plasma membrane, and its subsequent release extracellularly. The N-terminal proximal region is essential for its fusion ability.\ \N viral envelope ; GO:0019031 viral envelope fusion ; GO:0019064 21985 IPR003440

This is the glycosyltransferase 48 family CAZY:GT_48UDP-glucose + {(1,3)--D-glucosyl}(N)\ = UDP + {(1,3)--D-glucosyl}(N+1).

\ \ \ 1,3-beta-glucan synthase activity ; GO:0003843\ \ 1,3-beta-glucan synthase complex ; GO:0000148\ \N membrane ; GO:0016020 beta-1,3 glucan biosynthesis ; GO:0006075 21984 IPR003439

On the basis of sequence similarities a family of related ATP-binding proteins has been characterized [MEDLINE:91035372], [MEDLINE:88240299], [MEDLINE:87014804], [MEDLINE:87014805], [MEDLINE:91014687].

\ \ \

The proteins belonging to this family also contain one or two copies of the 'A' consensus sequence [MEDLINE:84236073] or the 'P-loop' [MEDLINE:91118233] (see IPR001687).

\ \ ATP binding activity ; GO:0005524 membrane ; GO:0016020 transport ; GO:0006810 21976 IPR003431

Phytase (EC: 3.1.3.8) (phytate 3-phosphatase) is a secreted enzyme which hydrolyses phytate to release inorganic phosphate. This family appears to represent a novel enzyme that shows phytase activity ([MEDLINE:98268943]) and has been shown to have a six- bladed propeller folding architecture ([MEDLINE:20122631]).

\ \N \N \N 21977 IPR003432 The bacterial replication terminator protein (RTP) plays a role in the termination of DNA replication by impeding replication fork movement. Two RTP dimers bind to the two inverted repeat regions at the termination site.\ DNA binding activity ; GO:0003677 \N DNA replication termination ; GO:0006274 21978 IPR003433 The virus capsid is composed of 60 icosahedral units of a combination of VP4, VP3, VP2 and VP1. Four different translation initiation sites of the densovirus capsid protein mRNA give rise to these four viral proteins, VP1 to VP4. This family represents VP4.\ structural molecule activity ; GO:0005198 viral capsid ; GO:0019028 \N 21979 IPR003434 This family consists of a conserved probable envelope protein or ORF2 in porcine reproductive and respiratory syndrome virus (PRRSV) also in the family is a minor structural protein from lactate dehydrogenase-elevating virus.\ \N \N \N 21980 IPR003435

The RbcX protein has been identified as having a possible chaperonin-like function [MEDLINE:98317287]. The rbcX gene is juxtaposed to and cotranscribed with rbcL and rbcS encoding RubisCO in Anabaena sp. CA. RbcX has been shown to possess a chaperonin-like function assisting correct folding of RubisCO in Escherichia coli expression studies and is needed for RubisCO to reach its maximal activity [MEDLINE:97315259].

\ chaperone activity ; GO:0003754 \N protein folding ; GO:0006457 21963 IPR003418 Fumarate reductase is a membrane-bound flavoenzyme consisting of four subunits, A-B. A and B comprise the membrane-extrinsic catalytic domain and C and D link the catalytic centers to the electron-transport chain. This family consists of the 13kDa hydrophobic subunit D. This component may be required to anchor the catalytic components of the fumarate reductase complex to the cytoplasmic membrane.\ \N membrane ; GO:0016020 fumarate metabolism ; GO:0006106 21964 IPR003420 Methanol dehydrogenase (MDH) (EC: 1.1.99.8) is a bacterial periplasmic quinoprotein that oxidizes methanol to formaldehyde. MDH is a tetramer of two

and two

subunits. This family contains the small

subunit.\ alcohol dehydrogenase activity ; GO:0004022 \N methanol oxidation ; GO:0015946 21965 IPR003421 This group of enzymes act on the CH-NH substrate bond using NAD(+) or NADP(+) as an acceptor. The family consists mainly of octopine and nopaline dehydrogenases (EC: 1.5.1.19) from Ti plasmids. Octopine dehydrogenase (EC: 1.5.1.11) is involved in the reductive condensation of octopine to octopinic acid. NADPH is the preferred cofactor, but NADH is also used.\ \N \N \N 21966 IPR003421 This group of enzymes act on the CH-NH substrate bond using NAD(+) or NADP(+) as an acceptor. The family consists mainly of octopine and nopaline dehydrogenases (EC: 1.5.1.19) from Ti plasmids. Octopine dehydrogenase (EC: 1.5.1.11) is involved in the reductive condensation of octopine to octopinic acid. NADPH is the preferred cofactor, but NADH is also used.\ \N \N \N 21967 IPR003422 The ubiquinol-cytochrome C reductase complex (cytochrome bc1 complex) is a respiratory multienzyme complex [MEDLINE:98316377]. The bc1 complex contains 11 subunits; 3 respiratory subunits (cytochrome B, cytochrome C1, Rieske protein), 2 core proteins and 6 low molecular weight proteins. This family represents the 'hinge' protein of the complex which is thought to mediate formation of the cytochrome c1 and cytochrome c complex.\ ubiquinol-cytochrome c reductase activity ; GO:0008121 ubiquinol-cytochrome c reductase complex (sensu Eukarya) ; GO:0015008 oxidative phosphorylation, ubiquinone to cytochrome c ; GO:0006122 21968 IPR003423 The OEP family (Outer membrane efflux protein) form trimeric channels that allow export of a variety of substrates in Gram negative bacteria. Each member of this family is composed of two repeats. The trimeric channel is composed of a 12stranded all

sheet barrel that spans the outer membrane, and a long all helical barrel that spans the periplasm. Examples include the Escherichia coli TolC outer membrane protein, which is required for proper expression of outer membrane protein genes; the Rhizobium nodulation protein; and the Pseudomonas FusA protein, which is involved in resistance to fusaric acid.\ \ transporter activity ; GO:0005215 \N transport ; GO:0006810 21969 IPR003424 This family consists of egg-laying hormone (ELH) precursor and atrial gland peptides from the little (Aplysia parvula) and california (Aplysia californica ) sea hares. The family also includes ovulation prohormone precursor from the great pond snail (Lymnaea stagnalis ). This family thus represents a conserved gastropoda ovulation and egg production prohormone. Note that many of the proteins present are further cleaved to give individual peptides [MEDLINE:98188314]. Neuropeptidergic bag cells of the marine mollusc A. californica synthesize an egg-laying hormone (ELH) precursor protein which is cleaved to generate several bioacitve peptides including ELH, bag cell peptides (BCP) and acidic peptide (AP) [MEDLINE:99449707].\ hormone activity ; GO:0005179 extracellular ; GO:0005576 development ; GO:0007275 21970 IPR003425 This family consists of a repeat found in conserved hypothetical integral membrane proteins. The function of this region and the proteins which possess it is unknown.\ \N membrane ; GO:0016020 \N 21971 IPR003426 Bacteriochlorophyll A protein is involved in the energy transfer system of green photosynthetic bacteria. The protein forms a homotrimer, with each monomer unit containing seven molecules of bacteriochlorophyll A.\ \N \N photosynthesis ; GO:0015979 21962 IPR003417 Core binding factor (CBF) is a heterodimeric transcription factor essential for genetic regulation of hematopoiesis and osteogenesis. The

subunit binds to the core site, 5'-PYGPYGGT-3', of a number of enhancers and promoters, including murine leukemia virus, polyomavirus enhancer, T-cell receptor enhancers etc. The

subunit enhances DNA-binding ability of the

subunit in vitro, and has been show to have a structure related to the OB fold [MEDLINE:99332048]. Also included in this family are the Drosophila melanogaster brother and big brother proteins, which regulate the DNA-binding properties of Runt.\ transcription co-activator activity ; GO:0003713 nucleus ; GO:0005634 \N 21974 IPR003429 This viral protein functions to block the host apoptotic response caused by infection by the virus. The apoptosis preventing protein (or early 35kD protein, P35) acts by blocking caspase protease activity. It is required for late and very late gene expression.\ apoptosis inhibitor activity ; GO:0008189 \N anti-apoptosis ; GO:0006916 21975 IPR003430 Bacterial phenol hydroxylase (EC: 1.14.13.7) is a multicomponent enzyme that catabolises phenol and some of its methylated derivatives. This family contains both the P1 and P3 polypeptides of phenol hydroxlase and the

and

chain of methanehydroxylase protein A. Methane hydroxylase protein A (EC: 1.14.13.25) is responsible for the initial oxygenation of methane to methanol in methanotrophs. It also catalyses the monohydroxylation of a variety of unactivated alkenes, alicyclic, aromatic and heterocyclic compounds. Also included in this family is toluene-4-monooxygenase system protein A (EC: 1.14.13.-), which hydroxylates toluene to form P-cresol.\ \ \N \N aromatic compound metabolism ; GO:0006725 21973 IPR003428 This mitochondrial matrix protein family contains members of the MAM33 family which bind to the globular 'heads' of C1Q.\ \N mitochondrial matrix ; GO:0005759 \N 21972 IPR003427

Histidine carboxylase (EC: 4.1.1.22) catalyses the formation of histamine from histidine. It requires a pyruvoyl group for its activity. Cleavage of the proenzyme PI chain yields two subunits, and , which arrange as a hexamer ( ) 6 by nonhydrolytic self-catalysis.

\ histidine decarboxylase activity ; GO:0004398 \N histidine metabolism ; GO:0006547 21958 IPR003415 The telomere-binding protein forms a heterodimer in ciliates consisting of an

and a

subunit. This complex may function as a protective cap for the single-stranded telomeric overhang, and may also participate in telomere length regulation during DNA replication. It binds specifically to the T4G4-containing extension on the 3' strand and protects this region of the telomere from nuclease digestion and chemical modification.\ DNA binding activity ; GO:0003677 nucleus ; GO:0005634 telomere capping ; GO:0016233 21961 IPR003416 The MgtC protein is found in an operon with the Mg2+ transporter protein MgtB. The function of MgtC and its homologues is not known, but it is thought that MgtC may act as an accessory protein for MgtB, thus mediating magnesium influx into the cytosol. Also included in this family are the Bacillus subtilis SapB protein and several hypothetical proteins.\ \N membrane ; GO:0016020 \N 21952 IPR003409 The MORN (Membrane Occupation and Recognition Nexus) motif is found in multiple copies in several proteins including junctophilins ([MEDLINE:20403299]). The function of this motif is unknown.\ \N \N \N 21953 IPR003410 This domain is known as the HYR (Hyalin Repeat) domain, after the protein hyalin that is composed exclusively of this repeat. This domain probably corresponds to a new superfamily in the immunoglobulin fold. The function of this domain isuncertain it may be involved in cell adhesion. In the Sushi repeat-containing protein (SrpX), this domain is found between two sushi repeats.\ \ \N \N \N 21954 IPR003411

This family consists of a 7 kDa coat protein from carlavirus and potexvirus\ \ \ [MEDLINE:94279547].

\ \ \N \N \N 21955 IPR003412 This is a family of structural glycoproteins from arterivirus that corresponds to open reading frame 4 (ORF4) of the virus.\ \N \N \N 21956 IPR003413 The bacterial general secretion pathway (GSP) is involved in the export of proteins (also called the type II pathway). This family includes GSPI and GSPJ, which contain the pre-pilin signal sequence [MEDLINE:94012544].\ protein transporter activity ; GO:0008565 type II protein secretion system complex ; GO:0015627 type II protein (Sec) secretion system ; GO:0015628 21957 IPR003414 Polyphosphate kinase (Ppk) (EC: 2.7.4.1) catalyzes the formation of polyphosphate from ATP, with chain lengths of up to a thousand or more orthophosphate molecules. It is a membrane protein and goes through an intermediate stage during the reaction where it is autophosphorylated with a phosphate group covalently linked to a basic amino acid residue through an N-P bond.\ polyphosphate kinase activity ; GO:0008976 polyphosphate kinase complex ; GO:0009358 polyphosphate biosynthesis ; GO:0006799 21942 IPR003398

This is a family of small proteins encoded on the chloroplast genome. PsbN is involved in photosystem II during photosynthesis, but its exact role is unknown.

\ \N membrane ; GO:0016020 photosynthesis ; GO:0015979 21943 IPR003399 This family of proteins contains the mce (mycobacterial cell entry) proteins from Mycobacterium tuberculosis. The archetype (Rv0169), was isolated as being necessary for colonization of, and survival within, the macrophage [MEDLINE:93377076]. This family also contains proteins of unknown function from other bacteria.\ \N \N \N 21944 IPR003400 This group of proteins are membrane bound transport proteins essential for ferric ion uptake in bacteria [MEDLINE:98037510]. The family consists of ExbD, and TolR which are involved in TonB-dependent transport of various receptor bound substrates including colicins [MEDLINE:87222192].\ transporter activity ; GO:0005215 membrane ; GO:0016020 transport ; GO:0006810 21945 IPR003402 The methionine-10 mutant allele of Neurospora crassa codes for a protein of unknown function. However, homologous proteins have been found in yeast, suggesting this protein may be involved in methionine biosynthesis, transport and/or utilization [MEDLINE:96009887].\ \N \N \N 21946 IPR003403 This regulatory protein is expressed from an immediate early gene in the cell cycle of herpesvirus. The protein is known by various names including IE-68, US1, ICP22 and IR4.\ \N \N \N 21947 IPR003404 Glycoprotein E (gE) of Alphaherpesvirus forms a complex with glycoprotein I (gI), functioning as an immunoglobulin G (IgG) Fc binding protein. gE is involved in virus spread but is not essential for propagation [MEDLINE:20338588].\ \N membrane ; GO:0016020 \N 21948 IPR003405

The SMC (structural maintenance of chromosomes) family of proteins, exist in virtually all organisms including both bacteria and archaea. The SMC proteins are essential for successful chromosome transmission during replication and segregation of the genome in all organisms and form three types of heterodimer (SMC1SMC3, SMC2SMC4,\ SMC5SMC6), which are core components of large multiprotein complexes.\ The best known complexes are cohesin, which is responsible for\ sister-chromatid cohesion, and condensin, which is required for full\ chromosome condensation in mitosis.

SMCs are generally present as single proteins in bacteria, and as at least six distinct proteins in eukaryotes. The proteins range in size from approximately 110 to 170 kDa, and share a five-domain structure, with globular N- and C-terminal (IPR003395) domains separated by a long\ (circa 100 nm or 900 residues) coiled coil segment in the centre of which is a globular ''hinge'' domain, characterized by a set of four highly conserved glycine residues\ that are typical of flexible regions in a protein. The amino-terminal domain contains a 'Walker A' nucleotide-binding domain (GxxGxGKS/T), which by mutational studies has been shown to be essential in several proteins. The carboxy-terminal domain contains a sequence (the DA-box) that resembles a 'Walker B' motif (XXXXD, where X is any hydrophobic residue), and a LSGG motif with homology to the signature sequence of the ATP-binding cassette (ABC) family of ATPases [MEDLINE:22247343].

All\ SMC proteins appear to form dimers, either forming homodimers with themselves, as in the case of prokaryotic\ SMC proteins, or heterodimers between different but related SMC proteins. The\ dimers are arranged in an antiparallel alignment. This orientation brings the N- and C-terminal globular domains (from either different or\ identical protamers) together, which unites an ATP binding site (Walker A motif) within the N-terminal domain\ with a Walker B motif (DA box) within the C-terminal domain, to form a potentially functional ATPase. Protein interaction and microscopy data suggest that SMC\ dimers form a ring-like structure which might embrace DNA molecules. Non-SMC subunits\ associate with the SMC amino- and carboxy-terminal domains. The sequence homology within the carboxy-terminal domain is relatively high within the SMC1-SMC4 group, whereas SMC5 and SMC6 show some divergence in both of these sequences.

SMCs share not only sequence similarity but also structural similarity with ABC proteins. SMC proteins function together with other proteins in a range of chromosomal transactions, including chromosome condensation, sister-chromatid cohesion, recombination, DNA repair and epigenetic silencing of gene expression [MEDLINE:21980168].

This signature represents a conserved domain towards the C-terminus of the SMC family of proteins. A second conserved domain is found at the N-terminus (IPR003395/>).

\ \ \ ATP binding activity ; GO:0005524 \N chromosome segregation ; GO:0007059 21951 IPR003408 This domain is specific to 5-aminolevulinic acid (ALA) synthase (EC: 2.3.1.37) which is involved in heme biosynthesis. The enzyme catalyses the conversion of succinyl-CoA and glycine to 5-aminolevulinate, CoA and carbon dioxide in the first and rate-limiting step of heme biosynthesis. The Aminotransferases class-II domain (IPR001917) is found to the C-terminus of this domain.\ \ 5-aminolevulinate synthase activity ; GO:0003870\ \N \N heme biosynthesis ; GO:0006783 21950 IPR003407 This family represents the immunodominant surface antigen of Theileria parasites including equi merozoite antigen-1 (EMA-1) and equi merozoite antigen-2 (EMA-2) [MEDLINE:98156747]. The protein shows variation at a putative glycosylation site, a potential mechanism for host immune response evasion [MEDLINE:96089836].\ defense/immunity protein activity ; GO:0003793 \N \N 21949 IPR003406

This is the glycosyltransferase family 14 CAZY:GT_14.

\ \ acetylglucosaminyltransferase activity ; GO:0008375 membrane ; GO:0016020 \N 21941 IPR003397

The pre-protein translocase of the mitochondrial inner membrane allows the import of pre-proteins from the cytoplasm. The translocase forms a complex with a number of proteins, including the Tim17, Tim23 and Tim44 subunits. Tim17 and Tim23 are thought to form the translocation channel of the inner membrane. The Tim22 subunit of the mitochondrial import inner membrane translocase is included in this family.

\ protein translocase activity ; GO:0015450 mitochondrial inner membrane translocase complex ; GO:0005744 protein transport ; GO:0015031 21938 IPR003393 Ammonia monooxygenase is an integral membrane protein, which plays a key role in the nitrogen cycle and degrades a wide range of hydrocarbons and halogenated hydrocarbons.\ monooxygenase activity ; GO:0004497 membrane ; GO:0016020 nitrogen metabolism ; GO:0006807 21939 IPR003394 Pathogenic Neisseria spp. possess a repertoire of phase-variable opacity proteins that mediate various pathogen/host cell interactions [MEDLINE:99155753]. These proteins are integral membrane proteins related to other porins and the Haemophilus influenzae OpA protein.\ porin activity ; GO:0015288 membrane ; GO:0016020 \N 21940 IPR003395

The SMC (structural maintenance of chromosomes) family of proteins exists in virtually all organisms including both bacteria and archaea. The SMC proteins are essential for successful chromosome transmission during replication and segregation of the genome in all organisms and form three types of heterodimer (SMC1SMC3, SMC2SMC4,\ SMC5SMC6), which are core components of large multiprotein complexes.\ The best known complexes are cohesin, which is responsible for\ sister-chromatid cohesion, and condensin, which is required for full\ chromosome condensation in mitosis.

SMCs are generally present as single proteins in bacteria, and as at least six distinct proteins in eukaryotes. The proteins range in size from approximately 110 to 170 kDa, and share a five-domain structure, with globular N- and C-terminal (IPR003405) domains separated by a long\ (circa 100 nm or 900 residues) coiled coil segment in the centre of which is a globular ''hinge'' domain, characterized by a set of four highly conserved glycine residues\ that are typical of flexible regions in a protein. The amino-terminal domain contains a 'Walker A' nucleotide-binding domain (GxxGxGKS/T), which by mutational studies has been shown to be essential in several proteins. The carboxy-terminal domain contains a sequence (the DA-box) that resembles a 'Walker B' motif (XXXXD, where X is any hydrophobic residue), and a LSGG motif with homology to the signature sequence of the ATP-binding cassette (ABC) family of ATPases [MEDLINE:22247343].

This domain is found at the N terminus of SMC proteins.

\ \ ATP binding activity ; GO:0005524 nucleus ; GO:0005634 chromosome segregation ; GO:0007059 21935 IPR003390 This domain is about 120 amino acids long. The function of this domain is unknown, however the distribution of conserved histidines and aspartates suggests that this may be a metal dependent phosphoesterase. This may be a nuclear domain as the hypothetical protein YacK from Bacillus subtilis also contains a Helix-hairpin-helix HHH motif that is characteristic of DNA binding proteins.\ \N \N \N 21936 IPR003391 This protein, also known as bellett protein, is covalently attached to the terminii of replicating DNA in vivo [MEDLINE:79160803] and may play a role in DNA replication.\ DNA binding activity ; GO:0003677 \N DNA replication ; GO:0006260 21937 IPR003392 The transmembrane protein, patched, is a receptor for the morphogene Sonic Hedgehog. In Drosophila melanogaster, this protein associates with the smoothened protein to transduce hedgehog signals, leading to the activation of wingless, decapentaplegic and patched itself. It participates in cell interactions that establish pattern within the segment and imaginal disks during development. The mouse homolog may play a role in epidermal development. The human Niemann-Pick C1 protein, defects in which cause Niemann-Pick type II disease, is also a member of this family. This protein is involved in the intracellular trafficking of cholesterol, and may play a role in vesicular trafficking in glia, a process that may be crucial for maintaining the structural functional integrity of nerve terminals.\ patched receptor activity ; GO:0008158 membrane ; GO:0016020 \N 21931 IPR003386 Lecithin:cholesterol acyltransferase (LACT) also known as phosphatidylcholine-sterol acyltransferase (EC: 2.3.1.43), is involved in extracellular metabolism of plasma lipoproteins, including cholesterol. It esterifies the free cholesterol transported in plasma lipoproteins, and is activated by apolipoprotein A-I. Defects in LACT cause Norum and Fish eye diseases.\ phosphatidylcholine-sterol O-acyltransferase activity ; GO:0004607 \N lipid metabolism ; GO:0006629 21932 IPR003387 Nodulin is a plant protein of unknown function. It is induced during nodulation in legume roots after rhizobium infection.\ \N \N \N 21933 IPR003388

Eukaryotic proteins of the reticulon (RTN) family all share an association with the endoplasmic reticulum (ER). Whereas amino-terminal regions are not related to one another, all reticulon proteins share a 200 amino acid residue region of sequence similarity at the C-terminal. This region contains twolarge hydrophobic regions separated by a 66 residue hydrophilic segment. The\ conserved hydrophobic C-terminal portion has been shown to play an essential\ role in the association of reticulons with the ER membrane. The hydrophobic\ portions are supposed to be membrane-embedded and the hydrophilic 66 residue\ localized to the lumenal/extracellular face of the membrane. Most reticulons\ have a di-lysine ER retention motif at the C-terminal. Because of their likely\ association with the rough as well as the smooth ER, the reticulons might play\ some role in transport processes or in regulation of intracellular calcium\ levels. It has been suggested that the reticulons may be serving as ER-associated channel-like complexes [MEDLINE:95146555], [MEDLINE:96429995], [MEDLINE:98360096], [MEDLINE:20129259].

\ \ molecular_function unknown ; GO:0005554 endoplasmic reticulum ; GO:0005783 \N 21934 IPR003389 Va2 protein can interact with the adenoviral packaging signal and this interaction involves DNA sequences that have previously been demonstrated to be required for packaging [MEDLINE:20148961]. During the course of lytic infection, the adenovirus major late promoter (MLP) is induced to high levels after replication of viral DNA has started. IVa2 is a transcriptional activator of themajor late promoter [MEDLINE:94267906].\ \ \N \N viral transcription ; GO:0019083 21929 IPR003384 The Hepatitis E virus (HEV) genome is a single-stranded, positive-sense RNA molecule of approximately 7.5 kb [MEDLINE:99380297]. Three open reading frames (ORF) were identified within the HEV genome: ORF1 encodes nonstructural proteins, ORF2 encodes the putative structural protein(s), and ORF3 encodes a protein of unknown function. ORF2 contains a consensus signal peptide sequence at its amino terminus and a capsid-like region with a high content of basic amino acids similar to that seen with other virus capsid proteins [MEDLINE:92024067].\ structural molecule activity ; GO:0005198 viral capsid ; GO:0019028 \N 21930 IPR003385

\ The enzymes in this entry (EC: 2.4.1.25) belong to the glycoside hydrolase family 77 CAZY:GH_77, and transfer a segment of a (1,4)-

-D-glucan to a new 4-position in an acceptor, which may be\ glucose or (1,4)-

-D-glucan [MEDLINE:93123262]. They belong to the disproportionating family of enzymes.\ \ \ 4-alpha-glucanotransferase activity ; GO:0004134\ \N \N carbohydrate metabolism ; GO:0005975 21923 IPR003378 The drosophila protein fringe (FNG) is a glucosaminyltransferase that controls the response of the Notch receptor to specific ligands. FNG is localised to the Golgi apparatus [MEDLINE:20359806] (not secreted as previously thought). Modification of Notch occurs through glycosylation by FNG. The xenopus homologue, lunatic fringe, has been implicated in a variety of functions.\ transferase activity, transferring glycosyl groups ; GO:0016757 membrane ; GO:0016020 \N 21924 IPR003379 This domain represents a conserved region in pyruvate carboxylase (PYC) (EC: 6.4.1.1), oxaloacetate decarboxylase

chain (OADA) (EC: 4.1.1.3), and transcarboxylase 5s subunit (EC: 2.1.3.1). The domain is found adjacent to the HMGL-like domain (IPR000891) of biotin requiring enzymes.\ \N \N \N 21925 IPR003380 The c-ski proto-oncogene has been shown to influence proliferation, morphological transformation and myogenic differentiation [MEDLINE:95092782]. It may play a role in treminal differentiation of skeletal muscle cells but not in the determination of cells to the myogenic lineage. Sno, a Ski proto-oncogene homologue, is expressed in two isoforms and plays a role in the response to proliferation stimuli.\ \N nucleus ; GO:0005634 cell growth and/or maintenance ; GO:0008151 21926 IPR003381

The late 100 kDa protein is a non-structural viral protein involved in the transport of hexon from the cytoplasm to the nucleus.

\ \N \N viral intracellular protein transport ; GO:0019060 21927 IPR003382 This domain is found in diverse flavoprotein enzymes, including epidermin biosynthesis protein, EpiD, which has been shown to be a flavoprotein that binds FMN [MEDLINE:92355511]. This enzyme catalyzes the removal of two reducing equivalents from the cysteine residue of the C-terminal meso-lanthionine of epidermin to form a --C==C-- double bond. This family also includes the B chain of dipicolinate synthase a small polar molecule that accumulates to high concentrations in bacterial endospores, and is thought to play a role in spore heat resistance, or the maintenance of heat resistance [MEDLINE:93347235]. Dipicolinate synthase catalyses the formation of dipicolinic acid from dihydroxydipicolinic acid. This family also includes phenylacrylic acid decarboxylase (EC 4.1.1.-) [MEDLINE:94237474].\ \N \N \N 21921 IPR003376 Peridinin-chlorophyll-protein, a water-soluble light-harvesting complex that has a blue-green absorbing carotenoid as its main pigment, is present in most photosynthetic dinoflagellates. These proteins are composed of two similar repeated domains. These domains constitute a scaffold with pseudo-twofold symmetry surrounding a hydrophobic cavity filled by two lipid, eight peridinin, and two chlorophyll a molecules [MEDLINE:96256477].\ \N \N \N 21922 IPR003377

The drosophila cornichon protein (gene: cni) [MEDLINE:95300228] is required in the germlinefor dorsal-ventral signaling. The dorsal-ventral pattern formation involves a\ reorganization of the microtubule network correlated with the movement of the\ oocyte nucleus, and depending on the initial correct establishment of the\ anterior-posterior axis via a signal from the oocyte produced by cornichon\ and gurken and received by torpedo protein in the follicle cells. The\ biochemical function of the cornichon protein is currently not known. It is a protein of 144 residues that seems to contain three transmembrane\ regions.

\ \ \N membrane ; GO:0016020 intracellular signaling cascade ; GO:0007242 21928 IPR003383 Circoviruses are small circular single stranded viruses. This family is the ORF-2 protein from viruses such as porcine circovirus\ \ \ [MEDLINE:98241772] and beak and feather disease virus\ \ \ \ Q9YUC8. These proteins are about 220 amino acids long and of unknown function.\ \ \N \N \N 21918 IPR003373 Escherichia coli has an iron(II) transport system (feo) which may make an important contribution to the iron supply of the cell under anaerobic conditions. FeoB has been identified as part of this transport system and may play a role in the transport of ferrous iron. FeoB is a large 700-800 amino acid integral membrane protein. The N terminus contains a P-loop motif suggesting that iron transport may be ATP dependent [MEDLINE:94012482].\ ferrous iron transporter activity ; GO:0015093 membrane ; GO:0016020 ferrous iron transport ; GO:0015684 21919 IPR003374 This prokaryotic family of lipoproteins are related to ApbE, from Salmonella typhimurium. ApbE is involved in thiamine synthesis [MEDLINE:98132385]. More specifically is may be involved in the conversion of aminoimidazole ribotide (AIR) to 4-amino-5-hydroxymethyl-2-methyl pyrimidine (HMP) during the biosynthesis of the pyrimidine moiety of thiamine.\ \N \N thiamin biosynthesis ; GO:0009228 21920 IPR003375 PsaE is a 69 amino acid polypeptide from photosystem I present on the stromal side of the thylakoid membrane. The structure is comprised of a well-defined five-stranded

-sheet similar to SH3 domains [MEDLINE:94250643]. This subunit may form complexes with ferredoxin and ferredoxin-oxidoreductase in the photosystem I reaction centre.\ \N photosystem I reaction center ; GO:0009538 electron transport ; GO:0006118 21908 IPR003361 The acetaldehyde dehydrogenase family (EC: 1.2.1.10) of bacterial enzymes catalyse the formation of acetyl-CoA from acetaldehyde in the 3-hydroxyphenylpropinoate degradation pathway.\ acetaldehyde dehydrogenase (acetylating) activity ; GO:0008774 \N carbon utilization ; GO:0015976 21909 IPR003362 This family represents a conserved region from a number of different bacterial sugar transferases, involved in diverse biosynthesis pathways. Examples include galactosyl-P-P-undecaprenol synthetase (EC: 2.7.8.6), which transfers galatose-1-phosphate to the lipid precursor undecaprenol phosphate in the first steps of O-polysaccharide biosynthesis; UDP-galactose-lipid carrier transferase, which is involved in the biosynthesis of amylovoran; and galactosyl transferase CpsD, which is essential for assembly of the group B Streptococci (GBS) type III capsular polysaccharide.\ \N \N \N 21910 IPR003363 Glycoprotein G (gG)is one of the seven external glycoproteins of HSV1 and HSV2. This family also contains the glycoprotein GX, (gX), initially identified in Pseudorabies virus.\ \N \N \N 21911 IPR003365 This is a family of viral ORFs from various plant and animal ssDNA circoviruses. Published evidence to support the annotated function "viral replication associated protein" has not been found.\ \N \N \N 21912 IPR003366 This domain is found in a family of hypothetical Caenorhabditis elegans proteins. The aligned region has no known function nor do any of the proteins which possess it. The aligned region is approximately 130 amino acids long and contains two conserved cysteine residues.\ \N \N \N 21913 IPR003367 Thrombospondin is an adhesive glycoprotein that mediates cell-to-cell and cell-to-matrix interactions. It can bind to fibrinogen, fibronectin, laminin and type V collagen. This repeat is found in the thrombospondin family of proteins and probably binds to calcium [MEDLINE:87057617]. Cartilage oligomeric matrix protein is also part of this family.\ calcium ion binding activity ; GO:0005509 \N cell adhesion ; GO:0007155 21914 IPR003368 Members of this family have been found in various species of Chlamydia. The protein is expressed on the bacterial surface and is found to be a major immunogen [MEDLINE:96406378], [MEDLINE:98187897].\ \N \N \N 21915 IPR003369 Members of this protein family are involved in a sec-independent translocation mechanism. This pathway has been called the DeltapH pathway in chloroplasts [MEDLINE:98035786]. Members of this family in Escherichia coli are involved in export of redox proteins with a "twin arginine" leader motif (S/T-R-R-X-F-L-K) [MEDLINE:98206471]. This sec-independent pathway is termed TAT for twin-arginine translocation system. This system mainly transports proteins with bound cofactors that require folding prior to export.\ protein transporter activity ; GO:0008565 \N protein transport ; GO:0015031 21916 IPR003370 Members of this family probably act as chromate transporters [MEDLINE:90094230], [MEDLINE:90202806], and are found in both bacteria and archaebacteria. The protein reduces chromate accumulation and is essential for chromate resistance. They are composed of one or two copies of this region. The alignment contains two conserved motifs, FGG and PGP.\ chromate transporter activity ; GO:0015109 \N chromate transport ; GO:0015703 21917 IPR003372

This family consists of the photosystem II reaction center protein PsbL from plants and Cyanobacteria. The function of this small protein is unknown. Interestingly the mRNA for this protein requires a post-transcriptional modification of an ACG triplet to form an AUG initiator codon [MEDLINE:93099270], [MEDLINE:92191997].

\ \N photosystem II reaction center ; GO:0009539 electron transport ; GO:0006118 21899 IPR003350 A class, also called ONECUT, of homeodomain proteins. The CUT domain is a DNA-binding motif which can bind independently or in cooperation with the homeodomain (IPR001356.\ \ DNA binding activity ; GO:0003677 \N \N 21900 IPR003351 This domain is specific to the signaling protein dishevelled. In Drosophila melanogaster, the dishevelled segment polarity protein is required to establish coherent arrays of polarized cells and segments in embryos. It plays a role in wingless signaling, possibly through the reception of the wingless signal by target cells and subsequent redistribution of arm protein in response to that signal in embryos.The domain is found adjacent to the PDZ domain (IPR001478).\ signal transducer activity ; GO:0004871 \N development ; GO:0007275 21901 IPR003352 The bacterial phosphoenolpyruvate: sugar phosphotransferase system (PTS) is a multi-protein system involved in the regulation of a variety of metabolic and transcriptional processes. The PTS catalyzes the phosphorylation of incoming sugar substrates concomitant with their translocation across the cell membrane. The general mechanism of the PTS is the following: a phosphoryl group from phosphoenolpyruvate (PEP) is transferred to enzyme-I (EI) of PTS which in turn transfers it to a phosphoryl carrier protein (HPr). Phospho-HPr then transfers the phosphoryl group to a sugar-specific permease which consists of at least three structurally distinct domains (IIA, IIB, and IIC) [MEDLINE:92165716] which can either be fused together in a single polypeptide chain or exist as two or three interactive chains, formerly called enzymes II (EII) and III (EIII). The IIC domain catalyzes the transfer of a phosphoryl group from IIB to the sugar substrate.\ sugar porter activity ; GO:0005351 membrane ; GO:0016020 phosphoenolpyruvate-dependent sugar phosphotransferase system ; GO:0009401 21902 IPR003353 The bacterial phosphoenolpyruvate: sugar phosphotransferase system (PTS) is a multi-protein system involved in the regulation of a variety of metabolic and transcriptional processes. The PTS catalyzes the phosphorylation of incoming sugar substrates concomitant with their translocation across the cell membrane. The general mechanism of the PTS is the following: a phosphoryl group from phosphoenolpyruvate (PEP) is transferred to enzyme-I (EI) of PTS which in turn transfers it to a phosphoryl carrier protein (HPr). Phospho-HPr then transfers the phosphoryl group to a sugar-specific permease which consists of at least three structurally distinct domains (IIA, IIB, and IIC) [MEDLINE:92165716] which can either be fused together in a single polypeptide chain or exist as two or three interactive chains, formerly called enzymes II (EII) and III (EIII). IIB (EC: 2.7.1.69) is is phosphorylated by phospho-IIA, before the phosphoryl group is transferred to the sugar substrate.\ sugar porter activity ; GO:0005351 membrane ; GO:0016020 phosphoenolpyruvate-dependent sugar phosphotransferase system ; GO:0009401 21907 IPR003360 This is the US22 protein family of hypothetical proteins from herpes virus. The name sake of this family US22 is an early nuclear protein that is secreted from cells [MEDLINE:92333249]. The US22 family may have a role in virus replication and pathogenesis [MEDLINE:99335607].\ \N \N \N 21903 IPR003354 This domain represents a conserved region in papovavirus small and middle T-antigens. It is found as the N-terminal domain in the small T-antigen, and is centrally located in the middle T-antigen.\ defense/immunity protein activity ; GO:0003793 \N \N 21904 IPR003356 This domain is fpound in N-6 adenine-specific DNA methylase (EC: 2.1.1.72) from Type I and Type IC restriction systems.These enzymes are responsible for the methylation of specific DNA sequences in order to prevent the host from digesting its own genome via its restriction enzymes. These methylases have the same sequence specificity as their corresponding restriction enzymes. The type I restriction and modification system is composed of three polypeptides R, M and S. The M and S subunits together form a methyltransferase that methylates two adenine residues in complementary strands of a bipartite DNA recognition sequence. In the presence of the R subunit, the complex can also act as an endonuclease, binding to the same target sequence but cutting the DNA some distance from this site. Whether the DNA is cut or modified depends on the methylation state of the target sequence. When the target site is unmodified, the DNA is cut. When the target site is hemimethylated, the complex acts as a maintenance methyltransferase, modifying the DNA so that both strands become methylated.\ \ N-methyltransferase activity ; GO:0008170 \N DNA methylation ; GO:0006306 21905 IPR003358 This is a family of hypothetical proteins which are putative methyltransferases. The aligned region contains the GXGXG S-AdoMet binding site suggesting a putative methyltransferase activity.\ \N \N \N 21906 IPR003359 This family consists of hypothetical Ycf4 proteins from various chloroplast genomes. It has been suggested that Ycf4 is involved in the assembly and/or stability of the photosystem I complex in chloroplasts [MEDLINE:98026885].\ \N \N \N 21888 IPR003339 Cobalt transport proteins are most often found in cobalamin (vitamin B12) biosynthesis operons. Salmonella typhimurium synthesizes cobalamin (vitamin B12) de novo under anaerobic conditions. Not all Salmonella and Pseudomonas cobalamin synthetic genes have apparent homologs in the other species suggesting that the cobalamin biosynthetic pathways differ between the two organisms [MEDLINE:93273696].\ \ cobalt ion transporter activity ; GO:0015087 \N vitamin B12 biosynthesis ; GO:0009236 21889 IPR003340 Two DNA binding proteins, RAV1 and RAV2 from Arabidopsis thaliana contain two distinct amino acid sequence domains found only in higher plant species. The N-terminal regions of RAV1 and RAV2 are homologous to the AP2 DNA-binding domain (see IPR001471. The AP2 and B3-like domains of RAV1 bind autonomously to the CAACA and CACCTG motifs, respectively, and together achieve a high affinity and specificity of binding. It has been suggested that the AP2 and B3-like domains of RAV1 are connected by a highly flexible structure enabling the two domains to bind to the CAACA and CACCTG motifs in various\ spacings and orientations [MEDLINE:99081843].\ \ DNA binding activity ; GO:0003677 \N regulation of transcription, DNA-dependent ; GO:0006355 21890 IPR003341 This signature describes a cysteine repeat C-X3-C-X3-C the function of which is unknown as is the function of the proteins in which they occur. Most of the sequences in this group are from Caenorhabditis elegans.\ \N \N \N 21891 IPR003342

Dolichyl-phosphate-mannose-protein mannosyltransferase proteins EC: 2.4.1.109 belong to the glycosyltransferase family 39 (CAZY:GT_39

The transfer of mannose to seryl and threonyl residues of secretory proteins is catalyzed by a family of protein mannosyltransferases in Saccharomyces cerevisiae coded for by seven genes (PMT1-7). Protein O-glycosylation is essential for cell wall rigidity and cell integrity and this protein modification is vital for S. cerevisiae PUB00007032.

\ \ mannosyltransferase activity ; GO:0000030 membrane ; GO:0016020 O-linked glycosylation ; GO:0006493 21892 IPR003343 Proteins that contain this domain are found in a variety of bacterial and phage surface proteins such as intimins. \ Intimin is a bacterial cell-adhesion molecule that mediates the intimate bacterial host-cell interaction. It contains three domains; two immunoglobulin-like domains and a C-type lectin-like module implying that carbohydrate recognition may be important in intimin-mediated cell adhesion [meldine:99215579].\ \ \N \N \N 21893 IPR003344 Proteins that contain this domain are found in a variety of bacterial and phage surface proteins such as intimins. \ Intimin is a bacterial cell-adhesion molecule that mediates the intimate bacterial host-cell interaction. It contains three domains; two immunoglobulin-like domains and a C-type lectin-like module implying that carbohydrate recognition may be important in intimin-mediated cell adhesion [meldine:99215579].\ \ \N \N \N 21894 IPR003345 This short repeat is found in multiple copies in bacterial M proteins. The M proteins bind to IgA and are closely associated with virulence.The M protein has been postulated to be a major group A streptococcal (GAS) virulence factor because of its contribution to the bacterial resistance to opsonophagocytosis [MEDLINE:96228693].\ \ \N membrane ; GO:0016020 \N 21895 IPR003346 Transposases are needed for efficient transposition of the insertion sequence or transposon DNA. This family includes transposases for IS116, IS110 and IS902. It is often found with the transposase IS111A/IS1328/IS1533 family (see IPR002525).\ transposase activity ; GO:0004803 \N DNA transposition ; GO:0006313 21896 IPR003347 Jumonji protein is required for neural tube formation in mice [MEDLINE:95278734].There is evidence of domain swapping within the jumonji family of transcription factors [MEDLINE:20299261]. This domain is often associated with jmjN (see IPR003349).\ \N \N \N 21897 IPR003348 This ATPase is involved in the removal of arsenate, antimonite, and arsenate from the cell.

In Escherichia coli an anion-translocating ATPase has been identified as the product of the arsenical resistance operon of resistance plasmid R773. This ATP-driven oxyanion pump catalyses extrusion of the oxyanions arsenite, antimonite and arsenate. Maintenance of a low intracellular concentration of oxyanion produces resistance to the toxic agents. The pump is composed of two polypeptides, the products of the arsA and arsB genes. This two-subunit enzyme produces resistance to arsenite and antimonite. A third gene, arsC, expands the\ substrate specificity to allow for arsenate pumping and resistance [MEDLINE:91126299].

The ArsA and ArsB proteins form a membrane-bound pump that functions as an oxyanion-translocating ATPase. The ArsC protein is an arsenate reductase that reduces arsenate to arsenite, which is subsequently pumped out of the cell [MEDLINE:95355341].

\ \ ATP binding activity ; GO:0005524 membrane ; GO:0016020 anion transport ; GO:0006820 21884 IPR003334 Latrophilin is a member of the secretin family of G protein-coupled receptors. Alpha-Latrotoxin (LTX) stimulates massive exocytosis of synaptic vesicles and may help to elucidate the mechanism of regulation of neurosecretion. Latrophilin is the synaptic Ca²⁺-independent LTX receptor. The extracellular domain of latrophilin is homologous to olfactomedin (see IPR003112.\ G-protein coupled receptor activity ; GO:0004930 membrane ; GO:0016020 G-protein coupled receptor protein signaling pathway ; GO:0007186 21885 IPR003335

\ The translocase itself comprises 7 proteins, including a chaperone protein (SecB), an ATPase (SecA), an integral\ membrane complex (SecCY, SecE and SecG), and two additional membrane proteins that promote the release of\ the mature peptide into the periplasm (SecD and SecF) [MEDLINE:90361702]. The chaperone protein SecB [MEDLINE:21235707] is a highly acidic homotetrameric protein that exists as a "dimer of dimers" in the bacterial cytoplasm.\ SecB maintains preproteins in an unfolded state after translation, and targets these to the peripheral membrane\ protein ATPase SecA for secretion [MEDLINE:99346703]. Together with SecY and SecG, SecE forms a multimeric\ channel through which preproteins are translocated, using both proton motive forces and ATP-driven secretion. The\ latter is mediated by SecA. The structure of the\ Escherichia coli SecYEG assembly revealed a sandwich of two membranes interacting through the extensive cytoplasmic\ domains [MEDLINE:22157987] ]. Each membrane is composed of dimers of SecYEG. The monomeric complex contains 15\ transmembrane helices. \

This family consists of various prokaryotic SecD and SecF protein export membrane proteins. The SecD and SecF equivalents of the\ Gram-positive bacterium Bacillus subtilis are jointly present in one polypeptide,\ denoted SecDF, that is required to maintain a high capacity for protein secretion.\ Unlike the SecD subunit of the pre-protein translocase of Escherichia coli, SecDF\ of B. subtilis was not required for the release of a mature secretory protein from\ the membrane, indicating that SecDF is involved in earlier translocation steps [MEDLINE:98362000].\ Comparison with SecD and\ SecF proteins from other organisms revealed the presence of 10 conserved\ regions in SecDF, some of which appear to be important for SecDF function.\ Interestingly, the SecDF protein of B. subtilis has 12 putative transmembrane\ domains. Thus, SecDF does not only show sequence similarity but also structural\ similarity to secondary solute transporters [MEDLINE:98362000].

\ \ protein transporter activity ; GO:0008565 type II protein secretion system complex ; GO:0015627 type II protein (Sec) secretion system ; GO:0015628 21898 IPR003349

Jumonji protein is required for neural tube formation in mice [MEDLINE:95278734].There is evidence of domain swapping within the jumonji family of transcription factors [MEDLINE:20299261]. This domain is often associated with JmjC (see IPR003347).

\ \N \N \N 21887 IPR003338 The VAT protein of the archaebacterium Thermoplasma acidophilum, like all other members of the Cdc48/p97 family of AAA ATPases, has two ATPase domains and a 185-residue amino-terminal substrate-recognition domain, VAT-N. VAT shows activity in protein folding and unfolding and thus shares the common function of these ATPases in disassembly and/or degradation of protein complexes.

VAT-N is composed of two equally sized subdomains. The amino-terminal subdomain VAT-Nn forms a double-psi -barrel whose pseudo-twofold symmetry is\ mirrored by an internal sequence repeat of 42 residues. The carboxy-terminal\ subdomain VAT-Nc forms a novel six-stranded -clam fold [MEDLINE:20003057]. Together, VAT-Nn and VAT-Nc form a kidney-shaped structure, in close agreement with results from electron microscopy. VAT-Nn is related to numerous proteins including prokaryotic transcription factors, metabolic enzymes, the protease cofactors UFD1 and PrlF, and aspartic proteinases.

\ \ ATP binding activity ; GO:0005524 \N \N 21886 IPR003337 Trehalose-phosphatases EC: 3.1.3.12 catalyse the de-phosphorylation of trehalose-6-phosphate to trehalose and orthophosphate. Trehalose is a common disaccharide of bacteria, fungi and invertebrates that appears to play a major role in desiccation tolerance. A pathway for trehalose biosynthesis may also exist in plants [MEDLINE:98345987]. The trehalose-phosphatase signature is found in the C-terminus of\ trehalose-6-phosphate synthase EC: 2.4.1.15 adjacent to the trehalose-6-phosphate synthase domain (see IPR001830 otsBA operon: otsA, the\ trehalose-6-phosphate synthase and otsB, trehalose-phosphatase (this family) have undergone gene fusion in\ most eukaryotes [MEDLINE:94320793].\ \ \N \N trehalose biosynthesis ; GO:0005992 21879 IPR003329

Synonym(s): CMP-N-acetylneuraminic acid synthetase

Acylneuraminate cytidylyltransferase (EC: 2.7.7.43) (CMP-NeuAc synthetase) catalyzes the reaction of CTP and NeuAc to form CMP-NeuAc, which is the nucleotide sugar donor used by sialyltransferases [MEDLINE:96279048]. The outer membrane lipooligosaccharides of some microorganisms contain terminal sialic acid attached to N-acetyllactosamine and so this modification may be important in pathogenesis.

\ \ \N \N lipopolysaccharide biosynthesis ; GO:0009103 21880 IPR003330 The immunogenic major surface antigen (MSG) also termed glycoprotein A (gpA) is involved in the immunopathogenesis of Pneumocystis carinii. MSG from all P. carinii has conserved secondary structure, as well as function [MEDLINE:98344138], [MEDLINE:98380374].\ \N \N \N 21881 IPR003331 UDP-N-acetylglucosamine 2-epimerase EC: 5.1.3.14 catalyses the production of UDP-ManNAc from UDP-GlcNAc. Some of the enzymes is this family are bifunctional. In microorganisms the epimerase is involved in in the synthesis of the capsule precursor UDP-ManNAcA [MEDLINE:98175678], [MEDLINE:98101481]. The protein from rat liver displays both epimerase and kinase activity [MEDLINE:97450955].\ UDP-N-acetylglucosamine 2-epimerase activity ; GO:0008761 \N lipopolysaccharide biosynthesis ; GO:0009103 21882 IPR003332 Decorin is a proteoglycan that decorates collagen fibres. Borrelia burgdorferi causes lyme disease, a tick-borne infection that can develop into a chronic, multisystemic disorder. Decorin may mediate the adherence of B. burgdorferi to collagen fibers in skin and other tissues [MEDLINE:95369901]. Borrelia burgdorferi decorin binding protein A (DbpA) facilitates this binding [MEDLINE:99003139].\ \N \N \N 21883 IPR003333

This entry represents cyclopropane-fatty-acyl-phospholipid synthase that is slosely related to methyltransferases.

Cyclopropane-fatty-acyl-phospholipid synthase or CFA synthase EC: 2.1.1.79 catalyses the reaction:

\
S-adenosyl-L-methionine + phospholipid olefinic fatty acid -> S-adenosyl-L-homocysteine + phospholipid cyclopropane fatty acid. \

The major mycolic acid produced by Mycobacterium tuberculosis contains two cis-cyclopropanes in the meromycolate chain. Cyclopropanation may contribute to the structural integrity of the cell wall complex [MEDLINE:96070840].

\ \ \ cyclopropane-fatty-acyl-phospholipid synthase activity ; GO:0008825 \N lipid biosynthesis ; GO:0008610 21878 IPR003328 Zonadhesin is a sperm-specific membrane protein containing multiple cell adhesion molecule-like domains [MEDLINE:96064658], [MEDLINE:98123114]. Pig zonadhesin binds to the extracellular matrix of the egg in a species-specific manner. The TILa domain is found five times in pig zonadhesin.It is a cysteine rich domain that occurs along side the TIL domain (IPR002919) and is likely to be a distantly related relative.\ \ \N membrane ; GO:0016020 binding of sperm to zona pellucida ; GO:0007339 21875 IPR003325 This domain is found in tellurite resistance proteins, cAMP binding protein, and chemical-damaging agent resistance proteins and general stress proteins. Tellurium compounds are used in several industrial processes, although they are\ relatively rare in the environment. Genes associated with tellurite resistance (TeR) are found in many pathogenic bacteria [MEDLINE:99226296]. \

The cellular slime mould, Dictyostelium discoideum, contains a cAMP-binding protein, CABP1, which is composed of two subunits. The C-terminal half of these subunits contain this domain [MEDLINE:91099678].

\ \ \N \N response to stress ; GO:0006950 21876 IPR003326 This domain is found in a family of proteins from Caenorhabditis elegans. The domain has no known function, but has 4 conserved cysteine residues and is a maximum of 175 residues long.\ \N \N \N 21877 IPR003327 This family consists of the leucine zipper dimerisation domain found in both cellular c-Myc proto-oncogenes and viral v-Myc oncogenes. Dimerisation via the leucine zipper motif with other basic helix-loop-helix-leucine zipper (b/HLH/lz) proteins is required for efficient DNA binding [MEDLINE:98347001]. The Myc-Max\ dimer is a transactivating complex activating expression of growth related genes promoting cell proliferation.\ The dimerisation is facilitated via interdigitating leucine residues every 7th position of the

helix. Like\ charge repulsion of adjacent residues in this region preturbs the formation of homodimers with heterodimers\ being promoted by opposing charge attractions. It has been demonstrated that in transgenic mice the balance between oncogene-induced proliferation and apoptosis in a given tissue can be a critical determinant in the initiation and maintenance of the tumor [MEDLINE:20145640].\ \ DNA binding activity ; GO:0003677 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 21873 IPR003323 Cysteine proteases from eukaryotes, viruses and pathogenic bacterium belong to this family [MEDLINE:20130692] and are homologous to the Ovarian Tumour (OTU) gene in Drosophila. The conserved cysteine and histidine, and possibly the aspartate, represent the catalytic residues in this putative group of proteases.\ \N \N \N 21874 IPR003324 This short repeat is found in the aggrecan cartilage proteoglycan core protein. The consensus of this repeat is SGXXSGXXXX where X can be any amino acid. \

In the rat cartilage proteoglycan core protein the major feature of the deduced protein sequence is a 1,104-residue segment containing 117 Ser-Gly sequences, the presumed chondroitin sulfate attachment sites. These are arranged in three domains of 428, 503, and 173 amino acids. The first domain contains 11 complete or partial repeats of a 40-residue unit, and the second domain is composed of six copies of a 100-residue repeating sequence. The first pattern is the more highly conserved, and may have given rise to the second. The carboxyl-terminal domain is a third globule which has homology with animal lectins [MEDLINE:88087070].

\ \ \N extracellular matrix ; GO:0005578 \N 21872 IPR003322 The provirus, simian endogenous retrovirus (SERV), is 8,393 nucleotides long and contains two long terminal repeats and complete genes for gag, pro, pol, and env [MEDLINE:97248412].

This family consists of various retroviral GAG (core) polyproteins and encompasses the p10 region producing the p10 protein upon proteolytic cleavage of GAG by retroviral protease. The p10 or matrix protein (MA) is associated with the virus envelope glycoproteins in most mammalian retroviruses and may be involved in virus particle assembly, transport and budding. Some of the GAG polyproteins have alternate cleavage sites leading to the production of alternative and longer cleavage products (e.g. P21411) the alignment\ of this family only covers the approximately N-terminal (GAG) 100 amino acid region of homology to p10.

\ \ \N viral capsid ; GO:0019028 \N 21871 IPR003321 The enzyme cytochrome c nitrite reductase (c552) catalyses the six-electron reduction of nitrite to ammonia as one of the key steps in the biological nitrogen cycle, where it participates in the anaerobic energy metabolism of dissimilatory nitrate ammonification. Cytochrome c nitrite reductase from Sulfurospirillum deleyianum is a functional dimer, with 10 close-packed haem groups of type c and an unusual lysine-coordinated high-spin haem at the active site [MEDLINE:99366992].\ nitrite reductase activity ; GO:0016666 \N nitrogen metabolism ; GO:0006807 21866 IPR003316 The mammalian transcription factor E2F plays an important role in regulating the expression of genes that are required for passage through the cell cycle. Multiple E2F family members have been identified that bind to DNA as heterodimers, interacting with proteins known as DP - the dimerisation partners [MEDLINE:95257935].\ \ transcription factor activity ; GO:0003700 transcription factor complex ; GO:0005667 regulation of transcription, DNA-dependent ; GO:0006355 21867 IPR003317 These proteins are cytochrome bd type terminal oxidases that catalyse quinol dependent, Na⁺ independent oxygen uptake [MEDLINE:96198179]. Members of this family are integral membrane proteins and contain a protoheame IX center B558.

\ \ \N membrane ; GO:0016020 electron transport ; GO:0006118 21868 IPR003318

\ Glucosyltransferases or sucrose 6-glycosyl transferases (GTF-S) (EC: 2.4.1.5, CAZY:GH_70).\ \ \N \N glucan biosynthesis ; GO:0009250 21869 IPR003319 Mitochondria, organelles specialized in energy conservation reactions in eukaryotic cells, have evolved from eubacteria-like endosymbionts whose closest known relatives are the rickettsial group of

-proteobacteria.A primitive mitochondrial genome, in the freshwater protozoon Reclinomonas americana has been described [MEDLINE:97311393] and seems to contain genes for 5S ribosomal RNA, the RNA component of RNase P, and at least 18 proteins not\ previously known to be encoded in mitochondria. \

This family consists of hypothetical proteins which are similar to the mitochondrial membrane protein YMF19 from wheat (P43650).

\ \ \N mitochondrion ; GO:0005739 \N 21870 IPR003320 The chloroperoxidase (EC: 1.11.1.-) from the fungus Curvularia inaequalis belongs to a class of vanadium enzymes that oxidize halides in the presence of hydrogen peroxide to the corresponding hypohalous acids [MEDLINE:96133943].\ peroxidase activity ; GO:0004601 \N peroxidase reaction ; GO:0006804 21864 IPR003314 This family consists of MuA-transposase and repressor protein CI. The phage Mu transposase is essential for integration, replication-transposition, and excision of Mu DNA. The N-terminus of the Mu transposase has considerable sequence homology with the Mu repressor and with the NH2 terminus of the transposase of the Mu-like phage D108. These three proteins are known to share binding sites on DNA. An internal sequence in the Mu A protein also shares these features [MEDLINE:86067968].

The repressor protein of bacteriophage Mu establishes and maintains lysogeny by shutting down transposition functions needed for phage DNA replication. It\ interacts with several repeated DNA sequences within the early operator,\ preventing transcription from two divergent promoters. It also directly represses transposition by competing with the MuA transposase for an internal activation sequence (IAS) that is coincident with the operator and required for efficient transposition. The transposase and repressor proteins compete for the\ operator/IAS region using homologous DNA-binding domains located at their\ amino termini [MEDLINE:99315213].

\ \ DNA binding activity ; GO:0003677 \N \N 21865 IPR003315 The small G protein Rab3A plays an important role in the regulation of neurotransmitter release. The crystal structure of the small G protein Rab3A complexed with the effector domain of rabphilin-3A shows that the effector domain of rabphilin-3A contacts Rab3A in two distinct areas. The first interface involves the Rab3A switch I and switch II regions, which are sensitive to the nucleotide-binding state of Rab3A. The second interface consists of a deep pocket in Rab3A that interacts with a SGAWFF structural element of rabphilin-3A. Sequence and structure analysis, and biochemical data suggest that this pocket, or Rab complementarity-determining region (RabCDR), establishes a specific interaction between each Rab protein and its effectors. It has been suggested that RabCDRs could be major determinants of effector specificity during vesicle trafficking and fusion [MEDLINE:99148269].\ \N \N intracellular protein transport ; GO:0006886 21859 IPR003308

Integrase mediates integration of a DNA copy of the viral genome into the host chromosome. Integrase is composed of three domains; the amino-terminal zinc binding domain, the central\ domain is the catalytic domain rve and the carboxyl terminal domain is a DNA binding domain. Often found as part of the POL polyprotein.

\ \ integrase activity ; GO:0008907 \N DNA integration ; GO:0015074 21860 IPR003309 A number of C2H2-zinc finger proteins contain a highly conserved N-terminal motif termed the SCAN domain. The SCAN domain may play an important role in the assembly and function of this newly defined subclass of transcriptional regulators [MEDLINE:20036809].\ transcription factor activity ; GO:0003700 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 21861 IPR003310 G:U mismatches resulting from deamination of cytosine are the most common promutagenic lesions occurring in DNA. Uracil is removed in a base-excision repair pathway by uracil DNA-glycosylase (UDG), which excises uracil from both single- and double-stranded DNA.

A biochemically distinct family of DNA repair enzymes which excises both uracil and thymine, but only from mispairs with guanine has been identified [MEDLINE:98149349]. Crystal structures of the mismatch-specific uracil DNA-glycosylase (MUG) from Escherichia coli, and of a DNA complex, reveal structural and functional homology to UDGs despite low sequence identity [MEDLINE:98149349].

\ \ hydrolase activity, acting on glycosyl bonds ; GO:0016798 \N DNA repair ; GO:0006281 21862 IPR003311 Transcription of the AUX/IAA family of genes is rapidly induced by the plant hormone auxin. Some members of this family are longer and contain an N-terminal DNA binding domain [MEDLINE:98151364] and may have an early function in the establishment of vascular and body patterns in embryonic and post-embryonic development in some plants.\ \ \N intracellular ; GO:0005622 regulation of translation ; GO:0006445 21863 IPR003313 This entry defines the arabinose-binding and dimerisation domain of the bacterial gene regulatory protein AraC. The crystal structure of the arabinose-binding and dimerization domain of the Escherchia coli gene regulatory protein AraC was determined in the presence and\ absence of L-arabinose. The arabinose-bound molecule shows that the protein adopts an unusual fold, binding sugar within a

barrel and completely burying the arabinose with the amino-terminal arm of the protein. Dimer contacts in the presence of arabinose are mediated by an antiparallel coiled-coil. In the uncomplexed protein, the amino-terminal arm is disordered, uncovering the sugar-binding pocket and allowing it to serve as an oligomerization interface [MEDLINE:97258946].\ \ \N \N regulation of transcription, DNA-dependent ; GO:0006355 21857 IPR003306 The WIF domain is found in the RYK tyrosine kinase receptors and WIF the Wnt-inhibitory-factor. The domain is extracellular and and contains two conserved cysteines that may form a disulphide bridge. This domain is Wnt binding in WIF, and it has been suggested that RYK may also bind to Wnt [MEDLINE:20105592].\ \ protein tyrosine kinase activity ; GO:0004713 \N \N 21858 IPR003307

This domain of unknown function is found at the C-terminus of several translation initiation factors [MEDLINE:96060092]. It was first detected at the very C-termini of the yeast protein GCD6, eIF-2B epsilon, and two other eukaryotic translation initiation factors, eIF-4 gamma and eIF-5 and it may be involved in the interaction of eIF-2B, eIF-4 gamma, and eIF-5 with eIF-2 [MEDLINE:96060092].

\ translation initiation factor activity ; GO:0003743 \N regulation of translational initiation ; GO:0006446 21853 IPR003302 SPRR genes (formerly SPR) encode a novel class of polypeptides (small proline rich proteins) that are strongly induced during differentiation of human epidermal keratinocytes in vitro and in vivo.The most characteristic feature of the SPRR gene family resides in the structure of the central segments of the encoded polypeptides that are built up from tandemly repeated units of either eight (SPRR1 and SPRR3) or nine (SPRR2) amino\ acids with the general consensus XKXPEPXX where X is any amino acid [MEDLINE:93315153].\ \ \N \N \N 21854 IPR003303 Filaggrins are filament-associated proteins that interact with keratin intermediate filaments of terminally differentiating mammalian epidermis\ via disulphide bond formation [MEDLINE:89296901]. They show wide species variations and\ their aberrant expression has been implicated in a number of keratinising\ disorders. The proteins are synthesised as large, insoluble, highly-\ phosphorylated precursors, containing multiple tandem repeats of 324 amino\ acids, which are not separated by a large linker. The precursor is\ deposited as keratohyalin granules. During terminal differentiation, it\ is dephosphorylated and proteolytically cleaved.\ \ structural molecule activity ; GO:0005198 \N \N 21855 IPR003304

\ EP3 receptors mediate contraction in a wide range of smooth muscles, \ including gastrointestinal and uterine. They also inhibit neurotransmitter release in central and autonomic nerves through a presynaptic action,\ and inhibit secretion in glandular tissues (e.g., acid secretion from\ gastric mucosa, and sodium and water reabsorption in the kidney). mRNA\ is found in high levels in the kidney and uterus, and in lower levels in\ the brain, thymus, lung, heart, stomach and spleen. The receptors activate\ adenylate cyclase via an uncharacterised G-protein, probably of the Gi/Go\ class.\

Sequence analysis shows the EP3 receptors to fall into distinct classes,\ based on their N- and C-terminal and loop signatures. For convenience,these classes have been designated types 1 to 3.

\ \ prostanoid receptor activity ; GO:0004954 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 21849 IPR003298 A novel antigen of Plasmodium falciparum has been cloned that contains hydrophobic domain typical of an integral membrane protein. The antigen is designated apical membrane antigen 1 (AMA-1) by virtue of appearing to \ be located in the apical complex [MEDLINE:89384584]. AMA-1 appears to be transported to \ the merozoite surface close to the time of schizont rupture. \

The 66kDa merozoite surface antigen (PK66) of Plasmodium knowlesi, a simian\ malaria, possesses vaccine-related properties believed to originate from a \ receptor-like role in parasite invasion of erythrocytes [MEDLINE:91009268]. The sequence\ of PK66 is conserved throughout Plasmodium, and shows high similarity to\ P.falciparum AMA-1. Following schizont rupture, the distribution of PK66 \ changes in a coordinate manner associated with merozoite invasion. Prior\ to rupture, the protein is concentrated at the apical end, following which\ it distributes itself entirely across the surface of the free merozoite.\ Immunofluorescence studies suggest that, during invasion, PK66 is excluded\ from the erythrocyte at, and behind, the invasion interface [MEDLINE:91009268].

\ \ defense/immunity protein activity ; GO:0003793 membrane ; GO:0016020 \N 21856 IPR003305 The 1,4-

-glucanase CenC from Cellulomonas fimi contains two cellulose-binding domains, CBD(N1) and CBD(N2), arranged in tandem at its\ N-terminus. These homologous CBDs are distinct in their selectivity for binding amorphous and not crystalline cellulose [MEDLINE:20170870].\ Multidimensional heteronuclear nuclear magnetic resonance (NMR) spectroscopy\ was used to determine the tertiary structure of the 152 amino acid N-terminal\ cellulose-binding domain from Cellulomonas fimi 1,4-

-glucanase CenC\ (CBDN1)[MEDLINE:97074498]. The tertiary\ structure of CBDN1 is strikingly similar to that of the bacterial\ 1,3-1,4-

-glucanases, as well as other sugar-binding proteins with jelly-roll folds.\ \ \N \N \N 21850 IPR003299 The protozoan parasite that causes Chagas' disease, Trypanosoma cruzi, contains a 24kDa protein that is recognised by antiera from both humans andexperimental animals infected with this organism. Near its C-terminus \ are two regions that have sequence similarity with E-F hand Ca²⁺-binding\ proteins [MEDLINE:90036966]. Indeed, the native trypanosome protein exhibits low Ca²⁺-binding capacity and high Ca²⁺-binding affinity, consistent with binding\ via E-F hand structures. Immunofluorescence assays have suggested that the\ protein is localised to the trypanosome's flagellum. This observation,\ coupled with the protein's Ca²⁺-binding properties, suggests that it may\ participate in molecular processes associated with the high motility of \ the parasite [MEDLINE:90036966]. \

A set of similar 24 kDa proteins, termed calflagins, are contained within\ the flagellum of Trypanosoma brucei. These contain three EF-hand Ca²⁺-\ binding domains and one degenerate EF-hand motif [MEDLINE:95118301].

\ \ calcium ion binding activity ; GO:0005509 flagellum (sensu Bacteria) ; GO:0009288 ciliary/flagellar motility ; GO:0001539 21851 IPR003300 The complete DNA sequence of the genome of vaccinia virus has been determined [MEDLINE:91021027]. 198 "major" protein-coding regions and 65 overlapping\ "minor" regions have been identified, with a total of 263 potential genes. The genes are compactly organised along the genome, with few noncoding\ regions [MEDLINE:91021027]. The function of the majority of proteins encoded by these open\ reading frames is so far undetermined. \

The D9 protein contains an evolutionarily conserved MutT domain core,\ which is also found in a variety of other viral, prokaryotic and eukaryotic\ proteins.

\ \ \N \N \N 21852 IPR003301 The complete DNA sequence of the genome of vaccinia virus has been determined [MEDLINE:91021027]. 198 "major" protein-coding regions and 65 overlapping\ "minor" regions have been identified, with a total of 263 potential genes. The genes are compactly organised along the genome, with few noncoding\ regions [MEDLINE:91021027]. The function of the majority of proteins encoded by these open\ reading frames is so far undetermined. \

The DNA sequence of the fowlpox virus genome corresponding to the vaccinia\ virus D6-A1 region has been deduced [MEDLINE:91108382]. Translation of the sequence reveals fowlpoxvirus gene homologues corresponding to the D6, D7, D9, D10, D11, D12, D13 and A1 genes of vaccinia virus. Insertion of a gene\ cartridge comprising the vaccinia virus p7.5 promoter and the lacZ gene\ into the fowlpox virus D8, D9 and D10 genes was carried out in vitro,\ followed by recombination into fowlpox virus\ \ \ \ [MEDLINE:91108382]. No stable insertion mutants were obtained for D10, suggesting that this gene probably encodes a function essential to virus replication [MEDLINE:91108382].

D10, like the D9 protein, contains an evolutionarily conserved MutT domain \ core, which is a characteristic of the NUDIX hydrolase family [MEDLINE:96411704].

\ \ \N \N \N 21847 IPR003296 Over a hundred cytokines have now been identified, including several putative new members of the IL-1 family. The IL-1 family consists of 2\ main classes, designated

(IL1A) and

(IL1B), as well as the more\ recently discovered IL-1 receptor antagonist (IL1RA). Sequence similarity \ is high within the IL1A and IL1B subfamilies (about 60-70%) but low between\ them (less than 30%). IL1As and IL1Bs are synthesised as larger precursors, \ which are processed to give mature carboxy fragments. IL1B requires this \ cleavage to become biologically active, but IL1A precursor is already \ active. Both IL1A and IL1B bind to the same IL1-specific receptor on the \ target cell, which is then internalised to initiate the relevant effects\ (which appear to be similar or identical).\

The crystal structures of IL1A and IL1B [MEDLINE:90099325] have been solved, showing them \ to share the same 12-stranded -sheet structure as both the heparin\ binding growth factors and the Kunitz-type soybean trypsin inhibitors [MEDLINE:92148835].\ The -sheets are arranged in 3 similar lobes around a central axis, 6\ strands forming an anti-parallel -barrel. Several regions, especially \ the loop between strands 4 and 5, have been implicated in receptor binding.

\ \ interleukin-1 receptor ligand activity ; GO:0005149 extracellular ; GO:0005576 immune response ; GO:0006955 21848 IPR003297 Over a hundred cytokines have now been identified, including several putative new members of the IL-1 family. The IL-1 family consists of 2\ main classes, designated

(IL1A) and

IL1RA binds to the IL1 receptor, blocking the effects of IL1A and IL1B\ whilst eliciting no response of its own. From sequence comparisons it seems\ to have arisen by gene duplication before IL1 diverged into IL1A and IL1B,\ as it has features of both [MEDLINE:91271363]. It seems likely to have the same fold as\ IL1A and IL1B.

\ \ interleukin-1 receptor antagonist activity ; GO:0005152 \N \N 21846 IPR003295 Over a hundred cytokines have now been identified, including several putative new members of the IL-1 family. The IL-1 family consists of 2\ main classes, designated

(IL1A) and

\ \ interleukin-1 receptor ligand activity ; GO:0005149 extracellular ; GO:0005576 immune response ; GO:0006955 21843 IPR003292

Glucagon-like peptide-1 (GLP-1), which is encoded by the glucagon gene and released from the gut in response to nutrients, is a potent stimulator of\ glucose-induced insulin secretion and proinsulin gene expression of\ pancreatic -cells [MEDLINE:94298957],[MEDLINE:95145713]. In humans, GLP-I exerts its physiological\ effect as an incretin. Patients with insulinoma tumors show uncontrolled \ insulin hypersecretion [MEDLINE:94298957]. The GLP-I receptor binds GLP-1 with high \ affinity and couples to activation of adenylate cyclase [MEDLINE:92409572]. The receptor\ specifically binds GLP-1 and not peptides of related structure and function,\ such as glucagon, gastric inhibitory peptide, VIP or secretin [MEDLINE:92409572]. It is\ thought that GLP-I might have effects beyond the pancreas, including the \ cardiovascular and central nervous systems, where a receptor with the same\ ligand-binding specificity is found [MEDLINE:95145713].

\ \ peptide receptor activity, G-protein coupled ; GO:0008528 membrane ; GO:0016020 G-protein coupled receptor protein signaling pathway ; GO:0007186 21844 IPR003293 An antisense transcript from the Xenopus laevis basic fibroblast growth factor (bFGF) gene has been shown to code for an unknown 24kDa protein [MEDLINE:90059883].\ The protein contains an evolutionarily conserved MutT domain core, which\ is a characteristic of the NUDIX hydrolase family [MEDLINE:96411704].\ \ \N \N \N 21845 IPR003294 Over a hundred cytokines have now been identified, including several putative new members of the IL-1 family. The IL-1 family consists of 2\ main classes, designated

(IL1A) and

\ \ interleukin-1 receptor ligand activity ; GO:0005149 extracellular ; GO:0005576 immune response ; GO:0006955 21842 IPR003291 The glucagon receptor (GR) plays a central role in regulating the level of blood glucose by controlling the rate of hepatic glucose production and \ insulin secretion [MEDLINE:96069600]. GR is expressed predominantly in liver, kidney, adrenal, lung and stomach, with lower levels of expression detected in\ brown and white adipose tissue, cerebellum, duodenum and heart [MEDLINE:96069600]. Their role in the control of blood glucose concentrations makes glucagon and GR especially important to studies of diabetes, in which the loss of control over blood glucose concentrations clinically defines the disease [MEDLINE:93206096]. GR is similar to the secretin-like receptor superfamily. It can transduce signals leading to the accumulation of two different second messengers - i.e., both cAMP and calcium [MEDLINE:93206096].\ \ glucagon receptor activity ; GO:0004967 membrane ; GO:0016020 G-protein coupled receptor protein signaling pathway ; GO:0007186 21841 IPR003290 The glucagon receptor (GR) plays a central role in regulating the level of blood glucose by controlling the rate of hepatic glucose production and \ insulin secretion [MEDLINE:96069600]. GR is expressed predominantly in liver, kidney, adrenal, lung and stomach, with lower levels of expression detected in\ brown and white adipose tissue, cerebellum, duodenum and heart [MEDLINE:96069600]. Their role in the control of blood glucose concentrations makes glucagon and GR especially important to studies of diabetes, in which the loss of control over blood glucose concentrations clinically defines the disease [MEDLINE:93206096]. GR is similar to the secretin-like receptor superfamily. It can transduce signals leading to the accumulation of two different second messengers - i.e., both cAMP and calcium [MEDLINE:93206096]. \

Glucagon-like peptide-1 (GLP-1), which is encoded by the glucagon gene and\ released from the gut in response to nutrients, is a potent stimulator of\ glucose-induced insulin secretion and proinsulin gene expression of\ pancreatic -cells [MEDLINE:94298957],[MEDLINE:95145713]. In humans, GLP-I exerts its physiological\ effect as an incretin. Patients with insulinoma tumors show uncontrolled \ insulin hypersecretion [MEDLINE:94298957]. The GLP-I receptor binds GLP-1 with high \ affinity and couples to activation of adenylate cyclase [MEDLINE:92409572]. The receptor\ specifically binds GLP-1 and not peptides of related structure and function,\ such as glucagon, gastric inhibitory peptide, VIP or secretin [MEDLINE:92409572]. It is\ thought that GLP-I might have effects beyond the pancreas, including the \ cardiovascular and central nervous systems, where a receptor with the same\ ligand-binding specificity is found [MEDLINE:95145713].

\ \ glucagon receptor activity ; GO:0004967 membrane ; GO:0016020 G-protein coupled receptor protein signaling pathway ; GO:0007186 21838 IPR003287 The major physiological role of calcitonin is to inhibit bone resorption thereby leading to a reduction in plasma Ca²⁺. Further, it enhances \ excretion of ions in the kidney, prevents absorption of ions in the \ intestine, and inhibits secretion in endocrine cells (e.g. pancreas and\ pituitary). In the CNS, calcitonin has been reported to be analgesic\ and to suppress feeding and gastric acid secretion. It is used to treat\ Paget's disease of the bone. Calcitonin receptors are found predominantly\ on osteoclasts or on immortal cell lines derived from these cells. It is\ found in lower amounts in the brain (e.g. in hypothalamus and pituitary\ tissues) and in peripheral tissues (e.g. testes, kidney, liver and\ lymphocytes). It has also been described in lung and breast cancer cell\ lines. The predominant signalling pathway is activation of adenylyl cyclase\ through Gs, but calcitonin has also been described to have both stimulatory\ and inhibitory actions on the phosphoinositide pathway. \

Calcitonin gene-related peptide (CGRP) is a neuropeptide with diverse\ biological effects including potent vasodilator activity [MEDLINE:96212201]. Messenger RNA for this receptor is predominantly expressed in the lung and heart, with specific localisation to lung alveolar cells and cardiac myocytes [MEDLINE:96212201]. In the rat lung, it is associated with blood vessels; the gene may therefore play an important role in the maintenance of vascular tone [MEDLINE:94037821]. mRNA is also found in the cerebellum [MEDLINE:95118359]. The ligand for this receptor-like protein remains to be discovered.

\ \ calcitonin receptor activity ; GO:0004948 membrane ; GO:0016020 G-protein coupled receptor protein signaling pathway ; GO:0007186 21839 IPR003288 Growth hormone (GH)-releasing hormone (GHRH) belongs to the family of gut- neuropeptide hormones that includes glucagon, secretin and vasoactive \ intestinal peptide (VIP) [MEDLINE:94020094]. The receptors for this peptide family involve\ similar signal transduction pathways - on hormone binding, they interact\ with G-protein 'Gs' and cause stimulation of adenylate cyclase [MEDLINE:94020094]. Acting\ through the GHRH receptor (GHRHR), GH plays a pivotal role in the regulation\ of GH synthesis and secretion in the pituitary, possibly serving other roles\ in different tissues [MEDLINE:94020094]. The \ human pituitary GHRHR is a 423-amino acid \ protein that has the characteristic 7TM signature of the secretin-like GPCR\ superfamily, sharing 47%, 42%, 35%, and 28% identity with receptors for \ VIP, secretin, calcitonin and PTH, respectively [MEDLINE:93188867].\ \ G-protein coupled receptor activity ; GO:0004930 membrane ; GO:0016020 G-protein coupled receptor protein signaling pathway ; GO:0007186 21840 IPR003289

Calcitonin gene-related peptide (CGRP) is a neuropeptide with diverse biological effects including potent vasodilator activity [MEDLINE:96212201]. Messenger RNA for this receptor is predominantly expressed in the lung and heart, with specific localisation to lung alveolar cells and cardiac myocytes [MEDLINE:96212201]. In the rat lung, it is associated with blood vessels; the gene may therefore play an important role in the maintenance of vascular tone [MEDLINE:94037821]. mRNA is also found in the cerebellum [MEDLINE:95118359]. The ligand for this receptor-like protein remains to be discovered.

\ \ G-protein coupled receptor activity ; GO:0004930 membrane ; GO:0016020 G-protein coupled receptor protein signaling pathway ; GO:0007186 21836 IPR003285 Elongation factors belong to a family of proteins that promote the GTP-dependent binding of aminoacyltRNA to the A site of ribosomes during protein biosynthesis, and catalyse the translocation of the\ synthesised protein chain from the A to the P site. The proteins are all relatively similar in the vicinity of\ their C-termini, and are also highly similar to a range of proteins that includes the nodulation Q protein from\ Rhizobium meliloti, bacterial tetracycline resistance proteins [MEDLINE:88298672] and yeast elongation factors.\

Although the yeast elongation factors, or omnipotent suppressor proteins,\ share a large degree of similarity with other eukaryotic elongation factors,\ the chief difference is that they possess an N-terminal extension rich in \ repetitive, glutamine-rich elements, and a central charged unit.\ Saccharomyces cerevisiae ERF2 expression has been shown to cause non-\ mendelian (all progeny to the first and second generation exhibit the\ phenotype) inheritance of nonsense suppression (stop-codon read-through),\ mediated by the N-terminal and charged regions. This observation has led to\ the hypothesis that the yeast elongation factors are 'yeast prions',\ showing the same properties as those theorised to exist in mammalian\ prions [MEDLINE:20141604].

\ \ GTP binding activity ; GO:0005525 \N translational termination ; GO:0006415 21837 IPR003286 Reverse transcriptases occur in a variety of mobile elements, including retrotransposons, retroviruses, group II introns, bacterial msDNAs, \ hepadnaviruses and caulimoviruses [MEDLINE:91006031]. The enzyme catalyses RNA-template-\ directed extension of the 3'-end of DNA strands one deoxynucleotide at a \ time; it cannot initiate a chain de novo, but requires an RNA or DNA primer,\ or DNA template.\

The structure of the unliganded reverse transcriptase (RT) from the human\ immunodeficiency virus type 1 has been solved to 3.2A resolution [MEDLINE:95166801]. The\ enzyme is a heterodimer, with domains termed "fingers," "thumb," "palm," \ and "connection" in both subunits, and a ribonuclease H domain in the\ larger subunit only [MEDLINE:95166801]. Ligand binding has been shown to induce changes\ in the orientation of the thumb. A C-terminal domain common to a group\ of sequences from the Caenorhabditis elegans sequencing project is revealed by sequence\ analysis to share a high level of similarity with the RT small subunit.

\ \ RNA-directed DNA polymerase activity ; GO:0003964 \N RNA dependent DNA replication ; GO:0006278 21834 IPR003283 Secretion of virulence factors in Gram-negative bacteria involves transportation of the protein across two membranes to reach the cell \ exterior. There have been four secretion systems described in \ animal enteropathogens such as Salmonella and Yersinia, with further \ sequence similarities in plant pathogens like Ralstonia and Erwinia. \

The type III secretion system is of great interest as it is used to \ transport virulence factors from the pathogen directly into the host cell \ [MEDLINE:99269264] and is only triggered when the bacterium comes into close contact with the host. The protein subunits of the system are very similar to those of bacterial flagellar biosynthesis [MEDLINE:20032050]. However, while the latter forms a ring structure to allow secretion of flagellin and is an integral part of\ the flagellum itself, type III subunits in the outer membrane translocate secreted proteins through a channel-like structure.

One of the outer membrane protein subunit families, termed "O" here for\ nomenclature purposes, aids in the structural assembly of the invasion \ complex [MEDLINE:96310365]. It is essential for the secretion of the Sip toxins in Salmonella and Shigella (SspaO gene). Members of this family also \ include YscQ protein (Yersinia), and the plant enteropathogen gene Y4YK \ (Rhizobium). The flagellar protein FliN also shares partial similarity, \ probably due to evolution of the type III secretion system from the \ flagellar biosynthetic pathway.

\ \ type III protein (virulence-related) secretor activity ; GO:0015448 \N protein secretion ; GO:0009306 21835 IPR003284 Salmonella typhimurium contains a 90kb plasmid that is associated with virulence [MEDLINE:90316693]. This plasmid encodes at least 6 genes needed by the bacterium for invading host macrophages during infection. These include the\ 70kDa mkaA protein [MEDLINE:92041614], a recognised virulence factor, and more recently described, four spv genes under the control of a regulator [MEDLINE:93247482]. The spv genes are induced under carbon-poor conditions at a stationary phase of growth, and their expression is under the control of both the spvR regulator, and the katF locus in Salmonella. It has been proposed that individual spv proteins may be required at different time points during \ infection [MEDLINE:97378124].\

SpvB is a 65kDa protein that has been localised to the bacterial cytoplasm \ [MEDLINE:97378124]. Its expression peaks during early stationary phase, but declines as the latent phase of the infection is reached, suggesting a role in initiating virulence.

\ \ \N cytoplasm ; GO:0005737 \N 21832 IPR003280

\ \ \ potassium channel activity ; GO:0005267 membrane ; GO:0016020 potassium ion transport ; GO:0006813 21833 IPR003282 Secretion of virulence factors in Gram-negative bacteria involves transportation of the protein across two membranes to reach the cell \ exterior. There have been four secretion systems described in \ animal enteropathogens such as Salmonella and Yersinia, with further \ sequence similarities in plant pathogens like Ralstonia and Erwinia. \

The type III secretion system is of great interest as it is used to \ transport virulence factors from the pathogen directly into the host cell \ [MEDLINE:99269264] and is only triggered when the bacterium comes into close contact with the host. The protein subunits of the system are very similar to those of bacterial flagellar biosynthesis [MEDLINE:20032050]. However, while the latter forms aring structure to allow secretion of flagellin and is an integral part of\ the flagellum itself, type III subunits in the outer membrane translocate secreted proteins through a channel-like structure.

One of the outer membrane protein subunit families, termed "K" here for\ nomenclature purposes, aids in the structural assembly of the invasion\ complex [MEDLINE:96310365]. It is also described as a lipoprotein. Members of this family include the Salmonella PrgK and SsaJ genes, MxiJ from Shigella, YscJ from Yersinia, and from the plant enteropathogens NolT (Rhizobium) and HrcJ \ (Erwinia). The flagellar M-ring protein FliF also shares a low level of\ similarity, presumably due to evolution of the type III secretion system\ from the flagellar biosynthetic pathway.

\ \ type III protein (virulence-related) secretor activity ; GO:0015448 \N protein secretion ; GO:0009306 21831 IPR003279

Kir6.x inward rectifier K+ channel family subunits associate with\ sulphonylurea receptors (SURs) to form ATP-sensitive K⁺ (KATP) channels. These are octameric complexes containing equal numbers of Kir and SUR\ subunits. The resulting channels are regulated by cytosolic nucleotides,\ such as ATP, and thus link cell metabolism to electrical activity, and K⁺ fluxes. They are important in the regulation of insulin secretion, the control of vascular and smooth muscle tone, and the response of the heart\ (and possibly the brain) to ischaemia.

Kir6.2 (also known as BIR/KATP) is thought to associate with SUR1 to form\ the pancreatic cell KATP channel that is involved in regulation of\ insulin secretion. Combination of Kir6.2 with splice variants of SUR2 is\ thought to produce the cardiac and smooth muscle KATP isoforms PUB00009384.

\ \ ATP-activated inward rectifier potassium channel activity ; GO:0015272 membrane ; GO:0016020 potassium ion transport ; GO:0006813 21830 IPR003278

Channels formed by the association of Kir6.1 (also known as u-KATP-1) with\ the SUR2B receptor are sensitive to K⁺ channel-opening drugs such as diazoxide and pinacidil, closely resembling the properties of native\ channels found in vascular tissues PUB00009384.

\ \ ATP-activated inward rectifier potassium channel activity ; GO:0015272 membrane ; GO:0016020 potassium ion transport ; GO:0006813 21828 IPR003276

The Kir3.x channel family is gated by G-proteins following G-protein\ coupled receptor (GPCR) activation. They are widely distributed in\ neuronal, atrial, and endocrine tissues and play key roles in generating\ late inhibitory postsynaptic potentials, slowing the heart rate and\ modulating hormone release. They are directly activated by G-protein -gamma subunits released from G-protein heterotrimers of the G(i/o)\ family upon appropriate receptor stimulation.

Kir3.3 does not generate receptor-evoked, or constitutively-active K+\ currents, when heterologously expressed in Xenopus oocytes. It may\ therefore contribute to Kir channel diversity by associating with other\ Kir3.x family members PUB00009384.

\ \ G-protein activated inward rectifier potassium channel activity ; GO:0015467 membrane ; GO:0016020 potassium ion transport ; GO:0006813 21829 IPR003277

Kir3.4 is thought to associate with Kir3.1, to form hetero-tetrameric\ acetylcholine-activated K+ channels, in the heart. Their activation,\ following stimulation of the vagus nerve, leads to slowing of the heart,\ and reduction in contractile force. In the brain, Kir3.4 distribution has\ been found to be quite restricted, being found in some neuronal populations,\ such as Purkinje cells and neurones of the globus pallidus and the ventral\ pallidum PUB00009384. A recent study has suggested that Kir3.4 may confer mechano-sensitive properties on Kir channels, since channels containing it are\ inactivated by membrane stretch forces [MEDLINE:98104108].

\ \ G-protein activated inward rectifier potassium channel activity ; GO:0015467 membrane ; GO:0016020 potassium ion transport ; GO:0006813 21827 IPR003275

Kir3.2 is thought to associate with Kir3.1 to form Kir channel heteromers\ in heart tissue. In central neurones, Kir3.2 homomers may exist, although\ these may contain combinations of the three splice variants of Kir3.2 that\ have been identified PUB00009384. Weaver mice, which suffer neurological and\ reproductive deficits, have a point mutation in the gene encoding Kir3.2.\ This lies in the pore-forming domain of the channel, and as a result they\ lose their selectivity for K+, allowing Na+ to pass through the channel \ pore [MEDLINE:20012966].

\ \ G-protein activated inward rectifier potassium channel activity ; GO:0015467 membrane ; GO:0016020 potassium ion transport ; GO:0006813 21826 IPR003274

The Kir3.x channel family is gated by G-proteins following G-protein\ coupled receptor (GPCR) activation. They are widely distributed in\ neuronal, atrial, and endocrine tissues and play key roles in generating\ late inhibitory postsynaptic potentials, slowing the heart rate and\ modulating hormone release. They are directly activated by G-protein -\ gamma subunits released from G-protein heterotrimers of the G(i/o) family\ upon appropriate receptor stimulation.

\ \

Kir3.1 channels are thought to form heteromers in vivo: in heart,\ consisting of Kir3.1 and Kir3.2, and in brain, Kir3.1 with Kir 3.4.

\ \ G-protein activated inward rectifier potassium channel activity ; GO:0015467 membrane ; GO:0016020 potassium ion transport ; GO:0006813 21825 IPR003273

Kir2.3 it thought to play a role in the maintenance of membrane potential\ in both neurones and myocardium. It is highly expressed in the forebrain,\ and has a distinctly smaller ionic conductance than other Kir2.x family\ members. By comparison with other Kir2.x channels, sequence analysis shows\ it to have a larger putative extracellular loop (~15 more amino acid\ residues) linking the first TM domain to the pore-forming (H5) domain, \ although the significance of this remains to be elucidated. Functional\ studies have revealed Kir2.3 channel activity to be modulated by channel\ phosphorylation, oxidation state, and changes in intracellular and\ extracellular pH.

\ \ \ \ inward rectifier potassium channel activity ; GO:0005242 membrane ; GO:0016020 potassium ion transport ; GO:0006813 21824 IPR003272

Kir2.2 (also known as IRK2/BIR8), like other Kir2.x family members, has\ been found to be expressed in the brain. Immuno-localisation studies have\ revealed it is primarily expressed in the cerebellum, as opposed to the\ forebrain (cf. Kir1.1). It is also expressed to lower extents in the\ kidney, heart and skeletal muscle. When heterologously expressed in Xenopus\ oocytes, human Kir2.2 produced strong, inwardly rectifying K⁺ currents.\ Co-expression of Kir2.2v (a closely related Kir2.x subunit) with Kir2.2\ caused an inhibition of induced K⁺ currents, indicating that it likely\ functions as a negative regulator of Kir2.2 PUB00009384.

\ \ \ inward rectifier potassium channel activity ; GO:0005242 membrane ; GO:0016020 potassium ion transport ; GO:0006813 21823 IPR003271

Kir2.1 (also known as IRK1) is thought to play a role in controlling the\ excitability of brain and heart tissues. Immuno-localisation studies have\ revealed it to be present on many cell types within the forebrain, including\ neurones, macroglia, endothelial, ependymal and vascular smooth muscle\ cells. Phosphatidylinositol 4,5-bisphosphate (PIP2) is thought to interact\ with Kir2.1 (as well as several other Kir subunits) via a C-terminal motif,\ promoting channel activity. Recently it has been demonstrated that nicotine\ can block Kir2.1 channels, this likely contributing to its ability to\ promote the occurrence of cardiac arrhythmias [medlie:20207020].

\ \ \ inward rectifier potassium channel activity ; GO:0005242 membrane ; GO:0016020 potassium ion transport ; GO:0006813 21821 IPR003269

The Kir1.2 channel (also known as Kir4.1, ROMK2, BIR10, KAB-2 and BIRK1) is found principally in the brain, where it is widely distributed. It has also been found on satellite cells of the rat cochlear ganglia, and at low levels within the kidney. Kir1.2 channel activity is dependent upon phosphorylation-state, with two serine residues within the C-terminus, likely the target of PKA protein kinase A, being involved PUB00009384. Kir1.2 has recently been shown to interact with a novel PDZ domain-containing protein, CIPP [MEDLINE:98313406].

\ \ inward rectifier potassium channel activity ; GO:0005242 membrane ; GO:0016020 potassium ion transport ; GO:0006813 21822 IPR003270

Kir1.3 (also known as Kir4.2) was cloned from human kidney, where it appears\ to be found most abundantly. At lower levels, it has also been detected in\ the pancreas and lung. It is most closely related to Kir1.2, to which it is\ 62% identical. Unlike the other Kir1.x family members, in the Kir1.3\ sequence, the Walker Type A consensus motif (for nucleotide binding) is\ not conserved. Heterologous expression of Kir1.3 in Xenopus oocytes did not\ lead to detectable channel activity. Indeed, co-expression of Kir1.3 with\ either Kir1.1 or Kir1.2 reduced currents resulting from expression of these\ inward rectifier subunits alone, consistent with a dominant negative\ influence of Kir1.3 on Kir1.1 and Kir1.2 expression PUB00009384.

\ \ inward rectifier potassium channel activity ; GO:0005242 membrane ; GO:0016020 potassium ion transport ; GO:0006813 21819 IPR003267 Keratinocytes from the skin epidermis are functionally specialised to protect against the damaging effects of external agents, including ultraviolet (UV) light. The presence of damage somewhere in genomic DNA activates a signal transduction cascade, which results in the expression of\ a number of genes, including the gene for small proline-rich proteins [MEDLINE:90356372].\ These proteins are rich in Pro, Cys and Gln and are either structural \ proteins or metal-binding proteins. They can also bind DNA, however, since \ they contain many Lys, Ser and Thr residues, which are known to mediate \ DNA-binding in repressor proteins. Small proline-rich proteins are also\ found in higher concentrations during normal keratinocyte differentiation, \ although the reason for this is unclear [MEDLINE:90356372].\ \ \N \N \N 21820 IPR003268

Kir1.1 channels (also known as ROMK1-6 and KAB-1) are thought to underlie\ K⁺ secretion in the kidney. Their activity is modulated by intracellular pH, with acidosis inhibiting the channel. Both N- and C-termini are thought to be involved in this modulation. Mutations in Kir1.1 lead to Bartter's syndrome type III, an inherited kidney disorder, which leads to salt-wasting, hypokalaemia and metabolic acidosis. All of the mutations that\ have been functionally characterised either abolish, or markedly reduce,\ Kir1.1 K⁺ currents.

\ \ inward rectifier potassium channel activity ; GO:0005242 membrane ; GO:0016020 potassium ion transport ; GO:0006813 21818 IPR003265

Endonuclease III (EC: 4.2.99.18) is a DNA repair enzyme which removes a number of damaged pyrimidines from DNA via its glycosylase activity and also cleaves the phosphodiester backbone at apurinic / apyrimidinic sites via a -elimination mechanism [MEDLINE:95292058], [MEDLINE:97184707]. The structurally related DNA glycosylase MutYrecognises and excises the mutational intermediate 8-oxoguanine-adenine mispair [MEDLINE:93015679]. The 3-D structures of E. coli endonuclease III [MEDLINE:93030750] and catalytic domain of MutY [MEDLINE:99061333] have been determined. The\ structures contain two all- domains: a sequence-continuous, six-helix domain (residues 22-132) and a Greek-key,\ four-helix domain formed by one N-terminal and three C-terminal helices (residues 1-21 and 133-211) together with the\ [Fe4S4] cluster. The cluster is bound entirely within the C-terminal loop by four cysteine residues with a ligation pattern\ Cys-(Xaa)6-Cys-(Xaa)2-Cys-(Xaa)5-Cys which is distinct from all other known Fe4S4 proteins. This structural motif is\ referred to as a [Fe4S4] cluster loop (FCL) [MEDLINE:95393988]. Two DNA-binding motifs have been proposed, one at either end of the\ interdomain groove: the helix-hairpin-helix (HhH) and FCL motifs (seeIPR003651). The primary role of the iron-sulphur cluster appears to\ involve positioning conserved basic residues for interaction with the DNA phosphate backbone by forming the loop of\ the FCL motif [MEDLINE:95393988], [MEDLINE:20361758].

\ \

The HhH-GPD domain gets its name from its hallmark helix-hairpin-helix and Gly/Pro rich loop followed by a conserved aspartate. This domain is found in a diverse range of structurally related DNA repair proteins that include: endonuclease III, EC: 4.2.99.18 and DNA glycosylase MutY, an A/G-specific adenine glycosylase. Both of these enzymes have a C terminal iron-sulfur cluster loop (FCL). The methyl-CPG binding protein (MBD4) also contain a related domain that is a thymine DNA glycosylase. The family also includes DNA-3-methyladenine glycosylase II EC: 3.2.2.21, 8-oxoguanine DNA glycosylases and other members of the AlkA family.

\ \ \N \N base-excision repair ; GO:0006284 21816 IPR003257

Bacterial transcription antitermination protein, NusG, is a component of thetranscription complex and interacts with the termination factor rho and RNA\ polymerase [MEDLINE:93138385], [MEDLINE:92210569]. NusG is a bacterial transcriptional\ elongation factor involved in transcription termination and anti-termination [MEDLINE:94093297]. This domain is found in putative NusG antitermination proteins.

\ \ transcriptional elongation regulator activity ; GO:0003711 \N regulation of transcription, DNA-dependent ; GO:0006355 21817 IPR003263

\ Some recognized functions of human tumor necrosis factor ligand superfamily member 5 (CD40 ligand) (CD40- L) (TNF-related activation protein) (TRAP) (T cell antigen Gp39) (CD154 antigen) are:\ \

Mediates B-cell proliferation in the absence of co-stimulus as well as IGE production in the presence of Il-4.

\ \

Involved in immunoglobulin class switching.

\ \

Defects in human tnfsf5 are the cause of an x-linked immunodeficiency with hyper-IGM (HIGM1), an immunoglobulin isotype switch defect characterized by elevated concentrations of serum IGM and decreased amounts of all other isotypes. Affected males present at an early age (usually within the first year of life) recurrent bacterial and opportunistic infections, including pneumocystis carinii pneumonia and intractable diarrhea due to cryptosporidium infection. Despite substitution treatment with intravenous immunoglobulin, the overall prognosis is rather poor, with a death rate of about 10% before adolescence.

\ \ \ tumor necrosis factor receptor ligand activity ; GO:0005164 membrane ; GO:0016020 immune response ; GO:0006955 21815 IPR003256

\ \ \

Ribosomal protein L24 is one of the proteins from the large ribosomal subunit. In their mature form, these proteins have 103 to 150 amino-acid residues. This domain is found in L24 and L26 ribosomal proteins.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 21812 IPR003251

Rubrerythrin (Rr), found in anaerobic sulphate-reducing bacteria [MEDLINE:95131793], is a fusion protein containing an N-terminal diiron-bindingdomain and a C-terminal domain homologous to rubredoxin [MEDLINE:92041914]. The physiological role of Rr has not been identified.

\ \

The 3-D structure of Desulfovibrio vulgaris rubrerythrin has been solved [MEDLINE:96227974]. The structure reveals a tetramer of two-domain\ subunits. In each monomer, the N-terminal 146 residues form a four--helix bundle containing the diiron-oxo site (centre I), and the C-terminal 45 residues form a rubredoxin-like FeS4 domain.

\ \ heavy metal binding activity ; GO:0005505 \N electron transport ; GO:0006118 21813 IPR003253 Cecropins [MEDLINE:88075837], [MEDLINE:91199190], [MEDLINE:92007880] are potent antibacterial proteins that constitute a main part of the cell-free immunity of insects. Cecropins are small proteins of about 35 amino acid \ residues active against both Gram-positive and Gram-negative bacteria. They seem to exert a lytic \ action on bacterial membranes. Cecropins isolated from insects other than Cecropia have been given \ various names; bactericidin, lepidopteran, sarcotoxin, etc. All of these peptides are structurally \ related. These are the fly cecropin and sarcotoxin proteins.\ \ antibacterial peptide activity ; GO:0003797 \N antibacterial humoral response (sensu Invertebrata) ; GO:0006961 21814 IPR003254 Cecropins [MEDLINE:88075837], [MEDLINE:91199190], [MEDLINE:92007880] are potent antibacterial proteins that constitute a main part of the cell-free immunity of insects. Cecropins are small proteins of about 35 amino acid \ residues active against both Gram-positive and Gram-negative bacteria. They seem to exert a lytic \ action on bacterial membranes. Cecropins isolated from insects other than Cecropia have been given \ various names; bactericidin, lepidopteran, sarcotoxin, etc. All of these peptides are structurally \ related. These are the insect cecropins and hyphancins.\ \ antibacterial peptide activity ; GO:0003797 \N antibacterial humoral response (sensu Invertebrata) ; GO:0006961 21808 IPR003247

The calponin homology domain (also known as CH-domain) is a superfamily of actin-binding domains found in both cytoskeletal proteins and signal transduction proteins [MEDLINE:96063701]. It comprises the following groups of actin-binding domains:

Actinin-type (including spectrin, fimbrin, ABP-280) (see IPR001589).
Calponin-type (see IPR001589/>).

A comprehensive review of proteins containing this type of actin-binding domains is given in [MEDLINE:96000088].

The CH domain is involved in actin binding in some members of the family. However in calponins there is evidence that the CH domain is not involved in its actin binding activity [MEDLINE:98290719]. Most proteins have two copies of the CH domain, however some proteins such as calponin and the human vav proto-oncogene (P15498) have only a single copy. This subtype is not found in the actinin or dystrophin proteins.

\ \ \N \N \N 21811 IPR003250 Uracil-DNA glycosylase EC: 3.2.2.- (UNG) [MEDLINE:89024574] is a DNA repair enzyme thatexcises uracil residues from DNA by cleaving the N-glycosylic bond. Uracil in\ DNA can arise as a result of misincorportation of dUMP residues by DNA\ polymerase or deamination of cytosine.\ The sequence of uracil-DNA glycosylase is extremely well conserved [MEDLINE:90059899] in\ bacteria and eukaryotes as well as in herpes viruses. More distantly related\ uracil-DNA glycosylases are also found in poxviruses\ \ \ \ [MEDLINE:93281610].\ In eukaryotic cells, UNG activity is found in both the nucleus and the\ mitochondria. Human UNG1 protein is transported to both the mitochondria and\ the nucleus [MEDLINE:93324318]. The N-terminal 77 amino acids of UNG1 seem to be required for\ mitochondrial localization [MEDLINE:93324318], but the presence of a mitochondrial transit\ peptide has not been directly demonstrated.\ The most N-terminal conserved region contains an aspartic acid residue which has been\ proposed, based on X-ray structures [MEDLINE:95147968], [MEDLINE:95211838] to act as a general base in the\ catalytic mechanism. This is the Poxvirus uracil-DNA glycosylase.\ \ uracil DNA N-glycosylase activity ; GO:0004844 \N DNA repair ; GO:0006281 21807 IPR003246 Blue or 'type-1' copper proteins are small proteins which bind a single copper atom and which are characterized by an intense electronic absorption band near 600 nm [MEDLINE:84135769], [MEDLINE:93164266]. The most \ well known members of this class of proteins are the plant chloroplastic plastocyanins, which exchange \ electrons with cytochrome c6, and the distantly related bacterial azurins, which exchange electrons with \ cytochrome c551. This family of proteins also includes amicyanin from bacteria such as Methylobacterium \ extorquens or Thiobacillus versutus that can grow on methylamine; auracyanins A and B from Chloroflexus \ aurantiacus\ \ \ \ [MEDLINE:92202194]; blue copper protein from Alcaligenes faecalis; cupredoxin (CPC) from cucumber \ peelings [MEDLINE:93106154]; cusacyanin (basic blue protein; plantacyanin, CBP) from cucumber; halocyanin from \ Natronobacterium pharaonis\ \ \ \ [MEDLINE:94253046], a membrane associated copper-binding protein; pseudoazurin from \ Pseudomonas; rusticyanin from Thiobacillus ferrooxidans\ \ \ \ [MEDLINE:91348256]; stellacyanin from the Japanese \ lacquer tree; umecyanin from horseradish roots; and allergen Ra3 from ragweed. Although there is an appreciable amount of divergence in the sequences of all these proteins, the copper ligand \ sites are conserved. This domain is found in bacterial azurins.\ \ copper ion binding activity ; GO:0005507 \N electron transport ; GO:0006118 21809 IPR003248 Phosphoserine aminotransferases (EC: 2.6.1.52) catalyse the conversion of O-phospho-L-serine and oxoglutarate to 3-phosphonooxypyruvate and L-glutamate in\ the major phosphorylated serine biosynthesis pathway. In bacteria it is also equired for\ the biosynthesis of pyridoxine. The enzyme requires pyridoxal phosphate as a cofactor,\ and is part of the aminotransferase class-V family.\ \ phosphoserine aminotransferase activity ; GO:0004646 \N serine biosynthesis ; GO:0006564 21810 IPR003249 Uracil-DNA glycosylase EC: 3.2.2.- (UNG) [MEDLINE:89024574] is a DNA repair enzyme thatexcises uracil residues from DNA by cleaving the N-glycosylic bond. Uracil in\ DNA can arise as a result of misincorportation of dUMP residues by DNA\ polymerase or deamination of cytosine.\ The sequence of uracil-DNA glycosylase is extremely well conserved [MEDLINE:90059899] in\ bacteria and eukaryotes as well as in herpes viruses. More distantly related\ uracil-DNA glycosylases are also found in poxviruses\ \ \ \ [MEDLINE:93281610].\ In eukaryotic cells, UNG activity is found in both the nucleus and the\ mitochondria. Human UNG1 protein is transported to both the mitochondria and\ the nucleus [MEDLINE:93324318]. The N-terminal 77 amino acids of UNG1 seem to be required for\ mitochondrial localization [MEDLINE:93324318], but the presence of a mitochondrial transit\ peptide has not been directly demonstrated.\ The most N-terminal conserved region contains an aspartic acid residue which has been\ proposed, based on X-ray structures [MEDLINE:95147968], [MEDLINE:95211838] to act as a general base in the\ catalytic mechanism.\ \ uracil DNA N-glycosylase activity ; GO:0004844 \N DNA repair ; GO:0006281 21798 IPR003236

\ \ \

Ribosomal protein L5 is one of the proteins from the large ribosomal subunit, which may be involved in binding 5S RNA to the large ribosomal subunit. L5 is a protein of about 180 amino-acid residues. This family includes the mitochondrial L5 ribosomal proteins.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 21805 IPR003244

Cystatins are a family of cysteine protease inhibitors that occur mainly as single domain proteins. However some extracellular proteins such as kininogen, His-rich glycoprotein (see also IPR002395) and fetuin also contain cystatin domains.\ Members of this family are inhibitors of cysteine (thiol) proteases PUB00005324, PUB00005324, [MEDLINE:91309737], which are found in the tissues and body fluids of animals, as well as in plants.

This entry describes the sarcocystatins.

\ \ cysteine protease inhibitor activity ; GO:0004869 \N \N 21806 IPR003245 Blue (type-1) copper proteins are small proteins which bind a single copper atom and which are characterized by an intense electronic absorption band near 600 nm [MEDLINE:84135769], [MEDLINE:93164266]. The most \ well known members of this class of proteins are the plant chloroplastic plastocyanins, which exchange \ electrons with cytochrome c6, and the distantly related bacterial azurins, which exchange electrons with \ cytochrome c551. This family of proteins also includes amicyanin from bacteria such as Methylobacterium \ extorquens or Thiobacillus versutus that can grow on methylamine; auracyanins A and B from Chloroflexus \ aurantiacus\ \ \ \ [MEDLINE:92202194]; blue copper protein from Alcaligenes faecalis; cupredoxin (CPC) from cucumber \ peelings [MEDLINE:93106154]; cusacyanin (basic blue protein; plantacyanin, CBP) from cucumber; halocyanin from \ Natronobacterium pharaonis\ \ \ \ [MEDLINE:94253046], a membrane associated copper-binding protein; pseudoazurin from \ Pseudomonas; rusticyanin from Thiobacillus ferrooxidans\ \ \ \ [MEDLINE:91348256]; stellacyanin from the Japanese \ lacquer tree; umecyanin from horseradish roots; and allergen Ra3 from ragweed. Although there is an appreciable amount of divergence in the sequences of all these proteins, the copper ligand \ sites are conserved. This domain is found in a variety of plant cyanins and pollern allergen.\ \

Some of the proteins in this family are allergens. Allergies are hypersensitivity reactions of the immune system to specific substances called allergens (such as pollen, stings, drugs, or food) that, in most people, result in no symptoms. A nomenclature system has been established for antigens (allergens) that cause IgE-mediated atopic allergies in humans [WHO/IUIS Allergen Nomenclature Subcommittee\ King T.P., Hoffmann D., Loewenstein H., Marsh D.G., Platts-Mills T.A.E.,\ Thomas W. Bull. World Health Organ. 72:797-806(1994)]. This nomenclature system is defined by a designation that is composed of\ the first three letters of the genus; a space; the first letter of the\ species name; a space and an arabic number. In the event that two species\ names have identical designations, they are discriminated from one another\ by adding one or more letters (as necessary) to each species designation.

The allergens in this family include allergens with the following designations: Amb a 3.

\ \ copper ion binding activity ; GO:0005507 \N electron transport ; GO:0006118 21797 IPR003235 Caenorhabditis elegans insulin-like peptides [MEDLINE:91330924] are evolutionary related to insulin; relaxin; insulin-like growth factors I and II [MEDLINE:90322988]; mammalian Leydig cell-specific insulin-like peptide (gene INSL3) [MEDLINE:94075362] and early placenta insulin-likepeptide (ELIP) (gene INSL4) [MEDLINE:96115599]; insect prothoracicotropic hormone (bombyxin) PUB00004620;\ locust insulin-related peptide (LIRP) PUB00004620; and Molluscan insulin-related peptides 1-5 [MEDLINE:98217375]. Structurally, all these peptides\ consist of two polypeptide chains (A and B) linked by two disulfide bonds. They all share a conserved\ arrangement of four cysteines in their A chain. The first of these cysteines is linked by a disulfide\ bond to the third one and the second and fourth cysteines are linked by interchain disulfide bonds to\ cysteines in the B chain. \

Insulin is involved in the regulation of normal glucose homeostasis, as well\ as other specific physiological functions [MEDLINE:80120725]. It is synthesised as a\ prepropeptide from which an endoplasmic reticulum-targeting sequence is cleaved to yield proinsulin.\ Prosinsulin contains regions A and B separated by an intervening connecting region, C. The\ connecting region is cleaved, liberating the active protein, which contains the A and B chains,\ held together by 2 disulphide bonds [MEDLINE:80054779].

\ \ hormone activity ; GO:0005179 extracellular ; GO:0005576 physiological processes ; GO:0007582 21804 IPR003243

This entry represents type 2 cystatins. The type 2 cystatins are molecules of about 115 amino acid residues, which contain one or two disulfide loops near their C-terminus.

\ \ cysteine protease inhibitor activity ; GO:0004869 \N \N 21803 IPR003242 Arteriviruses encode four envelope proteins, Gl, Gs, M and N. Gl envelope glycoproteinis heterogenously glycosylated with N-acetyllactosamine in a cell-type-specific manner. \ The Gl glycoprotein expresses the neutralization determinants [MEDLINE:96130216]. This domain is found in Equine arteritis virus envelope proteins\ \ \N viral envelope ; GO:0019031 \N 21800 IPR003239 Arteriviruses encode four envelope proteins, Gl, Gs, M and N. Gl envelope glycoproteinis heterogenously glycosylated with N-acetyllactosamine in a cell-type-specific manner. \ The Gl glycoprotein expresses the neutralization determinants [MEDLINE:96130216]. This domain is found in the porcine reproductive/respiratory syndrome virus major envelope glycoprotein.\ \ \N viral envelope ; GO:0019031 \N 21801 IPR003240 Arteriviruses encode four envelope proteins, Gl, Gs, M and N. Gl envelope glycoproteinis heterogenously glycosylated with N-acetyllactosamine in a cell-type-specific manner. \ The Gl glycoprotein expresses the neutralization determinants [MEDLINE:96130216]. This domain is found in the Porcine reproductive/respiratory syndrome virus M protein\ \ \N viral envelope ; GO:0019031 \N 21802 IPR003241 Arteriviruses encode four envelope proteins, Gl, Gs, M and N. Gl envelope glycoproteinis heterogenously glycosylated with N-acetyllactosamine in a cell-type-specific manner. \ The Gl glycoprotein expresses the neutralization determinants [MEDLINE:96130216]. This domain is found in Equine arteritis virus ORF5 proteins\ \ \N \N \N 21799 IPR003238 Adenosine triphosphate (ATP) synthase contains a rotary motor involved in biological energy conversion. Its membrane-embedded F0 sector has a rotation generator fueled by the proton-motive force, which provides the energy required for the synthesis of ATP by the F1 domain [MEDLINE:20044992]. Subunit 8 is one of the chains of the nonenzymatic component (F0) of the mitochondrial ATPase complex. This family includes the mammalian mitochondrial ATPase subunit 8.\ hydrogen-transporting two-sector ATPase activity ; GO:0003936 membrane ; GO:0016020 proton transport ; GO:0015992 21783 IPR003219 Cytochromes c (cytC) can be defined as electron-transfer proteins having one or several haem c groups, bound to the protein by one or, more \ generally, two thioether bonds involving sulphydryl groups of cysteine \ residues. The fifth haem iron ligand is always provided by a histidine \ residue. CytC possess a wide range of properties and function in a large \ number of different redox processes PUB00006083. \

Ambler PUB00006083 recognised four classes of cytC.

Class I includes the low-spin\ soluble cytC of mitochondria and bacteria, with the haem-attachment site\ towards the N-terminus, and the sixth ligand provided by a methionine\ residue about 40 residues further on towards the C-terminus. On the basis\ of sequence similarity, class I cytC were further subdivided into five\ classes, IA to IE. \ Class IB includes the eukaryotic mitochondrial cyt C\ and prokaryotic 'short' cyt C2 exemplified by Rhodopseudomonas globiformis\ cyt C2; Class IA includes 'long' cyt C2, such as Rhodospirillum rubrum\ cyt C2 and Aquaspirillum itersonii cyt C-550, which have several extra\ loops by comparison with Class IB cyt C.

\ \ electron transporter activity ; GO:0005489 \N electron transport ; GO:0006118 21784 IPR003220 Insertion elements are mobile elements in DNA, usually encoding proteins required for transposition, for example transposases. This protein is absolutely required for transposition of insertion element 1.\ \N \N DNA transposition ; GO:0006313 21785 IPR003221 DNA-dependent RNA polymerases (EC: 2.7.7.6) are ubiquitous enzymes necessaryfor the transcription of genomic DNA into RNA. Prokaryotes contain a single RNA\ polymerase compared to three in eukaryotes (not including mitochondrial and\ chloroplast polymerases). Most RNA polymerases are multimeric enzymes and are\ composed of a variable number of subunits. This subunit may be shared by all 3 eukaryotic RNA polymerases.\ \ DNA-directed RNA polymerase activity ; GO:0003899 nucleus ; GO:0005634 transcription ; GO:0006350 21786 IPR003222 The anititermination protein is mostly found in bacteriophages, where it modifies host RNA polymerase, which then transcribes through termination sites that would have prevented expression of these genes. In this way the protein positively regulates expression of some phage genes.\ DNA binding activity ; GO:0003677 \N regulation of transcription, DNA-dependent ; GO:0006355 21787 IPR003223 Flagellin is the subunit which polymerizes to form the filaments of bacterialflagella. The proteins in this family are transcriptional repressors of phase-1 flagellin genes.\ \ transcription factor activity ; GO:0003700 \N regulation of transcription, DNA-dependent ; GO:0006355 21788 IPR003224 This zinc finger domain is found in RNA viruses, and may be involved in RNA binding, possibly playing a regulatory role.\ RNA binding activity ; GO:0003723 \N \N 21789 IPR003225 This domain is found in hypothetical proteins of viruses.\ \N \N \N 21790 IPR003226 The function of this domain is not known, but it is found in several uncharacterised proteins and a probable metal dependent protein hydrolase.\ \N \N \N 21791 IPR003228 Human transcription initiation factor TFIID is composed of the TATA-binding polypeptide (TBP) and at least 13 TBP-associated factors (TAFs) that collectively or individually are involved in activator-dependent transcription [MEDLINE:95396764].\ \N transcription factor TFIID complex ; GO:0005669 transcription initiation ; GO:0006352 21782 IPR003218 Cytochromes c (cytC) can be defined as electron-transfer proteins having one or several haem c groups, bound to the protein by one or, more \ generally, two thioether bonds involving sulphydryl groups of cysteine \ residues. The fifth haem iron ligand is always provided by a histidine \ residue. CytC possess a wide range of properties and function in a large \ number of different redox processes PUB00006083. \

Ambler PUB00006083 recognised four classes of cytC.

Class I includes the low-spin\ soluble cytC of mitochondria and bacteria, with the haem-attachment site\ towards the N-terminus, and the sixth ligand provided by a methionine\ residue about 40 residues further on towards the C-terminus. On the basis\ of sequence similarity, class I cytC were further subdivided into five\ classes, IA to IE. \ Class IB includes the eukaryotic mitochondrial cytC\ and prokaryotic 'short' cyt c2 exemplified by Rhodopseudomonas globiformis\ cyt c2; class IA includes 'long' cyt c2, such as Rhodospirillum rubrum\ cyt c2 and Aquaspirillum itersonii cyt c-550, which have several extra\ loops by comparison with class IB cytC.

\ \ electron transporter activity ; GO:0005489 mitochondrial electron transport chain ; GO:0005746 electron transport ; GO:0006118 21796 IPR003234 Molluscan insulin-related peptides 1 to 5 (MIP) [MEDLINE:91330924] are evolutionary related to insulin; relaxin; insulin-like growth factors I and II [MEDLINE:90322988]; mammalian Leydig cell-specific insulin-like peptide (gene INSL3) [MEDLINE:94075362] and early placenta insulin-likepeptide (ELIP) (gene INSL4) [MEDLINE:96115599]; insect prothoracicotropic hormone (bombyxin) PUB00004620;\ locust insulin-related peptide (LIRP) PUB00004620; and C. elegans insulin-like peptides [MEDLINE:98217375]. Structurally, all these peptides\ consist of two polypeptide chains (A and B) linked by two disulfide bonds. They all share a conserved\ arrangement of four cysteines in their A chain. The first of these cysteines is linked by a disulfide\ bond to the third one and the second and fourth cysteines are linked by interchain disulfide bonds to\ cysteines in the B chain. \

\ \ hormone activity ; GO:0005179 extracellular ; GO:0005576 physiological processes ; GO:0007582 21795 IPR003232

Deoxycytidine triphosphate deaminase (dCTP) (EC: 3.5.4.13) specifically binds uridine. In Escherichia coli, most of the dUMP that is used as a substrate for thymidylate synthetase is generated from dCTP through the sequential action of dCTP deaminase and dUTPase [MEDLINE:92380941].

\ \N \N \N 21793 IPR003230 These proteins are involved in the biosynthesis of D-alanyl-lipoteichoic acid in bacteria.\ \N \N \N 21794 IPR003231

There are two types of fatty acid synthase systems. The type I system is found in metazoans and is carried outby a multifunctional polypeptide with multiple active sites. In contrast, the type II system found in bacteria and plants\ consists of a set of discrete monofunctional proteins, each encoded by a separate gene. ACP1 is central to both of these\ pathways because it functions to ferry the pathway intermediates between active site centers or enzymes. ACPs are also\ critical to the function of other metabolic pathways such as polyketide synthases.

The type II fatty acid synthase ACPs are\ abundant, small, acidic proteins that carry the acyl intermediates attached as thioesters to the terminus of the 4'-phosphopantetheine prosthetic group. This prosthetic group is\ added post-translationally to apoACP by holo-(acyl carrier protein) synthase (AcpS), which transfers the 4'-phosphopantetheine moiety of CoA to a serine reidue of apoACP.

\ \ acyl carrier activity ; GO:0000036 \N fatty acid biosynthesis ; GO:0006633 21792 IPR003229 This domain is found in outer membrane proteins of Haemophilus influenzae and Pasteurella multocida. The proteins may act as porins.\ \N membrane ; GO:0016020 \N 21768 IPR003203 This family is composed of a group of bifunctional cobalbumin biosynthesis enzymes which display cobinamide kinase and cobinamide phosphate guanyltransferase activity. The crystal structure of the enzyme reveals the molecule to be a trimer with a propeller-like shape [MEDLINE:98263165].\ \N \N \N 21769 IPR003204

Cytochrome c oxidase (EC: 1.9.3.1) is an oligomeric enzymatic complex which is a component of the respiratory chain complex and is involved in the transfer of electrons from \ cytochrome c to oxygen [MEDLINE:83257235]. \ In eukaryotes this enzyme complex is located in the mitochondrial inner membrane; in \ aerobic prokaryotes it is found in the plasma membrane.

\ \ cytochrome c oxidase activity ; GO:0004129 \N electron transport ; GO:0006118 21770 IPR003205

\ \ cytochrome c oxidase activity ; GO:0004129 \N electron transport ; GO:0006118 21771 IPR003206 This family contains the large subunit of the trimeric diol dehydratases and glycerol dehydratases. These enzymes are produced by some enterobacteria in response to growth substances.\ \N \N \N 21772 IPR003207 This family contains the small subunit of the trimeric diol dehydratases and glycerol dehydratases. These enzymes are produced by some enterobacteria in response to growth substances.\ \N \N \N 21773 IPR003208 This family contains the medium subunit of the trimeric diol dehydratases and glycerol dehydratases. These enzymes are produced by some enterobacteria in response to growth substances.\ \N \N \N 21774 IPR003209 Methenyltetrahydromethanopterin cyclohydrolase EC: 3.5.4.27 is involved in methanogenesis in bacteria and archaea, producing methane from carbon monoxide or carbon dioxide.\ \N \N \N 21775 IPR003210 The signal recognition particle (SRP) is a multimeric protein involved in targeting secretory proteins to the rough endoplasmic reticulum membrane. SRP14 and SRP9 form a complex essential for SRP RNA binding. \ RNA binding activity ; GO:0003723 signal recognition particle ; GO:0005786 protein targeting ; GO:0006605 21761 IPR003196 Accurate transcription in vivo requires at least six general transcription initiation factors, in addition to RNA polymerase II. Transcription initiation factor IIF (TFIIF) is a tetramer of two

subunits associate with two

subunits which interacts directly with RNA polymerase II. The

subunit of TFIIF is required for recruitment of RNA polymerase II onto the promoter. \ ATP binding activity ; GO:0005524 transcription factor TFIIF complex ; GO:0005674 transcription initiation from Pol II promoter ; GO:0006367 21781 IPR003216 Linker histone H1 is an essential component of chromatin structure. H1 links nucleosomes into higher order structures.Histone H5 performs the same\ function as histone H1, and replaces H1 in certain cells. \ The structure of GH5, the globular domain of the linker\ histone H5 is known [MEDLINE:93211475], [MEDLINE:87017002]. The fold is similar to the DNA-binding\ domain of the catabolite gene activator protein, CAP, thus providing a\ possible model for the binding of GH5 to DNA.\ \ DNA binding activity ; GO:0003677 nucleus ; GO:0005634 chromosome organization and biogenesis (sensu Eukarya) ; GO:0007001 21779 IPR003214 NADH-ubiquinone oxidoreductase, chain 4L (EC: 1.6.5.3) catalyses the reductionof ubiquinone to ubiquinol. This domain is present in the mitochondria as\ part of the respiratory-chain NADH dehydrogenase (also known as complex I or\ NADH-ubiquinone oxidoreductase), an oligomeric enzymatic complex.\ \ NADH dehydrogenase (ubiquinone) activity ; GO:0008137 \N oxidative phosphorylation, NADH to ubiquinone ; GO:0006120 21780 IPR003215 NADH-ubiquinone oxidoreductase, chain 4L (EC: 1.6.5.3) catalyses the reductionof ubiquinone to ubiquinol. It is present in either mitochondria or chloroplasts as\ part of the respiratory-chain NADH dehydrogenase (also known as complex I or\ NADH-ubiquinone oxidoreductase), an oligomeric enzymatic complex.\ \ NADH dehydrogenase (ubiquinone) activity ; GO:0008137 \N oxidative phosphorylation, NADH to ubiquinone ; GO:0006120 21778 IPR003213

\ \ cytochrome c oxidase activity ; GO:0004129 mitochondrion ; GO:0005739 electron transport ; GO:0006118 21777 IPR003212 This family contains members of the hyperthermophilic archaebacterium 7kD DNA-binding/endoribonuclease P2 family. There are five 7 kDa DNA-binding proteins, 7a-7e, found as monomers in the cell. Protein 7e shows the tightest DNA-binding ability.\ endoribonuclease activity ; GO:0004521 \N \N 21776 IPR003211 This family includes UreI and proton gated urea channel as well as putative amide transporters [MEDLINE:20111397].\ \N membrane ; GO:0016020 transport ; GO:0006810 21767 IPR003202 The DNA polymerase processivity factor (UL42) of herpes simplex virus forms a heterodimer with UL30 to create the viral DNA polymerase complex. UL42 functions to increase the processivity of polymerisation and makes little contribution to the catalytic activity of the polymerase.\ DNA binding activity ; GO:0003677 \N DNA replication ; GO:0006260 21766 IPR003201 Transposons are mobile DNA sequences capable of replication and insertion into the chromosome. Typically transposons code for the transposase enzyme, which catalyses insertion, found between terminal inverted repeats. Tn5 has a unique method of self- regulation in which a truncated version of the transposase enzyme acts as an inhibitor [MEDLINE:99223516].\ transposase activity ; GO:0004803 \N DNA transposition ; GO:0006313 21765 IPR003200 This family of proteins represents the nicotinate-nucleotide- dimethylbenzimidazole phosphoribosyltransferase (NN:DBI PRT) enzymes involved in dimethylbenzimidazole synthesis. This function is essential to de novo cobalamin (vitamin B12) production in bacteria. \ \N \N \N 21764 IPR003199 This family of choloylglycine hydrolases includes conjugated bile acid hydrolase (CBAH) EC: 3.5.1.24 and penicillin acylase EC: 3.5.1.11 which cleave carbon-nitrogen bonds, other than peptide bonds, in linear amides. \ \N \N \N 21762 IPR003197

The cytochrome bd type terminal oxidases catalyse quinol dependent, Na⁺ independent oxygen uptake [MEDLINE:96198179]. Members of this family are integral membrane proteins and contain a protoheame IX center B558.

\ \

The 14 kDa (or VI) subunit of the complex is not directly involved in electron transfer, but has a role in assembly of the complex [MEDLINE:95288364].

\ \ ubiquinol-cytochrome c reductase activity ; GO:0008121 \N oxidative phosphorylation, ubiquinone to cytochrome c ; GO:0006122 21763 IPR003198 This family contains glycine (EC: 2.1.4.1) and inosamine (EC: 2.1.4.2) amidinotransferases, enzymes involved in creatine and streptomycin biosynthesis respectively. \ \N \N \N 21749 IPR003186 PA28 activator complex (also known as 11s regulator of 20S proteasome) is a ring shaped hexameric structure of alternating

and

subunits. This family represents the

subunit. The activator complex binds to the 20S proteasome and stimulates peptidase activity in and ATP-independent manner.\ proteasome activator activity ; GO:0008538 proteasome activator complex ; GO:0008537 \N 21750 IPR003187 Phospholipase A1 is a bacterial outer membrane bound acyl hydrolase with a broad substrate specificity EC: 3.1.1.32. It has been proposed that Ser164 is the active site for P00631\ \ \ [MEDLINE:91249806].\ \ phospholipase activity ; GO:0004620 membrane ; GO:0016020 lipid metabolism ; GO:0006629 21751 IPR003188 The bacterial phosphoenolpyruvate: sugar phosphotransferase system (PTS) is a multi-protein system involved in the regulation of a variety of metabolic and transcriptional processes. The lactose/cellobiose-specific family are one of four structurally and functionally distinct group IIA PTS system enzymes. This family of proteins normally function as a homotrimer, stabilized by a centrally located metal ion [MEDLINE:97410387]. Separation into subunits is thought to occur after phosphorylation.\ sugar porter activity ; GO:0005351 membrane ; GO:0016020 phosphoenolpyruvate-dependent sugar phosphotransferase system ; GO:0009401 21752 IPR003189 This family represents the B subunit of shiga-like toxin (SLT or verotoxin) produced by some strains of Escherichia coli associated with hemorrhagic colitis and hemolytic uremic syndrome. SLT s are composed of one enzymatic A subunit and five cell binding B subunits.\ toxin activity ; GO:0015070 extracellular ; GO:0005576 pathogenesis ; GO:0009405 21753 IPR003190 Decarboxylation of aspartate is the major route of alanine production in bacteria, and is catalysed by the enzyme aspartate decarboxylase EC: 4.1.1.11. The enzyme is translated as an inactive proenzyme of two chains, A and B. This family contains both chains of aspartate decarboxylase.\ aspartate 1-decarboxylase activity ; GO:0004068 \N alanine biosynthesis ; GO:0006523 21754 IPR003191 Transcription of the anti-viral guanylate-binding protein (GBP) is induced by interferon-gamma during macrophage induction. This family contains GBP1 and GPB2, both GTPases capable of binding GTP, GDP and GMP. \ GTP binding activity ; GO:0005525 \N immune response ; GO:0006955 21755 IPR003191 Transcription of the anti-viral guanylate-binding protein (GBP) is induced by interferon-gamma during macrophage induction. This family contains GBP1 and GPB2, both GTPases capable of binding GTP, GDP and GMP. \ GTP binding activity ; GO:0005525 \N immune response ; GO:0006955 21756 IPR003192 Maltoporin (LamB protein) forms a trimeric structure which facilitates the diffusion of maltodextrins across the outer membrane of Gram-negative bacteria. The membrane channel is formed by an antiparallel

-barrel [MEDLINE:95125460].\ sugar porter activity ; GO:0005351 membrane ; GO:0016020 transport ; GO:0006810 21757 IPR003193

CD38, the HUGO gene name, is also called T10 or ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase (EC: 3.2.2.5). CD38 is a novel enzyme capable of catalysing multiple reactions, including NAD glycohydrolase, ADP-ribosyl cyclase, cyclic ADP ribose hydrolase and base-exchange activities Two of the enzymatic products, cyclic ADP-ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate (NAADP), are calcium messengers in a wide variety of cells from protist, plant, and mammal to human. CD38 is a positive and negative regulator of cell activation and proliferation, depending on the cellular environment. It is involved in adhesion between human lymphocytes and endothelial cells and is involved in the metabolism of two calcium messengers, cADPR and NAADP.

\ \

CD157 (also called BP-3/IF-7, BST-1 or Mo5) has ADP-ribosyl cyclase and cyclic ADP-ribose hydrolase activities. CD157 supports the growth of a pre-B cell line, DW34. Anti-CD157 mAb IF-7 has synergistic effects on anti-CD3-induced growth of T progenitor cells, and facilitates the development of\ [][] TCR+ cells in fetal thymic organ culture system.

\ \

CD molecules are leucocyte antigens on cell surfaces. CD antigens nomenclature is updated at http://www.ncbi.nlm.nih.gov/PROW/guide/45277084.htm \

\ \ \ NAD+ nucleosidase activity ; GO:0003953 \N \N 21758 IPR003194 Accurate transcription in vivo requires at least six general transcription initiation factors, in addition to RNA polymerase II. Transcription initiation factor IIA (TFIIA) is a multimeric protein which facilitates the binding of TFIID to the TATA box. \ RNA polymerase II transcription factor activity ; GO:0003702 transcription factor TFIIA complex ; GO:0005672 transcription initiation from Pol II promoter ; GO:0006367 21759 IPR003194 Accurate transcription in vivo requires at least six general transcription initiation factors, in addition to RNA polymerase II. Transcription initiation factor IIA (TFIIA) is a multimeric protein which facilitates the binding of TFIID to the TATA box. \ RNA polymerase II transcription factor activity ; GO:0003702 transcription factor TFIIA complex ; GO:0005672 transcription initiation from Pol II promoter ; GO:0006367 21760 IPR003195

This family includes the Spt3 yeast transcription factors and the 18 kDa subunit from human transcription initiation factor IID (TFIID-18). Determination of the crystal structure reveals an atypical histone fold [MEDLINE:98359123].

\ RNA polymerase II transcription factor activity ; GO:0003702 transcription factor complex ; GO:0005667 transcription initiation ; GO:0006352 21739 IPR003178 Methyl-coenzyme M reductase (MCR) is the enzyme responsible for microbial formation of methane. It is a hexamer composed of 2

, 2

, and 2 gamma subunits with two identical nickel porphinoid active sites [MEDLINE:98035783].\ \N \N \N 21740 IPR003179 Methyl-coenzyme M reductase (MCR) is the enzyme responsible for microbial formation of methane. It is a hexamer composed of 2

, 2

, and 2 gamma subunits with two identical nickel porphinoid active sites [MEDLINE:98035783].\ \N \N \N 21741 IPR003179 Methyl-coenzyme M reductase (MCR) is the enzyme responsible for microbial formation of methane. It is a hexamer composed of 2

, 2

, and 2 gamma subunits with two identical nickel porphinoid active sites [MEDLINE:98035783].\ \N \N \N 21742 IPR003180 Methylpurine-DNA glycosylase is a base excision-repair protein. It is responsible for the hydrolysis of the deoxyribose N-glycosidic bond, excising 3-methyladenine and 3-methylguanine from damaged DNA. \ alkylbase DNA N-glycosylase activity ; GO:0003905 \N base-excision repair ; GO:0006284 21743 IPR003181 The virus capsid is composed 60 icosahedral units, each of which is composed of one copy of each of the two coat proteins. This family contains the large coat protein (LCP) [MEDLINE:92188543] of the comoviridae viral family.\ structural molecule activity ; GO:0005198 viral capsid ; GO:0019028 \N 21744 IPR003182 The virus capsid is composed 60 icosahedral units, each of which is composed of one copy of each of the two coat proteins. This family contains the small coat protein (SCP) [MEDLINE:92188543] of the comoviridae viral family.\ structural molecule activity ; GO:0005198 viral capsid ; GO:0019028 \N 21745 IPR003183 Methyl-coenzyme M reductase (MCR) is the enzyme responsible for microbial formation of methane. It is a hexamer composed of 2

, 2

, and 2 gamma subunits with two identical nickel porphinoid active sites [MEDLINE:98035783].\ \N \N \N 21746 IPR003183 Methyl-coenzyme M reductase (MCR) is the enzyme responsible for microbial formation of methane. It is a hexamer composed of 2

, 2

, and 2 gamma subunits with two identical nickel porphinoid active sites [MEDLINE:98035783].\ \N \N \N 21730 IPR003169 The GYF domain is named because of the presence of Gly-Tyr-Phe residues. The GYF domain is a proline-binding domain in CD2-binding protein O95400.\ \N \N \N 21731 IPR003170 Members of this family are UDP-N-acetylenolpyruvoylglucosamine reductase enzymes EC: 1.1.1.158 This enzyme is involved in the biosynthesis of peptidoglycan. \ \N \N \N 21732 IPR003171 This family includes the 5,10-methylenetetrahydrofolate reductase EC: 1.7.99.5 from bacteria and methylenetetrahydrofolate reductase EC: 1.5.1.20 from eukaryotes. The structure for this domain is known [MEDLINE:99215588] to be a TIM barrel.\ methylenetetrahydrofolate reductase (NADPH) activity ; GO:0004489 \N methionine metabolism ; GO:0006555 21733 IPR003172

The allergens in this family include allergens with the following designations: Lep d 1, Der f 1, Der m 1 and Der p 1.

\ \

This family includes E1 protein, an epididymal secretory protein as well as the house dust mite allergens.

\ \ \N \N \N 21734 IPR003173 p15 has a bipartite structure composed of an amino-terminal regulatory domain and a carboxy-terminal cryptic DNA-binding domain [MEDLINE:94340741]. The DNA-binding activity of the carboxy-terminal is disguised by the amino-terminal p15 domain. Activity is controlled by protein kinases that target the regulatory domain.\ transcription co-activator activity ; GO:0003713 \N regulation of transcription, DNA-dependent ; GO:0006355 21747 IPR003184 This family of orthopoxvirus secreted proteins (also known as T1 and A41) interact with members of both the CC and CXC superfamilies of chemokines. It has been suggested that these secreted proteins modulate leukocyte influx into virus-infected tissues [MEDLINE:97236237].\ \N \N \N 21748 IPR003185 PA28 activator complex (also known as 11s regulator of 20S proteasome) is a ring shaped hexameric structure of alternating

and

subunits. This family represents the

subunit. The activator complex binds to the 20S proteasome and stimulates peptidase activity in and ATP-independent manner.\ proteasome activator activity ; GO:0008538 proteasome activator complex ; GO:0008537 \N 21726 IPR003164 Alpha adaptin is a hetero tetramer which regulates clathrin-bud formation. The carboxyl-terminal appendage of the

subunit regulates translocation of endocytic accessory proteins to the bud site.\ structural molecule activity ; GO:0005198 coated pit ; GO:0005905 \N 21727 IPR003165

This domain is found in the stem cell self-renewal protein Piwi and its relatives in Drosophila melanogaster\ \ \ [MEDLINE:99069219].

\ \ \N \N \N 21728 IPR003166 General transcription factor TFIIE consists of two subunits, TFIIE

IPR002853 and has a winged helix fold.\ RNA polymerase II transcription factor activity ; GO:0003702 transcription factor TFIIE complex ; GO:0005673 transcription initiation from Pol II promoter ; GO:0006367 21729 IPR003168 Nitrile hydratases EC: 4.2.1.84 are unusual metalloenzymes that catalyse the hydration of nitriles to their corresponding amides. They are used as biocatalysts in acrylamide production, one of the few commercial scale bioprocesses, as well as in environmental remediation for the removal of nitriles from waste streams. Nitrile hydratases are composed of two subunits,

and

, and they contain one iron atom per

unit [MEDLINE:97341231].\ \N \N \N 21738 IPR003177

\ \ electron transporter activity ; GO:0005489 \N electron transport ; GO:0006118 21736 IPR003175 Cell cycle progression is negatively controlled by cyclin-dependent kinases inhibitors (CDIs). CDIs are involved in cell cycle arrest at the G1 phase. \ cyclin-dependent protein kinase inhibitor activity ; GO:0004861 nucleus ; GO:0005634 cell cycle arrest ; GO:0007050 21737 IPR003176 This family represents the C-terminal domain of the viral DNA- binding protein, a multi functional protein involved in DNA replication and transcription control.\ DNA binding activity ; GO:0003677 host cell nucleus ; GO:0042025 transcription ; GO:0006350 21735 IPR003174 Alpha-TIF, a virion protein (VP16), is involved in transcriptional activation of viral immediate early (IE) promoters (

genes). Specificity of P23990.\ DNA binding activity ; GO:0003677 \N regulation of transcription, DNA-dependent ; GO:0006355 21716 IPR003153 Cbl is an adaptor protein that binds EGF receptors (or other tyrosine kinases) and SH3 domains, functioning as a negative regulator of many signaling pathways. The N-terminal domain is evolutionarily conserved, and is known to bind to phosphorylated tyrosine residues.\ signal transducer activity ; GO:0004871 nucleus ; GO:0005634 cell surface receptor linked signal transduction ; GO:0007166 21717 IPR003153 Cbl is an adaptor protein that binds EGF receptors (or other tyrosine kinases) and SH3 domains, functioning as a negative regulator of many signaling pathways. The N-terminal domain is evolutionarily conserved, and is known to bind to phosphorylated tyrosine residues.\ signal transducer activity ; GO:0004871 nucleus ; GO:0005634 cell surface receptor linked signal transduction ; GO:0007166 21718 IPR003153 Cbl is an adaptor protein that binds EGF receptors (or other tyrosine kinases) and SH3 domains, functioning as a negative regulator of many signaling pathways. The N-terminal domain is evolutionarily conserved, and is known to bind to phosphorylated tyrosine residues.\ signal transducer activity ; GO:0004871 nucleus ; GO:0005634 cell surface receptor linked signal transduction ; GO:0007166 21719 IPR003154 This family contains both S1 and P1 nucleases (EC: 3.1.30.1) which cleave RNA and single stranded DNA with no base specificity. \ endonuclease activity ; GO:0004519 \N DNA catabolism ; GO:0006308 21720 IPR003156

This domain is often found adjacent to the DHH domain, found in the RecJ-like phosphoesterase family IPR001667, suggesting that it may have an RNA binding function. The domain is about 60 residues long and contains a conserved GG motif.

\ nucleic acid binding activity ; GO:0003676 \N \N 21721 IPR003157 This bacterial family of Acyl transferases (or myristoyl-acp-specific thioesterases) catalyse the first step in the bioluminescent fatty acid reductase system.\ acyltransferase activity ; GO:0008415 \N fatty acid metabolism ; GO:0006631 21722 IPR003158 Photosynthesis in purple bacteria is dependent on light-induced electron transfer in the reaction centre (RC), coupled to the uptake of protons from the cytoplasm. The RC contains a cytochrome c subunit which re-reduces the oxidized electron donor.\ electron transporter activity ; GO:0005489 \N electron transport ; GO:0006118 21723 IPR003159 This family consists of a group of secreted bacterial lyase enzymes EC: 4.2.2.1 capable of acting on hyaluronan and chondroitin in the extracellular matrix of host tissues, contributing to the invasive capacity of the pathogen. This domain if almost always associated with the polysaccharide lyase family 8, C-terminal domain (see IPR004103).\ lyase activity ; GO:0016829 extracellular ; GO:0005576 \N 21724 IPR003162 Human transcription initiation factor TFIID is composed of the TATA-binding polypeptide (TBP) and at least 13 TBP-associated factors (TAFs) that collectively or individually are involved in activator-dependent transcription [MEDLINE:95396764].

TAFII-31 protein is a transcriptional coactivator of the p53 protein [MEDLINE:95281615].

\ \ \N transcription factor TFIID complex ; GO:0005669 transcription initiation ; GO:0006352 21725 IPR003163 This DNA-binding domain is found in several yeast proteins involved in transcriptional regulation. Often these proteins also contain the ank domain IPR002110. The resolved structure of this domain reveals DNA-binding motif characteristic of the CAP family of helix-turn-helix transcription factors.\ transcription factor activity ; GO:0003700 \N regulation of transcription, DNA-dependent ; GO:0006355 21697 IPR003132 This family contains the B domain of Staphylococcal protein A, which specifically binds to the Fc portion of immunoglobulin G.\ \N membrane ; GO:0016020 \N 21698 IPR003133 This domain of large T antigen binds to the SV40 origin of DNA replication [MEDLINE:97102430].\ DNA replication origin binding activity ; GO:0003688 \N DNA replication ; GO:0006260 21699 IPR003134 The function of this repeat is unknown. Seven copies are found in cortactin Q14247.\ \N \N \N 21700 IPR003135 The ATP-grasp domain has an unusual nucleotide-binding fold, also referred to as palmate, and is found in a superfamily of enzymes including D-alanine-D-alanine ligase, glutathione synthetase, biotin carboxylase, and carbamoyl phosphatesynthetase, the ribosomal protein S6 modification enzyme (RimK), urea amidolyase, tubulin-tyrosine ligase, and three enzymes of purine biosynthesis. This family does not contain all known ATP-grasp domain members. All the enzymes of this family possess ATP-dependent carboxylate-amine ligase activity, and their catalytic mechanisms are likely to include acylphosphate intermediates.\ \ \N \N \N 21701 IPR003136 Cytidylate kinase EC: 2.7.4.14 catalyzes the phosphorylation of cytidine 5 -monophosphate (dCMP) to cytidine 5 -diphosphate (dCDP) in the presence of ATP or GTP. \ ATP binding activity ; GO:0005524 \N nucleobase, nucleoside, nucleotide and nucleic acid metabolism ; GO:0006139 21702 IPR003137 The PA (Protease associated) domain is found as an insert domain in diverse proteases. The PA domain is also found in a plant vacuolar sorting receptor O22925.\ peptidase activity ; GO:0008233 \N proteolysis and peptidolysis ; GO:0006508 21703 IPR003138 VP1, VP2, VP3 and VP4 are the four basic units that form the icosahedral coat of picornaviruses. Five symmetry-related N termini of coat protein VP4 form a ten-stranded, antiparallel

barrel around the base of the icosahedral fivefold axis [MEDLINE:97238938].\ structural molecule activity ; GO:0005198 viral capsid ; GO:0019028 \N 21704 IPR003139 p19 is a component of the inner protein layer of the viral nucleocapsid.\ structural molecule activity ; GO:0005198 viral nucleocapsid ; GO:0019013 \N 21705 IPR003140 This family consists of both phospholipases [MEDLINE:98308497] and carboxylesterases with broad substrate specificity, and is structurally related to

hydrolases IPR000073\ \ \ [MEDLINE:98104086].\ \ \N \N \N 21706 IPR003141 The PHP (Polymerase and Histidinol Phosphatase) domain is a putative phosphoesterase domain. This family is often associated with a C terminal region.\ DNA-directed DNA polymerase activity ; GO:0003887 \N DNA replication ; GO:0006260 21707 IPR003142 The function of this structural domain is unknown. It is found to the C terminus of the biotin protein ligase domain IPR004143.\ biotin-apoprotein ligase activity ; GO:0000106 \N protein modification ; GO:0006464 21708 IPR003143 Cytochrome cd1 (nitrite reductase) catalyses the conversion of nitrite to nitric oxide in the nitrogen cycle. This family represents the d1 heme binding domain of cytochrome cd1, in which His/Tyr side chains ligate the d1 heme iron of the active site in the oxidized state [MEDLINE:97456472].\ electron transporter activity ; GO:0005489 \N electron transport ; GO:0006118 21709 IPR003146 Carboxypeptidases are found in abundance in pancreatic secretions. The pro-segment moiety (activation peptide) accounts for up to a quarter of the total length of the peptidase, and is responsible for modulation of folding and activity of the pro-enzyme. \ carboxypeptidase activity ; GO:0004180 \N proteolysis and peptidolysis ; GO:0006508 21710 IPR003147 Protein L is a bacterial protein with immunoglobulin (Ig) light chain-binding properties. It contains a number of homologous b1 repeats towards the N-terminus. These repeats have been found to be responsible for the interaction of protein L with Ig light chains [MEDLINE:92316971].\ \N \N \N 21711 IPR003148

This domain is found in a wide variety of proteins. These protein include potassium channels P31069, and various other transporters. This domain binds to NAD.

\ \N \N potassium ion transport ; GO:0006813 21712 IPR003149 This family represents the small subunit of the Fe-only hydrogenases EC: 1.18.99.1. The subunit is comprised of alternating random coil and

helical structures that encompass the large subunit in a novel protein fold [MEDLINE:99148109].\ electron transporter activity ; GO:0005489 \N electron transport ; GO:0006118 21713 IPR003150 RFX is a regulatory factor which binds to the X box of MHC class II genes and is essential for their expression. The DNA-binding domain of RFX is the central domain of the protein and binds ssDNA as either a monomer or homodimer [MEDLINE:91071581].\ DNA binding activity ; GO:0003677 \N regulation of transcription, DNA-dependent ; GO:0006355 21714 IPR003151 The FAT domain is a domain present in the PIK-related kinases. Members of the family of PIK-related kinases may act as intracellular sensors that govern radial and horizontal pathways.[MEDLINE:20245681].\ \N \N \N 21715 IPR003152 The FATC domain is found at the C-terminal end of the PIK-related kinases. Members of the family of PIK-related kinases may act as intracellular sensors that govern radial and horizontal pathways.[MEDLINE:20245681].\ \N \N \N 21688 IPR003123 This domain is present in yeast vacuolar sorting protein 9 and other proteins.\ \N \N \N 21689 IPR003124 The WH2 domain (for Wiskott Aldrich syndrome homology region 2) has been shown in WASP P42768 and Scar1 (mammalian homolog) to interact via their WH2 domains with actin.\ \N \N \N 21690 IPR003125 This domain has no known function and is found in Caenorhabditis elegans proteins normally at the N-terminal.\ \N \N \N 21691 IPR003126

The N-end rule-based degradation signal, which targets a protein for ubiquitin-dependent proteolysis, comprises a destabilizing amino-terminal residue and a specific internal lysine residue. This entry describes a putative zinc finger in N-recognin, a recognition component of the N-end rule pathway.

\ ubiquitin-protein ligase activity ; GO:0004842 \N ubiquitin cycle ; GO:0006512 21692 IPR003127 This domain was first found in the peptide hormone sorbin and later in the ponsin/ArgBP2/vinexin family of proteins.\ \N \N \N 21693 IPR003128

Villin is an F-actin bundling protein involved in themaintenance of the microvilli of the absorptive epithelia. The villin-type "headpiece" domain is a modular motif found at the extreme C-terminus of larger "core" domains in over 25\ cytoskeletal proteins in plants and animals, often in assocation with the Gelsolin repeat. Although the headpiece is classified as an F-actin-binding domain, it has been shown \ that not all headpiece domains are intrinsically F-actin-binding motifs, surface charge distribution\ may be an important element for F-actin recognition [MEDLINE:22020908]. An autonomously folding, 35 residue, thermostable subdomain (HP36) of the full-length 76 amino acid residue villin\ headpiece, is the smallest known example of a cooperatively folded domain of a naturally occurring protein. The structure of HP36, as determined by NMR\ spectroscopy, consists of three short helices surrounding a tightly packed hydrophobic core [MEDLINE:22090789].

\ \ actin binding activity ; GO:0003779 \N cytoskeleton organization and biogenesis ; GO:0007010 21694 IPR003129 Thrombospondin is an adhesive glycoprotein that mediates cell-to-cell and cell-to-matrix interactions. It can bind to fibrinogen, fibronectin, laminin and type V collagen. This is the heparin-binding and cell adhesion domain of thrombospondin.\ structural molecule activity ; GO:0005198 \N cell adhesion ; GO:0007155 21695 IPR003130 Dynamin GTPase effector domain found in proteins related to dynamin. Dynamin is a microtubule-associated, force-producing protein involved in the production ofmicrotubule bundles.\ \ GTP binding activity ; GO:0005525 \N \N 21696 IPR003131

The N-terminal, cytoplasmic tetramerization domain (T1) of voltage-gated K⁺ channels encodes molecular determinants for subfamily-specific assembly of -subunits into functional tetrameric channels [MEDLINE:99101381]. This domain is found in a subset of a larger group of proteins that obtain BTB/POZ domain.

\ voltage-gated potassium channel activity ; GO:0005249 membrane ; GO:0016020 potassium ion transport ; GO:0006813 21672 IPR003107 The HAT (Half A TPR) repeat is found in several RNA processing proteins [MEDLINE:98138616]. They are structurally and sequentially thought to be similar to TPRs (tetratricopeptide repeats).\ \N intracellular ; GO:0005622 RNA processing ; GO:0006396 21673 IPR003108

The growth-arrest-specific protein 2 domain is found associated with the spectrin repeat, calponin homology domain and EF hand in many proteins.

\ \N \N cell cycle arrest ; GO:0007050 21674 IPR003109 This is the LGN motif found in putative GEFs specific for G-

GTPase, and regulators of g-protein signaling. RGS12, or regulator of G-protein signalling 12, inhibits signal transduction by increasing the GTPase activity of G-protein

subunits, thus pushing them into their inactive GDP-bound form.\ GTPase activator activity ; GO:0005096 \N signal transduction ; GO:0007165 21675 IPR003110

Phosphorylated immunoreceptor signaling motifs (ITAMs) exhibit unique abilities to bind and activate Lyn and Syk tyrosine kinases [MEDLINE:96062274]. Motif may be dually phosphorylated on tyrosine that links antigen receptors to downstream signalling machinery.

\ \ transmembrane receptor activity ; GO:0004888 membrane ; GO:0016020 cell surface receptor linked signal transduction ; GO:0007166 21676 IPR003111 The lon gene in Escherichia coli is a heat-shock gene which encodes the ATP-dependent protease, La. The tetrameric enzyme contains four binding sites for ATP, a DNA-binding domain, a proteolytic site, and a regulatory site that binds unfolded polypeptides. An ATP-binding pocket exists on each subunit as shown by consensus sequences and elements of secondary structure resembling those on other nucleotide-binding proteins (e.g. adenylate kinase, RecA) [MEDLINE:88298842].\ ATP-dependent peptidase activity ; GO:0004176 \N ATP-dependent proteolysis ; GO:0006510 21677 IPR003112 The Olfactomedin-like domain is found in proteins belonging to the olfactomedin family and is found in proteins such as olfactomedin, myocilin, pancortin and latrophilin.\ \N \N \N 21678 IPR003113 This is the region of the p110 phosphatidylinositol 3-kinase (PI3-Kinase) that binds the p85 subunit.\ \ 1-phosphatidylinositol 3-kinase complex ; GO:0005942\ phosphatidylinositol 3-kinase activity ; GO:0016303 \N signal transduction ; GO:0007165 21679 IPR003114 This domain is found associated with PX domains. The PX (phox) domain [MEDLINE:97084820] occurs in a variety of eukaryotic proteins associated with intracellular signaling pathways.\ \N \N intracellular signaling cascade ; GO:0007242 21680 IPR003115 Plasmid RK2 ParB preferentially cleaves single-stranded DNA. ParB also nickssupercoiled plasmid DNA preferably at sites with potential single-stranded\ character, like AT-rich regions and sequences that can form cruciform structures. ParB also exhibits 5-->3 exonuclease activity.\ \ DNA binding activity ; GO:0003677 extrachromosomal circular DNA ; GO:0005727 \N 21681 IPR003116 This is the Ras-binding domain found in proteins related to Ras. It is foundin association with the PE-bind and pkinase domains.\ \ receptor signaling protein activity ; GO:0005057 \N signal transduction ; GO:0007165 21682 IPR003117

In the absence of cAMP, Protein Kinase A (PKA) exists as an equimolar tetramer of regulatory (R) and catalytic (C) subunits [MEDLINE:21592579]. In addition to its role as an inhibitor of the C subunit, the R subunit anchors the holoenzyme to specific intracellular locations and prevents the C subunit from entering the nucleus. All R subunits have a conserved domain structure consisting of the N-terminal dimerization domain, inhibitory region, cAMP-binding domain A and cAMP-binding domain B. R subunits interact with C subunits primarily through the inhibitory site. The cAMP-binding domains show extensive sequence similarity and bind cAMP cooperatively.

Two types of R subunit exist - Type I and Type II - which differ in molecular weight, sequence, autophosphorylation cabaility, cellular location and tissue distribution. Types I and II were further sub-divided into and subtypes, based mainly on sequence similarity. This family of RII , the regulatory subunit portion of type II PKA proteins, contains the dimerisation interface and binding site for A-kinase-anchoring proteins (AKAPs).

\ \ cAMP-dependent protein kinase, regulator activity ; GO:0008603 \N signal transduction ; GO:0007165 21686 IPR003121 This is the BAF60b domain of the SWIB complex also found in the SWI/SNF complex 60 kda subunit and prokaryotic DNA topoisomerases.\ \N \N \N 21687 IPR003122 This family consists of homologues of the ligand binding domain of the wild-type bacterial aspartate receptor, Tar.\ transmembrane receptor activity ; GO:0004888 membrane ; GO:0016020 signal transduction ; GO:0007165 21685 IPR003120 This family consists of transcription factors related to STE and is found associated with the C2H2 zinc finger in some proteins.\ transcription factor activity ; GO:0003700 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 21684 IPR003119 Saposins are small lysosomal proteins that serve as activators of variouslysosomal lipid-degrading enzymes [MEDLINE:96048294]. They probably act by isolating the\ lipid substrate from the membrane surroundings, thus making it more \ accessible to the soluble degradative enzymes. All mammalian saposins\ are synthesized as a single precursor molecule (prosaposin) which contains\ four Saposin-B domains, yielding the active saposins after proteolytic\ cleavage, and two Saposin-A domains that are removed in the activation\ reaction. \ The Saposin-B domains also occur in other \ proteins, many of them active in the lysis of membranes [MEDLINE:94272336], [MEDLINE:97021725].\ \ \N \N \N 21683 IPR003118

Transcription factors are protein molecules that bind to specific DNAsequences in the genome, resulting in the induction or inhibition of gene\ transcription [MEDLINE:90299137]. The ets oncogene is such a factor, possessing a region \ of 85-90 amino acids known as the ETS (erythroblast transformation specific) domain [MEDLINE:90299137], [MEDLINE:91071573]. This domain is rich in\ positively-charged and aromatic residues, and binds to purine-rich segments\ of DNA. The ETS domain IPR000418 has been identified in other transcription factors\ such as PU.1, human erg, human elf-1, human elk-1, GA binding protein, and\ a number of others [MEDLINE:90299137], [MEDLINE:91071573], [MEDLINE:93145976].\ It is generally localized at the C-terminus of the protein,\ with the exception of ELF-1, ELK-1, ELK-3, ELK-4 and ERF where it is found at\ the N-terminus.

\ \

This entry describes a subfamily of the SAM domain a widespread domain in signalling and nuclear proteins that occurs along with the ETS domain.

\ \ DNA binding activity ; GO:0003677 nucleus ; GO:0005634 \N 21667 IPR003102 The nuclear factor CREB activates transcription of target genes in part through direct interactions with the KIX domain of the coactivator CBP in a phosphorylation-dependent manner. CBP and P300 bind to the pKID (phosphorylated kinase-inducible-domain) domain of CREB [MEDLINE:98074795].\ protein binding activity ; GO:0005515 \N regulation of transcription, DNA-dependent ; GO:0006355 21668 IPR003103

BAG domains are present in Bcl-2-associated athanogene 1 and silencer of death domains. The BAG proteins are modulators of chaperone activity, they bind to HSP70/HSC70 proteins and promote substrate release. The proteins have anti-apoptotic activity and increase the anti-cell death function of BCL-2 induced by various stimuli. BAG-1 binds to theserine/threonine kinase Raf-1 or Hsc70/Hsp70 in a mutually exclusive interaction. BAG-1 promotes cell growth by binding to and stimulating Raf-1 activity. The binding of Hsp70 to BAG-1 diminishes Raf-1\ signaling and inhibits subsequent events, such as DNA synthesis, as well as arrests the cell cycle. BAG-1 has been suggested to function as a molecular switch that\ encourages cells to proliferate in normal conditions but become quiescent under a stressful environment [MEDLINE:22293827].

BAG-family proteins contain a single\ BAG domain, except for human BAG-5 which has four BAG repeats. The BAG domain is a conserved region located at the C-terminus of the BAG-family\ proteins that binds the ATPase domain of Hsc70/Hsp70. The BAG domain is evolutionarily conserved, and BAG domain containing proteins have been\ described and/or proven in a variety of organisms including mice, Xenopus, Drosophila, Bombyx mori (silk worm), Caenorhabditis elegans, Saccharomyces\ cerevisiae, Schizosaccharomyces pombe, and Arabidopsis thaliana.

The BAG domain has\ 110124 amino acids and is comprised of three anti-parallel -helices, each approximately 3040 amino acids in length. The first and second\ helices interact with the serine/threonine kinase Raf-1 and the second and third helices are the sites of the BAG domain interaction with the\ ATPase domain of Hsc70/Hsp70. Binding of the BAG domain to the ATPase domain is mediated by both electrostatic and\ hydrophobic interactions in BAG-1 and is energy requiring.

\ \ apoptosis regulator activity ; GO:0016329 \N apoptosis ; GO:0006915 21669 IPR003104

FH proteins control rearrangements of the actin cytoskeleton, especially in the context of cytokinesis and cell polarisation. Members of this family have been found to interact with\ Rho-GTPases, profilin and other actin-assoziated proteins. These interactions are mediated\ by the proline-rich FH1 domain, usually located in front of FH2.\ Despite this cytosolic function, vertebrate formins have been assigned functions within the\ nucleus. A set of Formin-Binding Proteins (FBPs) has been shown to bind FH1 with their\ WW domain.

\ \ actin binding activity ; GO:0003779 \N \N 21670 IPR003105

This is a domain in SET domain containing proteins and other proteins of unknown function. In mouse it is found in a nuclear protein associated with cell proliferation [MEDLINE:99099250].

\ \N \N \N 21671 IPR003106 This region is a plant specific leucine zipper that is always foundassociated with a homeobox.\ \ DNA binding activity ; GO:0003677 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 21659 IPR003093 Active cell suicide (apoptosis) is induced by events such as growth factor withdrawal and toxins.It is controlled by regulators, which have either an inhibitory effect on programmed cell death\ (anti-apoptotic) or block the protective effect of inhibitors (pro-apoptotic) PUB00001030,\ PUB00001030. Many viruses have found a way of countering defensive apoptosis by encoding their own\ anti-apoptosis genes preventing their target-cells from dying too soon. All proteins belonging to\ the Bcl-2 family [MEDLINE:97067261] contain either a BH1, BH2, BH3, or BH4 domain. All anti-apoptotic\ proteins contain BH1 and BH2 domains, some of them contain an additional N-terminal BH4 domain\ (Bcl-2, Bcl-x(L), Bcl-w), which is never seen in pro-apoptotic proteins, except for Bcl-x(S). On the\ other hand, all pro-apoptotic proteins contain a BH3 domain (except for Bad) necessary for\ dimerization with other proteins of Bcl-2 family and crucial for their killing activity, some of them\ also contain BH1 and BH2 domains (Bax, Bak). The BH3 domain is also present in some anti-apoptotic\ protein, such as Bcl-2 or Bcl-x(L). Proteins that are known to contain these domains include vertebrate\ Bcl-2 (

and

isoforms) and Bcl-x (isoforms (Bcl-x(L) and Bcl-x(S)); mammalian proteins Bax and\ Bak; mouse protein Bid; Xenopus laevis proteins Xr1 and Xr11; human induced myeloid leukemia cell\ differentiation protein MCL1 and C. elegans protein ced-9.\ \ apoptosis regulator activity ; GO:0016329 \N apoptosis ; GO:0006915 21660 IPR003094 6-Phosphofructo-2-kinase (EC: 2.7.1.105, EC: 3.1.3.46) is a bifunctional enzyme that catalyses both the synthesis and the degradation of fructose-2, 6-bisphosphate. The fructose-2,6-bisphosphatase reaction involves a phosphohistidine intermediate. The catalytic pathway is:

\
ATP + D-fructose 6-phosphate = ADP + D-fructose 2,6-bisphosphate\

\ \ \ \

\
D-fructose 2,6-bisphosphate + H₂O = 6-fructose 6-phosphate + P_i\

\ The enzyme is important in the regulation of hepatic carbohydrate metabolism and is found in greatest quantities in the liver, kidney and heart. In mammals, several genes often encode different isoforms, each of which differs in its tissue distribution and enzymatic activity [MEDLINE:98314509]. The family described here bears a resemblance to the ATP-driven phospho-fructokinases, however, they share little sequence similarity, although a few residues seem key to their interaction with fructose 6-phosphate [MEDLINE:98440822].\ \ ATP binding activity ; GO:0005524 \N fructose 2,6-bisphosphate metabolism ; GO:0006003 21663 IPR003097 Flavoprotein pyridine nucleotide cytochrome reductases [MEDLINE:92084635] (FPNCR) catalyse the interchange of reducing equivalents between one-electron carriers and the two-electron-carrying nicotinamide dinucleotides. The enzymes include ferredoxin:NADP⁺reductases (FNR) [MEDLINE:94299474], plant and fungal NAD(P)H:nitrate reductases [MEDLINE:92084635], [MEDLINE:22155041], NADH:cytochrome b5 reductases [MEDLINE:86195916], NADPH:P450 reductases [MEDLINE:91344276], NADPH:sulphite\ reductases [MEDLINE:89380164], nitric oxide synthases [MEDLINE:91287795], phthalate dioxygenase reductase [MEDLINE:94129395], and various\ other flavoproteins.\ \ oxidoreductase activity ; GO:0016491 \N electron transport ; GO:0006118 21664 IPR003099 Members of this family are prephenate dehydrogenases EC: 1.3.1.12 involved in tyrosine biosynthesis. \ prephenate dehydrogenase (NADP+) activity ; GO:0004665 \N tyrosine biosynthesis ; GO:0006571 21665 IPR003100 This domain is named after the proteins Piwi Argonaut and Zwille. It is also found in the CAF protein from A. thaliana . The function of the domain is unknown.\ \N \N \N 21666 IPR003101 The nuclear factor CREB activates transcription of target genes in part through direct interactions with the KIX domain of the coactivator CBP in a phosphorylation-dependent manner [MEDLINE:98074795]. This provides a model for\ activator:coactivator interactions. The KIX domain of CBP also binds to transactivation domains of other nuclear factors including Myb and Jun.\ \ protein binding activity ; GO:0005515 \N regulation of transcription, DNA-dependent ; GO:0006355 21661 IPR003095 DnaJ, a prokaryotic heat shock protein, interacts with dnaK, a chaperone hsp70-like protein [MEDLINE:94287451]. DnaJ comprises a 70-residue N-terminal domain\ (the J-domain); a 30-residue glycine-rich region (the G-domain); a central\ domain containing 4 repeats of a CxxCxGxG motif (the CRR-domain); and a\ 120-170 residue C-terminal region. The J- and CRR-domains are found in many prokaryotic and eukaryotic\ proteins [MEDLINE:92263470], either together or separately.\ \ chaperone activity ; GO:0003754 \N \N 21662 IPR003096 Calponin is a smooth muscle-specific, actin-, tropomyosin- and calmodulin-binding protein believed to be involved in regulation or modulation of contraction [MEDLINE:93380560]; interaction of the protein with actin inhibits actomyosin\ MgATPase activity. Multiple isoforms are found in smooth muscle [MEDLINE:94193769]. Calponin is a basic protein of ~34 Kd [MEDLINE:96132935]. The protein contains three repeats of a\ well-conserved 26-residue domain (see IPR000557).\ \ \N \N \N 21658 IPR003092

TASK is a member of the TWIK-related (two P-domain) K⁺ channel family\ identified in human tissues PUB00009384. It is widely distributed, being\ particularly abundant in the pancreas and placenta, but it is also found in\ the brain, heart, lung and kidney. Its amino acid identity to TWIK-1 and\ TREK-1 is rather low, being about 25-28%. However, it is thought to share\ the same topology of four TM segments, with two P-domains. TASK is very\ sensitive to variations in extracellular pH in the physiological range,\ changing from fully-open to closed in approximately 0.5 pH units around\ pH 7.4. Thus, it may well be a biological sensor of external pH variations.

\ \ potassium channel activity ; GO:0005267 membrane ; GO:0016020 potassium ion transport ; GO:0006813 21657 IPR003091

\ \ \ voltage-gated potassium channel activity ; GO:0005249 voltage-gated potassium channel complex ; GO:0008076 potassium ion transport ; GO:0006813 21656 IPR003090

The crystallins are water-soluble structural proteins that occur in high concentration in the cytoplasm of eye lens fiber cells. Four major\ groups of crystallin have been distinguished on the basis of size,\ charge and immunological properties: -, - and gamma-crystallins\ occur in all vertebrate classes (though gamma-crystallins are low or\ absent in avian lenses); and delta-crystallin is found exclusively in\ reptiles and birds\ \ \ \ [MEDLINE:90085307], [MEDLINE:95360718].

Alpha-crystallin occurs as large aggregates, comprising two types of related\ subunits (A and B) that are highly similar to the small (15-30kDa) heat\ shock proteins (HSPs), particularly in their C-terminal halves. The\ relationship between these families is one of classic gene duplication\ and divergence, from the small HSP family, allowing adaptation to novel\ functions. Divergence probably occurred prior to evolution of the eye\ lens, -crystallin being found in small amounts in tissues outside\ the lens [MEDLINE:90085307].

\ \ \N \N \N 21654 IPR003088 Cytochromes c (cytC) can be defined as electron-transfer proteins having one or several haem c groups, bound to the protein by one or, more \ generally, two thioether bonds involving sulphydryl groups of cysteine \ residues. The fifth haem iron ligand is always provided by a histidine \ residue. CytC possess a wide range of properties and function in a large \ number of different redox processes PUB00006083. \

Ambler PUB00006083 recognised four classes of cytC.

Class I includes the low-spin soluble cytC of\ mitochondria and bacteria, with the haem-attachment site towards the\ N-terminus, and the sixth ligand provided by a methionine residue about\ 40 residues further on towards the C-terminus.

\ \ electron transporter activity ; GO:0005489 mitochondrial electron transport chain ; GO:0005746 electron transport ; GO:0006118 21655 IPR003089 The

hydrolase fold [MEDLINE:93028317] is common to a number of hydrolytic enzymesof widely differing phylogenetic origin and catalytic function. The core\ of each enzyme is an

-sheet (rather than a barrel), containing 8\ strands connected by helices [MEDLINE:93028317]. The enzymes are believed to have diverged\ from a common ancestor, preserving the arrangement of the catalytic\ residues. All have a catalytic triad, the elements of which are borne on\ loops, which are the best conserved structural features of the fold.\ \ hydrolase activity ; GO:0016787 \N aromatic compound metabolism ; GO:0006725 21652 IPR003086 A number of gram-positive bacteria (including Pseudomonas fluorescens, Erwinia chrysanthemi, Serratia marcescens, Pseudomonas tolaasii and\ Pseudomonas aeruginosa) secrete a monomeric inhibitor of the extracellular\ proteases a, b and c of the 50Kda extracellular metalloprotease or other\ alkaline protease [MEDLINE:96090159]. It forms a non-covalent interaction with its target\ protease and may prevent its autocatalytic cleavage in the periplasm.\

Structurally and functionally these proteins are closely related to the \ lipocalins, fatty acid-binding proteins, avidins and the enigmatic triabin.\ Together these five protein families constitute the calycin superfamily [MEDLINE:93264947]. \ The proteins are characterised by their high specificity for small hydro-\ phobic molecules and by their ability to form complexes with soluble macro-\ molecules either through intramolecular disulphides or protein-protein \ interactions [MEDLINE:96358478].

The crystal structure of a metalloprotease inhibitor has\ reveals the characteristic calycin-like fold: \ an 8-stranded anti-parallel -barrel [MEDLINE:95271655].

\ \ endopeptidase inhibitor activity ; GO:0004866 periplasmic space (sensu Gram-negative Bacteria) ; GO:0030288 \N 21653 IPR003087 Murine neutrophil gelatinase-associated lipocalin precursor (NGAL) exhibits a 7-10-fold increase in expression in cultured mouse kidney cells infected\ by simian-virus 40 or other viruses [MEDLINE:96235131]. NGAL has been identified as a \ major secretory product of lipopolysaccharide-stimulated cultured mouse \ macrophages, suggesting that the protein might function in defence against\ infection [MEDLINE:93329135]. Recently, NGAL has been shown to be identical to SIP24, a \ previously identified secretory product of quiescent mouse fibroblasts \ induced by serum, dexamethasone, basic fibroblast growth factor, and phorbol\ ester [MEDLINE:95403463]. Mouse plasma levels of NGAL rise as a result of increased \ expression levels in the liver, in response to intramuscular turpentine \ injection. Tumour necrosis factor can regulate NGAL expression in cultured \ liver cells. These findings indicate that NGAL is a positive acute phase\ protein and may possess immunosuppressive or anti-inflammatory properties, \ possibly linked to its regulation of neutrophil gelatinase or other plasma\ protein [MEDLINE:93106190]. The uterus is also a major site of NGAL synthesis, especially\ at parturition, when expression increases significantly, suggesting a\ physiological role for the protein in uterine secretions [MEDLINE:95373594].\ \ \ binding activity ; GO:0005488 \N transport ; GO:0006810 21651 IPR003085 Histones can be reversibly acetylated on several lysine residues.Regulation of transcription is caused in part by this\ mechanism. Histone deacetylases catalyse the removal\ of the acetyl group. Histone deacetylases, acetoin utilization proteins and acetylpolyamine amidohydrolases are all members of this ancient protein superfamily [MEDLINE:97426514]. \ \

Histone deacetylases (HDA), acetoin utilisation proteins (ACUC) and\ acetylpolyamine amidohydrolases (APHA) form an ancient protein superfamily\ and are all believed to catalyse the deacetylation of a substrate [MEDLINE:97426514]. HDAs are found in eukaryotes, from yeast to humans; ACUCs are found in eubacteria; and APHAs occur in archaeal bacteria, eubacteria and some eukaryotic organisms [MEDLINE:97426514]. HDA nomenclature is confusing: the family can also be identified by the codes RPD, HOS, HD and HDAC, regardless of\ specific sequence similarities. HDAs may have evolved at least twice from APHAs, the more recent gene duplication event resembling APHAs more closely [MEDLINE:97426514].

Disrupting the expression of ACUC results in diminished growth of bacteria on acetoin and butanediol. Acetoin is a bacterial fermentation product that can be converted to acetate via the butanediol cycle in the absence of other carbon sources; its degradation is believed to be caused by deacetylation mediated by ACUC [MEDLINE:97426514].

\ \ \N \N \N 21650 IPR003084 Histones can be reversibly acetylated on several lysine residues.Regulation of transcription is caused in part by this\ mechanism. Histone deacetylases catalyse the removal\ of the acetyl group. Histone deacetylases, acetoin utilization proteins and acetylpolyamine amidohydrolases are all members of this ancient protein superfamily [MEDLINE:97426514].\

HDAs function in multi-subunit complexes, reversing the acetylation of\ histones by histone acetyltransferases [MEDLINE:99257494], [MEDLINE:99172034], and are also believed to deacetylate general transcription factors such as TFIIF and sequence-specific transcription factors such as p53 [MEDLINE:99257494]. Thus, HDAs contribute to the regulation of transcription, in particular transcriptional repression[MEDLINE:99172034]. At N-terminal tails of histones, removal of the acetyl group from the epsilon-amino group of a lysine side chain will restore its positivecharge, which may stabilise the histone-DNA interaction and prevent activating transcription factors binding to promoter elements [MEDLINE:97426514]. HDAs play important roles in the cell cycle and differentiation, and their\ deregulation can contribute to the development of cancer [MEDLINE:99172034],6].\

HDAs function in multi-subunit complexes, reversing the acetylation of\ histones by histone acetyltransferases [MEDLINE:99257494],[MEDLINE:99172034], and are also believed to\ deacetylate general transcription factors such as TFIIF and sequence-\ specific transcription factors such as p53 [MEDLINE:99257494]. Thus, HDAs contribute to \ the regulation of transcription, in particular transcriptional repression. At N-terminal tails of histones, removal of the acetyl group from\ the epsilon-amino group of a lysine side chain will restore its positive\ charge, which may stabilise the histone-DNA interaction and prevent\ activating transcription factors binding to promoter elements [MEDLINE:97426514]. HDAs\ play important roles in the cell cycle and differentiation, and their\ deregulation can contribute to the development of cancer [MEDLINE:99172034],[MEDLINE:99257411].

\ \ \N \N \N 21649 IPR003083

S-crystallins of cephalopod are the major protein constituent of the lens in cephalopods. Their primary protein sequences show a high degree (41%) of identity with the cephalopod digestive gland sigma-class glutathione transferase (GST). In spite of the sequence similarity, lens S-crystallin shows little if any GST activity. S-crystallins fail to bind to an S-hexylglutathione affinity column (marker for glutathione affinity) and have very little GST activity in a typical substitution reaction with glutathione and 1-chloro-2,4-dinitrobenzene [MEDLINE:99130281]. Nevertheless, pH rate profiles indicate that any\ reactions that do take place proceed via the same mechanism as GSTs [MEDLINE:96425005].

The three-dimensional structure of the sigma-class GST from squid has been\ determined to 2.4A resolution [MEDLINE:95244455]. The protein is characterised by two \ domains, one of which has a 3-layer(aba) sandwich architecture, the other\ being largely helical. The modelled S-crystallin structure has a similar \ topology to the squid sigma-class GST, with longer helices 4 and 5, \ corresponding to a long insertion. The insertion causes the active centre\ to be in a more closed conformation than sigma-class GSTs and may explain\ the low affinity for glutathione [MEDLINE:99130281].

The function of glutathione S-transferases (GST) is the conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. The isoenzymes appear to play a central role in the parasite detoxification system. Glutathione S-transferases form homodimers, but in eukaryotes can also form heterodimers of the A1 and A2 or YC1 and YC2 subunits. The GST domain is also found in S-crystallins from squid, and proteins with no known GST activity, such as eukaryotic elongation factors 1-gamma and the HSP26 family of stress-related proteins, which include auxin-regulated proteins in plants and stringent starvation proteins in Escherichia coli.

\ \ \ \N \N \N 21648 IPR003082

\ \

Pi-class GSTs are recognised by ethacrynic acid substrate specificity [MEDLINE:99032826]. The pi-class H subsite has been found to be comparatively open [MEDLINE:99458665], perhaps explaining specificity towards the lesser hydrophobic substrates. This class has received particular interest in relation to carcinogenesis. Pi-class GSTs have been found to be markedly increased in the early stages of rat liver carcinogenesis. Expression levels of GST-P have also been found to be elevated in many human tumours. In addition, polycyclic aromatic hydrocarbon (a carcinogen found in cigarette smoke) induced tumourigenesis is increased in mice lacking this enzyme [MEDLINE:98226805].

\ \ glutathione transferase activity ; GO:0004364 \N glutathione conjugation reaction ; GO:0006803 21647 IPR003081

\ \

Human mu-class GSTs have been subdivided into 5 isoforms based on differing substrate specificities [MEDLINE:93232050]. Mu-class GSTs are thought to be\ involved in the detoxification of reactive oxygen species (cyclised\ o-quinones) produced via oxidative metabolism of catecholamines. These\ toxins are thought to be involved in neurological disorders of the\ nigrostriatal and mesolimbic systems (Parkinsons and Schizophrenia,\ respectively). Indeed, mu-class GSTs are expressed in the substantia nigra\ and have preferential substrate specificity for the cyclised o-quinones\ formed by catecholamine metabolism [MEDLINE:99182415]. Mu-class GSTs possess the so-called "mu-loop", which occurs between strand -2 and helix -3. This is a consequence of an insertion in the primary sequence and the loop allows the overall domain I topology to remain [MEDLINE:94192655].

\ \ glutathione transferase activity ; GO:0004364 \N glutathione conjugation reaction ; GO:0006803 21645 IPR003079

Steroid or nuclear hormone receptors (4A nuclear receptor, NRs) constitute an important superfamily of transcription regulators that are involved in widely diverse physiological functions, including control of embryonic development, cell differentiation and homeostasis. Members of the superfamily include the steroid hormone receptors and receptors for thyroid hormone, retinoids, 1,25-dihydroxy-vitamin D3 and a variety of other ligands. The proteins function as dimeric molecules in nuclei to regulate the transcription of target genes in a ligand-responsive manner [MEDLINE:95206940], [MEDLINE:94218237]. In addition to C-terminal ligand-binding domains, these nuclear receptors contain a highly-conserved, N-terminal zinc-finger that mediates specific binding to target DNA sequences, termed ligand-responsive elements. In the absence of ligand, steroid hormone receptors are thought to be weakly associated with nuclear components; hormone binding greatly increases receptor affinity.

NRs are extremely important in medical research, a large number of them being implicated in diseases such as cancer, diabetes, hormone resistance syndromes, etc. While several NRs act as ligand-inducible transcription factors, many do not yet have a defined ligand and are accordingly termed "orphan" receptors. During the last decade, more than 300 NRs have been described, many of which are orphans, which cannot easily be named due to current nomenclature confusions in the literature. However, a new system has recently been introduced in an attempt to rationalise the increasingly complex set of names used to describe superfamily members.

\ \ \

Three isoforms of a novel member of the steroid hormone nuclear receptor\ superfamily related to retinoic acid receptors have been identified.\ The isoforms (designated ROR 1, ROR 2 and ROR 3) share\ common DNA- and putative ligand-binding domains but are characterised by\ distinct N-terminal domains generated by alternative RNA processing.\ These differences in the N-terminal domains result in differential DNA-\ binding activity for the different isoforms: ROR 1 binds to and \ constitutively activates transcription from a large subset of ROR elements,\ while ROR 2 recognises ROR elements with strict specificity and \ displays weaker transcriptional activity. The N-terminal domain and\ zinc finger region work in concert to confer high affinity and specific \ DNA-binding properties to the ROR isoforms and suggest a novel strategy \ to control DNA-binding activity of nuclear receptors [MEDLINE:95011560].

Synonym(s): 1F nuclear receptor

\ \ ligand-dependent nuclear receptor activity ; GO:0004879 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 21646 IPR003080

\ \

Alpha-class GSTs show substrate specificity for cumene hydroperoxide (CuOOH)\ and 7-chloro-4-nitrobenz-2-oxa-1,3-diazole (NBD-C1), amongst others. In \ addition, this class exhibits a number of differences from the\ characteristic GST structure: within domain II, there is a short 3-residue -strand near the C-terminal segment and a longer -7 helix (due to\ insertions at the N-terminus and near to the middle of this helix); domain I\ is formed from two separate segments of the sequence. This occurs because\ an extra helix (-11) formed via folding of the C-terminal region of the\ polypeptide chain is also part of this domain [MEDLINE:94192655]. This helix covers the substrate bound in the H subsite, which is thought to explain the preference of class GSTs for more hydrophobic compounds [MEDLINE:99458665].

\ \ glutathione transferase activity ; GO:0004364 \N glutathione conjugation reaction ; GO:0006803 21644 IPR003078

\ \ \

The retinoic acid receptors (RAR) belong to the large family of ligand \ responsive gene regulatory proteins that includes receptors for steroid and\ thyroid hormones. These proteins contain two highly conserved domains\ that are involved in determining their DNA and ligand-binding activities [MEDLINE:91187677]. Three distinct RARs have been identified (termed RAR , , and gamma) and are encoded by genes on separate chromosomes. Additional isoforms of the receptors have been described, all of which differ in the N-terminal regions. Comparison of the amino acid sequences of human and mouse RARs indicates that interspecies conservation in members of the RAR subfamily (either , or gamma) is much higher than conservation of the\ receptors within species [MEDLINE:89315787]. These observations indicate that RAR-, - and -gamma may perform specific functions. hRAR-gamma RNA has \ been shown to be the predominant RAR RNA species in human skin, suggesting\ that hRAR-gamma mediates some of the retinoid effects in this tissue [MEDLINE:91187677].

The crystal structure of the ligand-binding domain (LBD) of the hRAR-gamma\ bound to all-trans retinoic acid has been determined to 2.0A resolution [MEDLINE:96107307].\ Overall, the fold is similar to that of the human RXR- apo-LBD, except\ for the C-terminal portion, which folds back towards the LBD core, \ contributing to the hydrophobic ligand pocket and 'sealing' its entry site. A 'mouse trap' mechanism is thus proposed, whereby a ligand-induced \ conformational transition re-positions the amphipathic -helix of the\ activating domain and forms a transcriptionally active receptor [MEDLINE:96107307].

Synonym(s): 1B nuclear receptor

\ \ retinoic acid receptor activity ; GO:0003708 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 21643 IPR003077

\ \ \

Peroxisome proliferator-activated receptors (PPAR) are ligand-activated\ transcription factors that belong to the nuclear hormone receptor \ superfamily. Three cDNAs encoding PPARs have been isolated from Xenopus laevis: xPPAR , and gamma [MEDLINE:94100165]. All three xPPARs appear to be activated by both synthetic peroxisome proliferators and naturally occurring fatty acids, suggesting a common mode of action for all members of this subfamily of receptors [MEDLINE:94100165]. Furthermore, the multiplicity of the receptors suggests the existence of hitherto unknown cellular signalling pathways for xenobiotics and putative endogenous ligands [MEDLINE:92191267].

A human cognate of the mouse PPAR-gamma (hPPAR gamma) has been cloned from\ a placental cDNA library [MEDLINE:96305359]. Sequence analysis reveals a high degree of similarity to the mouse receptor (mPPAR) and, like other PPARs, hPPAR gamma forms heterodimers with RXR . hPPAR gamma is expressed strongly in \ adipose tissue, but significant levels are also detectable in placenta, lung and ovary [MEDLINE:96305359]. In vitro trans-activation data suggest hPPAR gamma is only poorly activated by xenobiotic peroxisome proliferators, although certain fatty acids and eicosanoids are potent activators of this receptor. Both mPARR and hPPAR gamma may be activated by thiazolidinedione drugs, although the receptors appear to differ in their sensitivity to these compounds. These data suggest a high degree of structural and functional similarity between mPARR and hPPAR gamma, and provide evidence for variation in human receptor structure that may result in differential sensitivity to \ activators [MEDLINE:96305359].

\ \ ligand-dependent nuclear receptor activity ; GO:0004879 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 21642 IPR003076

\ \ \

PPAR is thought to play an important role in lipid metabolism due to\ its ability to activate transcription of a reporter gene through the \ promoter of the acyl-CoA oxidase (ACO) gene . ACO catalyses the rate-limiting step in the peroxisomal -oxidation of fatty acids [MEDLINE:92191267]. \ Activation is achieved by the binding of xPPAR on a regulatory element\ (DR1) found in the promoter region of this gene. xPPAR and gamma\ recognise the same type of element and, like PPAR , form heterodimers\ with retinoid X receptor [MEDLINE:94100165].

\ \ ligand-dependent nuclear receptor activity ; GO:0004879 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 21641 IPR003075

\ \ \

A PPAR -related cDNA from mouse (designated PPAR delta, and\ subsequently renamed ) has been cloned and characterised. The , and gamma PPAR isoforms display widely divergent patterns of expression\ during embryogenesis and in the adult [MEDLINE:94316694]. PPAR gamma and are not activated by pirinixic acid, a potent peroxisome proliferator and activator of PPAR ; they are, however, activated by the structurally distinct peroxisome proliferator LY-171883 and linoleic acid, respectively, \ indicating that each isoform can act as a regulated activator of\ transcription [MEDLINE:94316694]. Thus tissue-specific responsiveness to peroxisome proliferators, including certain fatty acids, may be partly a consequence of differential expression of multiple, pharmacologically distinct PPAR isoforms [MEDLINE:94316694].

\ \ ligand-dependent nuclear receptor activity ; GO:0004879 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 21640 IPR003074

\ \ \

Synonym(s): 1C nuclear receptor

\ \ \ \ \ ligand-dependent nuclear receptor activity ; GO:0004879 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 21639 IPR003073

\ \ \

A rat orphan nuclear hormone receptor, designated Nurr1 (Nur-related factor 1), has been isolated from a brain cortex cDNA library. The protein\ contains 598 amino acids and has a predicted molecular mass of 65kDa. The\ deduced sequence shows strong similarity to the mouse Nurr1 and human NOT1\ orphan nuclear hormone receptors of the NGFI-B/Nur77/NAK1 gene subfamily [MEDLINE:97364974].

Rat nurr1 is thought to be an immediate-early gene that is differentially\ induced by electroconvulsive seizure vs. kindled seizures. As Nurr1 \ appears to be predominantly located in brain tissue, it may have a role \ in regulation of gene expression in the central nervous system [MEDLINE:93149122]. \ Moreover, given that Nurr1 is prominently expressed in specific brain sites \ associated with memory acquisition and consolidation, it may be involved\ in memory processing [MEDLINE:97364974].

\ \ ligand-dependent nuclear receptor activity ; GO:0004879 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 21638 IPR003072

\ \ \

Human NOR-1 mRNA has been detected in adult heart and skeletal muscle, as\ well as in foetal brain, indicating that its expression is not restricted \ to events that occur during neural development [MEDLINE:96404972]. It has been shown that \ in a skeletal myxoid chondrosarcoma, the EWS gene becomes fused to NOR1 [MEDLINE:96152889].\ The chimaeric EWS-NOR gene encodes a EWS-NOR fusion protein in which the \ C-terminal RNA-binding domain of EWS is replaced by the entire NOR protein,\ comprising a long N-terminal domain, a central DNA binding domain and a\ C-terminal ligand-binding/dimerisation domain [MEDLINE:96152889].

\ \ ligand-dependent nuclear receptor activity ; GO:0004879 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 21637 IPR003071

\ \ \

NGFI-B is an early response protein and orphan member of the steroid\ hormone receptor superfamily [MEDLINE:92229411]. It is expressed in the lung, brain and superior cervical ganglia, and high levels are also seen in adrenal\ tissue. While members of this superfamily typically bind DNA as dimers, \ NGFI-B binds as a monomer. A domain separate from the NGFI-B zinc fingers\ (the so-called A box) has been identified and is required for recognition\ of two adenine-thymidine base pairs at the 5' end of the NGFI-B DNA binding\ element [MEDLINE:92229411].

\ \ ligand-dependent nuclear receptor activity ; GO:0004879 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 21636 IPR003070

\ \ \

Novel members of the steroid receptor superfamily designated NOR-1 (neuron\ derived orphan receptor) [MEDLINE:95110348], Nurr1 (Nur-related factor 1) [MEDLINE:93149122], and NGFI-B [MEDLINE:92229411] have been identified from forebrain neuronal cells undergoing apoptosis, from brain cortex, and from lung, superior cervical ganglia and adrenal tissue respectively. The NOR-1 protein binds to the B1a response-element, which has been identified as the target sequence of the Nur77 family, suggesting that three members of the Nur77 family may transactivate common target gene(s) at different situations [MEDLINE:93149122], [MEDLINE:92229411]. Ewing's sarcoma is characterised by chromosomal translocations that involve the NOR protein [MEDLINE:96152889]

\ \ ligand-dependent nuclear receptor activity ; GO:0004879 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 21635 IPR003069

\ \ \

In Drosophila melanogaster, the steroid hormone ecdysone triggers larval-to-\ adult metamorphosis, a process in which the hormone induces imaginal tissues\ to generate adult structures, and larval tissues to degenerate [MEDLINE:93313962]. The\ ecdysone receptor (EcR) binds DNA with high specificity at ecdysone response\ elements. EcR is nuclear and is found in larval wing discs, pupal wings and\ in prothoracic glands.

In the mosquito Aedes aegypti, 20-hydroxyecdysone plays an important role\ in the regulation of egg maturation [MEDLINE:95227190]. There are three EcR transcripts(of 4.2kb, 6kb and 11kb) in adult mosquitoes; 4.2kb mRNA is predominantly expressed in female mosquitoes during vitellogenesis. In both the fat body and ovaries of the female mosquito, the level of EcR mRNA is high at the previtellogenic period and after the onset of vitellogenesis [MEDLINE:95227190].

Synonym(s): 1H nuclear receptor

\ \ \ steroid binding activity ; GO:0005496 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 21633 IPR003067 The circumsporozoite (CS) protein is the most prominant surface antigen on the sporozoite of the malaria parasite, Plasmodium spp. The sporozoite is\ the infectious stage of the Plasmodium life cycle, the form in which malaria\ is passed from the mosquito vector to the mammalian host [MEDLINE:20107079]. Antibodies to\ this protein are used in the field to detect exposure to malaria [MEDLINE:20106725] and it \ is a target for several vaccines [MEDLINE:20163000].\

The sequence of the CS protein consists of head and tail regions, which are\ largely conserved, and a large set of low-complexity repeats, which are \ variant across strain and species [MEDLINE:87102878]. The C-terminal region is probably used for anchoring the protein to the cell membrane, while the central\ repeat sequences would be the surface antigen of the organism. The repeats,\ which encode the immunodominant epitope of the CS protein (see IPR000884), diverge more\ rapidly than the remainder of the gene. It is thought that the maintenance\ and evolution of the repeats is achieved via a mechanism that acts not at\ the protein level, but rather directly on the DNA sequence [MEDLINE:87102878].

\ \ defense/immunity protein activity ; GO:0003793 \N \N 21634 IPR003068

\ \ \

Chicken ovalbumin upstream promoter-transcription factor (COUP-TF) genes\ encode transcription factors that belong to the orphan group of the\ steroid/thyroid hormone receptor superfamily [MEDLINE:94240155]. COUP-TF binds to the ovalbumin promoter and, in conjunction with the S300-II protein, stimulates initiation of transcription. The protein binds to both direct repeats and palindromes of the 5'-AGGTCA-3' motif.

Murine homologues of members of the COUP-TF family, COUP-TF1, ARP-1 and \ EAR2, have been isolated and shown to be highly similar to their human\ counterparts [MEDLINE:95034311]. Although these three genes appear to be expressed in tissues derived from all three germ layers, COUP-TF1 and ARP-1 have been found to be expressed predominantly in the developing central nervous \ system in mutually exclusive domains. Strong ARP-1 expression has\ also been detected in lung and kidney [MEDLINE:95034311]. Results from such studies suggest an important role for the members of the COUP-TF family in the \ hormonal control of gene expression regulating embryogenesis, and in the\ development and differentiation of the CNS, including the specification\ of diencephalic neuromeres [MEDLINE:94240155].

Synonym(s): 2F nuclear receptor

\ \ \ ligand-dependent nuclear receptor activity ; GO:0004879 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 21631 IPR003065 The Salmonella typhimurium surface presentation of antigens K/invasion protein B gene (SpaK/InvB) is one of 12 that form a cluster responsible for \ invasion properties. The gene product is required for entry by the \ bacterium into epithelial cells, and is thus considered to be a virulence \ factor [MEDLINE:94008985]. Other Spa genes in the cluster are related to invasion (Inv) genes in similar Salmonella and Shigella species [MEDLINE:95272391], and to flagella \ biosynthesis genes in Helicobacter pylori\ \ \ \ [MEDLINE:99185204]. A further analogous gene in \ Yersinia (Spa15 homologue) has also been found [MEDLINE:94321319].\

The SpaK/InvB protein has a molecular mass of 15kDa, and is believed to play a part in the sec-independent type III protein secretion system of \ Salmonella typhimurium and Shigella flexneri\ \ \ \ [MEDLINE:0]. In the organisation of the \ Spa/Inv locus, the SpaK/InvB gene is found adjacent to SpaL/InvC [MEDLINE:94321319], and \ may play a part in the ATPase activity possessed by the latter.

\ \ type III protein (virulence-related) secretor activity ; GO:0015448 \N protein secretion ; GO:0009306 21632 IPR003066 The Salmonella typhimurium surface presentation of antigens N/invasion protein J gene (SpaN/InvJ) is one of 12 that form a cluster responsible for \ invasion properties. The gene product is required for entry by the \ bacterium into epithelial cells, and is thus considered to be a virulence \ factor [MEDLINE:94008985]. Other Spa genes in the cluster are related to invasion (Inv) genes in similar Salmonella and Shigella species [MEDLINE:97221599], and to flagella biosynthesis genes in Helicobacter pylori\ \ \ \ [MEDLINE:99185204].\

Functional analysis of the gene product from SpaN/InvJ has revealed the\ protein to have a molecular weight of 36.4 kDa [MEDLINE:95272391]. It is required by the organism to gain access to mammalian epithelial cells, and cellular mutants (InvJ-) fail successfully to infect these cells.\ It has been found, also, that the inv-spa loci of Salmonella species \ encode a type III protein secretion system, essential to the bacterium's\ host cell invasion process [MEDLINE:96355856]. Suprisingly, type III-secreted proteins\ lack the customary signal sequence characteristic of most bacterial\ secretory peptides [MEDLINE:95272391].\

\ \ type III protein (virulence-related) secretor activity ; GO:0015448 \N protein secretion ; GO:0009306 21628 IPR003061 The microcin E1 immunity protein is able to protect a cell that harbours the plasmid ColE1 encoding colicin E1 against colicin E1; it is thus\ essential both for autonomous replication and colicin E1 immunity [MEDLINE:80010893].\ \ \N \N \N 21629 IPR003063 The cloacin immunity protein complexes with cloacin in equimolar quantities and inhibits it by binding with high affinity to the cloacin C-terminal\ catalytic domain. The immunity protein is relatively small, containing 85\ amino acids.

An extra ribosome binding site has been found to precede the immunity gene on the polycistronic Clo DF13 mRNA [MEDLINE:81053773], which perhaps accounts for the fact that, in cloacinogenic cells, more immunity protein than cloacin is synthesised [MEDLINE:81053773]. Comparison of the complete amino acid sequence of the Clo DF13 immunity protein with that of the Col E3 and Col E6 immunity proteins reveals extensive similarities in primary structure, although Col E3 and Clo DF13 immunity proteins are exchangeable only to a low extent in vivo and in vitro [MEDLINE:81053773].

\ \ \N \N \N 21630 IPR003064 Norrie disease is a severe, X-linked, recessive neurodevelopmental disorder characterised by progressive atrophy of the eyes, deafness and mental \ retardation [MEDLINE:93265104]. The Norrie disease gene is expressed in retina, choroid\ and foetal brain [MEDLINE:93265103]. X-linked Familial Exudative Vitreoretinopathy (XLFEVR)\ is a hereditary eye disorder that affects both the retina and the vitreous\ body and is characterised by abnormal vascularisation of the peripheral\ retina. It has been shown that phenotypes of both XLFEVR and Norrie\ disease can result from mutations in the same gene [MEDLINE:94129616].\

Norrie disease protein (NDP) is thought to have a tertiary structure\ similar to that of transforming growth factor (TGF ). Molecular modelling studies have suggested that NDP is a member of an\ emerging family of growth factors containing a cystine knot motif [MEDLINE:94129616].\ NDP is thought to be involved in a pathway that regulates neural cell\ differentiation and proliferation, and may have a role in neuroectodermal cell-cell interaction.

\ \ \N \N \N 21626 IPR003059 The lysis proteins of the ColE2, ColE1 and CloDF13 plasmids are almost identical except in the N-terminal regions, which themselves are similar tolipoprotein signal peptides . Processing of the ColE2 prolysis protein to the mature form is prevented by globomycin, a specific inhibitor of the\ lipoprotein signal peptidase [MEDLINE:85239907]. The mature ColE2 lysis protein is located in the cell envelope.\ \ \N \N \N 21627 IPR003060 This family includes bacterial colicin and pyocin immunity proteins [MEDLINE:96270557], [MEDLINE:96302249]. These immunity proteins can bind specifically to the DNase-type colicins and pyocins and inhibit their bactericidal activity. The1.8-angstrom crystal structure of the ImmE7 protein consists of four antiparallel

-helices [MEDLINE:96270557].\

Pyocins S1 and S2 are S-type bacteriocins of Pseudomonas aeruginosa with\ different receptor recognition specificities [MEDLINE:93259934]. The genetic determinants of these pyocins have been cloned from the NIH-H and PAO chromosomes of P.aeruginosa. The determinants each constitute an operon that encodes two proteins of molecular weight 65,600 and 10,000 (pyocin S1) or 74,000 and 10,000 (pyocin S2) with a characteristic sequence (P box), a possible \ regulatory element involved in the induction of pyocin production, in the \ 5' upstream region [MEDLINE:93259934]. These pyocins have almost identical sequences, except in the N-terminal portions of the large proteins, which are\ substantially different. This similarity suggests that S1 and S2 pyocins, \ like pyocin AP41, originated from a common ancestor of the E2 group colicins. Purified pyocins S1 and S2 constitute a complex of the two proteins.\ Both pyocins cause breakdown of chromosomal DNA and complete inhibition of\ lipid synthesis in sensitive cells. The large protein (not the complex),\ shows in vitro DNase activity. This activity is inhibited by the small\ protein of either pyocin [MEDLINE:93259934].

\ \ endonuclease activity ; GO:0004519 \N defense response ; GO:0006952 21623 IPR003056

CD97 is a member of the EGF-TM7 family of class II G-protein coupled receptors that can bind to CD55(DAF). CD97 has highly related 7TM sequences but diverse, large extracellular regions. The extracellular regions are generally unrelated in sequence but usually contain cell adhesion motifs. The family is conserved in Drosophila and C. elegans. For receptors with N-terminal EGF domains the designation EGF-TM7 family has been introduced. Typically, isoforms with variable number of EGF domains exist.\ So far, the EGF-TM7 family consists of CD97 and EMR1, the human homologue of F4/80. Family members are preferentially expressed by cells of the immune\ system [MEDLINE:95363161]. High surface expression of CD97 has been found at sites of inflammation in skin and lung and in rheumatoid arthritis. At the same sites, elevated\ levels of soluble CD97 are detectable. Analysis of epithelial tumors revealed CD97 expression on the malignant cells in thyroid cancer and adenocarcinomas of the\ gastro-intestinal tract [MEDLINE:95363161].

\ \

CD molecules are leucocyte antigens on cell surfaces. CD antigens nomenclature is updated at http://www.ncbi.nlm.nih.gov/PROW/guide/45277084.htm \

\ \ \ G-protein coupled receptor activity ; GO:0004930 membrane ; GO:0016020 \N 21624 IPR003057 The lipocalins are a diverse, interesting, yet poorly understood family of proteins composed, in the main, of extracellular ligand-binding proteins\ displaying high specificity for small hydrophobic molecules [MEDLINE:85168267]. Functions\ of these proteins include transport of nutrients, control of cell regulation, pheromone transport, cryptic colouration, and the enzymatic synthesis\ of prostaglandins.\ The crystal structures of several lipocalins have been solved and show a \ novel 8-stranded anti-parallel

-barrel fold well conserved within the\ family. Sequence similarity within the family is at a much lower level and\ would seem to be restricted to conserved disulphides and 3 motifs, which\ form a juxtaposed cluster that may act as a common cell surface receptor\ site [MEDLINE:92028985], [MEDLINE:93264947]. By contrast, at the more variable end of the fold are found an \ internal ligand binding site and a putative surface for the formation of \ macromolecular complexes PUB00003448. The anti-parallel

-barrel fold is also\ exploited by the fatty acid-binding proteins, which function similarly by\ binding small hydrophobic molecules. Similarity at the sequence level,\ however, is less obvious, being confined to a single short N-terminal motif.\

A number of lipocalins act in invertebrate colouration: bilin binding\ protein from the cabbage white butterfly (Pieris brassicae), the closely\ related protein insecticyanin from Manduca sexta (tobacco hornworm) and the\ lobster protein crustacyanin. Like other members of the family, they bind \ small molecules, and gain their colourant properties from interaction with\ their ligands.

\ \ binding activity ; GO:0005488 \N transport ; GO:0006810 21625 IPR003058 Colicins are polypeptide toxins produced by, and active against, Escherichia coli and closely related bacteria. The bacteriocin cloacin DF13 inactivates\ ribosomes by hydrolysing 16S RNA in 30S ribosomes at a specific site. The\ protein consists of 561 amino acids and has a molecular weight of ~59kD. \ Sequence analysis reveals the N-terminal third of the cloacin molecule,\ which is involved in translocation of the protein across the cell membrane,\ to be relatively hydrophobic and rich in glycine. The C-terminal portion\ is rich in positively charged amino acids, possibly reflecting the RNase \ activity located within this domain. Sequence comparisons reveal similarities with colicin E3 and E6, but not with Col E1, despite striking\ similarities in codon usage [MEDLINE:83220797].\ \ endonuclease activity ; GO:0004519 extrachromosomal circular DNA ; GO:0005727 \N 21622 IPR003055 The tsx gene of Escherichia coli encodes an outer membrane protein, Tsx, which constitutes the receptor for colicin K and bacteriophage T6, and \ functions as a substrate-specific channel for nucleosides and deoxy-\ nucleosides [MEDLINE:91092502]. The protein contains 294 amino acids, the first 22 of which are characteristic of a bacterial signal sequence peptide. The putative mature form of Tsx contains 272 residues with a calculated Mr of\ 31418. The Tsx sequence shows an even distribution of charged residues\ and lacks extensive hydrophobic stretches [MEDLINE:91092502]. Tsx shows no significant similarities to the channel-forming proteins OmpC, OmpF, PhoE and LamB from the E.coli outer membrane.\ \ nucleoside transporter activity ; GO:0005337 membrane ; GO:0016020 \N 21621 IPR003054

Intermediate filaments (IF) [MEDLINE:96367075], [MEDLINE:89024584], [MEDLINE:90226678] are proteins which are primordial components of the cytoskeleton and the nuclear envelope. They generally form filamentous structures 8 to 14 nm wide.

Type II keratins are the basic or neutral courterparts to the acidic type I\ keratins. Each type II keratin forms a heterodimer with a specific acidic\ keratin, and the heterodimers are organised into tetramers and then into\ chains [MEDLINE:90226678]. Type II keratins consist of head-, rod- and tail-like\ structures, the rod being constructed from three linked coils: 1A, 1B and 2.\ The head and tail structures of the type 2 keratins are highly variable\ low-complexity regions.

\ \ \N \N \N 21620 IPR003053

\ Corticotropin-releasing factor (CRF) is the principal neuroregulator of the\ hypothalamic-pituitary-adrenocortical axis, playing an important role in\ coordinating the endocrine, autonomic and behavioral responses to stress\ and immune challenge [MEDLINE:94022296]. The CRF receptor has been found in human cortex tissue, pituitary, brainstem and testis [MEDLINE:94063063]. The protein comprises 415 amino acid residues with the characterstic 7TM architecture of the\ secretin-like GPCR superfamily. Three isoforms (designated CRF-R1, CRF-R2\ and CRF-R3) are produced as a result of alternative splicing of the same\ gene: CRF-R1 appears to be the predominant form; CRF-R3 does not bind to\ CRF with a high affinity [MEDLINE:94022296].\

For the CRF-R2 receptor, at least 2 splice forms with different 5'-coding sequences (CRF2 and CRF2 ) have been identified in rat\ \ \ \ [MEDLINE:96107120]. The sequence of the CRF-R is highly conserved between species, the majority of the sequence divergence occuring in the putative signal peptide and extracellular N-terminal domain. The relative abundance of CRF-R2 messenger RNA appears to be lower in humans than in rats for the heart and skeletal tissues studied to date [MEDLINE:96107120]. CRF-R2 stimulates cAMP production in response to CRF and known CRF-like agonists [MEDLINE:95148632]. CRF and the non-mammalian CRF-related peptides sauvagine and urotensin I stimulate adenylate cyclase\ activity in a dose-dependent manner, with a rank order of potency that\ differs from that of the CRF1 receptor (sauvagine>urotensin>=rat/human \ CRF>ovine CRF). The differences in the pharmacological profiles and \ tissue distributions of CRF-R1 and CRF-R2 suggests important functional\ differences between the two receptors [MEDLINE:95148632].

\ \ G-protein coupled receptor activity ; GO:0004930 membrane ; GO:0016020 \N 21619 IPR003052

The sequence of the CRF-R is highly conserved from avian to mammalian\ species, the majority of the sequence divergence occuring in the putative\ signal peptide and extracellular N-terminal domain [MEDLINE:96107136]. Five additional\ amino acids are inserted in the N-terminus of the avian receptor, and \ despite its overall similarity to the type 1 mammalian CRF-R, its ligand \ binding properties are similar to those of the type 2 receptor (i.e., it \ has a higher affinity for urotensin I than for CRF) [MEDLINE:96107136].

\ \ G-protein coupled receptor activity ; GO:0004930 membrane ; GO:0016020 \N 21617 IPR003050

P2X purinoceptors are cell membrane ion channels, gated by adenosine 5'-triphosphate (ATP) and other nucleotides; they have been found to be widely expressed on mammalian cells, and, by means of their functional properties, can be differentiated into three sub-groups. The first group is almost equally well activated by ATP and its analogue alphabetamethyleneATP, whereas, the second group is not activated by the latter compound. A third type of receptor (also called P2Z) is distinguished by the fact that repeated or prolonged agonist application leads to the opening of much larger pores, allowing large molecules to traverse the cell membrane. This increased permeability rapidly leads to cell death, and lysis.

Molecular cloning studies have identified seven P2X receptor subtypes, designated P2X1-P2X7. These receptors are proteins that share 35-48% amino acid identity, and possess two putative transmembrane (TM) domains, separated by a long (~270 residues) intervening sequence, which is thought to form an extracellular loop. Around 1/4 of the residues within the loop are invariant between the cloned subtypes, including 10 characteristic cysteines.

\ \

Studies of the functional properties of heterologously expressed P2X receptors, together with the examination of their distribution in native tissues, suggests they likely occur as both homo- and heteromultimers in vivo [MEDLINE:99342764], [MEDLINE:22232053].

\ \

When the P2X7 receptor is expressed, it is found to have different functional properties from those of P2X1-P2X6. Key properties of the current\ produced are little rectification or desensitisation, and strong\ potentiation of responses when the concentration of extracellular Ca2+\ and/or Mg2+ are reduced. It is also found to be relatively insensitive to\ ATP. In certain studies, prolonged activation of expressed P2X7 receptors\ causes cell permeabilisation, and lysis, suggesting that the P2X7 receptor\ may correspond to the native P2Z receptor, which responds similarly.

\ \ ATP binding activity ; GO:0005524 membrane ; GO:0016020 ion transport ; GO:0006811 21618 IPR003051

Corticotropin-releasing factor (CRF) is the principal neuroregulator of the\ hypothalamic-pituitary-adrenocortical axis, playing an important role in\ coordinating the endocrine, autonomic and behavioral responses to stress\ and immune challenge [MEDLINE:94022296]. The CRF receptor has been found in human cortex tissue, pituitary, brainstem and testis [MEDLINE:94063063]. The protein comprises 415 amino acid residues with the characterstic 7TM architecture of the\ secretin-like GPCR superfamily. Three isoforms (designated CRF-R1, CRF-R2\ and CRF-R3) are produced as a result of alternative splicing of the same\ gene: CRF-R1 appears to be the predominant form; CRF-R3 does not bind to\ CRF with a high affinity [MEDLINE:94022296].

\ \ G-protein coupled receptor activity ; GO:0004930 membrane ; GO:0016020 \N 21616 IPR003049

\ \

The P2X6 receptor (along with P2X2, P2X4 and P2X5) falls into a group of\ receptors that are sensitive to ATP, but not alphabetamethyleneATP. There\ is some evidence that P2X6 may heteropolymerise with P2X4, since they are\ often found together in native tissues, and can be co-immunoprecipitated.

\ \ ATP binding activity ; GO:0005524 membrane ; GO:0016020 ion transport ; GO:0006811 21614 IPR003047

\ \

The P2X4 receptor (along with P2X2, P2X5 and P2X6) falls into a group of receptors that are sensitive to ATP, but not alphabetamethyleneATP. There is some evidence that P2X4 may heteropolymerise with P2X6, since they are often found together in native tissues, and can be co-immunoprecipitated. Splice variants of the P2X4 receptor have been detected [MEDLINE:99342764].

\ \ ATP binding activity ; GO:0005524 membrane ; GO:0016020 ion transport ; GO:0006811 21613 IPR003046

\ \

When expressed, P2X3 receptors (like P2X1 receptors) are found to be equally well activated by alphabetamethyleneATP and ATP. P2X3 receptors desensitise rapidly, with the decay being best-fit by two exponentials, with time constants of ~50 and 300 ms [MEDLINE:99342764].

\ \ ATP binding activity ; GO:0005524 membrane ; GO:0016020 ion transport ; GO:0006811 21611 IPR003044

\ \

Expression of P2X1 receptors produces receptors that are equally well activated by alphabetamethyleneATP and ATP. The properties of the currents so generated are quite comparable to those determined for native P2X receptors, such as those found to be present in smooth muscle [MEDLINE:99342764].

\ \ ATP binding activity ; GO:0005524 membrane ; GO:0016020 ion transport ; GO:0006811 21615 IPR003048

\ \

The P2X5 receptor (along with P2X2, P2X4 and P2X6) falls into a group of\ receptors that are sensitive to ATP, but not alphabetamethyleneATP. Splice\ variants of P2X5 have been detected [MEDLINE:99342764].

\ \ ATP binding activity ; GO:0005524 membrane ; GO:0016020 ion transport ; GO:0006811 21612 IPR003045

\ \

P2X2 receptors (which have been found to be alternatively spliced), are\ half-maximally activated by a concentration of ATP of ~10 micromolar. \ In contrast, alphabetamethyleneATP is found to be largely ineffective. This\ agonist profile has been found to be shared by the P2X4, P2X5 and P2X6\ receptors. The single-channel properties of the P2X2 receptor are quite\ similar to those noted for the native receptor present on PC12 cells [MEDLINE:99342764].

\ \ ATP binding activity ; GO:0005524 membrane ; GO:0016020 ion transport ; GO:0006811 21609 IPR003042 Bacterial aromatic-ring hydroxylases (flavoprotein monooxygenases) incorporate one hydroxyl group into substrates. In this reaction, two atoms of dioxygen are reduced to one hydroxyl group and one H₂O molecule by the concomitant oxidation of NAD(P)H. Flavoprotein hydroxylases that catalyze the monohydroxylation of the aromatic ring carry out two reactions on a single polypeptide chain; the oxidation of NAD(P)H to generate two reducing equivalents, and the hydroxylation of substrates [MEDLINE:93073723].\ oxidoreductase activity ; GO:0016491 \N metabolism ; GO:0008152 21610 IPR003043

S-adenosyl-L-methionine-dependent uroporphyrinogen III C-methyltransferase (SUMT)(EC: 2.1.1.107) is likely to be involved in the biosynthesis of siroheme and cobalamin.[MEDLINE:91310569]. Siroheme, the prosthetic group for both nitrite and sulfite reductases, is a methylated, iron-containing modified tetrapyrrole. This enzyme is found in a wide taxonomic range: archaebacteria, eukaryotes and bacteria.

S-adenosyl-L-methionine-dependent uroporphyrinogen III methyltransferase from Arabidopsis thaliana may catalyze transmethylation in a multistep process\ involving the formation of a covalently linked complex with S-adenosyl-L-methionine. The product has a sequence at the amino terminus that resembles a transit peptide for localization to mitochondria or plastids [MEDLINE:97160579].

\ \ methyltransferase activity ; GO:0008168 \N porphyrin biosynthesis ; GO:0006779 21607 IPR003036 P30 is essential for viral assembly [MEDLINE:86045840].Cleavage of P70 in vitro can be accompanied by a shift from a concentrically coiled internal strand ("immature") to a collapsed ("mature") form of the virus core [MEDLINE:78012237].\ \ \N \N viral assembly ; GO:0019068 21608 IPR003038 Members of this family are thought to be integral membraneproteins. Some members of this family have been shown to\ cause apoptosis if mutated [MEDLINE:94019310], these proteins are known as\ DAD for defender against death. The family also includes\ the epsilon subunit of the oligosaccharyltransferase that\ is involved in N-linked glycosylation [MEDLINE:96017708].\ \ \N \N \N 21605 IPR003034 The SAP (after SAF-A/B, Acinus and PIAS) motif is a putativeDNA binding domain found in diverse nuclear proteins involved in chromosomal organization [MEDLINE:20175786].\ \ DNA binding activity ; GO:0003677 nucleus ; GO:0005634 \N 21606 IPR003035 This domain is named RWP-RK after a conserved motif at the C terminus of the domain. The domain is found in algal minus dominance proteins as well as plant proteins involved in nitrogen-controlled development [MEDLINE:20110932].\ \ \N \N \N 21602 IPR003031 The vertebrate lens is a transparent tissue containing high levels ofsoluble protein, packed with short-range order in precisely aligned,\ elongated cells [MEDLINE:95360718]. In birds, the main lens proteins are the

- and delta-crystallins. Mammalian lenses have a lower water\ content than their avian counterparts, and contain gamma- instead\ of delta-crystallins. Delta-crystallin evolved in a common ancestor of reptiles and birds, by the overexpression of arginosuccinate lyase in the lens. At this time, a gene duplication took place, since when the lens gene has accumulated\ mutations in the coding sequence, rendering it enzymatically inactive.\ The proteins belong to a superfamily of distantly-related metabolic\ enzymes, all of which are active as homotetramers: they include fumarase,\ aspartase, adenylosuccinase and 3-carboxy-cis,cis-muconate lactonising\ enzyme. \

The structure of delta-crystallin comprises mainly -helical domains [MEDLINE:95360718]. One domain is a bundle of 5 long helices, which forms a 20-helix\ bundle at the core of the tetramer. The structure reveals a putative\ active-site cleft, located on the boundary between 3 subunits of the\ tetramer.

\ \ \N \N \N 21601 IPR003029

\ \ \

The S1 domain was originally identified in ribosomal protein S1 but is found in a large number of RNA-associated proteins. The structure of the S1 RNA-binding domain from the E.coli polynucleotide phosphorylase has been determined using NMR methods and consists of a five-stranded antiparallel barrel. Conserved residues on one face of the barrel and adjacent loops form the putative RNA-binding site [MEDLINE:97160844].

The structure of the S1 domain is very similar to that of cold shock proteins. This suggests that they may both be derived from an ancient nucleic acid-binding protein [MEDLINE:97160844].

\ \ RNA binding activity ; GO:0003723 \N \N 21603 IPR003032 This domain is called RyR for Ryanodine receptor [MEDLINE:20130691]. The domain is found in four copies in the ryanodine receptor. The function of this domain is unknown.\ \N \N \N 21604 IPR003033 This domain is involved in binding sterols. The human sterol carrier protein 2 (SCP2) is a basic protein that is believed to participate in the intracellular transport of cholesterol and various other lipids [MEDLINE:94063072]. The unc-24 protein of Caenorhabditis elegans contains a domain similar to part of two ion channel regulators (the erythrocyte integral membrane protein stomatin and the C. elegans neuronal protein MEC-2) juxtaposed to a domain similar to nonspecific lipid transfer protein (nsLTP; also called sterol carrier protein 2) [MEDLINE:96301894].\ sterol carrier activity ; GO:0005498 \N \N 21598 IPR003026 Otx proteins constitute a class of vertebrate homeodomain-containingtranscription factors that have been shown to be essential for anterior\ head formation, including brain morphogenesis. They are orthologous to the\ product of the Drosophila head gap gene, orthodenticle (Otd), and appear to\ play similar roles in both, since the developmental abnormalities caused by\ disruption of these transcription factors in one, can be recovered by\ substitution of the factor(s) from the other. Such studies have provided\ strong evidence that there exists a conserved genetic programme for insect\ and mammalian brain development, which presumably arose in a more primitive\ common ancestor [MEDLINE:99213728], [MEDLINE:99369633].\

Two vertebrate orthodenticle-related transcription factors have been\ indentified, Otx1 and Otx2, which have sizes of 355 and 289 residues\ respectively. They contain a bicoid-like homeodomain, which features a\ conserved lysine residue at position 9 of the DNA recognition helix, which\ is thought to confer high-affinity binding to TAATCC/T elements on DNA [MEDLINE:99297465].\ Otd-like transcription factors have also been found in zebrafish and \ certain lamprey species. Studies of mice lacking Otx1 (due to targeted gene disruption) have shed light on its role in development, such mice showing impaired corticogenesis and sense organ development. Phenotypic abnormalities noted in the cerebral cortices include reduced cell proliferation and total cell number, together with disruption of the formation of the normally well-ordered cortical cell layers, which are characteristic of these structures. Abnormalities are also observed in the eye and inner ear.

\ \ transcription factor activity ; GO:0003700 nucleus ; GO:0005634 development ; GO:0007275 21599 IPR003027 REC1 of Ustilago maydis plays a key role in regulating the genetic systemof the fungus. REC1 mutants are very sensitive to UV light - mutation\ leads to a complex phenotype with alterations in DNA repair, recombination,\ mutagenesis, meiosis and cell division. The predicted product of the\ REC1 gene is a polypeptide of 522 amino acid residues with molecular mass \ 57 kD. The protein shows 3'-->5' exonuclease activity, but only in cells\ over-expressing REC1. While it is distinguishable from the major\ bacterial nucleases, the protein has certain enzymatic features in common\ with epsilon, the proof-reading exonuclease subunit of E.coli DNA polymerase\ III holoenzyme [MEDLINE:94103303].\ \ \ 3'-5' exodeoxyribonuclease activity ; GO:0008296\ damaged DNA binding activity ; GO:0003684 nucleus ; GO:0005634 DNA repair ; GO:0006281 21600 IPR003028

Neurotransmitter transport systems are integral to the release, re-uptake and recycling of neurotransmitters at synapses. High affinity tranport proteins found in the plasma membrane of presynaptic nerve terminals and glial cells are responsible for the removal from the extracellular space of released-transmitters, thereby terminating their actions PUB00001020. Plasma membrane neurotransmitter transporters fall into two structurally and mechanistically distinct families. The majority of the transporters constitute an extensive family of homologous proteins that derive energy from the co-transport of Na⁺ and Cl^-, in order to transport neurotransmitter molecules into the cell against their concentration gradient. The family has a common structure of 12 presumed transmembrane helices and includes carriers for gamma-aminobutyric acid (GABA), noradrenaline/adrenaline, dopamine, serotonin, proline, glycine, choline, betaine and taurine. They are structurally distinct from the second more-restricted family of plasma membrane transporters, which are responsible for excitatory amino acid tranport. The latter couple glutamate and aspartate uptake to the cotransport of Na⁺ and the counter-transport of K⁺, with no apparent dependence on Cl^- PUB00001020. In addition, both of these transporter families are distinct from the vesicular neurotransmitter transporters [MEDLINE:93379443], [MEDLINE:95123328].

Sequence analysis of the Na⁺/Cl^- neurotransmitter superfamily reveals that it can be divided into four subfamilies, these being transporters for monoamines, the amino acids proline and glycine, GABA, and a group of orphan transporters [MEDLINE:98452500].

Glycine is known to serve two contrasting roles as a neurotransmitter in\ the central nervous system. Firstly, it serves as an inhibitory\ neurotransmitter in the spinal cord, brainstem and retina, where it activates a\ ligand-gated Cl^- channel. Secondly, it is an obligatory co-agonist for\ activation of the N-methyl-D-aspartate (NMDA) receptor - unless glycine\ is also bound to the NMDA receptor, glutamate cannot activate this ion\ channel. Not surprisingly, then, plasma membranes possess glycine\ transporters in order to regulate its concentration. Two independent genes\ have been identified that encode Na⁺ and Cl^- -coupled glycine transporters.\ Their products, referred to as GLYT-1 and GLYT-2, have differing\ distribution patterns within the central nervous system, suggesting they\ may subserve unique functions [MEDLINE:96407095]. Indeed the distribution of the GLYT-1\ transporter suggests it may play a role in regulating glycine\ concentrations in brain regions containing glycine-dependent NMDA receptors\ [MEDLINE:94043045]. Three different mRNA isoforms for GLYT-1 have been detected. These\ arise as a result of differential splicing, or the usage of multiple\ promoter sites. They encode transporters of 633, 638 and 692 amino acid\ residues, all three having 50-60% similarity to other transporters in the\ Na⁺ and Cl^- -coupled neurotransmitter transporter superfamily.

\ \ sodium:amino acid transporter activity ; GO:0005283 membrane ; GO:0016020 neurotransmitter transport ; GO:0006836 21596 IPR003024

Na⁺/HCO₃^- co-transport proteins are involved in cellular HCO₃^- absorptionand secretion, and also with intracellular pH regulation. They mediate the\ coupled movement of Na⁺ and HCO₃^- across plasma membranes in most of the\ cell types so far investigated. A single HCO₃^- is transported together with\ one to three Na⁺; this transport mode is therefore often electrogenic. In\ the kidney, an electrogenic Na⁺/HCO₃^- co-transporter is the principal\ HCO₃^-\ transporter of the renal proximal tubule, and is responsible for\ reabsorption of more than 85% of the filtered load of HCO₃^- [MEDLINE:97405315]. Until\ recently, the molecular nature of these Na⁺/HCO₃^- co-transporters had\ remained undiscovered, as initial attempts to clone them based on presumed\ homology to Cl^-/HCO₃^- (anion) exchangers had proved unsuccessful. Instead,\ an expression cloning strategy was successfully utilised to identify the\ Na⁺/HCO₃^- co-transporter from salamander kidney, an organ previously found\ to possess electrogenic Na⁺/HCO₃^- co-transport activity [MEDLINE:97305959]. The cloned\ cotransporter consists of 1035 amino acids, and shows ~25-30% sequence\ identity to anion exchanger proteins, which is distributed along the entire\ sequence length. They also share very similar hydropathy plots, suggesting\ they have ~10 transmembrane (TM) domains.

At least 3 mammalian Na⁺/HCO₃^- co-transporters have since been cloned, with\ similar primary sequence lengths and putative membrance topologies. One of\ these has been found to be a kidney-specific isoform [MEDLINE:97382229], which is\ near-identical (except for a varying N-terminal region) to a more\ widely-distributed co-transporter cloned from pancreatic tissue [MEDLINE:98316338].

\ \ \ inorganic anion exchanger activity ; GO:0005452 membrane ; GO:0016020 anion transport ; GO:0006820 21597 IPR003025 Otx proteins constitute a class of vertebrate homeodomain-containingtranscription factors that have been shown to be essential for anterior\ head formation, including brain morphogenesis. They are orthologous to the\ product of the Drosophila head gap gene, orthodenticle (Otd), and appear to\ play similar roles in both, since the developmental abnormalities caused by\ disruption of these transcription factors in one, can be recovered by\ substitution of the factor(s) from the other. Such studies have provided\ strong evidence that there exists a conserved genetic programme for insect\ and mammalian brain development, which presumably arose in a more primitive\ common ancestor [MEDLINE:99213728], [MEDLINE:99369633].\

\ \ transcription factor activity ; GO:0003700 nucleus ; GO:0005634 development ; GO:0007275 21595 IPR003023 Amphiphysins are proteins that are thought to be involved in clathrin-mediated endocytosis, actin function, and signalling pathways. They arehighly concentrated in nerve terminals, where they may act as linkers\ between the clathrin coat and dynamin in the endocytosis of synaptic\ vesicles. Such recycling of synaptic vesicles is necessary for\ neurotransmission to continue, following neurotransmitter release.\ Amphiphysin family members share a similar three-domain organisation: the\ N-terminal domain contains six heptad repeats, which are predicted to form\ a coiled-coiled structure, thought to be involved in the dimerisation of\ amphiphysin molecules; the central region binds the heavy chain of clathrin\ and the clathrin adaptor protein AP-2, through distinct sites; and the\ C-terminal domain contains a Src-homology-3 (SH3) domain that binds the \ GTPase dynamin and the inositol-5'-phosphatase synaptojanin-1. The \ interactions mediated by both the central and C-terminal domains are\ believed to be modulated by proten phosphorylation [MEDLINE:98385555], [MEDLINE:20030572].\

Amphiphysin 2 was the second amphiphysin family member found in mammals.\ The gene encoding it has been found to be alternatively spliced. The\ various products have been named: BIN-1, Sh3P9, BRAMP-2 and ALP-1. They\ have different distribution patterns, with the largest form (~95 kD) being\ expressed solely in the brain, where it shares a very similar (if not\ identical) distribution pattern to amphiphysin 1 [MEDLINE:98385555].

\ \ \N \N synaptic vesicle endocytosis ; GO:0008099 21594 IPR003022 Otx proteins constitute a class of vertebrate homeodomain-containingtranscription factors that have been shown to be essential for anterior\ head formation, including brain morphogenesis. They are orthologous to the\ product of the Drosophila head gap gene, orthodenticle (Otd), and appear to\ play similar roles in both, since the developmental abnormalities caused by\ disruption of these transcription factors in one, can be recovered by\ substitution of the factor(s) from the other. Such studies have provided\ strong evidence that there exists a conserved genetic programme for insect\ and mammalian brain development, which presumably arose in a more primitive\ common ancestor [MEDLINE:99213728], [MEDLINE:99369633].\

Mice completely lacking Otx2 (due to targeted gene disruption) die during\ early embryogenesis. Analysis reveals that they lack the neuroectoderm\ that is destined to become the forebrain, midbrain and rostral hindbrain.\ They also show major abnomalities in their body plan. Mice that have\ artificially-reduced levels of Otx2 develop head abnormalities reminiscent\ of otocephaly [MEDLINE:96067157].

\ \ transcription factor activity ; GO:0003700 nucleus ; GO:0005634 development ; GO:0007275 21593 IPR003021 REC1 of Ustilago maydis plays a key role in regulating the genetic systemof the fungus. REC1 mutants are very sensitive to UV light. Mutation\ leads to a complex phenotype with alterations in DNA repair, recombination,\ mutagenesis, meiosis and cell division [MEDLINE:94103303]. The predicted product of the\ REC1 gene is a polypeptide of 522 amino acid residues with molecular mass \ 57 kD. The protein shows 3'-->5' exonuclease activity, but only in cells\ over-expressing REC1 [MEDLINE:94103303]. While it is distinguishable from the major\ bacterial nucleases, the protein has certain enzymatic features in common\ with epsilon, the proof-reading exonuclease subunit of E.coli DNA polymerase\ III holoenzyme [MEDLINE:94103303].\ The rad1 gene of Schizosaccharomyces pombe comprises three exons and encodes\ a 37 kD protein that exhibits partial similarity to the REC1 gene of \ Ustilago maydis\ \ \ \ [MEDLINE:95011649]. The two genes share putative functional similarities\ in their respective organisms.\ \ exonuclease activity ; GO:0004527 nucleus ; GO:0005634 DNA repair ; GO:0006281 21592 IPR003020

Bicarbonate (HCO₃^-) transport mechanisms are the principal regulators of pHin animal cells. Such transport also plays a vital role in acid-base\ movements in the stomach, pancreas, intestine, kidney, reproductive organs\ and the central nervous system. Functional studies have suggested four\ different HCO₃^- transport modes. Anion exchanger proteins exchange\ HCO₃^- for Cl^- in a reversible, electroneutral manner [MEDLINE:91147304].\ Na⁺/HCO₃^- co-transport\ proteins mediate the coupled movement of Na⁺ and HCO₃^- across plasma\ membranes, often in an electrogenic manner [MEDLINE:97405315]. Na^-\ driven Cl^-/HCO₃^- exchange\ and K⁺/HCO₃^- exchange activities have also been detected in\ certain cell types, although the molecular identities of the proteins\ responsible remain to be determined.

Sequence analysis of the two families of HCO₃^- transporters that have been\ cloned to date (the anion exchangers and Na⁺/HCO₃^- co-transporters) reveals\ that they are homologous. This is not entirely unexpected, given that they\ both transport HCO₃^- and are inhibited by a class of pharmacological agents\ called disulphonic stilbenes [MEDLINE:97382229]. They share around ~25-30% sequence\ identity, which is distributed along their entire sequence length, and have\ similar predicted membrane topologies, suggesting they have ~10\ transmembrane (TM) domains.

\ \ inorganic anion exchanger activity ; GO:0005452 membrane ; GO:0016020 anion transport ; GO:0006820 21589 IPR003017 Amphiphysins are proteins that are thought to be involved in clathrin-mediated endocytosis, actin function, and signalling pathways. They arehighly concentrated in nerve terminals, where they may act as linkers\ between the clathrin coat and dynamin in the endocytosis of synaptic\ vesicles. Such recycling of synaptic vesicles is necessary for\ neurotransmission to continue, following neurotransmitter release.\ Amphiphysin family members share a similar three-domain organisation: the\ N-terminal domain contains six heptad repeats, which are predicted to form\ a coiled-coiled structure, thought to be involved in the dimerisation of\ amphiphysin molecules; the central region binds the heavy chain of clathrin\ and the clathrin adaptor protein AP-2, through distinct sites; and the\ C-terminal domain contains a Src-homology-3 (SH3) domain that binds the \ GTPase dynamin and the inositol-5'-phosphatase synaptojanin-1. The \ interactions mediated by both the central and C-terminal domains are\ believed to be modulated by protein phosphorylation [MEDLINE:98385555], [MEDLINE:20030572].\

Amphiphysin 1 was first identified in 1992 as a brain protein that was\ partially-associated with synaptic vesicles. Following its cloning, it was\ also realised to be a human auto-antigen that is detected in a rare\ neurological disease, Stiff-Man Syndrome, and also in certain types of\ cancer [MEDLINE:99148289].

\ \ \N \N synaptic transmission ; GO:0007268 21588 IPR003016

The 2-oxo acid dehydrogenase multienzyme complexes [MEDLINE:89193463] from bacterial andeukaryotic sources catalyze the oxidative decarboxylation of 2-oxo acids to\ the corresponding acyl-CoA. The three members of this family of multienzyme\ complexes are:

Pyruvate dehydrogenase complex (PDC).
2-oxoglutarate dehydrogenase complex (OGDC).
Branched-chain 2-oxo acid dehydrogenase complex (BCOADC).

These three complexes share a common architecture: they are composed of\ multiple copies of three component enzymes - E1, E2 and E3. E1 is a thiamine\ pyrophosphate-dependent 2-oxo acid dehydrogenase, E2 a dihydrolipamide\ acyltransferase, and E3 an FAD-containing dihydrolipamide dehydrogenase.

\ \

E2 acyltransferases have an essential cofactor, lipoic acid, which is\ covalently bound via a amide linkage to a lysine group. The E2 components of\ OGCD and BCOACD bind a single lipoyl group, while those of PDC bind either one\ (in yeast and in Bacillus), two (in mammals), or three (in Azotobacter and in\ Escherichia coli) lipoyl groups [MEDLINE:91152093].

\ \

In addition to the E2 components of the three enzymatic complexes described\ above, a lipoic acid cofactor is also found in the following proteins:

H-protein of the glycine cleavage system (GCS) [MEDLINE:86250806]. GCS is a multienzyme\ complex of four protein components, which catalyzes the degradation of\ glycine. H protein shuttles the methylamine group of glycine from the P\ protein to the T protein. H-protein from either prokaryotes or eukaryotes\ binds a single lipoic group.
Mammalian and yeast pyruvate dehydrogenase complexes differ from that of\ other sources, in that they contain, in small amounts, a protein of unknown\ function - designated protein X or component X. Its sequence is closely\ related to that of E2 subunits and seems to bind a lipoic group [MEDLINE:90046867].
Fast migrating protein (FMP) (gene acoC) from Alcaligenes eutrophus\ \ \ \ [MEDLINE:91286190].\ This protein is most probably a dihydrolipamide acyltransferase involved in\ acetoin metabolism.

\ \ \N \N \N 21591 IPR003019

This original classification system has been found to be limited, in the sense that it does not allow clear differentiation of patterns of structural similarities, either between or within classes. Consequently, all class I and class II MTs (the proteinaceous sequences) have now been grouped into families of phylogenetically-related and thus alignable sequences. This system subdivides the MT superfamily into families, subfamilies, subgroups, and isolated isoforms and alleles.

The metallothionein superfamily comprises all polypeptides that resemble equine renal metallothionein in several respects [MEDLINE:88029881]: e.g., low molecular weight; high metal content; amino acid composition with high Cys and low aromatic residue content; unique sequence with characteristic distribution of cysteines, and spectroscopic manifestations indicative of metal thiolate clusters. A MT family subsumes MTs that share particular sequence-specific features and are thought to be evolutionarily related. The inclusion of a MT within a family presupposes that its amino acid sequence is alignable with that of all members. Fifteen MT families [http://www.unizh.ch/~mtpage/MT.html] have been characterised, each family being identified by its number and its taxonomic range: e.g., Family 1: vertebrate MTs.

\ \

This entry is a superfamily of metallothioneins, containing 3 families.

\ \ heavy metal binding activity ; GO:0005505 \N \N 21590 IPR003018 This domain is present in phytochromes and cGMP-specific phosphodiesterases. cGMP-dependent 3',5'-cyclic phosphodiesterase (EC: 3.1.4.17) catalyses the conversion of guanosine 3',5'-cyclic phosphate to guanosine 5'-phosphate.A phytochrome is a regulatory photoreceptor which exists in 2 forms that are reversibly interconvertible by light, the PR form that absorbs maximally in the red region of the spectrum, and the PFR form that absorbs maximally in the far-red region. This domain is also found in NifA, a transcriptional activator which is required for activation of most Nif operons which are directly involved in nitrogen fixation. \ NifA interacts with sigma-54.\ \ \N \N \N 21582 IPR003009 This signature is found in a variety of proteins which bind FMN and related compounds. Most of these proteins are enzymes that use the FMN as a cofactor.\ \N \N \N 21583 IPR003010

This family contains nitrilases that break carbon-nitrogen bonds and appear to be involved in the reduction of organic nitrogen compounds and ammonia production [MEDLINE:95078742]. They all have distinct substrate specificity and include cyanide hydratases, aliphatic amidases, -alanine synthase, and a few other proteins with unknown molecular function. Sequence conservation over the entire length, as well as the similarity in the reactions catalyzed by the known enzymes in this family, points to a common catalytic mechanism. They have an invariant cysteine that is part of the catalytic site in nitrilases. Another highly conserved motif includes an invariant glutamic acid that might also be involved in catalysis [MEDLINE:95078742].

\ hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds ; GO:0016810 \N nitrogen metabolism ; GO:0006807 21584 IPR003011 The rad1 gene of Schizosaccharomyces pombe comprises three exons and encodes a 37 kDa protein that exhibits partial similarity to the REC1 gene of \ Ustilago maydis . The two genes share putative functional similarities\ in their respective organisms.\ \ exonuclease activity ; GO:0004527 \N DNA repair ; GO:0006281 21585 IPR003012

\ \ \N \N \N 21586 IPR003013 Erythropoietin, a plasma glycoprotein, is the primary physiological mediator of erythropoiesis [MEDLINE:87039105]. It is involved in the regulation of the level of peripheral \ erythrocytes by stimulating the differentiation of erythroid progenitor cells, found in \ the spleen and bone marrow, into mature erythrocytes [MEDLINE:88153657]. It is primarily \ produced in adult kidneys and foetal liver, acting by attachment to specific binding \ sites on erythroid progenitor cells, stimulating their differentiation [MEDLINE:87055236]. Severe kidney dysfunction causes reduction in the plasma levels of erythropoietin,\ resulting in chronic anaemia - injection of purified erythropoietin into the blood stream \ can help to relieve this type of anaemia. Levels of erythropoietin in plasma fluctuate \ with varying oxygen tension of the blood, but androgens and prostaglandins also modulate \ the levels to some extent [MEDLINE:87055236]. \

Erythropoietin glycoprotein sequences are well \ conserved, a consequence of which is that the hormones are cross-reactive among mammals,\ i.e. that from one species, say human, can stimulate erythropoiesis in\ other species, say mouse or rat [MEDLINE:93042015]. This signature is specific for erythropoietin .

\ \ erythropoietin receptor ligand activity ; GO:0005128 extracellular ; GO:0005576 \N 21587 IPR003014

It has been shown that, the N-terminal N domains of members of the plasminogen/hepatocyte growth factor family, the apple domains of the plasma prekallikrein/coagulation factor XI family, and domains of various nematode proteins belong to the same module superfamily, the PAN module [MEDLINE:20029744]. PAN contains a conserved core of three disulphidebridges. In some members of the family there is an additional\ fourth disulphide bridge that links the N and C termini of the\ domain. The domain is found in diverse proteins, in some the domain\ mediates protein-protein interactions, in others it mediates\ protein-carbohydrate interactions.

\ \ \N \N \N 21579 IPR003007 Secreted forms of the

subunit of recombinant Mus musculus (mouse) meprin A include an NH2-terminal prosequence, a catalytic domain, and three COOH-terminal\ domains designated as MAM (meprin, A-5 protein, receptor protein-tyrosine\ phosphatase mu), MATH (meprin and TRAF homology), and AM (after MATH). The MAM domain may be necessary for correct folding and transport through the secretory pathway, the MATH domain may be required for folding of an activable zymogen, and the AM domain may be important for activity against proteins and efficient secretion of the protein [MEDLINE:99074311].\ \ astacin activity ; GO:0008533 \N proteolysis and peptidolysis ; GO:0006508 21580 IPR003008 This family includes the tubulin

and gamma chains, aswell as the bacterial FtsZ family of proteins. Members of this family\ are involved in polymer formation. FtsZ is the polymer-forming protein\ of bacterial cell division. It is part of a ring in the middle of the\ dividing cell that is required for constriction of cell membrane and\ cell envelope to yield two daughter cells. FtsZ and tubulin are GTPases.\ FtsZ can polymerise into tubes, sheets, and rings in vitro and is\ ubiquitous in eubacteria and archaea. Tubulin is the major component\ of microtubules.\ \ \N \N \N 21577 IPR003005 Amphiphysins are proteins that are thought to be involved in clathrin-mediated endocytosis, actin function, and signalling pathways. They are highly concentrated in nerve terminals, where they may act as linkersbetween the clathrin coat and dynamin in the endocytosis of synaptic\ vesicles. Such recycling of synaptic vesicles is necessary for\ neurotransmission to continue, following neurotransmitter release.\ Amphiphysin family members share a similar three-domain organisation: the\ N-terminal domain contains six heptad repeats, which are predicted to form\ a coiled-coiled structure, thought to be involved in the dimerisation of\ amphiphysin molecules; the central region binds the heavy chain of clathrin\ and the clathrin adaptor protein AP-2, through distinct sites; and the\ C-terminal domain contains a Src-homology-3 (SH3) domain that binds the \ GTPase dynamin and the inositol-5'-phosphatase synaptojanin-1. The \ interactions mediated by both the central and C-terminal domains are\ believed to be modulated by protein phosphorylation [MEDLINE:98385555], [MEDLINE:20030572].\ \ \N \N synaptic transmission ; GO:0007268 21578 IPR003006

Some of the proteins in this group are responsible for the molecular basis of the blood group antigens, surface markers on the outside of the red blood cell membrane. Most of these markers are proteins, but some are carbohydrates attached to lipids or proteins [Reid M.E., Lomas-Francis C. The Blood Group Antigen FactsBook Academic Press, London / San Diego, (1997)]. Lutheran blood group glycoprotein (B-CAM cell surface glycoprotein) (Auberger B antigen) (F8/G253 antigen) belongs to the Lutheran blood group system and is associated with Lu(a/b), Au(a/b), LU6 to LU20 antigens.

\ \ \N \N \N 21574 IPR003002

A large family of candidate chemosensory receptors have been identified in the genome of C.elegans, and related nematodes. This family isvery, divergent and is greatly expanded in the nematode worm C.elegans.

\ \ \N \N \N 21575 IPR003003

A large family of candidate chemosensory receptors have been identified in the genome of Caenorhabditis elegans, and related nematodes. This family isvery, divergent and is greatly expanded in the nematode worm C.elegans.

\ \ G-protein coupled receptor activity ; GO:0004930 membrane ; GO:0016020 \N 21576 IPR003004

The general (type II) secretion pathway (GSP) within Gram-negative bacteriais a signal sequence-dependent process responsible for protein export [MEDLINE:93174466], [MEDLINE:95099573], [MEDLINE:92276315]. The process has two stages: exoproteins are first translocated across the inner membrane by the general signal-dependent export pathway (GEP), and then across the outer membrane by a species-specific accessory mechanism.

The GSP is a composite of several proteins, one of which is termed general secretion pathway protein F (GSPF), which is thought to be located within the inner membrane [MEDLINE:92269572]. This suggests that protein F is part of the GEP apparatus, which aids translocation of exoproteins from the cytoplasm to the periplasm, prior to transport across the outer membrane. GSPF is a highly hyrdophobic protein containing ~400 amino acids.

\ \ protein transporter activity ; GO:0008565 type II protein secretion system complex ; GO:0015627 type II protein (Sec) secretion system ; GO:0015628 21572 IPR002999 The Drosophila tudor protein is encoded by a 'posterior group' gene,which when mutated disrupt normal abdominal segmentation and pole\ cell formation. Another Drosophila gene, homeless, is required for\ RNA localization during oogenesis. The tudor protein contains\ multiple repeats of a domain which is also found in homeless [MEDLINE:97200561].\ The tudor domain is found in many proteins that colocalize with\ ribonucleoprotein or single-strand DNA-associated complexes in the\ nucleus, in the mitochondrial membrane, or at kinetochores.\ It is not known whether the domain binds directly to RNA and ssDNA, or\ controls interactions with the nucleoprotein complexes. At least one\ tudor-containing protein, homeless, also contains a zinc finger\ typical of RNA-binding proteins.\ [MEDLINE:97200561]\ \ nucleic acid binding activity ; GO:0003676 \N \N 21573 IPR003000 These sequences represent the Sir2 family of NAD+-dependent deacetylases. Silent Information Regulator protein of Saccharomyces cerevisiae (Sir2p) is one of several factors criticalfor silencing at least three loci. Among them, it is unique because\ it silences the rDNA as well as the mating type loci and telomeres. Sir2p\ interacts in a complex with itself and with Sir3p and Sir4p, two proteins that\ are able to interact with nucleosomes. In addition Sir2p also interacts with\ ubiquitination factors and/or complexes [MEDLINE:97357311].\ Unlike Sir3p and Sir4p, for which no homologues are known, Sir2p is part of a\ multigene family in yeast, the homolgues being HST1, HST2, HST3 and HST4. \ \ \ Highly conserved structural homologues also occur in other organisms ranging from bacteria to man and plants. Proteins of this family have been proposed to play a role in\ silencing, chromosome stability and ageing[MEDLINE:96101589]. In addition, an in\ vitro ADP ribosyltransferase activity has been associated with Escherichia coli and\ human members of this family [MEDLINE:99310604].\ Homologues of Sir2 share a core domain including the GAG and NID motifs and a\ putative C4 Zinc finger. The regions containing these three conserved motifs\ are individually essential for Sir2 silencing function, as are the four\ cysteins [MEDLINE:99402809]. In addition, the conserved residues HG next to the putative Zn\ finger have been shown to be essential for the ADP ribosyltransferase activity\ [MEDLINE:99310604]. \ \ \ Sir2-like enzymes catalyze a reaction in which the cleavage of NAD(+)and histone and/or protein\ deacetylation are coupled to the formation of O-acetyl-ADP-ribose, a novel metabolite. The dependence of the reaction on both\ NAD(+) and the generation of this potential second messenger offers new clues to understanding the function and regulation of nuclear,\ cytoplasmic and mitochondrial Sir2-like enzymes [MEDLINE:22406503].\ \ \ \ \ DNA binding activity ; GO:0003677 chromatin silencing complex ; GO:0005677 regulation of transcription, DNA-dependent ; GO:0006355 21568 IPR002993 Ornithine decarboxylase antizyme (ODC-AZ) [MEDLINE:95112349] binds to, and destabilizes,ornithine decarboxylase (ODC), a key enzyme in polyamine synthesis. ODC is\ then rapidly degraded. The expression of ODC-AZ requires programmed, ribosomal\ frameshifting which is modulated according to the cellular concentration of\ polyamines. High levels of polyamines induce a +1 ribosomal frameshift in the\ translation of mRNA for the antizyme leading to the expression of a full-\ length protein.\ At least two forms of ODC-AZ exist in mammals [MEDLINE:99000830] and the protein has been\ found in Drosophila (protein Gutfeeling).\ \ ornithine decarboxylase inhibitor activity ; GO:0008073 \N \N 21569 IPR002994

The surfeit locus 1 gene (SURF1 or surf-1) encodes a conserved protein ofabout 300 amino-acid residues that seems to be involved in the biogenesis of\ cytochrome c oxidase [MEDLINE:99057338]. Vertebrate SURF1 is evolutionary related to yeast\ protein SHY1. There seems to be two transmembrane regions in these proteins,\ one in the N-terminal, the other in the C-terminal.\ Rickettsia prowazekii protein RP733 is also a member of this protein family.

\ \ \N \N \N 21570 IPR002995

The surfeit locus gene SURF4 (or surf-4) encodes a conserved integral eukaryotic membrane protein of about 270 to 300 amino-acid residues that seems to be located in the endoplasmic reticulum [MEDLINE:95316062].

\ \N \N \N 21571 IPR002996 A number of receptors for lymphokines, hematopoeitic growth factors and growthhormone-related molecules have been found [MEDLINE:90056480], [MEDLINE:90384924], [MEDLINE:90342065], [MEDLINE:89376553], [MEDLINE:91069534] to share a common binding\ domain. Receptors known to belong to this family include cytokine receptor common

chain, which is common to the IL-3, IL-5 and GM-CSF receptors;\ cytokine receptor common gamma chain, which is common to the IL-2, IL-4, IL-7 and IL-13 receptors; ciliary neurotrophic factor receptor (CNTFR); erythropoietin receptor (EPOR); granulocyte colony-stimulating factor receptor (G-CSFR); granulocyte-macrophage colony-stimulating factor receptor

chain (GM-CSFR); interleukin-2 receptor

chain (IL2R-

); interleukin-3 receptor

chain (IL3R); interleukin-4 receptor

chain (IL4R); interleukin-5 receptor

chain (IL5R); interleukin-6 receptor (IL6R); interleukin-7 receptor

chain (IL7R); interleukin-9 receptor (IL9R); growth hormone receptor (GRHR); prolactin receptor (PRLR); and thrombopoeitin receptor (TPOR).\ The conserved region constitutes all or part of the extracellular ligand-\ binding region and is about 200 amino acid residues long. In the N-terminal of\ this domain there are two pairs of cysteines known, in the growth hormone\ receptor, to be involved in disulfide bonds.\ \ \N \N \N 21566 IPR002988

The protein G-related albumin-binding (GA)) module iscomposed of three helices [MEDLINE:97240805]. This module is\ found in a range of bacterial cell surface proteins.\ The GA module from the Peptostreptococcus magnus albumin-binding protein (PAB) shows a strong affinity\ for albumin.

\ \ \N \N \N 21567 IPR002989 These repeats are found in many mycobacterial proteins. The repeatsare most common in the PPE family of proteins IPR000030, where they\ are found in the MPTR subfamily. The function of\ these repeats is unknown. The repeat can be approximately described as\ XNXGX, where X can be any amino acid. These repeats are similar to\ A(D/N)LXX repeats IPR000030/>\ \ \ \ [MEDLINE:98318059], however it is not clear if these two families are\ structurally related.\ \ \N \N \N 21565 IPR002987

\ \

NCX1 is the principal Na⁺/Ca²⁺ exchanger of cardiac myocytes, where it is\ thought to play an important role in excitation-contraction coupling. It is\ also found in a variety of other tissues, suggesting it serves as a\ housekeeping protein, maintaining low cytosolic Ca²⁺ concentration. Alternatively\ spliced variants of NCX1 have been identified, expression of which is cell\ type-specific. Sequence analysis reveals two sets of tandem repeats are\ found within the NCX1 protein sequence, which are usually referred to as and . The repeats are thought to be involved in the ion\ binding and translocation reactions of the exchanger, and the first repeat may be part of a regulatory site that responds to Ca²⁺ concentration.

\ \ calcium:sodium antiporter activity ; GO:0005432 membrane ; GO:0016020 calcium ion transport ; GO:0006816 21563 IPR002985 Pyridoxal-dependent decarboxylases that act on ornithine-, lysine-, arginine- and related substrates can be classified into different families\ on the basis of sequence similarity [MEDLINE:89056708], [MEDLINE:94237165]. One of these families includes\ eukaryotic ornithine decarboxylase (ODC), which catalyses the transformation \ of ornithine into putrescine; prokaryotic diaminopimelic acid decarboxylase\ (DAPDC), which catalyses the conversion of diaminopimelic acid into lysine,\ the final step of lysine biosynthesis; Pseudomonas syringae pv. tabaci\ protein, tabA, which is probably involved in tabtoxin biosynthesis and\ is similar to DAPDC; and bacterial and plant biosynthetic arginine\ decarboxylase (ADC), which catalyses the transformation of arginine \ into agmatine, the first step in putrescine synthesis from arginine.\

Although these proteins, which are known collectively as group IV\ decarboxylases [MEDLINE:94237165], probably share a common evolutionary origin, their\ levels of sequence similarity are low, being confined to a few short\ conserved regions.\ The tomato ADC gene contains an open reading frame encoding a polypeptide\ of 502 amino acids and a predicted molecular mass of ~55 kD [MEDLINE:94294562]. The \ predicted amino acid sequence shares 47 and 38% identify with oat and \ E.coli ADCs, respectively. Gel blot hybridisation experiments show that,\ in tomato, ADC is encoded by a single gene and is expressed as a transcript\ of ~2.2 kb in the fruit pericarp and leaf tissues [MEDLINE:94294562].

\ \ arginine decarboxylase activity ; GO:0008792 \N spermidine biosynthesis ; GO:0008295 21564 IPR002986

Pyridoxal-dependent decarboxylases that act on ornithine-, lysine-, arginine- and related substrates can be classified into different families\ on the basis of sequence similarity [MEDLINE:89056708], [MEDLINE:94237165]. One of these families includes\ eukaryotic ornithine decarboxylase (ODC), which catalyses the transformation\ of ornithine into putrescine; prokaryotic diaminopimelic acid decarboxylase\ (DAPDC), which catalyses the conversion of diaminopimelic acid into lysine,\ the final step of lysine biosynthesis; Pseudomonas syringae pv. tabaci\ protein, tabA, which is probably involved in tabtoxin biosynthesis and\ is similar to DAPDC; and bacterial and plant biosynthetic arginine\ decarboxylase (ADC), which catalyses the transformation of arginine \ into agmatine, the first step in putrescine synthesis from arginine.

Although these proteins, which are known collectively as group IV\ decarboxylases [MEDLINE:94237165], probably share a common evolutionary origin, their\ levels of sequence similarity are low, being confined to a few short\ conserved regions. These conserved motifs suggest a common structural\ arrangement for positioning of substrate and the cofactor pyridoxal\ 5'-phosphate among bacterial DAP decarboxylases, eukaryotic ornithine\ decarboxylases and arginine decarboxylases [MEDLINE:94028923].

\ \ diaminopimelate decarboxylase activity ; GO:0008836 \N lysine biosynthesis via diaminopimelate ; GO:0009089 21562 IPR002984

A Na⁺ and Cl^- -coupled creatine transporter has been cloned from human and\ rodent tissues. Initially it was mistaken for a choline transporter [MEDLINE:95204629], [MEDLINE:94128110].\ The creatine transporter species homologues are near identical (98% identity\ human vs. rat and rabbit) and they are most closely related to the\ transporters reported for taurine, GABA and betaine. Northern blot analysis of\ creatine transporter distribution reveals that the highest levels of mRNA\ expression are in: skeletal muscle, kidney and heart, with lower levels in\ brain and other tissues. Within the brain, the highest levels were detected\ in the cerebellum and hippocampus. This expression pattern correlates well\ with those tissues known to possess a high creatine uptake capacity [MEDLINE:95041084].

\ \ creatine:sodium symporter activity ; GO:0005309 membrane ; GO:0016020 neurotransmitter transport ; GO:0006836 21561 IPR002983

Cells regulate their volume and adapt to alterations in the tonicity of\ their local environment by adjusting their solute content accordingly.\ Resultant water movements rapidly establish osmotic balance. Solutes\ utilised in this manner are referred to as osmolytes and include:\ glycerophosphorylcholine, betaine, myo-inositol, sorbitol and taurine [MEDLINE:95162643].\ Cell membrane transporters for betaine and taurine have been cloned, and by\ sequence similarity they have been shown to belong to the Na⁺ and Cl^-\ -coupled neurotransmitter transporter superfamily. Functional studies of\ the cloned betaine transporter (BGT-1) have revealed that it can also\ transport GABA, and that its mode of transport is electrogenic, with uptake\ of betaine depolarising the cell [MEDLINE:99287858]. In humans, the gene maps to chromosome\ 12p13, and is found to be expressed in: the kidney, brain, liver, heart,\ skeletal muscle and placenta.

\ \ GABA:sodium symporter activity ; GO:0005332 membrane ; GO:0016020 neurotransmitter transport ; GO:0006836 21560 IPR002982

GABA is the major inhibitory transmitter in the mammalian brain, and is\ widely distributed throughout the nervous system. Molecular cloning\ studies have resulted in the cloning of three Na⁺ and Cl^- -coupled GABA\ transporters (known as GAT-1, GAT-2, GAT-3) and a betaine/GABA transporter\ (BGT-1). Each transporter shows varying affinities for GABA, different\ substrate and blocker pharmacologies, and different tissue localisation [MEDLINE:96371106].\ Brain regions containing GAT-3 mRNA transcripts include the retina,\ olfactory bulb, subfornical organ, hypothalamus, midline thalamus and\ brainstem. GAT-3 mRNA was found to be absent from the neocortex and\ cerebellar cortex, and very weak in the hippocampus [MEDLINE:96371106]. Furthermore,\ immunocytological studies have demonstrated that this transporter may be\ localised solely to glial (non-neuronal) cells, suggesting that glial GABA\ uptake may function to limit the spread of GABA from the synapse, as well\ as to regulate overall GABA levels.

\ \ GABA:sodium symporter activity ; GO:0005332 membrane ; GO:0016020 neurotransmitter transport ; GO:0006836 21559 IPR002981

GABA is the major inhibitory transmitter in the mammalian brain, and is\ widely distributed throughout the nervous system. Molecular cloning\ studies have resulted in the cloning of three Na⁺ and Cl^- -coupled GABA\ transporters (known as GAT-1, GAT-2, GAT-3) and a betaine/GABA transporter\ (BGT-1). Each transporter shows varying affinities for GABA, different\ substrate and blocker pharmacologies, and different tissue localisation [MEDLINE:96371106].\ GAT-2 protein expression has been studied with immunocytochemistry. High\ levels of expression were detected in: the leptomeninges, choroid plexus,\ and ependyma, with lower levels in the cortical parenchyma. GAT-2-positive\ neuronal elements included perikarya, dendrites and axon terminals.\ Non-neuronal elements expressing GAT-2 included cells forming the pia and\ arachnoid mater, astrocytic processes, ependymal cells and epithelial cells\ of the choroid plexuses. This widespread cellular expression of GAT-2\ suggests that it may have several functional roles in the overall regulation\ of GABA levels in the brain [MEDLINE:99306500].

\ \ GABA:sodium symporter activity ; GO:0005332 membrane ; GO:0016020 neurotransmitter transport ; GO:0006836 21557 IPR002979

Anion exchange proteins are thought to participate in pH and cell volumeregulation. They are glycosylated, plasma-membrane transport proteins that\ exchange hydrogen carbonate (HCO₃^-) for chloride (Cl^-) in a reversible,\ electroneutral manner [MEDLINE:91147304], [MEDLINE:91254050]. To date three anion exchanger isoforms have\ been identified (AE1-3), AE1 being the previously-characterised erythrocyte\ band 3 protein. They share a predicted topology of 12-14 transmembrane (TM)\ domains, but have differing distribution patterns and cellular localisation.\ The best characterised isoform, AE1, is known to be the most abundant\ membrane protein in mature erythrocytes. It has a molecular mass of ~95 kDa\ and consists of two major domains. The N-terminal 390 residues form a \ water-soluble, highly elongated domain that serves as an attachment site for the\ binding of the membrane skeleton and other cytoplasmic proteins. The\ remainder of the protein is a 55-kDa hydrophobic domain that is responsible\ for catalysing anion exchange. The function of the analogous domains of AE2\ and AE3 remains to be determined [MEDLINE:98152067].

\ \

AE3 is an anion exchanger that is primarily expressed in the brain and\ heart. Several tissue-specific variants have been identified, which arise\ due to both alternative promoter and exon usage. Two AE3-encoding cDNAs have\ been isolated from human heart. These clones share long portions of common\ sequence but have different 5' ends, therefore encoding distinct N-terminal\ amino acid sequences. The longer AE3 polypeptide (1232 amino acids) displays\ ~96% amino acid sequence identity to the rat and mouse AE3 'brain isoforms'.\ The shorter polypeptide (1034 amino acids) corresponds to the rat AE3\ 'cardiac isoform'. Studies of Cl^- transport suggest that both isoforms are capable of anion exchange [MEDLINE:92218461], [MEDLINE:95008042].

\ \ inorganic anion exchanger activity ; GO:0005452 membrane ; GO:0016020 anion transport ; GO:0006820 21558 IPR002980

GABA is the major inhibitory transmitter in the mammalian brain, and is\ widely distributed throughout the nervous system. Molecular cloning\ studies have resulted in the cloning of three Na⁺ and Cl^- -coupled GABA\ transporters (known as GAT-1, GAT-2, GAT-3) and a betaine/GABA transporter\ (BGT-1). Each transporter shows varying affinities for GABA, different\ substrate and blocker pharmacologies, and different tissue localisation [MEDLINE:96371106].\ GAT-1 (~599 amino acids) has been found to be widely expressed in the\ rodent brain, mRNA transcripts being observed in: the retina, olfactory\ bulb, neocortex, ventral pallidum, hippocampus and cerebellum. The overall\ distribution parallels that observed for GABA [MEDLINE:96371106]. Further studies have\ suggested that it is found in both neuronal and glial cell types [MEDLINE:96066795].

\ \ GABA:sodium symporter activity ; GO:0005332 membrane ; GO:0016020 neurotransmitter transport ; GO:0006836 21556 IPR002978

\ \

AE2 (~1240 amino acids) is a non-erythroid anion exchanger. It was cloned\ from choroid plexus but has been detected in many organs including the\ gastrointestinal tract and kidney. It is expressed in both epithelial and\ non-epithelial cells, and may be present in the Golgi apparatus in addition\ to the cell membrane [MEDLINE:90319095]. Three AE2 N-terminal variants have been described,\ arising due to the presence of alternative promoter sites within the gene.\ They are referred to as AE2a-c and have differing distribution patterns:\ AE2a is expressed in all tissues; AE2b exhibits a more restricted\ distribution, with highest levels in the stomach; and AE2c is expressed\ only in the stomach [MEDLINE:96205979].

\ \ inorganic anion exchanger activity ; GO:0005452 membrane ; GO:0016020 anion transport ; GO:0006820 21555 IPR002977

\ \

Naturally-occuring mutations have been characterised in the AE1 gene, which\ give rise to forms of several inherited human diseases. Around 20% of\ hereditary spherocytosis cases arise from heterozygosity for AE1 mutations,\ and result in the absence or decrease of the mutant protein in the red cell\ membrane. Similarly, familial distal renal tubular acidosis, a condition\ associated with kidney stones, has been shown to be associated with\ mutations of AE1 of the renal collecting duct -intercalated cell, and\ it has been postulated that such mutations may affect the targeting of the\ AE1 protein, which is usually directed to the basolateral membrane of\ these cells [MEDLINE:99280171].

Some of the proteins in this group are responsible for the molecular basis of the blood group antigens, surface markers on the outside of the red blood cell membrane. Most of these markers are proteins, but some are carbohydrates attached to lipids or proteins [Reid M.E., Lomas-Francis C. The Blood Group Antigen FactsBook Academic Press, London / San Diego, (1997)]. Band 3 anion transport protein (Anion exchange protein 1) belongs to the Diego blood group system and is associated with Di(a/b), Wr(a/b), Wd(a), Rb(a and WARR antigens.

\ \ inorganic anion exchanger activity ; GO:0005452 membrane ; GO:0016020 anion transport ; GO:0006820 21554 IPR002976 Guanine nucleotide binding proteins (G-proteins) are a family of membrane-associated proteins that couple extracellularly-activated integral-membrane\ receptors to intracellular effectors, such as ion channels and enzymes that\ vary the concentration of second messenger molecules [MEDLINE:92366949], [MEDLINE:91354032], [MEDLINE:91227903]. G-proteins are\ composed of 3 subunits (

and gamma) which, in the resting state,\ associate as a trimer at the inner face of the plasma membrane. The

subunit has a molecule of guanosine diphosphate (GDP) bound to it.\ Stimulation of the G-protein by an activated receptor leads to its exchange\ for GTP (guanosine triphosphate). This results in the separation of the

from the

and gamma subunits, which always remain tightly\ associated as a dimer. Both the

and

-gamma subunits are then able\ to interact with effectors, either individually or in a cooperative manner.\ The intrinsic GTPase activity of the

subunit hydrolyses the bound GTP\ to GDP. This returns the

subunit to its inactive conformation and\ allows it to reassociate with the

-gamma subunit, thus restoring the\ system to its resting state.\

G-protein subunits are 350-400 amino acids in length and have\ molecular weights in the range 40-45 kD. \ G-proteins have been isolated from a variety of plant species. These\ may play a role in signal transduction from hormone receptors [MEDLINE:95161691]. Plant subunits are highly conserved between species, but share relatively\ low sequence similarity with mammalian G-proteins. However, the GTP-binding\ and hydrolysis regions are well conserved.

\ \ GTP binding activity ; GO:0005525 \N G-protein coupled receptor protein signaling pathway ; GO:0007186 21553 IPR002975 Guanine nucleotide binding proteins (G-proteins) are a family of membrane-associated proteins that couple extracellularly-activated integral-membrane receptors to intracellular effectors, such as ion channels and enzymes that vary the concentration of second messenger molecules [MEDLINE:92366949], [MEDLINE:91354032], [MEDLINE:91227903]. G-proteins are\ composed of 3 subunits (

and gamma) which, in the resting state,\ associate as a trimer at the inner face of the plasma membrane. The

from the

and gamma subunits, which always remain tightly\ associated as a dimer. Both the

and

-gamma subunits are then able\ to interact with effectors, either individually or in a cooperative manner.\ The intrinsic GTPase activity of the

subunit hydrolyses the bound GTP\ to GDP. This returns the

subunit to its inactive conformation and\ allows it to reassociate with the

-gamma subunit, thus restoring the\ system to its resting state.\

G-protein subunits are 350-400 amino acids in length and have\ molecular weights in the range 40-45 kD. \ A number of fungal subunits have been identified. In\ S.cerevisiae, the G-protein -1 subunit (GP1-) is involved in\ mating factor signal transduction, while the -2 subunit is thought to\ regulate intracellular levels of cyclic AMP [MEDLINE:99117513]. Unlike in mammalian cells,\ in yeast it is the -gamma dimer that activates the effector rather than\ the subunit. The sequence identity between different fungal subunits is relatively low and is equivalent to the level of similarity\ observed between mammalian subtypes. The GTP-binding and hydrolysis\ regions, however, show remarkable conservation.

\ \ \ GTP binding activity ; GO:0005525 \N G-protein coupled receptor protein signaling pathway ; GO:0007186 21552 IPR002974 P450 enzymes constitute a superfamily of haem-thiolate proteins [MEDLINE:92007836],widely distributed in bacteria, fungi, plants and animals. The enzymes\ are involved in metabolism of a plethora of both exogenous and endogenous\ compounds [MEDLINE:87297459]. Usually, they act as terminal oxidases in multi-component\ electron transfer chains, called P450-containing monooxygenase systems.\ Current P450 nomenclature, based on divergent evolution of the P450\ superfamily, was proposed and developed by Nebert et al. [MEDLINE:93135827]. On the basis\ of sequence similarity, all P450s can be categorised into 2 main classes,\ the so-called B- and E-classes: P450 proteins of prokaryotic 3-component\ systems and fungal P450nor (CYP55) belong to the B-class; all other known\ P450s from distinct systems are of the E-class PUB00005920. E-class P450S may be\ further divided into 5 subclasses (groups) according to protein sequence\ similarities. \ On the basis of sequence similarity, Nelson introduced the concept of a \ higher order classification of P450 families into clans, which is \ similar to the previous grouping into B- and E-classes; both classifications\ are still used. According to Nelson's system, clans 3 and 4 correspond to\ the E-class group II proteins PUB00005920.

\ Group II P450s are distributed widely in life, i.e., in eubacteria (family \ CYP102), cyanobacteria (CYP110), fungi (CYP52, CYP53 and CYP56), insects \ (CYP4 and CYP6) and mammals (CYP3, CYP4 and CYP5). Many group II P450s \ catalyse hydroxylation of linear chains such as alkanes (CYP52), alcohols \ and fatty acids (CYP4, CYP5, CYP102); Aspergillus niger CYP53 carries out\ para-hydroxylation of benzoate; yeast CYP56 is possibly involved in \ oxidation of tyrosine residues; insect CYP6 metabolises a wide range of \ toxic compounds; and members of the CYP3 family are omnivorous. The\ existence of two prokaryotic P450s in group II strongly suggests that the\ divergence of the P450 superfamily into B- and E-classes, and further\ divergence into stable P450 groups within the E-class, must be very ancient\ and had occured before the appearance of eukaryotes\ \ \ \ PUB00005920.\ The CYP52 family is only present in Candida species. \ CYP52 proteins belong to the eukaryote-like cluster of bacterial P450s,\ which includes CYP102 and CYP110. In the original nomenclature, this would \ be group II E-class proteins, while in Nelson's classification the cluster\ adjoins CYP4 (clan 4), which includes fatty acid hydroxylases. It has been \ suggested that if the distribution of CYP52 sequences is only among fungi \ related to Candida, they might represent a novel development of Candida\ yeasts.

The 3D structure of the P450 domain of P450BM-3 (CYP102) has been determined\ PUB00005920 and is used as a model for microsomal P450s. The P450 molecule is an / protein, shaped like a triangular prism: the overall structure\ can be roughly divided into -rich ('right side') and -rich ('left \ side') domains. However, this division appears to be artificial since the - and -rich domains comprise discontinuous assemblies of secondary\ structure elements, and do not constitute independent folding units.

\ \ monooxygenase activity ; GO:0004497 \N metabolism ; GO:0008152 21551 IPR002972 The lipocalins are a diverse, interesting, yet poorly understood family of proteins composed, in the main, of extracellular ligand-binding proteins\ displaying high specificity for small hydrophobic molecules [MEDLINE:85168267], [MEDLINE:96358478]. Functions\ of these proteins include transport of nutrients, control of cell regulation, pheromone transport, cryptic colouration and the enzymatic synthesis\ of prostaglandins.\

\ The crystal structures of several lipocalins have been solved and show a \ novel 8-stranded anti-parallel -barrel fold well conserved within the\ family. Sequence similarity within the family is at a much lower level and\ would seem to be restricted to conserved disulphides and 3 motifs, which\ form a juxtaposed cluster that may act as a common cell surface receptor\ site [MEDLINE:96358478]. By contrast, at the more variable end of the fold are found an \ internal ligand binding site and a putative surface for the formation of \ macromolecular complexes PUB00003448. The anti-parallel -barrel fold is also\ exploited by the fatty acid-binding proteins (which function similarly by\ binding small hydrophobic molecules), by avidin and the closely related\ metalloproteinase inhibitors, and by triabin. Similarity at the sequence \ level, however, is less obvious, being confined to a single short \ N-terminal motif.\ The lipocalin family can be subdivided into kernal and outlier sets. The\ kernal lipocalins form the largest self consistent group, comprising the subfamily of prostaglandin D synthases. The outlier lipocalins form several smaller distinct subgroups: \ the OBPs, the von Ebner's gland proteins, -1-acid glycoproteins, \ tick histamine binding proteins and the nitrophorins.

Glutathione-independent prostaglandin D (PGD2) synthase (EC: 5.3.99.2) is the\ main factor involved in synthesis of PGD2 in the brain, accounting for over\ 90% of activity in the rat; it is responsible for catalysing the conversion\ of PGH2 into PGD2 in the presence of various thiol compounds. PGD2 is\ a major prostaglandin in mammalian brains, functioning in the central \ nervous system as both a neuromodulator and a trophic factor. The enzymatic\ activity of PGD synthase makes it unique among the lipocalins. It is \ localised in the choroid plexus, meninges and oligodendrocytes, but is also \ a major component of cerebrospinal fluid. Immunocytochemistry indicates that\ the protein is associated with the rough endoplasmic reticulum and the outer\ nuclear membranes of rat oligodendrocytes, and seems to be a peripheral \ membrane protein easily dissociated by detergents.\ A near homologue of PGD2 synthase has been identified in cane-toad (Bufo \ marinus) choroid plexus, where it is the most abundant protein secreted into\ the cerebrospinal fluid PUB00003448. It is also found in other areas of the brain,\ albeit at much lower levels, and is expressed throughout amphibian \ metamorphosis. The choroid plexus helps form the barrier between blood and \ cerebrospinal fluid, and it has been suggested that this lipocalin may help \ transport lipophilic molecules across the blood/brain barrier.

\ \ \ prostaglandin-D synthase activity ; GO:0004667 \N transport ; GO:0006810 21550 IPR002971

Rodent urinary proteins (mouse MUPs and rat -2u globulins) are the major protein components of rodent urine and transport pheromones [MEDLINE:93063349].\ Rodent urine contains an unusually large amount of protein. The major site of MUP synthesis is the liver; the protein is secreted by the liver into serum, \ where it circulates at relatively low levels before being rapidly filtered\ by the kidney and excreted.\ The sex-dependent expression of MUP (adult male mice secrete 5-20 times \ as much MUP as do females) and its ability to bind a number of odorant \ molecules is consistent with the suggestion that MUP acts as a pheromone\ transporter; the protein may be excreted into the urine carrying a bound\ pheromone, which is released as the urine dries and the protein denatures.\ The crystal structure of MUP has been solved [MEDLINE:93063349] and is known to be a \ member of the lipocalin family. \ Alpha-2u-globulin, a close homologue of MUP, accounts for 30-50% of total\ excreted protein in adult male rat urine. As its electrophoretic mobility\ is similar to that of serum a2 globulin, it was named '-2u-globulin',\ the subscript 'u' denoting its origin in urine. Alpha-2u-globulin is \ secreted into the plasma by a number of tissues, where it circulates before\ filtration through the kidney; between 20 and 50% is reabsorbed by the\ proximal tubule of the nephron, the rest being excreted. Although the exact\ physiological role of -2u-globulin is unclear, there is circumstantial\ evidence that it functions in pheromone transport. This is consistent with\ its observed binding properties, its close similarity with MUP and the known\ properties of male rat urine.

\ \

The allergens in this family include allergens with the following designations: Mus m 1 and Rat m 1.

\ \ \ pheromone binding activity ; GO:0005550 \N transport ; GO:0006810 21549 IPR002970 The lipocalins are a diverse, interesting, yet poorly understood family of proteins composed, in the main, of extracellular ligand-binding proteins\ displaying high specificity for small hydrophobic molecules [MEDLINE:85168267], [MEDLINE:96358478]. Functions\ of these proteins include transport of nutrients, control of cell regulation, pheromone transport, cryptic colouration and the enzymatic synthesis\ of prostaglandins.\

\ The crystal structures of several lipocalins have been solved and show a \ novel 8-stranded anti-parallel -barrel fold well conserved within the\ family. Sequence similarity within the family is at a much lower level and\ would seem to be restricted to conserved disulphides and 3 motifs, which\ form a juxtaposed cluster that may act as a common cell surface receptor\ site [MEDLINE:96358478]. By contrast, at the more variable end of the fold are found an \ internal ligand binding site and a putative surface for the formation of \ macromolecular complexes PUB00003448. The anti-parallel -barrel fold is also\ exploited by the fatty acid-binding proteins (which function similarly by\ binding small hydrophobic molecules), by avidin and the closely related\ metalloprotease inhibitors, and by triabin. Similarity at the sequence\ level, however, is less obvious, being confined to a single short \ N-terminal motif.\ The lipocalin family can be subdivided into kernal and outlier sets. The\ kernal lipocalins form the largest self-consistent group, comprising the subfamily of tick histamine-binding proteins. The outlier lipocalins form several smaller distinct subgroups: \ the OBPs, the von Ebner's gland proteins, -1-acid glycoproteins, \ tick histamine binding proteins and the nitrophorins.

The tick histamine binding proteins are the most recently identified set of \ outlier lipocalins. The structure of one tick histamine binding protein has\ been solved PUB00003448 and has shown the proteins to have the characteristic \ lipocalin fold but without any appreciable sequence similarity. The tick\ histamine binding proteins are secreted into the saliva of the ixodid tick \ Rhipicephalus appendiculatus and share functional similarity with the \ nitrophorins, sequestering histamine at the wound site. Because the tick\ histamine binding proteins outcompete histamine receptors, they are able to\ overcome host inflammatory and immune responses. This enables the ticks to\ feed for extended periods, lasting from days to several weeks, and are able \ to gorge themselves on large blood meals increasing their body mass 100 fold.\ Unlike nitrophorins, the tick proteins do not bind haem (or other cofactor),\ but ligate histamine directly in two rigid orthogonally-arranged binding \ sites, at opposing ends of the lipocalin anti-parallel -barrel, which\ have an unusually polar character.

\ \ \N \N transport ; GO:0006810 21548 IPR002969

The outlier lipocalins form several smaller distinct subgroups: the OBPs, the von Ebner's gland proteins, -1-acid glycoproteins, \ tick histamine binding proteins and the nitrophorins.

Apolipoprotein D (apoD) is a mammalian plasma protein. Although well characterised, its precise biological function remains unclear. The majority of apoD \ constitutes a minor but significant protein component of high density \ lipoprotein particles (HDLs), representing about 5% of total HDL protein,\ and that its interaction with other apolipoproteins is of considerable\ importance [MEDLINE:81013877], [MEDLINE:81255961]. By contrast with most apolipoproteins, human apoD is relatively small (189 residues, MW 18500). ApoD is 18% glycosylated, at\ either or both of two asparagines (positions 65 and 98 [MEDLINE:87057347]). Human apoD is distributed in a number of tissues, including kidney, liver, pancreas, spleen, intestine, placenta, \ adrenal gland and foetal brain tissue [MEDLINE:87246069]. There is some evidence that the expression of apoD is regulated by steroid\ hormones [MEDLINE:91330150]. ApoD is found in a number of mammalian species, \ including humans and other primates, rats, rabbits and goat, but it is absent from pig, dog, cow and\ horse. The gene sequences of human, rat and rabbit apoD are of similar length and are well conserved.\ Analysis of the human sequence revealed that apoD is a lipocalin family \ member showing the greatest apparent similarity to insect colourant proteins.\ The expected 8-membered -barrel structure of ApoD contrasts with the \ structure of other apoliproteins. Apoliprotein A is a modular protein known\ to be composed of several kringle domains, whilst apolipoprotein E and apophorin E are helix bundles. Membership of the lipocalin family suggests apoD may function by binding a\ hydrophobic ligand; the nature of this molecule remains uncertain, although\ cholesterol, bilin, progesterone and pregnenolone have all been suggested.\ Almost all apoD in plasma is found as part of a supramolecular complex. It \ is localised primarily in an HDL, with most of the remainder in very high \ density lipoprotein (VHDL) particles, and only trace amounts in low density \ lipoprotein (LDL) and very low density lipoprotein (VLDL) particles. The\ apoD protein contains two distinct antigenic sites, which are \ apparently shared by other, higher molecular weight plasma proteins [MEDLINE:87057347].

\ \ lipid binding activity ; GO:0008289 \N transport ; GO:0006810 21545 IPR002965 This entry matches protein sequences characterised by multiple tandem pro-ser-rich repeats (often ser-pro-pro-pro-pro penta-peptide repeats or variations of these), in which the proline residue is hydroxylated and then\ glycosylated. This pattern is found in a variety of proteins from prokaryotes and eukaryotes, including a group of extensins. Extensins are plant cell-wall proteins; they can account for up to 20% of\ the dry weight of the cell wall PUB00006182. They are highly-glycosylated, possibly\ reflecting their interactions with cell-wall carbohydrates. Amongst their functions is cell wall strengthening in response to mechanical stress (e.g.,\ during attack by pests, plant-bending in the wind, etc.). \ \ \N \N \N 21546 IPR002967 Microtubules are polymers of tubulin, a dimer of two 55 kD subunits, designated

and

[MEDLINE:85277991], [MEDLINE:90304955]. Within the microtubule lattice,

heterodimers associate in a head-to-tail fashion, giving rise to microtubule \ polarity. Fluorescent labelling studies have suggested that tubulin is\ oriented in microtubules with

-tubulin toward the plus end [MEDLINE:93355288]. \ For maximal rate and extent of polymerisation into microtubules, tubulin \ requires GTP. Two molecules of GTP are bound at different sites, termed N \ and E. At the E (Exchangeable) site, GTP is hydrolysed during incorporation\ into the microtubule. Close to the E site is an invariant region rich in \ glycine residues, which is found in both chains and is thought to control\ access of the nucleotide to its binding site [MEDLINE:88058878]. \ Most species, excepting simple eukaryotes, express a variety of closely-\ related

- and

-isotypes. A third family member, gamma tubulin, has\ also been identified in a number of species. Gamma tubulin is found at \ microtubule-organising centres, such as the spindle poles or the centrosome, \ suggesting that it is involved in minus-end nucleation of microtubule \ assembly [MEDLINE:94099776]. More recently, a new delta-type tubulin has been identified\ in Chlamydomonas rheinhardtii and mouse , and is likely to be found\ in a number of other species.\ \ \ structural molecule activity ; GO:0005198 microtubule ; GO:0005874 microtubule-based movement ; GO:0007018 21547 IPR002968

The lipocalin family can be subdivided into kernal and outlier sets. The \ kernal lipocalins form the largest self consistent group, comprising the subfamily of -1-microglobulins. The outlier lipocalins form several smaller distinct subgroups: \ the OBPs, the von Ebner's gland proteins, -1-acid glycoproteins, \ tick histamine binding proteins and the nitrophorins.

Alpha-1-microglobulin (A1M), also known as protein HC (for Heterogeneous \ Charge), is a low molecular weight protein component of plasma first discovered in pathological human urine. It is a member of the lipocalin superfamily. Although much is now known of its structure and properties, the function and physiological role of A1M remains unclear, although evidence suggests that it functions in the regulation of the immune system. A1M is known to exist in both a free form and complexed to other macromolecules: immunoglobulin A (IgA) in humans and -1-inhibitor-3 in the rat. Free A1M is a monomeric protein composed of one 188 residue polypeptide and contains three cysteines, two of which (residues 75 and 173) form a conserved intra-molecular disulphide link [MEDLINE:90342058]. A1M is glycosylated by three separate carbohydrate chains: two complex carbohydrates are N-linked to asparagines at residues 17 and 96, and the other simple carbohydrate is O-linked to threonine at position 5. 22% of the total molecular mass of the protein is derived from carbohydrate. Free A1M is extremely heterogeneous in charge, and is found tightly associated with a chromophore. This chromophoric group is covalently bound to the free cysteine residue at position 34. It also binds retinol as a major ligand, but this is probably distinct from the its covalent chromophore. The glycosylation is different between species.

\ The principal sites of A1M synthesis are the liver and kidney. Half of all human plasma A1M (about 0.03mg/ml) forms a 1:1 complex with about 5% of plasma immunoglobulin A. The resulting macromolecular complex has a molecular weight of 200000, and\ a plasma concentration of 0.3mg/ml. It can exhibit both antibody activity and affect many of the biological actions of free A1M [MEDLINE:90342058]. \ A1M has many affects on the immune system. It inhibits stimulation of cultured lymphocytes by protein antigens; it can induce cell division of lymphocytes, a mitogenic effect that can either be enhanced or inhibited by the action of other plasma components; it inhibits neutrophil granulocyte migration in vitro; and it inhibits chemotaxis.

\ \ \ \N \N transport ; GO:0006810 21542 IPR002962

Peropsin is a visual pigment-like protein found in ocular tissues.The protein has been localised to the apical face of the retinal pigment\ epithelium (RPE), most prominently to the microvilli that surround the\ photoreceptor outer segments. It is believed that peropsin may play a\ role in RPE physiology, either by detecting light directly, or by monitoring\ the concentration of retinoids or other photoreceptor-derived compounds [MEDLINE:97420780].

\ \ rhodopsin-like receptor activity ; GO:0001584 integral to membrane ; GO:0016021 vision ; GO:0007601 21543 IPR002963 Expansins are unusual proteins that mediate cell wall extension in plants. They are believed to act as a sort of chemical grease, allowingpolymers to slide past one another by disrupting non-covalent hydrogen\ bonds that hold many wall polymers to one another. This process is not\ degradative and hence does not weaken the wall, which could otherwise\ rupture under internal pressure during growth.\ Sequence comparisons indicate at least four distinct expansin cDNAs in\ rice and at least six in Arabidopsis. The proteins are highly conserved in\ size and sequence (75-95% amino acid sequence similarity between any \ pairwise comparison), and phylogenetic trees indicate that this multigene\ family formed before the evolutionary divergence of monocotyledons and \ dicotyledons. Sequence and motif analyses show no similarities to known\ functional domains that might account for expansin action on wall extension\ [MEDLINE:96016146]. It is thought that several highly-conserved tryptophans may function \ in expansin binding to cellulose, or other glycans. The high conservation \ of the family indicates that the mechanism by which expansins promote wall\ extensin tolerates little variation in protein structure.\ \ \N \N cell wall organization and biogenesis (sensu Magnoliophyta) ; GO:0009664 21544 IPR002964 An impressive property of mussels is their ability to stick to wet surfaces.Exactly how they do this is unclear, but they are known to exploit bundles\ of threads, each of which has a fibrous collagenous core coated with \ adhesive proteins [MEDLINE:94318724]. These proteins are able to displace water from a wet\ surface and then set to form tight junctions.\ The adhesive protein of Mytilus coruscus contains 848 amino acids, including\ a 20-residue signal peptide, a 21-residue non-repetitive linker and a \ repetitive domain that constitutes the bulk of the protein. The \ representative repeat motif of this domain, YKPK(I/P)(S/T)YPP(T/S), is\ similar to that of M.galloprovincialis . The codon usage patterns for \ the same amino acids differ in different positions of the decapeptide motif\ [MEDLINE:94318724], [MEDLINE:96394686]. Almost identical nucleotide sequences appear several times in the\ repetitive region, suggesting that mussel adhesive protein genes have\ evolved through repeat duplication [MEDLINE:96394686]. \ The repeat motif is reminiscent of repeat units found in extensins, a group\ of plant proteins involved in the strengthening of the cell wall in response\ to mechanical stress.\ \ \N extracellular ; GO:0005576 \N 21540 IPR002960

Lymphotoxin- (LT- or TNF-) and lymphotoxin- (LT-) are\ related cytokines produced by lymphocytes. The proteins are cytotoxic for a\ wide range of tumour cells in vitro and in vivo.

The structure of TNF- has been determined to 1.9 A using X-ray \ crystallography and phase determination via molecular replacement using \ TNF-. Like TNF-, lymphotoxin folds to form a 'jellyroll' -\ sheet sandwich. Three-fold related LT subunits form a trimer primarily\ stabilised by hydrophobic interactions. A cluster of 6 basic residues \ around the 3-fold axis is thought to account for the acid lability of the\ trimer. Although the structural cores of TNF- and LT are similar,\ insertions and deletions relative to TNF- occur in loops at the 'top'\ of the LT trimer, significantly altering the local structure. The\ sites of two mutations (Asp-50 and Tyr-108) that abolish the cytotoxicity \ of LT are contained within poorly-ordered loops that flank the cleft between\ neighboring subunits at the base of the molecule, suggesting that the\ receptor recognises an intersubunit binding site [MEDLINE:92129275].

\ \ tumor necrosis factor receptor ligand activity ; GO:0005164 membrane ; GO:0016020 immune response ; GO:0006955 21541 IPR002961

Lymphotoxin- (LT- or TNF-) and lymphotoxin- (LT-) are\ related cytokines produced by lymphocytes. The proteins are cytotoxic for a\ wide range of tumour cells in vitro and in vivo. The gene for LT- is\ found next to the TNF-LT locus in the major histocompatibility complex (MHC),\ a region of the MHC with possible linkage to autoimmune disease [MEDLINE:93208881]. It is\ possible that a surface LT-/LT- complex may have a specific role\ in immune regulation distinct from the functions ascribed to TNF [MEDLINE:93208881].

\ \ tumor necrosis factor receptor ligand activity ; GO:0005164 membrane ; GO:0016020 immune response ; GO:0006955 21539 IPR002959

The structure of human TNF has been determined to 2.9 A using X-ray crystallography. The protein is trimeric, each subunit consisting of an anti-parallel -sandwich. The subunits trimerise via a novel edge-to-face packing of -sheets [MEDLINE:89159409]. It is believed that each TNF molecule has three \ receptor-interaction sites (between the three subunits), thus allowing\ signal transmission by receptor clustering [MEDLINE:91184128].

TNF- is a soluble cytokine with a wide variety of functions: it causes\ damage to tumour cells but has no effect on normal cells; it is involved in \ the induction of cachexia; it is a potent pyrogen, causing fever by direct\ action or by stimulation of interleukin-1 secretion; and it can stimulate\ cell proliferation and induce cell differentiation under certain conditions.

\ \ tumor necrosis factor receptor ligand activity ; GO:0005164 membrane ; GO:0016020 immune response ; GO:0006955 21538 IPR002958 Occludin was the first molecular component of the tight junction to beidentified. These are specialised membrane domains that form intercellular\ contacts between epithelial cells and create a regulated barrier to the\ paracellular movement of water, solutes and immune cells. They also provide\ a second type of barrier that contributes to cell polarity by restricting\ the lateral diffusion of lipids and proteins within cell membranes [MEDLINE:99288720].\ Occludin is an ~65 kDa type II integral membrane protein, which has been\ shown to have four transmembrane (TM) domains, two extracellular loops and\ cytoplasmic N- and C-termini. The extracellular loops are chemically quite\ distinctive, particularly the first, which has an unusually high content of\ tyrosine and glycine residues (~65%) that alternate along the sequence [MEDLINE:99288720].\ Gene knockout experiments have suggested occludin is an accessory, rather\ than principal, structural component of tight junctions, since occludin-deficient cells are still able to form tight junctions when cultured in\ vitro [MEDLINE:99299665].\ \ \N \N \N 21537 IPR002957 Keratins are a well known group of intermediate filament proteins. Like actin filaments, keratins are flexible but provide a firm cell skeleton.\ Unlike actin, however, no known keratins are associated with motor \ functions. Approximately 10 keratins form the basis of hair or claw,\ with a further 20 found in internal body cavity epithelia. They are also\ found at desmosomes and hemi-desmosomes (cell/cell and cell/matrix contacts \ respectively) PUB00005933.\ Type I keratins are a group of acidic intermediate filament proteins that\ exist as chains of hetero-dimers with basic type II keratins. Each type\ I keratin consists of head-, rod- and tail-like structures, the rod being\ constructed from three linked coils: 1A, 1B and 2. Type I proteins are \ associated with a number of inherited developmental disorders, such as \ baldness, beading of hair, and skin blistering.\ \ \N \N \N 21535 IPR002955

Tau proteins are microtubule-associated proteins that are involved inmicrotubule assembly and stabilisation. They may also play a wider role in cellular shape, motility and signal transduction [MEDLINE:22362738]. Tau mRNA is expressed predominantly\ in neurones, and particularly in their axons. Quite a number of isoforms\ have been detected, which in human brain have been shown to arise from\ alternative splicing of an mRNA from a single gene located on chromosome 17.\ The isoforms contain 352-441 amino acid residues. A larger tau isoform has\ also been detected, which is expressed principally in the peripheral nervous\ system [MEDLINE:99000279].

Each isoform contains a variable number of C-terminal repeat\ regions that are thought to be responsible for tubulin-binding. The acidic N-terminal region projects from the micro-tubule surface when Tau is bound and may interact with other cytoskeletal elements. The middle region is proline-rich and may be a further binding site. It contains the target sites of many kinases, phosphorylation of this region may result in a change in the conformational state of the protein, and affect its ability to bind microtubules [MEDLINE:22362738].

\ \ Tau does not appear to be an essential protein, since transgenic mice\ lacking tau appear to develop a normal nervous system with only mild\ alterations in the structure of certain small-calibre axons [MEDLINE:94261183]. However,\ it has received much recent attention due to its possible role in the\ aetiogenesis of a number of human neurodegenerative diseases, filamentous\ inclusions containing tau having been found in the brains of patients\ diagnosed with Alzheimer's disease, Pick's disease and progressive\ supranuclear palsy. Furthermore, tau gene mutations have been found in\ patients suffering familial frontotemporal dementia, which result in\ abnormal tau protein aggregates forming in the brain tissue [MEDLINE:99307371].

\ \ \N \N \N 21536 IPR002956 During development of the Drosophila retina, the bride of sevenless (boss)gene is required in photoreceptor neuron R8 for the development of\ photoreceptor neuron R7, suggesting that boss encodes or regulates an\ R7-specific inductive cue [MEDLINE:91115074]. The induction of R8 photoreceptor neuron\ neighbouring cells to assume an R7 cell fate is believed to be mediated by\ a direct interaction of boss with sevenless [MEDLINE:91115074], [MEDLINE:91312442]. An alternative model has\ been proposed in which the boss protein functions as a receptor, based on \ a (superficial) similarity to the G-protein-coupled family of membrane \ receptors [MEDLINE:91312442]. \ The boss gene encodes a protein of 896 amino acids with a putative \ N-terminal signal sequence, a large N-terminal extra-cellular domain, seven\ transmembrane (TM) segments and a C-terminal cytoplasmic tail [MEDLINE:91115074], [MEDLINE:93281693]. The\ boss protein from Drosophila virilis shares a high level of amino acid\ identity with the D.melanogaster homologue, with highest levels of\ similarity in the TM domains [MEDLINE:93281693].\ \ sevenless binding activity ; GO:0005118 membrane ; GO:0016020 vision ; GO:0007601 21533 IPR002953 The filoviridae are a group of viruses that cause haemorrhagic fevers witha high mortality rate. The family currently contains three viruses: Ebola, \ Marburg and Reston, named after their corresponding outbreak regions. \ They possess negative-stranded RNA genomes, which encode at least 7 proteins.\ The VP35 protein is found in the genomes of all filoviruses. Its function is \ presently unknown, but it is thought to share the function of the \ phosphorylated proteins (polymerase subunits) of rhabdoviruses and \ paramyxoviruses due to its position in the genome. There is no evidence \ however, to suggest that VP35 is phosphorylated PUB00006185, PUB00006185.\ \ \N \N \N 21534 IPR002954 The Salmonella typhimurium Surface Presentation of Antigens M gene (SpaM)is one of 12 that form a cluster responsible for invasion properties [MEDLINE:94008985].\ The gene product is required for entry by the bacterium into epithelial\ cells, and is thus considered to be a virulence factor [MEDLINE:94008985]. Other Spa genes \ in the cluster are related to invasion (Inv) genes in similar Salmonella \ and Shigella species [MEDLINE:95272391], and flagella biosynthesis genes in Helicobacter\ pylori\ \ \ \ [MEDLINE:99185204].\ \

A homologue of this protein has been found recently in Salmonella enterica\ \ \ \ [MEDLINE:97221599]. The protein, named InvI, is required by the organism to gain access to\ mammalian epithelial cells, and cellular mutants (InvI-) failed to\ successfully infect these cells. It has also been found that the inv-spa \ loci of this particular species encode for a type III protein secretion\ system, essential in the bacterium's host cell invasion process [MEDLINE:96355856].

\ \ type III protein (virulence-related) secretor activity ; GO:0015448 \N protein secretion ; GO:0009306 21531 IPR002951 Human genes containing triplet repeats can markedly expand in length, leading to neuropsychiatric disease. Expansion of triplet repeats \ explains the phenomenon of anticipation, i.e. the increasing severity or \ earlier age of onset in successive generations in a pedigree [MEDLINE:93315145]. \ Dentatorubral pallidoluysian atrophy (DRPLA, or Smith's disease) is one of \ five disorders now known to result from expansion of a CAG trinucleotide\ repeat encoding glutamine [MEDLINE:96262314].\ The reported full length cDNA sequence encodes a serine repeat and a region\ of alternating acidic and basic amino acids, in addition to the glutamine\ repeat [MEDLINE:96262314], [MEDLINE:95144175]. It is believed that the pathology of DRPLA may arise from the \ altered structure and function of the abnormal protein [MEDLINE:96262314]. Although the \ function of the protein is still unknown, its unusual amino acid composition\ may provide clues toward understanding neurodegenerative diseases associated\ with triplet repeat expansion [MEDLINE:95144175].\ \ \N \N \N 21532 IPR002952 The complete sequence for a major eggshell protein gene from the humanparasite Schistosome mansoni has been determined [MEDLINE:89097083]. The deduced amino \ acid sequence demonstrates an abundance of glycine and tyrosine residues\ evenly distributed throughout the chain, an asymmetrical distribution of\ charged residues, and five well-conserved tandem repeats of 16-18 residues\ in the N-terminal region. Acidic residues are confined to the N-terminal\ portion, and basic residues are largely found towards the C-terminus.\ A model structure composed of short anti-parallel

-strands has been\ proposed, in which glycines and residues with small side chains lie within\ the strands, and tyrosines and cysteines are arranged at the bends, where \ they could be involved in cross-linking. Four strands form one of the \ tandem repeats, which are predicted to form a stack of five closely-packed

-sheets, each with three strands and linked by the more variable fourth\ strand [MEDLINE:89097083]. The C-terminal region could form a similar, but less compact,\ structure. Birefringence studies have shown an ordered structure of the\ schistosome eggshell [MEDLINE:70156944], which could be formed by packing of the polypeptides such that the N-terminal domain contributes counter ions or cross-links to the C-terminal domain of adjacent molecules.\ \ \N \N \N 21530 IPR002949 P450 enzymes constitute a superfamily of haem-thiolate proteins [MEDLINE:92007836],widely distributed in bacteria, fungi, plants and animals. The enzymes\ are involved in metabolism of a plethora of both exogenous and endogenous\ compounds [MEDLINE:99138395]. Usually, they act as terminal oxidases in multi-component\ electron transfer chains, called P450-containing monooxygenase systems. \ On the basis \ of sequence similarity, all P450s can be categorised into 2 main groups, \ the so-called B- and E-classes: P450 proteins of prokaryotic 3-component \ systems and fungal P450nor (CYP55) belong to the B-class; all other known \ P450s from distinct systems are of the E-class. By contrast with the B-class, containing water-soluble haemoproteins, \ most E-class P450s are membrane-bound. Membranous P450s can be divided into\ those from the inner mitochondrial membrane (mitochondrial type), and those\ from membranes of the endoplasmic reticulum (ER) (microsomal type). In the\ mitochondrial P450-containing monooxygenase system, P450 can be reduced by\ the 2Fe-2S iron-sulphur protein adrenodoxin, which can accept electrons\ from NADPH-dependent adrenodoxin reductase. Both adrenodoxin and\ adrenodoxin reductase are soluble, and located in the mitochondrial matrix \ PUB00003474. Microsomal P450s depend on a single NADPH:P450 reductase; the P450s\ and the reductase are located on the cytosolic side of the ER membrane, and\ are anchored to the membrane by hydrophobic amino-terminal segments PUB00003474. \ To date, only animal mitochondrial P450s have been sequenced. A cDNA encoding 25-hydroxyvitamin D3 24-hydroxylase (P450cc24) has been\ isolated from rat kidney. The cDNA contained a 1542bp open reading\ frame encoding 514 amino acids, including an N-terminal presequence typical\ of mitochondrial enzymes. The sequence shows less than 30% similarity \ to those of other cytochrome P450s, and hence P450cc24 constitutes a novel\ P450 family [MEDLINE:91122283]. The enzyme catalyses the conversion of 25-hydroxyvitamin\ D3 and 1-

, 25-dihydroxyvitamin D3 to 24,25-dihydroxyvitamin D3 and\ 1,24,25-trihydroxyvitamin D3, respectively [MEDLINE:97307664].\ \ monooxygenase activity ; GO:0004497 mitochondrion ; GO:0005739 electron transport ; GO:0006118 21528 IPR002946

Chloride (Cl^-) channels are known to be present in the plasma andintracellular membranes of many cell types. Whilst the molecular identity\ of plasma membrane Cl^- channels has been known for some time, only recently\ have intracellular Cl^- channels been characterised. Initially, a 64 kDa\ protein was purified from solubilised kidney cortical membranes, which, when\ reconstituted into phospholipid vesicles, gave rise to chloride channel\ activity [MEDLINE:92237239]. An antibody generated against this protein (p64) was\ subsequently used to identify and clone it. The predicted amino acid\ sequence for p64 shows that it contains two, or possibly four, putative\ transmembrane (TM) domains and a number of possible phosphorylation sites.\ Expression studies have revealed that it is targeted to intracellular\ organelles, not the plasma membrane [MEDLINE:93315471].

\ \

Subsequently, a number of homologous cDNAs have been identified, which,\ when expressed, give rise to Cl^- channels in the membranes of both cell\ nuclei and endoplasmic reticulum [MEDLINE:97284733], [MEDLINE:97442460]. They do not show significant\ sequence similarity to the CLC family of plasma membrane voltage-gated Cl^-\ channels.

\ \ voltage-gated chloride channel activity ; GO:0005247 membrane ; GO:0016020 chloride transport ; GO:0006821 21529 IPR002948

The thiazide-sensitive Na-Cl co-transporter is a large integral membraneprotein (~1000 amino acids) that mediates the coupled transport of Na⁺ and\ Cl^- in an electrically silent manner. In the mammalian kidney, it is the\ dominant mechanism mediating Cl^- absorption in the early distal tubule, and\ here it is the target of the widely-used thiazide class of diuretic drugs.\ It is also known to be present in the urinary bladder of the winter\ flounder, from where the gene encoding it was initially cloned [MEDLINE:93219361].

Hydrophobicity analysis predicts the Na-Cl co-transporter to have 12\ transmembrane (TM) domains and comparisons with other cloned ion\ co-transporters reveals that a superfamily of electroneutral cation-chloride\ co-transporters exists, which includes the K-Cl co-transporters (PR01081)\ and the Na-K-Cl co-transporters (PR01081/>). All share a similar predicted\ membrane topology in a central hydrophobic domain, together with\ hydrophilic N- and C-termini that are likely cytoplasmic [MEDLINE:98306149].

Mutations in the thiazide-sensitive Na-Cl co-transporter have been\ found that give rise to Gitelman's variant of Bartter's syndrome,\ an inherited kidney disease characterised by hypokalaemic alkalosis [MEDLINE:96122035].

\ \ transporter activity ; GO:0005215 membrane ; GO:0016020 ion transport ; GO:0006811 21527 IPR002945

The ability to transport glucose across the plasma membrane is a feature common to nearly all cells, from simple bacteria through to highly specialised mammalian neurones. Facilitative sugar transport is mediated by members of the GLUT transporter family, which form an aqueous pore across the membrane through which sugars can move in a passive (i.e., energy-independent) manner; in consequence, they can only transport sugars down their concentration gradient. The GLUT family of glycosylated transmembrane proteins are predicted to span the membrane 12\ times with both amino- and carboxyl-termini located in\ the cytosol. On the basis of sequence homology and\ structural similarity, three subclasses of sugar transporters have been defined:\ Class I (GLUTs 14) are glucose transporters; Class II (GLUTs 5, 7, 9 and 11) are\ fructose transporters; and Class III (GLUTs 6, 8, 10, 12 and HMIT1) are\ structurally atypical members of the GLUT family, which are poorly defined at\ present, indeed GLUT6 may only be a pseudo-gene [MEDLINE:90194363], [MEDLINE:93374885], [MEDLINE:85272595], [MEDLINE:89008414],[MEDLINE:99004677].

The confirmed isoforms are expressed in a tissue and cell-specific manner, and exhibit distinct kinetic and regulatory properties, presumably reflecting their specific functional roles. They belong to a much larger 'major facilitator superfamily' of 12 TM transporters that are involved in the transport of a variety of hexoses and other carbon compounds, and include: bacterial sugar-proton symporters (H⁺/xylose and H⁺/arabinose); bacterial transporters of carboxylic acids and antibiotics; and sugar transporters in various yeast, protozoa and higher plants. Nevertheless, amino acid identity within the superfamily may be as low as ~25% [MEDLINE:87115869], [MEDLINE:93174460]. Besides the 12 presumed TM domains, the most characteristic structural feature of the superfamily is a five residue motif (RXGRR, where X is any amino acid). In the GLUT transporters, this motif is present in the presumed cytoplasmic loops connecting TM domains 2 with 3, and also 8 with 9. The 12 TM transporter superfamily appears to be structurally unrelated to the Na⁺-coupled, Na⁺/glucose co-transporters (SGLT1-3) found in the intestine and kidney, which are able to transport glucose against its concentration gradient [MEDLINE:88065856].

Comparison of the hydropathy profiles for GLUT1-5 reveals that they are virtually superimposable, despite the fact that their primary structures may differ by up to 60%. Of the presumed TM domains, the fourth, fifth and sixth are the most highly conserved, and conserved residues are also found in the short exofacial loops joining the putative TM regions. The presumed cytoplasmic N- and C-termini, and the extracellular loop between the first and second TM domains, show the greatest divergence, both in terms of primary structure and size.

GLUT3 is the most prominent glucose transporter isoform expressed in adult\ brain, where it tends to be preferentially located in neurones, rather\ than in other cell types, such as glia or endothelial cells. It is also\ widely distributed in other human tissues, having been detected in the\ liver, kidney and placenta. In other species, it shows a more restricted\ expression pattern. It consists of 496 amino acids (human isoform) and\ shares 64% amino acid identity with GLUT1 and 52% with GLUT2.

\ \ glucose transporter activity ; GO:0005355 membrane ; GO:0016020 transport ; GO:0006810 21526 IPR002944

On the basis of behavioural interactions with mutations in the Shaker K⁺\ channel gene of Drosophila, mutations in a new gene, called inebriated\ (ine), were isolated. Considering the distinctive phenotype displayed by\ these flies, it was postulated that the ine mutation might increase\ neuronal excitability [MEDLINE:93094951]. Subsequently the ine mutation was mapped, and\ the gene was cloned. The ine gene encodes a protein of 658 amino acids\ with a high degree of sequence similarity to members of the Na⁺/Cl^-\ -dependent neurotransmitter transporter superfamily. Therefore ine\ mutations may cause increased excitability of the Drosophila motor neuron,\ as a result of defective re-uptake of its substrate neurotransmitter,\ the identity of which remains to be determined [MEDLINE:97075153].

\ \ neurotransmitter:sodium symporter activity ; GO:0005328 membrane ; GO:0016020 neurotransmitter transport ; GO:0006836 21525 IPR002942

\ \ \

The S4 domain is a small domain consisting of 60-65 amino acid residues\ that was detected in the Bacteria ribosomal protein S4, eukaryotic\ ribosomal S9, two families of pseudouridine synthases, a novel family\ of predicted RNA methylases, a yeast protein containing a pseudouridine\ synthetase and a deaminase domain, bacterial tyrosyl-tRNA synthetases,\ and a number of uncharacterized, small proteins that may be involved in\ translation regulation [MEDLINE:99193178]. The S4 domain probably mediates binding to\ RNA.

\ \ RNA binding activity ; GO:0003723 \N \N 21524 IPR002941 This domain is found in DNA methylases. In prokaryotes, the major role of DNA methylation is to protect host DNA against degradation by restriction enzymes. This family contains both N-4 cytosine-specific DNA methylases and N-6 Adenine-specific DNA methylases. N-4 cytosine-specific DNA methylases (EC: 2.1.1.113) [MEDLINE:95331587] are enzymes that specifically methylate the amino group at the C-4 position of cytosines in\ DNA. Such enzymes are found as components of type II restriction-modification\ systems in prokaryotes. Such enzymes recognize a specific sequence in DNA and\ methylate a cytosine in that sequence. By this action they protect DNA from\ cleavage by type II restriction enzymes that recognize the same sequence. N-6 adenine-specific DNA methylases (EC: 2.1.1.72) (A-Mtase) are enzymes that specifically methylate the amino group at the C-6 position of adenines in DNA. Such enzymes are found in the three existing types of bacterial restriction-modification systems (in type I system the A-Mtase is the product of the hsdM gene, and in type III it is the product of the mod gene). All of these enzymes recognize a specific sequence in DNA and methylate an adenine in that sequence.\ \ N-methyltransferase activity ; GO:0008170 \N DNA methylation ; GO:0006306 21522 IPR002938 Monooxygenases incorporate one hydroxyl group into substrates and are found in many metabolic pathways. In this reaction, two atoms of dioxygen are reduced to one hydroxyl group and one H₂O molecule by the concomitant oxidation of NAD(P)H [MEDLINE:93073723]. P-hydroxybenzoate hydroxylase from Pseudomonas fluorescens contains this sequence motif (present in in flavoprotein hydroxylases) with a putative dual function in FAD and NADPH binding [MEDLINE:99148809].\ monooxygenase activity ; GO:0004497 \N aromatic compound metabolism ; GO:0006725 21523 IPR002939 This family consists of the C-terminal region form the DnaJ protein. Although the function of this region is unknown, it is always found associated with IPR001623.DnaJ is a chaperone associated with the Hsp70 heat-shock system involved in protein folding and renaturation after stress.\ \ chaperone activity ; GO:0003754 \N \N 21517 IPR002932

Ferredoxin-dependent glutamate synthases have been implicated in a number of functions including photorespiration in Arabidopsis where they may also play a role in primary nitrogen assimilation in roots [MEDLINE:98258997]. This region is expressed as a seperate subunit in the glutamate synthase subunit from archaebacteria, or part of a large multidomain enzyme in other organisms.

The aligned region of these proteins contains a putative FMN binding site and Fe-S cluster.

\ \ glutamate synthase activity ; GO:0015930 \N glutamate biosynthesis ; GO:0006537 21518 IPR002933

This family includes a range of zinc metallopeptidases belonging to several families in the peptidase classification [MEDLINE:95405261]. Members of M20 family are glutamate carboxypeptidases. Peptidase family M25 contains X-His dipeptidases.

\ metallopeptidase activity ; GO:0008237 \N proteolysis and peptidolysis ; GO:0006508 21519 IPR002934

A small region that overlaps with a nuclear localization signal and binds to the RNA primer contains three aspartates that are essential for catalysis. Sequence and secondary structure comparisons of regions surrounding these aspartates with sequences of other polymerases revealed a significant homology to the palm structure of DNA polymerase , terminal deoxynucleotidyltransferase and DNA polymerase IV of Saccharomyces cerevisiae, all members of the family X of polymerases. This homology extends as far as cca: tRNA nucleotidyltransferase and streptomycin adenylyltransferase, an antibiotic resistance factor [MEDLINE:96005605], [MEDLINE:96221320].

\ Proteins containing this domain include kanamycin nucleotidyltransferase (KNTase) which is a plasmid-coded enzyme responsible for some types of bacterial resistance to aminoglycosides. KNTase inactivates antibiotics by catalysing the addition of a nucleotidyl group onto the drug. In experiments, Mn2+ strongly stimulated this reaction due to a 50-fold lower Ki for 8-azido-ATP in the presence of Mn2+. Mutations of the highly conserved\ Asp residues 113, 115, and 167, critical for metal binding in the catalytic domain of bovine poly(A) polymerase, led to a strong\ reduction of cross-linking efficiency, and Mn2+ no longer stimulated the reaction. Mutations in the region of the "helical turn motif"\ (a domain binding the triphosphate moiety of the nucleotide) and in the suspected nucleotide-binding helix of bovine poly(A) polymerase\ impaired ATP binding and catalysis. The results indicate that ATP is bound in part by the helical turn motif and in part by a region that\ may be a structural analogue of the fingers domain found in many polymerases.

\ \ \N \N \N 21520 IPR002935 Members of this family are O-methyltransferases. The family includes also bacterial O-methyltransferases that may be involved in antibiotic production [MEDLINE:97090395].\ O-methyltransferase activity ; GO:0008171 \N \N 21521 IPR002937 This family consists of various amine oxidases, including maize polyamine oxidase (PAO) [MEDLINE:98258926], L-amino acid oxidases (LAO) and various flavin containing monoamine oxidases (MAO). The aligned region includes the flavin binding site of theseenzymes.\ In vertebrates MAO plays an important role regulating the intracellular levels of amines via there oxidation; these include various neurotransmitters, neurotoxins and trace amines [MEDLINE:97306298]. In lower eukaryotes\ such as aspergillus and in bacteria the main role of amine oxidases is to provide a source of ammonium [MEDLINE:95287865].\ PAOs in plants, bacteria and protozoa oxidase spermidine and spermine to an aminobutyral, diaminopropane and hydrogen peroxide and are involved in the catabolism of polyamines [MEDLINE:98258926].\ Other members of this family include tryptophan 2-monooxygenase, putrescine oxidase, corticosteroid binding proteins and antibacterial glycoproteins.\ \ \N \N electron transport ; GO:0006118 21513 IPR002928

The myosin molecule is a multi-subunit complex made up of two heavy chains and four light chains it is a fundamental contractile protein found in all eukaryote cell types [MEDLINE:87060988].This family consists of the coiled-coil myosin heavy chain tail region.\ The coiled-coil is composed of the tail from two molecules of myosin.\ These can then assemble into the macromolecular thick filament [MEDLINE:87060988].\ The coiled-coil region provides the structural backbone of the thick filament [MEDLINE:87060988].

\ \ \N \N \N 21514 IPR002929

This family consists mainly of the potato leaf roll virus readthrough protein. This is generated via a readthrough of open reading frame 3 a coat protein allowing transcription of open reading frame 5 to give an extended coat proteinwith a large c-terminal addition or read through domain [MEDLINE:94233771].\ The readthrough protein is thought to play a role in the circulative aphid transmission of potato leaf roll virus\ \ \ \ [MEDLINE:94233771].\ Also in the family is open reading frame 6 from beet western yellows virus and potato leaf roll virus both luteovirus and an unknown protein from cucurbit aphid-borne yellows virus a closterovirus.

\ \ \N \N \N 21515 IPR002930

This is a family of glycine cleavage H-proteins, part of the glycine cleavage multienzyme complex (GCV) found in bacteria and the mitochondria of eukaryotes. GCV catalyses the catabolism of glycine in eukaryotes.A lipoyl group is attached to a completely conserved lysine residue.\ The H protein shuttles the methylamine group of glycine from the P protein to the T protein.

\ \ \N glycine cleavage system complex ; GO:0005960 glycine catabolism ; GO:0006546 21516 IPR002931

This domain is found in many proteins known to have transglutaminase activity, i.e. which cross-link proteins through an acyl-transfer reaction between the gamma-carboxamide group of peptide-bound glutamine and the\ epsilon-amino group of peptide-bound lysine, resulting in a epsilon-(gamma-glutamyl)lysine isopeptide bond. Tranglutaminases have been found in a diverse range of species, from bacteria through to mammals. The enzymes require calcium binding and their activity leads to post-translational\ modification of proteins through acyl- transfer reactions, involving peptidyl glutamine residues\ as acyl donors and a variety of primary amines as acyl acceptors, with the generation of\ proteinase resistant isopeptide bonds [MEDLINE:22328673].

Sequence conservation in this superfamily primarily involves three motifs that center around conserved cysteine, histidine, and aspartate residues that form the catalytic triad in the structurally characterized transglutaminase, the human blood clotting factor XIIIa' [MEDLINE:94316682]. On the basis of the experimentally demonstrated activity of the Methanobacterium phage pseudomurein endoisopeptidase [MEDLINE:99009353], it is proposed that many, if not all, microbial homologs of the transglutaminases are proteases and that the eukaryotic transglutaminases have evolved from an ancestral\ protease [MEDLINE:99379687].

A subunit of plasma Factor XIII revealed that each Factor XIIIA subunit is\ composed of four domains (termed N-terminal -sandwich, core domain (containing the\ catalytic and the regulatory sites), and C-terminal -barrels 1 and 2) and that two monomers\ assemble into the native dimer through the surfaces in domains 1 and 2, in opposite\ orientation. This organization in four domains is highly conserved during evolution among\ transglutaminase isoforms [MEDLINE:22328673].

\ \ \N \N \N 21510 IPR002925 Dienelactone hydrolases play a crucial role in chlorocatechol degradation via the modified ortho cleavage pathway. Enzymes induced in 4-fluorobenzoate-utilizing bacteria have been classified into three groups on the basis of their specificity towards cis- and trans-dienelactone [MEDLINE:93259944].Some proteins contain repeated small fragments of this domain (for example rat kan-1 protein).\ \ hydrolase activity ; GO:0016787 \N \N 21511 IPR002926 The Arabidopsis thaliana CONSTANS (CO) gene promotes flowering in long days. Two regions of the proteins of this type are particularly well conserved, a N-terminal region with two putative zinc fingers (the CONSTANS zinc finger) and a C-terminal region which may contain a nuclear localization signal [MEDLINE:98341711].\ DNA binding activity ; GO:0003677 \N \N 21502 IPR002915 This family includes the enzyme deoxyribose-phosphate aldolase EC: 4.1.2.4, which is involved in nucleotide metabolism.

2-deoxy-D-ribose 5-phosphate = D-glyceraldehyde 3-phosphate + acetaldehyde

\ The family also includes a group of related bacterial proteins of unknown function, see examples Q57843.\ \ aldolase activity ; GO:0016228 \N \N 21503 IPR002916 This family includes a common region in the transmembrane proteins mammalian cytochrome b-245 heavy chain (gp91-phox), ferric reductase transmembrane component in yeastmand respiratory burst oxidase from mouse-ear cress.This may be a family of flavocytochromes capable of moving electrons across the plasma membrane [MEDLINE:93309468] that include a potential FAD binding domain.\ Mutations in the sequence of cytochrome b-245 heavy chain (gp91-phox)\ lead to the X-linked chronic granulomatous disease. The bacteriocidal\ ability of phagocytic cells is reduced and is characterised by the\ absence of a functional plasma membrane associated NADPH oxidase [MEDLINE:87258189].\

The chronic granulomatous disease gene codes for the chain of\ cytochrome b-245 and cytochrome b-245 is missing from patients with\ the disease [MEDLINE:87258190].

\ \ oxidoreductase activity ; GO:0016491 membrane ; GO:0016020 electron transport ; GO:0006118 21512 IPR002927 This family consists of virion host shutoff (VHS) proteins from various herpes viruses as well as varicella zoster virus and pseudorabies virus.The VHS proteins inhibit cellular gene expression in infected cells.\ The VHS polypeptide destabilizes preexisting host mRNAs and ensures rapid turn over of viral mRNAs [MEDLINE:97456474].\ \ \N \N regulation of transcription, DNA-dependent ; GO:0006355 21504 IPR002917 Human HSR1, has been localized to the human MHC class I region and is highly homologous to a putative GTP-binding protein, MMR1 from mouse. These proteins represent a new subfamily of GTP-binding proteins that has both prokaryote and eukaryote members [MEDLINE:94235953].\ \N \N \N 21505 IPR002918 Lipases or triacylglycerol acylhydrolases hydrolyse ester bonds in triacylglycerol giving diacylglycerol, monoacylglycerol, glycerol and free fatty acids [MEDLINE:92329538]. These have been called class 2 as they are not clearly related to other lipase families.

These enzymes catalyse the reaction:

Triacylglycerol + H₂O = diacylglycerol + a fatty acid anion

\ \ lipase activity ; GO:0016298 \N lipid catabolism ; GO:0016042 21506 IPR002919 This domain is found in trypsin inhibitors as well as in many extracellular proteins. The domain typically contains ten cysteine residues that form five disulphide bonds. The cysteine residues that form the disulphide bondsare 1-7, 2-6, 3-5, 4-10 and 8-9.\ \ \N \N \N 21507 IPR002921

Triglyceride lipases are lipolytic enzymes that hydrolyse ester linkages oftriglycerides [MEDLINE:89150316]. Lipases are widely distributed in animals, plants and prokaryotes. This family of lipases have been called Class 3 as they are not closely related to other lipase families.

\ \ triacylglycerol lipase activity ; GO:0004806 \N lipid metabolism ; GO:0006629 21508 IPR002922 This family includes P32318. This enzyme is involved in the biosynthesis of the thiamine precursor thiazole, and is repressed by thiamine.\ \N \N thiamin biosynthesis ; GO:0009228 21509 IPR002924

This family consists of adenovirus E1B 19 kDa protein or small t-antigen. The E1B 19 kDa protein inhibits E1A induced apoptosis and hence prolongs the viability of the host cell [MEDLINE:94365959].It can also inhibit apoptosis mediated by tumor necrosis factor and Fas antigen [MEDLINE:94365959]. E1B 19 kDa blocks apoptosis by interacting with and inhibiting the p53-inducible and death-promoting Bax protein [MEDLINE:96178771].\ The E1B region of adenovirus encodes two proteins E1B 19 kDa the small t-antigen as found in this family and E1B 55 kDa the\ large t-antigen which is not found in this family; both\ of these proteins inhibit E1A induced apoptosis [MEDLINE:94365959].

\ \ apoptosis inhibitor activity ; GO:0008189 \N anti-apoptosis ; GO:0006916 21497 IPR002909 This family consists of a domain that has an immunoglobulin like fold. These domains are found in cell surface receptors such as Met and Ron as well as in intracellular transcription factors where it is involved in DNA binding.The Ron tyrosine kinase receptor shares with the members of its subfamily (Met and Sea) a unique functional feature: the control of cell dissociation, motility, and invasion of extracellular matrices (scattering) [MEDLINE:96413302].\ \ \N \N \N 21498 IPR002910 This family consists of various plant development proteins which are homologues of Floricaula (FLO) and leafy (LFY) proteins which are floral meristemidentity proteins.\ Mutations in the sequences of these proteins affect flower and leaf development.\ \ \N \N \N 21499 IPR002912 The ACT domain is found in a variety of contexts and is proposed to be a conserved regulatory binding fold. ACT domains are linked to a wide range of metabolic enzymes that are regulated by amino acid concentration. The archetypical ACT domain is the C-terminal regulatory domain of 3-phosphoglycerate dehydrogenase (3PGDH), which folds with a ferredoxin-like topology. A pair of ACT domains form an eight-stranded antiparallel sheet with two molecules of allosteric inhibitor serine bound in the interface. Biochemical exploration of a few other proteins containing ACT domains supports the suggestions that these domains contain the archetypical ACT structure. [MEDLINE:21622562]\ amino acid binding activity ; GO:0016597 \N metabolism ; GO:0008152 21500 IPR002913

START (StAR-related lipid-transfer) is a lipid-binding domain in StAR, HD-ZIP and signalling proteins [MEDLINE:99257451]. StAR (Steroidogenic Acute Regulatory protein) is a mitochondrial protein that is synthesised in response to luteinising hormone stimulation [MEDLINE:95050616]. Expression of the protein in the absence of hormone stimulation is sufficient to induce\ steroid production, suggesting that this protein is required in the acute regulation of\ steroidogenesis. Representatives of the START domain family have\ been shown to bind different ligands such as sterols (StAR protein) and\ phosphatidylcholine (PC-TP). Ligand binding by the START domain can also\ regulate the activities of other domains that co-occur with the START domain\ in multidomain proteins such as Rho-gap, the homeodomain,\ and the thioesterase domain [MEDLINE:99257451], [MEDLINE:21173595].

\ The crystal structure of START domain of human MLN64 shows an / fold built around an U-shaped incomplete -barrel. Most\ importantly, the interior of the protein encompasses a 26 x 12 x 11 Angstroms\ hydrophobic tunnel that is apparently large enough to bind a single\ cholesterol molecule [MEDLINE:20264523]. The START domain structure revealed an unexpected\ similarity to that of the birch pollen allergen Bet v 1 and to bacterial\ polyketide cyclases/aromatases [MEDLINE:21173595], [MEDLINE:20264523].

\ \ \N \N \N 21501 IPR002914

The allergens in this family include allergens with the following designations: Lol p 5, Pha a 5, Phl p 5, Phl p 6, Phl p 11 and Poa p 9.

\ \ \

Grass pollen allergens are one of the major causes of type I allergies (including allergic rhinoconjunctivitis, allergic bronchial asthma and hayfever), afflicting 15-20% of a genetically predisposed population [MEDLINE:91093232]. The predicted molecular masses of the known pollen allergen proteins range from 28.3 to 37.8 kD [MEDLINE:91093232]. Northern analysis indicates that expression of the genes is confined to pollen tissue. A low level of similarity is observed between the Phl p 5 allergens and the N-terminal sequences of Poa p 9 proteins [MEDLINE:91268549] (see IPR001778).

The N-terminal region of Poa p 9 has been shown to possess epitopes that cross-react with the acidic group V allergens of Timothy grass\ \ \ \ [MEDLINE:91268549]. Comparison of amino acid sequences of recombinant Poa p 9 proteins with those of Lol p 5 isoallergens revealed a low level of similarity between the N-terminal sequences of these proteins [MEDLINE:91268549]. A C-terminal region (IPR001778/>), conserved in Poa p 9 allergens, appears to contain epitopes unique to these proteins [MEDLINE:91268549].

\ \ \N \N \N 21495 IPR002906

\ \ \

This family of ribosomal proteins consists mainly of the 40S ribosomal protein S27a which is synthesized as a C-terminal extension of ubiquitin (CEP) (IPR000626). The S27a\ domain compromises the C-terminal half of the protein.\ The synthesis of ribosomal proteins as extensions of ubiquitin promotes their incorporation into nascent ribosomes by a transient metabolic stabilization and is required for efficient ribosome biogenesis [MEDLINE:89181925]. The ribosomal extension protein S27a contains a basic region that is proposed to form a zinc finger; its fusion gene is proposed as a mechanism to maintain a fixed ratio between ubiquitin necessary for degrading proteins and ribosomes a\ source of proteins [MEDLINE:89181932].

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 21494 IPR002905 This enzyme EC: 2.1.1.32 uses S-adenosyl-L-methionine to methylate tRNA:

 S-AdoMet + tRNA = S-adenosyl-L-homocysteine + tRNA containing N2-methylguanine

\ The TRM1 gene of Saccharomyces cerevisiae is necessary for the N2,N2-dimethylguanosine modification of both mitochondrial and cytoplasmic tRNAs [MEDLINE:98352211]. The enzyme is found in both eukaryotes and archaebacteria\ \ \ \ [MEDLINE:87260951].\ \ tRNA (guanine-N2-)-methyltransferase activity ; GO:0004809 \N tRNA processing ; GO:0008033 21496 IPR002908 The frataxin-like domain is related to the globular C-terminus of frataxin the protein that is mutated in Friedreich's ataxia [MEDLINE:97084946]. Friedreich ataxia is a progressive neurodegenerative disorder caused by loss of function mutations in the gene encoding frataxin (FRDA). Frataxin mRNA is predominantly expressed in tissues with a high metabolic rate (including liver, kidney, brown fat and heart). Mouse and yeast frataxin homologues contain a potential N-terminal mitochondrial targeting sequence, and human frataxin has been observed to co-localise with a mitochondrial protein. Furthermore, disruption of the yeast gene has been shown to result in mitochondrial dysfunction. Friedreich's ataxia is thus believed to be a mitochondrial disease caused by a mutation in the nuclear genome (specifically, expansion of an intronic GAA triplet repeat) [MEDLINE:96173952], [MEDLINE:96399023], [MEDLINE:97385237].

This domain is found in a family of bacterial proteins. The function of this domain is currently unknown.

\ \ \N \N \N 21488 IPR002898 This family groups together integral membrane proteins that appear to be involved in translocation of proteins across a membrane. These proteins are probably proton channels. MotA is an essential component of the flageller motor that uses a proton gradient to generate rotational motion in the flageller [MEDLINE:99287838]. ExbB is part of the TonB-dependent transduction complex. The TonB complex uses the proton gradient across the inner bacterial membrane to transport large molecules across the outer bacterial membrane.\ \ protein transporter activity ; GO:0008565 membrane ; GO:0016020 transport ; GO:0006810 21489 IPR002900

This domain has no known function. It is found in many proteins from Caenorhabditis elegans. The domain is found associated with the cyclin-like F-box IPR001810.

\ \ \N \N \N 21490 IPR002901 This family includes mannosyl-glycoprotein endo-

-N-acetylglucosamidase EC: 3.2.1.96. Also included in this family is the flagellar protein J P75942 that has been shown tohydrolyse peptidoglycan [MEDLINE:99175455].\ \ amidase activity ; GO:0004040 \N peptidoglycan catabolism ; GO:0009253 21491 IPR002902 This domain is found in plants and it has no known function. It is found in serine/threonine kinases, associated with the Eukaryotic protein kinase domain IPR000719. The domain contains four conserved cysteines.\ \N \N \N 21492 IPR002903 This is a family of methyltransferases. Methyltransferases are responsible for the transfer of methyl groups between two molecules.\ methyltransferase activity ; GO:0008168 \N \N 21493 IPR002904

\ \

Class-II tRNA synthetases do not share a high degree of similarity, however at least three conserved regions are present [MEDLINE:94099781], [MEDLINE:91272282], [MEDLINE:91305088].

\ \

\ \ ATP binding activity ; GO:0005524 \N lysyl-tRNA aminoacylation ; GO:0006430 21487 IPR002896 Herpesviruses are dsDNA viruses with no RNA stage. This family consists of glycoprotein-D (gD or gIV) which is common to herpes simplex virus types 1 and 2, as well as equine herpes, bovine herpes and Marek's disease virus. Glycoprotein-D has been found on the viral envelope and the plasma membrane of infected cells. gD immunisation can produce an immune response to bovine herpes virus (BHV-1). This response is stronger than that of the other major glycoproteins gB (gI) and gC (gIII) in BHV-1 [MEDLINE:95133156].\ \N \N \N 21482 IPR002891 Enzyme that catalyses the phosphorylation of adenylylsulfate to 3'-phosphoadenylylsulfate. This domain contains an ATP binding P-loop motif [MEDLINE:99003196].\ transferase activity, transferring phosphorus-containing groups ; GO:0016772 \N sulfate assimilation ; GO:0000103 21483 IPR002892 This domain is found in a large number of, as yet, uncharacterised Caenorhabditis elegans proteins. It is about 240 amino acids long and contains a cluster of four conserved cysteines.\ \N \N \N 21484 IPR002893 This domain is found in some suppressors of cell cycle entry [MEDLINE:96203118], [MEDLINE:98079069]. The MYND zinc finger (ZnF) domain is one of two domains in AML/ETO fusion protein required for repression of basal transcription from the multidrug resistance 1 (MDR-1) promoter. The other domain is a hydrophobic heptad repeat (HHR) motif [MEDLINE:98252948]. The AML-1/ETO fusion protein is created by the (8;21) translocation, the second most frequent chromosomal abnormality associated with acute myeloid leukemia. In the fusion protein the AML-1 runt homology domain, which is responsible for DNA binding and CBF

interaction is linked to ETO, a gene of unknown function [MEDLINE:96068903].\ \N \N \N 21485 IPR002894 This domain is found in HypB, a hydrogenase expression / formation protein, and UreG a urease accessory protein. Both these proteins contain a P-loop nucleotide binding motif [MEDLINE:97352660], [MEDLINE:93139028]. HypB has GTPase activity and is a guanine nucleotide binding protein [MEDLINE:93139028]. It is not known whether UreG binds GTP or some other nucleotide. Both enzymes are involved in nickel binding. HypB can store nickel and is required for nickel dependent hydrogenase expression [MEDLINE:97285753]. UreG is required for functional incorporation of the urease nickel metallocenter.[MEDLINE:92325016] GTP hydrolysis may required by these proteins for nickel incorporation into other nickel proteins [MEDLINE:97285753].\ heavy metal binding activity ; GO:0005505 \N \N 21486 IPR002895 The G surface protein of Paramecium primaurelia has important internal homologies and a periodic structure, which could be dictated in part by the rigid scaffolding of cysteine residues. The predicted secondary structure shows a quasi absence of

-helix and an abundance of

-pleated sheets and random coils. The monotony of the amino acid sequence is in favour of a structural role for the protein [MEDLINE:87060934]. This structure is based on the presence of 37 periods of about 75 residues, each period containing eight cysteine residues [MEDLINE:90172419]. Homologies with other proteins are limited to surface antigens of trypanosomes\ \N \N \N 21477 IPR002885

This repeat has no known function and appears to be greatly expanded in plants. The repeat occurs in PET309 P32522 that has a domain organization similar to the human BRCA1 protein.

\ \N \N \N 21478 IPR002886

B-lytic endopeptidases are bacterial metallopeptidases that belong to theM23 protease family [MEDLINE:95405261], see protease Database http://merops.sanger.ac.uk/merops.htm]. Cleavage is specific for glycine bonds,\ especially in -Gly-Gly+Xaa sequences (Xaa is any aliphatic hydrophobic\ residue). They lyse the cell walls of Gram-positive bacteria in which the\ peptidoglycan cross-links contain glycine residues. The enzymes contain\ zinc, but the exact position of the metal-binding ligands is uncertain. On\ the basis of similarity with D-Ala-D-Ala-carboxypeptidase, it has been\ suggested that a conserved His-X-His motif (where X is any amino acid)\ forms part of the binding site [MEDLINE:95405261]. Members of this family are the peptidase family M37, which are Gly-Gly endopeptidases, and the peptidase family M23. This family also includes some bacterial lipoproteins such as P33648 for which no proteolytic activity has been demonstrated.

\ \ metalloendopeptidase activity ; GO:0004222 \N proteolysis and peptidolysis ; GO:0006508 21476 IPR002884 Cellular trafficking of subtilisin/kexin-like precursor convertases (PCs) may be regulated by a number of motifs, some of which are present within the P-domain and in the C-terminal sequence. A conserved RGD sequence is present within the P domain [MEDLINE:99230264]. The integrity of the RGD sequence of proprotein convertase PC1 is critical for its zymogen and C-terminal\ processing and for its cellular trafficking [MEDLINE:97439715]. \

This domain is also found in Aeromonas salmonicida bacteria.

\ \ subtilase activity ; GO:0004289 \N proteolysis and peptidolysis ; GO:0006508 21480 IPR002889 The WSC domain is a putative carbohydrate binding domain. The domaincontains up to eight conserved cysteine residues that may be involved\ in disulphide bridges.\ The Trichoderma harzianum

-1,3 exoglucanase contains two copies of the WSC domain, while the yeast SLG1 protein contains only one.\ \ \N \N \N 21481 IPR002890 The proteinase-binding

-macroglobulins (A2M) [MEDLINE:89308535] are large glycoproteins found in the plasma of vertebrates, in the hemolymph of some invertebrates and in reptilian and avian egg white. A2M-like proteins are able to inhibit all four classes of proteinases by a 'trapping' mechanism. They have a peptide stretch, called the 'bait region', which contains specific cleavage sites for different proteinases. When a proteinase cleaves the bait region, a conformational change is induced in the protein, thus trapping the proteinase. The entrapped enzyme remains active against low molecular weight substrates, whilst its activity toward larger substrates is greatly reduced, due to steric hindrance. Following cleavage in the bait region, a thiol ester bond, formed between the side chains of a cysteine and a glutamine, is cleaved and mediates the covalent binding of the A2M-like protein to the proteinase. This family includes the N-terminal region of the

-2-macroglobulin family.\ endopeptidase inhibitor activity ; GO:0004866 \N \N 21479 IPR002888 The [2Fe-2S] binding domain is found in a range of enzymes including dehydrogenases, oxidases and oxidoreductases.

The aldehyde oxido-reductase (Mop) from the sulfate reducing anaerobic Gram-negative bacterium Desulfovibrio gigas is a homodimer of 907 amino acid residues subunits and is a member of the xanthine oxidase family. The protein contains a molybdopterin cofactor (Mo-co) and two different [2Fe-2S] centers. It is folded into four domains of which the first two bind the iron sulfur centers and the last two are involved in Mo-co binding. Mo-co is a molybdenum molybdopterin cytosine dinucleotide. Molybdopterin forms a tricyclic system with the pterin bicycle annealed to a pyran ring. The molybdopterin dinucleotide is deeply buried in the protein. The cis-dithiolene group of the pyran ring binds the molybdenum, which is coordinated by three more (oxygen) ligands [MEDLINE:96072968].

\ \ \N \N \N 21467 IPR002873 This family consists of rotaviral non-structural RNA binding protein 34 (NS34 or NSP3). The NSP3 protein has been shown to bind viral RNA. The NSP3 protein consists of 3 conserved functional domains; a basic region which binds ssRNA, a region containing heptapeptide repeats mediating oligomerisation and a leucine zipper motif [MEDLINE:92410649]. NSP3 may play a central role in replication and assembly of genomic RNA structures [MEDLINE:92410649]. Rotaviruses have a dsRNA genome and are a major cause cause of acute gastroenteritis in the young of many species [MEDLINE:95176561].\ RNA binding activity ; GO:0003723 \N \N 21468 IPR002874 This family consists of glycoprotein I from various members of the alphaherpesvirinae. These include herpesvirus, varicella-zoster virus and pseudorabies virus. Glycoprotein I (gI) is important during natural infection, mutants lacking gI produce smaller lesions at the site of infection and show reduced neuronal spread [MEDLINE:96357074]. gI forms a heterodimeric complex with gE; this complex displays Fc receptor activity (binds to the Fc region of immunoglobulin) [MEDLINE:96357074]. Glycoproteins are also important in the production of virus-neutralizing antibodies and cell mediated immunity [MEDLINE:94267406]. The alphaherpesvirinae have a dsDNA genome and have no RNA stage during viral replication.\ \N \N \N 21469 IPR002876 This domain is found in bacteria, plants, and yeast proteins. It compromises the entire length or central region of most of the proteins in the family, all of which are hypothetical with no known function. The average length of this domain is approximately 230 amino acids long.\ \N \N \N 21470 IPR002877 This family consists of FtsJ from various bacterial and archaeal sources. FtsJ is a methyltransferase, it has no effect on cell division. FtsJ's substrate is the 23S rRNA. The 1.5 A crystal structure of FtsJ in complex with its cofactor S-adenosylmethionine revealed that FtsJ has a methyltransferase fold. This family also includes the N terminus of flaviviral NS5 protein. It has been hypothesized that the N-terminal domain of NS5 is a methyltransferase involved in viral RNA capping [MEDLINE:20437276]. \ \N \N \N 21454 IPR002858 Several multicopy gene families have been described in Plasmodiumfalciparum, including the stevor family of subtelomeric open reading\ frames and the rif interspersed repetitive elements. Both families\ contain three predicted transmembrane segments. It has been proposed\ that stevor and rif are members of a larger superfamily that code\ for variant surface antigens [MEDLINE:99094504].\ \ \N \N \N 21455 IPR002859 Sequence similarity between a region of the autosomal dominant polycystic kidney disease (ADPKD) protein, polycystin-1 and a sea urchin sperm glycoprotein involved in fertilization, the receptor for egg jelly (suREJ) has been known for some time. The suREJ protein binds the glycoprotein coat of the egg (egg jelly), triggering the acrosome reaction, which transforms the sperm into a fusogenic cell. The sequence similarity and expression pattern suggests that the predicted human PKDREJ protein is a mammalian equivalent of the suREJ protein and therefore may have a central role in human fertilization [MEDLINE:99138702].\ \N \N \N 21475 IPR002883

The recycling of photosynthetically fixed carbon in plant cell walls is a key microbial process. Enzyme systems that\ attack the plant cell wall contain noncatalytic carbohydrate-binding modules that mediate attachment to this composite\ structure and play a pivotal role in maximizing the hydrolytic process. In anaerobes, the\ degradation is carried out by a high molecular weight,\ multifunctional complex termed the cellulosome. This\ consists of a number of independent enzyme\ components, each of which contains a conserved 40-residue \ dockerin domain, which functions to bind the enzyme to a\ cohesin domain within the scaffoldin protein [MEDLINE:96077124], [MEDLINE:96094325].

In\ anaerobic bacteria that degrade plant cell walls, exemplified by\ Clostridium thermocellum, the dockerin domains of the\ catalytic polypeptides can bind equally well to any cohesin from\ the same organism. More recently, anaerobic fungi, typified by Piromyces equi,\ have been suggested to also\ synthesize a cellulosome complex, although the dockerin\ sequences of the bacterial and fungal enzymes are completely\ different [MEDLINE:21415764]. For example, the fungal enzymes contain one, two or\ three copies of the dockerin sequence in tandem within the\ catalytic polypeptide. In contrast, all the C. thermocellum\ cellulosome catalytic components contain a single dockerin\ domain. The anaerobic bacterial dockerins are homologous to EF hands\ (calcium-binding motifs) and\ require calcium for activity whereas the fungal dockerin does not require calcium. Finally, the interaction between cohesin and dockerin\ appears to be species specific in bacteria, there is almost no species specificity of binding within fungal\ species and no identified\ sites that distinguish different species.

The structure of dockerin from Piromyces equi contains two helical stretches and four short -strands which form an\ antiparallel sheet structure adjacent to an\ additional short twisted parallel strand. The N- and C-termini are\ adjacent to each other.

Aerobic bacteria contain related regions, however these appear to function as cellulose/carbohydrate binding domains.

\ \ \ hydrolase activity, hydrolyzing O-glycosyl compounds ; GO:0004553 \N carbohydrate metabolism ; GO:0005975 21473 IPR002881

This domain is found in a family of prokaryotic proteins that have no known function. Proteins belonging to this family include hypothetical proteins from eubacteria and archaebacteria. Some of these proteins also contain the Von Willebrand factor, type A domain (see IPR002035).

\ \N \N \N 21474 IPR002882 The function of this family is unknown. Proteins belonging to this family include hypothetical proteins from several prokaryotes.\ \N \N \N 21471 IPR002878 This domain has no known function and is found in conserved hypothetical archaeaand bacterial proteins. The domain is approximately 120 amino acids long.\ \ \N \N \N 21472 IPR002880 This family includes the N terminal region of the pyruvate ferredoxin oxidoreductase, corresponding to the first two structural domains. This region is involved in inter subunit contacts [MEDLINE:99140300]. Pyruvate oxidoreductase (POR) catalyses the final step in the fermentation of carbohydrates in anaerobic microorganisms [MEDLINE:96125254]. This involves the oxidative decarboxylation of pyruvate with the participation of thiamine followed by the transfer of an acetyl moiety to coenzyme A for the synthesis of acetyl-CoA [MEDLINE:96125254]. The family also includes pyruvate flavodoxin oxidoreductase as encoded by the nifJ gene in cyanobacterium which is required for growth on molecular nitrogen when iron is limited [MEDLINE:94022264].\ oxidoreductase activity ; GO:0016491 \N electron transport ; GO:0006118 21466 IPR002872 The proline oxidase/dehydrogenase EC: 1.5.99.8 is responsible for the first step in the conversion of proline to glutamate for use as a carbon and nitrogen source. The enzyme requires FAD as a cofactor, and is induced by proline.It is found in combination with IPR002086 in bacteria.\ \ proline dehydrogenase activity ; GO:0004657 \N proline catabolism ; GO:0006562 21464 IPR002870

Metalloendopeptidase M12B contains a sequence motif similar to the 'cysteine switch' of the matrixins. Many of the proteins with this domain are zinc proteases that may mediate cell-cell or cell-matrix interactions.

\ metalloendopeptidase activity ; GO:0004222 \N proteolysis and peptidolysis ; GO:0006508 21465 IPR002871

Pioneering investigations on the maturation of Fe-S proteins were performed in bacteria and have led to the identification of two operons termed nif (nitrogen fixation) and isc (iron-sulfur cluster assembly) that function in Fe-S-cluster biosynthesis. The nif operon encodes proteins that execute specific functions in the assembly of nitrogenase, a complex metalloenzyme that catalyses the fixation of nitrogen; some of the Nif proteins are specifically involved in the formation of the Fe-S cluster of nitrogenase and these are found in organisms that do not fix nitrogen. The isc operon encodes proteins necessary for the maturation of bacterial Fe-S proteins.

\ \

In a number of organisms, for example Azotobacter vinelandii, NifU is a protein associated with the nif operon. It contains two domains, the N-terminal, presented in this entry, and the C-terminal (IPR001075). These domains exist either together or on different polypeptides, both domains being found in organisms that do not fix nitrogen e.g. yeast, so they have a broader significance in the cell than nitrogen fixation. It has been proposed that they are specifically required for the formation and maturation of Fe-S clusters that in eukaryotes occurs in the mitochondrial matrix. In yeast, for example, deletion of the C-terminal domain does not markedly affect Fe-S biosynthesis but in combination with inactivation of ISU1 there is a defect in mitochondrial FE-S-protein maturation.

\ \ \ \N \N \N 21461 IPR002867 A cysteine-rich domain (C6HC), present in Triad1, is conserved in other proteins encoded by various eukaryotes. The C6HC consensus pattern C-x(4)-C-x(14-30)-C-x(1-4)-C-x(4)-C-x(2)-C-x(4)-H-x(4)-C defines this structure as the fourth family member of the zinc-binding RING, LIM, and LAP/PHD fingers. Strikingly, in most of the proteins the C6HC domain is flanked by two RING finger structures IPR001841.\ \N \N \N 21462 IPR002868 The molecular function of the non-structural 5a viral protein is uncertain.The NS5a protein is phosphorylated when expressed in mammalian cells.\ It is thought to interact with the dsRNA-dependent (interferon\ inducible) kinase PKR, P19525\ \ \ \ [MEDLINE:98378533], [MEDLINE:97288299].\ \ \N \N \N 21463 IPR002869 This family is found in prokaryotes. It includes a region of the large protein pyruvate-flavodoxin oxidoreductase and the whole pyruvate ferredoxin oxidoreductase gamma subunit protein. It is not known whether thegamma subunit has a catalytic or regulatory role. Pyruvate\ oxidoreductase (POR) catalyses the final step in the fermentation\ of carbohydrates in anaerobic microorganisms [MEDLINE:96125254]. This involves the\ oxidative decarboxylation of pyruvate with the participation of\ thiamine followed by the transfer of an acetyl moiety to coenzyme\ A for the synthesis of acetyl-CoA [MEDLINE:96125254]. The family also includes\ pyruvate flavodoxin oxidoreductase as encoded by the nifJ gene in\ cyanobacterium which is required for growth on molecular nitrogen\ when iron is limited [MEDLINE:94022264].\ \ oxidoreductase activity ; GO:0016491 \N electron transport ; GO:0006118 21460 IPR002866 This region is found in plant potential maturases, which probably assist in splicing chloroplast group II introns. The function of this region is unknown [MEDLINE:94077696].\ \N \N \N 21458 IPR002862

Proteins that contain this domain are of unknown function. It appears to occur towards the C-terminus of proteins from Mycoplasma pneumoniae\ \ \ [MEDLINE:97105885].

\ \ \N \N \N 21459 IPR002864 This family is found in plants. It consists of various acyl-acyl carrier protein (ACP) thioesterases (TE) which terminate fatty acyl group extension via hydrolyzing an acyl group on a fatty acid [MEDLINE:96068671].\ acyl carrier activity ; GO:0000036 \N fatty acid biosynthesis ; GO:0006633 21456 IPR002860 BNR repeats are short repeats never found closer than 40 residues together, which suggests that the repeat is structurally longer. These repeats are found in many glycosyl hydrolases as well as other extracellular proteins of unknown function.\ \ \N \N \N 21457 IPR002861 Extracellular matrix (ECM) proteins play an important role in early cortical development, specifically in the formation of neural connections and in controlling the cyto-architecture of the central nervous system. The product of the reeler gene in mouse is reelin,a large extracellular protein secreted by pioneer neurons that coordinates cell positioning during neurodevelopment [MEDLINE:97478533]. F-spondin and mindin are a family of matrix-attached adhesion molecules that share structural similarities and overlapping domains of expression. \ Both F-spondin and mindin promote adhesion and outgrowth of hippocampal embryonic neurons and bind to a putative receptor(s) expressed on both hippocampal and sensory neurons [MEDLINE:99339921].\ \

This domain of unknown function is found at the N terminus of reelin\ and F-spondin (see http://www.bork.embl-heidelberg.de/Modules/07-matrix.gif).

\ \ \N \N \N 21450 IPR002854

The archaeal proteins in this family have no known function.

\ \N \N \N 21451 IPR002855

The archaeal proteins in this family have no known function.

\ \N \N \N 21452 IPR002856 The enzyme tetrahydromethanopterin S-methyltransferase EC: 2.1.1.86is composed of eight subunits, MtrA-H [MEDLINE:95255265]. The enzyme is a membrane-\ associated enzyme complex which catalyzes an energy-conserving,\ sodium-ion-translocating step in methanogenesis from hydrogen and\ carbon dioxide [MEDLINE:95255265].\

Subunit MtrH catalyzes the methylation reaction and was\ shown to exhibit methyltetrahydromethanopterin:cob(I)alamin methyltransferase activity [MEDLINE:99268446].

\
CH3-H4MPT + cob(I)alamin --> H4MPT + CH3-cob(III)alamin\
(H4MPT = tetrahydromethanopterin)\
\

\ \ methyltransferase activity ; GO:0008168 \N methanogenesis ; GO:0015948 21453 IPR002857

\ This domain contains eight conserved cysteine residues\ that bind to zinc. The CXXC domain is found in proteins\ that methylate cytosine, proteins that bind to methyl\ cytosine and HRX related proteins.\ \ zinc ion binding activity ; GO:0008270 \N \N 21440 IPR002844 This archaeal enzyme family is involved in formation of methane fromcarbon dioxide EC: 1.5.99.9. The enzyme requires coenzyme F420 [MEDLINE:95155355].\ \ hydrogenase activity ; GO:0008901 \N methanogenesis ; GO:0015948 21441 IPR002845

The archaebacterial proteins in this family have no known function.

\ \N \N \N 21442 IPR002846 These archaebacterial proteins have no known function.The domain is found duplicated in some sequences.\ \ \N \N \N 21443 IPR002847

This prokaryotic protein family has no known function. The signature is sometimes found at the N-terminal of proteins that also contain the nitroreductase family signature IPR000415.

\ \N \N \N 21448 IPR002852

The bacterial and archaeal proteins in this family have no known function.

\ \N \N \N 21449 IPR002853 The general transcription factor TFIIE has an essential role in eukaryotictranscription initiation together with RNA polymerase II and other\ general factors. Human TFIIE consists of two subunits TFIIE-

P29083 and joins the preinitiation\ complex after RNA polymerase II and TFIIF [MEDLINE:92065982]. This family consists\ of the conserved amino terminal region of eukaryotic TFIIE-

and proteins from archaebacteria that are presumed to be TFIIE-

subunits also [MEDLINE:98049343].\ \ RNA polymerase II transcription factor activity ; GO:0003702 transcription factor TFIIE complex ; GO:0005673 transcription initiation from Pol II promoter ; GO:0006367 21445 IPR002849 This archaebacterial protein family has no known function.The proteins are predicted to contain two transmembrane\ helices.\ \ \N \N \N 21446 IPR002850

The prokaryotic proteins in this family have no known function.

\ \ \N \N \N 21447 IPR002851

This family of proteins has no known function. It has been found in Archaea and yeast and contains a lysine-rich domain.

\ \ \ \N \N \N 21444 IPR002848

Translins are DNA-binding proteins that specifically recognise consensus sequences at the breakpoint junctions in chromosomal translocations, mostly involving immunoglobulin (Ig)/T-cell receptor gene segments. They seem to recognise single-sranded DNA ends generated by staggered breaks occuring at recombination hot spots [MEDLINE:97165975].

\ \N \N \N 21436 IPR002838

The prokaryotic proteins in this family have no known function.

\ \N \N \N 21437 IPR002840

This archaebacterial protein family has no known function.

\ \N \N \N 21438 IPR002842

\ \

\ \ \ \ \ \ \ \ \

This family also includes the vacuolar ATP synthase\ E subunit [MEDLINE:91009356], as well as the archaebacterial ATP\ synthase E subunit [MEDLINE:96324968].

\ \

\ \ \ \ \ \ \ \ \

This family includes the AC39 subunit from vacuolar ATP\ synthase [MEDLINE:93286119], and the C subunit from archaebacterial\ ATP synthase [MEDLINE:96324968]. The family also includes subunit C from the\ Sodium transporting ATP synthase from Enterococcus hirae\ \ \ \ [MEDLINE:94209269].

\ \ hydrogen-transporting two-sector ATPase activity ; GO:0003936 \N proton transport ; GO:0015992 21432 IPR002834

This archaebacterial domain has no known function. It is attached to aDNA-binding domain of one protein suggesting that this domain might be involved in recognizing some regulatory molecule.

\ \ \N \N \N 21433 IPR002835

The function of the prokaryotic proteins in this family is unknown.

\ \N \N \N 21434 IPR002836

This protein family is found in archaea and eukaryota. The human TFAR19 encodes a protein which shares significant homology to the corresponding proteins of species ranging from yeast to mice. TFAR19 exhibits a ubiquitous expression pattern and its expression is upregulated in the tumor cells undergoing apoptosis. TFAR19 may play a general role in the apoptotic process [MEDLINE:99121216]. Also included in this family is a DNA-binding protein from the archaea, Methanobacterium thermoautotrophicum.

\ \N \N \N 21435 IPR002837

This archaebacterial domain has no known function. In Methanococcus jannaschii it occurs with an endonuclease domain IPR003265.

\ \N \N \N 21419 IPR002818

The role of this family is unclear.This family includes proteins involved in RNA-protein interaction regulation,\ thiamine biosynthesis, Ras-related signal transduction, and protease activity.

\ \ \N \N \N 21420 IPR002820 The DMSO reductase of Rhodobacter capsulatus contains a pterin molybdenum cofactor (Moco) that is located in the periplasm . There are four genes involved in the biosynthesis of the Moco (moaA, moaD, moeB and moaC) [MEDLINE:99337076]. MoaA and moaC from Escherichia coli catalyse the first steps in MoCo synthesis [MEDLINE:98400256].\ \N \N Mo-molybdopterin cofactor biosynthesis ; GO:0006777 21421 IPR002821 This family includes the enzymes hydantoinase and oxoprolinase (EC: 3.5.2.9).Both reactions involve the hydrolysis of 5-membered rings via hydrolysis\ of their internal imide bonds [MEDLINE:97113037].\ \ hydrolase activity ; GO:0016787 \N \N 21422 IPR002822

The proteins in this family have no known function.

\ \N \N \N 21423 IPR002823 Members of this prokaryotic family have no known function but are similar to a protein in a tartrate utilization region (TAR) of Agrobacterium vitis a common pathogen of grapevine. Most grapevine strains utilize tartrate, an abundant compound in grapevine [MEDLINE:96252899].\ \N \N \N 21417 IPR002816

pAD1 is a hemolysin/bacteriocin plasmid originally identified inEnterococcus faecalis DS16. It encodes a mating response to a peptide\ sex pheromone, cAD1, secreted by recipient bacteria. Once the plasmid\ pAD1 is acquired, production of the pheromone ceases, a trait related\ in part to a determinant designated traB [MEDLINE:94302142]. However, this family also contains plant and mammalian proteins, suggesting that the protein may have a somewhat wider function.

\ \ \N \N \N 21418 IPR002817 ThiC is found within the thiamin biosynthesis operon. ThiC is involved inthiamin biosynthesis [MEDLINE:99311269]. The precise catalytic\ function of ThiC is still not known. ThiC participates in the formation of\ 4-Amino-5-hydroxymethyl-2-methylpyrimidine from AIR, an intermediate in\ the de novo pyrimidine biosynthesis.\ \ \ \N \N thiamin biosynthesis ; GO:0009228 21431 IPR002833 This domain has no known function, and has been found in yeast, archaebacteria and eubacteria. In Caenorhabditis elegans this domain occurs with the ubiquitin-associated domain (see IPR000449).\ \N \N \N 21430 IPR002831 Members of this protein family have not been characterised however they appear to contain a helix-turn-helix motif. Therefore they are likely to be transcriptional regulators. \ \N \N \N 21429 IPR002830

This family of proteins are found in procaryotes and yeast. They are related to a carboxy-lyase from Escherichia coli that is involved in ubiquinone biosynthesis [MEDLINE:20485580].

\ \N \N \N 21428 IPR002829 These archaebacterial proteins have no known function.Members of this family contain seven conserved cysteines and\ may also be an integral membrane protein.\ \ \N \N \N 21424 IPR002824

The function of the archaebacterial proteins in this family is unknown.

\ \N \N \N 21425 IPR002825

The function of the archaebacterial proteins in this family is unknown.

\ \N \N \N 21426 IPR002826

The archaebacterial proteins in this family have no known function.

\ \N \N \N 21427 IPR002828

Members of this family are acid phosphatases, EC: 3.1.3.2\ \ \ [MEDLINE:93046805].\ In bacteria they may be involved in the stress response [MEDLINE:95014035]. Escherichia coli cells with the surE gene disrupted are found to survive poorly in stationary phase [MEDLINE:95014035].

\ \ \N \N \N 21403 IPR002801 Aspartate carbamoyltransferase (ATCase) EC: 2.1.3.2 exists as a dimer of catalytic trimers (3x33kDa) that are held together by three dimeric (2x17kDa) regulatory subunits ((c3)2(r2)3). ATCase plays a central role in the regulation of the pyrimidine pathway in bacteria. In (c3)2(r2)3 ATCases, the association of the catalytic subunits c3 with the regulatory subunits r2 is responsible for\ the establishment of positive co-operativity between catalytic sites for the binding of\ aspartate and it dictates the pattern of allosteric response toward nucleotide effectors. ATCase from Escherichia coli is the most extensively studied allosteric enzyme [MEDLINE:95311753]. The crystal structure of the T-state, the T-state with CTP bound, the R-state with N-phosphonacetyl-L-aspartate (PALA) bound, and the R-state with phosphonoacetamide plus malonate bound have been used in interpreting kinetic and mutational studies.\

A high-resolution structure of E.coli ATCase in the presence of PALA (a bisubstrate\ analog) allows a detailed description of the binding at the active site of the enzyme \ and allows a detailed model of the tetrahedral intermediate to be constructed. The\ entire regulatory chain has been traced showing that the N-terminal regions\ of the regulatory chains R1 and R6 are located in close proximity to each other\ and to the regulatory site. This portion of the molecule may be involved in the \ observed asymmetry between the regulatory binding sites as well as in the heterotropic \ response of the enzyme [MEDLINE:20114708].

ATCase from Erwinia herbicola differs from the\ other investigated enterobacterial ATCases by its absence of homotropic\ co-operativity toward the substrate aspartate and its lack of response to ATP which is\ an allosteric effector (activator) of this family of enzymes. Nevertheless, the E.\ herbicola ATCase has the same quaternary structure, two trimers of catalytic chains\ with three dimers of regulatory chains ((c3)2(r2)3), as other enterobacterial ATCases\ and shows extensive primary structure conservation [MEDLINE:20069957].

\ \ \N aspartate carbamoyltransferase complex ; GO:0009347 'de novo' pyrimidine base biosynthesis ; GO:0006207 21404 IPR002802

The function of the archaebacterial proteins in this family is unknown.

\ \N \N \N 21405 IPR002803

The function of this family of proteins from the Archaea is unknown. A single homolog is found in the bacterium, Aquifex aeolicus.

\ \N \N \N 21399 IPR002797 Members of this family are integral membrane proteins [MEDLINE:94162682], and many are implicated in the productionof polysaccharide. The family includes RfbX part of the O antigen biosynthesis\ operon [MEDLINE:94292434], and SpoVB from Bacillus subtilis\ \ \ \ Q00758,\ which is involved in spore cortex biosynthesis [MEDLINE:92078103].\ \ \N membrane ; GO:0016020 polysaccharide biosynthesis ; GO:0000271 21400 IPR002798 Members of this family have several predicted transmembrane regions. The majority of the family members are uncharacterised. Q9V182 is annotated as "Stage II sporulation protein M related"; and weakly related to other proteins with similar annotation.\ \ \N \N \N 21401 IPR002800

Proteins that belong to this group are restricted to the Mycobacteria and the Archaea and have no known function.

\ \N \N \N 21402 IPR002801 Aspartate carbamoyltransferase (ATCase) EC: 2.1.3.2 exists as a dimer of catalytic trimers (3x33kDa) that are held together by three dimeric (2x17kDa) regulatory subunits ((c3)2(r2)3). ATCase plays a central role in the regulation of the pyrimidine pathway in bacteria. In (c3)2(r2)3 ATCases, the association of the catalytic subunits c3 with the regulatory subunits r2 is responsible for\ the establishment of positive co-operativity between catalytic sites for the binding of\ aspartate and it dictates the pattern of allosteric response toward nucleotide effectors. ATCase from Escherichia coli is the most extensively studied allosteric enzyme [MEDLINE:95311753]. The crystal structure of the T-state, the T-state with CTP bound, the R-state with N-phosphonacetyl-L-aspartate (PALA) bound, and the R-state with phosphonoacetamide plus malonate bound have been used in interpreting kinetic and mutational studies.\

\ \ \N aspartate carbamoyltransferase complex ; GO:0009347 'de novo' pyrimidine base biosynthesis ; GO:0006207 21415 IPR002814

The flagellar accessory protein FlaJ is an integral membrane protein.

\ \N \N \N 21416 IPR002815

In all organisms, type II DNA topoisomerases are essential for untanglingchromosomal DNA [MEDLINE:20012926]. The structure of the DNA-binding core of the \ Methanococcus jannaschii DNA topoisomerase VI A subunit has been determined\ to 2.0A resolution. The overall structure of the subunit is unique, demonstrating that archaeal type II enzymes are distinct from other type II\ topoisomerases. Nevertheless, the core structure contains a pair of domains that are also found in type IA and classic type II topoisomerases. Such regions may form the basis of a DNA cleavage mechanism shared among these enzymes [MEDLINE:20012926].

The core A subunit is a dimer, with a deep groove spanning both protomers\ [MEDLINE:20012926]. The dimer architecture is such that DNA is thought to bind in the groove, across the A subunit interface, and the monomers are thought to\ separate during DNA transport. The A subunit of topoisomerase VI is similar to the meiotic recombination factor, Spo11.

Spo11 is a meiosis-specific protein in yeast that covalently binds to DNA\ double-strand breaks (DSBs) during the early stages of meiosis [MEDLINE:20005938]. These DSBs initiate homologous recombination, which is required for chromosomal \ segregation and generation of genetic diversity during meiosis. Mouse and human homologues of Spo11 have been cloned and characterised. The proteins are 82% identical and share ~25% identity with other family members. Mouse Spo11 has been localised to chromosome 2H4, and human SPO11 to chromosome 20q13.2-q13.3, a region amplified in some breast and ovarian tumours [MEDLINE:20005938]. Similarity between SPO11 and archaebacterial TOP6A proteins points to evolutionary specialisation of a DNA-cleavage function for meiotic recombination [MEDLINE:20086432].

\ \ ATP binding activity ; GO:0005524 \N DNA topological change ; GO:0006265 21411 IPR002810

This entry describes prokaryotic proteins of unknown function.

\ \N \N \N 21412 IPR002811 This family has no known function. It is found tocomprise the complete protein in archaebacteria and\ a single domain in a large Caenorhabditis elegans protein.\ \ \N \N \N 21413 IPR002812

This entry describes proteins of unknown function.

\ \N \N \N 21414 IPR002813

Members of the ArgJ family catalyse the first EC: 2.3.1.35 and fifth steps EC: 2.3.1.1 in arginine biosynthesis [MEDLINE:93232760].

\ glutamate N-acetyltransferase activity ; GO:0004358 \N arginine biosynthesis ; GO:0006526 21408 IPR002806 This archaebacterial protein family has no known function.\ \N \N \N 21409 IPR002808

This entry describes prokaryotic proteins of unknown function.

\ \N \N \N 21410 IPR002809 This archaebacterial protein family has no known function.Members are predicted to be integral membrane proteins.\ \ \N \N \N 21407 IPR002805

This entry describes proteins of unknown function.

\ \N \N \N 21406 IPR002804

The function of this family of proteins from the Archaea is unknown. A single homolog is found in the bacterium, Aquifex aeolicus.

\ \N \N \N 21398 IPR002795 A highly diverged class of S-adenosylmethionine synthetases have been identified in the archaea. S-adenosylmethionine is the primary alkylating agent in all known organisms. ATP:L-methionine S-adenosyltransferase (MAT) catalyzes the only known biosynthetic route to this central metabolite. Although the amino acid sequence of MAT is strongly conserved among bacteria and eukarya (see IPR002133. Three bacterial genomes encode both the archaeal and eukaryal/bacterial types of MAT [MEDLINE:20127883].\ \ ATP binding activity ; GO:0005524 \N one-carbon compound metabolism ; GO:0006730 21393 IPR002790

This entry describes archaebacterial proteins of unknown function.

\ \N \N \N 21394 IPR002791

This family of prokaryotic proteins have not been characterized. The proteins have two closely spaced conserved cysteines at their N terminus and a single conserved cysteine at their C terminus.

\ \N \N \N 21395 IPR002792

Saccharomyces cerevisiae contains an endoexonuclease NucR that has been implicated in both recombination and repair. The N-terminal half of the protein shows homology (approximately 50%) with human rho genes, while the C-terminal region, which is related to the Escherichia coli recC protein, apparently encodes the endoexonuclease activity [MEDLINE:93027264].

\ \ \N \N \N 21396 IPR002793

The function of these prokaryotic proteins is unknown.

\ \N \N \N 21397 IPR002794 Members of this family have several predicted transmembrane helices. The function of these prokaryotic proteins is unknown.\ \N \N \N 21389 IPR002785

Proteins of this family are associated with CRISPR repeats in a wide set of prokaryotic genomes; their function is unknown.

\ \N \N \N 21390 IPR002786

This is a family of prokaryotic proteins of unknown function.

\ \N \N \N 21391 IPR002787

This is a family of prokaryotic proteins of unknown function.

\ \N \N \N 21392 IPR002789

This prokaryotic protein family has no known function. It contains several conserved aspartates and histidines that could be metal ligands.

\ \N \N \N 21385 IPR002780

HypD is involved in hydrogenase formation. It containsmany possible metal binding residues, which may bind to nickel.\ Transposon Tn5 insertions into HypD resulted in R.\ leguminosarum mutants that lacked any hydrogenase activity in\ symbiosis with peas\ \ \ \ [MEDLINE:93316844].

\ \ \N \N \N 21386 IPR002781

This domain is found in integral membrane proteins of prokaryotes which are uncharacterized.

\ \N \N \N 21387 IPR002782

This prokaryotic family of proteins have no known function.The proteins contain four conserved cysteines that may be involved in metal binding or disulphide bridges.

\ \ \N \N \N 21388 IPR002784

\ \ \

This family includes the eukaryotic ribosomal protein L14, which binds to the 60S ribosomal subunit, and archaebacterial ribosomal protein L14E, which binds to the 50S ribosomal subunit.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 21375 IPR002770 Formylmethanofuran: tetrahydromethanopterin N-formyltransferase EC: 2.3.1.101 is involved in archaebacteria in the formation of methane from carbon dioxide. This enzyme catalyses the following reaction:\

\
N-formylmethanofuran + 5,6,7,8-tetrahydromethanopterin = methanofuran + 5-formyl-5,6,7,8-tetrahydromethanopterin\

Formylmethanofuran: tetrahydromethanopterin formyltransferase (Ftr) from the methanogenic Archaeon Methanopyrus kandleri (optimum growth temperature 98 degrees C) is a hyperthermophilic enzyme that is absolutely dependent on the presence of lyotropic salts for activity and thermostability. The crystal structure of Ftr, determined to a reveals a homotetramer composed essentially of two dimers. Each subunit is subdivided into two tightly associated lobes both consisting of a predominantly antiparallel sheet flanked by helices forming an / sandwich structure. The approximate location of the active site was detected in a region close to the dimer interface [MEDLINE:97341227].

\ \ transferase activity ; GO:0016740 \N methanogenesis ; GO:0015948 21376 IPR002771

Members of this family are integral membrane proteins that includes the antibiotic resistance protein MarC. These proteins may be transporters.

\ \N \N \N 21377 IPR002772

Glycoside hydrolase family 3 CAZY:GH_3); exo-1,3-1,4-glucanase (EC: 3.2.1.-).

These enzymes are two-domain globular proteins that are N-glycosylated at three sites [MEDLINE:99148125]. This domain is often C-terminal to the glycoside hydrolase family 3, N terminal domain IPR001764.

\ \ hydrolase activity, hydrolyzing O-glycosyl compounds ; GO:0004553 \N carbohydrate metabolism ; GO:0005975 21384 IPR002779 Members of this family have been found in prokaryotes and Caenorhabditis elegans. The function of proteins in this group is unknown although a hypothetical 1,3-propanediol dehydrogenase (DhaT) from Clostridium pasteurianum\ \ \ [MEDLINE:97457194], Salmonella typhimurium\ \ \ \ [MEDLINE:98012959] and Aeropyrum pernix has this signature.\ \ \N \N \N 21379 IPR002774 Members of this family are the proteins that form the flagellain archaebacteria\ \ \ \ [MEDLINE:88330827]. Each bacterium has\ multiple members of this family.\ \ structural molecule activity ; GO:0005198 \N cell motility ; GO:0006928 21380 IPR002775

Members of this family are small archaebacterial proteins with no known function.

\ \N \N \N 21381 IPR002776 In archaea the function of this protein family is unknown. In bacteria there is some indication that the proteins may be involved in toxin-antitoxin systems [MEDLINE:99000513] or may be a transposase [MEDLINE:94245608].\ \N \N \N 21382 IPR002777

This is a family of proteins restricted to the eukaryea and archaea. Prefoldin is a chaperone that delivers unfolded proteins to cytosolic chaperonin [MEDLINE:98292183]. Related proteins may contain a DNA binding leucine zipper motif [MEDLINE:95129859].

\ \N \N \N 21383 IPR002778 The signal recognition particle (SRP) binds to the signal peptide ofproteins as they are being translated. The binding of the SRP halts\ translation and the complex is then transported to the endoplasmic\ reticulum's cytoplasmic surface. The SRP then aids translocation of\ the protein through the ER membrane. The SRP is a ribonucleoprotein\ that is composed of a small RNA and several proteins. One of these\ proteins is the Srp19 protein [MEDLINE:89041541] (Sec65 in yeast\ \ \ \ [MEDLINE:92220168], [MEDLINE:92220169]).\ \ \ 7S RNA binding activity ; GO:0008312\ RNA binding activity ; GO:0003723 signal recognition particle ; GO:0005786 protein targeting ; GO:0006605 21378 IPR002773 Eukaryotic initiation factor 5A (eIF-5A) contains an unusual amino acid,hypusine [N epsilon-(4-aminobutyl-2-hydroxy)lysine]. The first step in the\ post-translational formation of hypusine is catalysed by the enzyme\ deoxyhypusine synthase (DS) EC: 2.5.1.46. The enzyme catalyses the following reaction:\

\
Spermidine + [eIF-5A]-lysine = 1,3-diaminopropane + [eIF-5A]-deoxyhypusine\

\ The modified version of eIF-5A,\ and DS, are required for eukaryotic cell proliferation [MEDLINE:98154315]. The structure is known for this enzyme [MEDLINE:98154315] in complex with its NAD⁺ cofactor.\ \ deoxyhypusine synthase activity ; GO:0004171 \N hypusine biosynthesis from peptidyl-lysine ; GO:0008612 21363 IPR002759

This family contains proteins found in some eukaryotes and archaebacteria that are related to yeast ribonuclease P. This enzyme is essential for tRNA processing generating 5'-termini of mature tRNA molecules [MEDLINE:95249563]. tRNA processing enzyme ribonuclease P (RNase P) consists of an RNA molecule associated with at least eight protein subunits, hPop1, Rpp14, Rpp20, Rpp25, Rpp29,\ Rpp30, Rpp38, and Rpp40 [MEDLINE:99146772].

\ \ \N \N \N 21364 IPR002760

This family contains archaebacterial proteins of unknown function. Members of thisfamily may be transmembrane proteins.

\ \ \N \N \N 21365 IPR002761

This domain is about 200 amino acids long with a strongly conserved motifSGGKD at the N-terminal. In some members of the family e.g.\ Q12429, another domain of unknown function.

\ \ \N \N \N 21366 IPR002762

The function of CbiX is uncertain, however it is foundin cobalamin biosynthesis operons and so may have a\ related function. Some CbiX proteins contain a striking\ histidine-rich region at their C-terminus, which suggests\ that it might be involved in metal chelation [MEDLINE:98416126].

\ \ \N \N \N 21367 IPR002763 The function of this family is unknown. Aquifex aeolicus has two copies of this protein. A probable aspartyl-tRNA synthetase from Escherichia coli\ \ \ [MEDLINE:91088291] belongs to this group.\ \ \N \N \N 21368 IPR002764

Members of this archaebacterial family have no known function.

\ \N \N \N 21369 IPR002765

This family of bacterial proteins have not been characterized.

\ \N \N \N 21370 IPR002766 This family contains archaebacterial proteins of unknown function. Members of thisfamily may be transmembrane proteins. It seems that all archaebacteria contains two members\ of this family.\ \ \N \N \N 21371 IPR002767 This family contains proteins of unknown function. Members of this familyare found in archaebacteria, eukaryotes and eubacteria.\ \ \N \N \N 21372 IPR002768

\ \ \

The ribosomal protein LX appears to be specific to archaebacteria.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 21374 IPR002770 Formylmethanofuran: tetrahydromethanopterin N-formyltransferase EC: 2.3.1.101 is involved in archaebacteria in the formation of methane from carbon dioxide. This enzyme catalyses the following reaction:\

\
N-formylmethanofuran + 5,6,7,8-tetrahydromethanopterin = methanofuran + 5-formyl-5,6,7,8-tetrahydromethanopterin\

\ \ transferase activity ; GO:0016740 \N methanogenesis ; GO:0015948 21373 IPR002769 This family includes eukaryotic translation initiation factor6 as well as presumed archaebacterial homologues.\ Eukaryotic translation initiation factor 6 (eIF6) binds to the 60S ribosomal subunit and\ prevents its association with the 40S ribosomal subunit. The Saccharomyces cerevisiae\ gene that encodes the 245-amino-acid eIF6 (calculated Mr 25,550), designated TIF6, has\ been cloned and expressed in Escherichia coli. The purified recombinant protein prevents\ association between 40S and 60S ribosomal subunits to form 80S ribosomes [MEDLINE:99108114].\ \ translation initiation factor activity ; GO:0003743 \N translational initiation ; GO:0006413 21342 IPR002735 This domain is found in the N-terminus of eIF-5 P55010, andthe C-terminus of eIF-2

P55010/>. This region\ corresponds to the whole of the archaebacterial eIF-2

homolog. It contains a putative zinc binding C4 finger.\ \ translation initiation factor activity ; GO:0003743 \N translational initiation ; GO:0006413 21343 IPR002736

The citG gene is found in a gene cluster with citrate lyasesubunits [MEDLINE:98117048]. The CitG protein catalyzes the conversion of ATP and dephospho-CoA to adenine and\ 2'-(5"-triphosphoribosyl)-3'-dephospho-CoA, the predicted precursor of the citrate lyase prosthetic\ group [MEDLINE:20498929].

\ \ \N \N \N 21344 IPR002737

This family of proteins, from all branches of life, have not been characterized.

\ \N \N \N 21345 IPR002738

Members of this protein family are part of the ribonuclease P complex (EC: 3.1.26.5) that takes part in endonucleolytic cleavage of RNA, removing 5'-extra-nucleotide from tRNA precursor. This process is essential for tRNA processing.

\ \N \N \N 21346 IPR002739

These archaebacterial proteins have no known function.

\ \N \N \N 21347 IPR002740

This family of prokaryotic proteins has no known function.

\ \N \N \N 21348 IPR002742 Desulfoferrodoxins contains two types of iron: an Fe-S4 site verysimilar to that found in desulfoferrodoxin from Desulfovibrio gigas\ and an octahedral coordinated high-spin ferrous site most probably\ with nitrogen/oxygen-containing ligands. Due to this rather unusual\ combination of active centers, this novel protein is named\ desulfoferrodoxin [MEDLINE:91072356].\ \ oxidoreductase activity ; GO:0016491 \N electron transport ; GO:0006118 21349 IPR002743 This archaebacterial and bacterial protein family has no known function.\ \N \N \N 21350 IPR002744 This family includes prokaryotic proteins of unknownfunction. The family also includes PhaH O84984\ from Pseudomonas putida. PhaH forms a complex with\ PhaF O84984/>, PhaG O84983,\ which hydroxylates phenylacetic acid to 2-hydroxyphenylacetic\ acid [MEDLINE:98263372]. So members of this family may all be components\ of ring hydroxylating complexes.\ \ \N \N \N 21351 IPR002745

The final step of tRNA splicing in Saccharomyces cerevisiae requires 2'-phosphotransferase (Tpt1) to transfer the 2'-phosphate from ligated tRNA to NAD, producing mature tRNA and ADP ribose-1' '-2' '-cyclic phosphate. Yeast and mouse Tpt1 protein and bacterial KptA protein can catalyze the conversion of the\ generated intermediate to both product and the original substrate, these enzymes\ likely use the same reaction mechanism. Step 1 of this reaction is strikingly similar to the\ ADP-ribosylation of proteins catalyzed by a number of bacterial toxins.

KptA, a functional Tpt1\ protein homologue from Escherichia coli is strikingly similar to yeast Tpt1 in its kinetic parameters, although\ Escherichia coli is not known to have a 2'-phosphorylated RNA substrate [MEDLINE:99115601],[MEDLINE:21562386].

\ \ transferase activity, transferring phosphorus-containing groups ; GO:0016772 \N tRNA splicing ; GO:0006388 21361 IPR002756

This family contains archaebacterial proteins of unknown function.

\ \N \N \N 21362 IPR002758

This family contains archaebacterial proteins of unknown function some of which are possibly transmembrane proteins.

\ \N \N \N 21360 IPR002755

DNA primase [MEDLINE:91219475] synthesizes the RNA primers for the Okazakifragments in lagging strand DNA synthesis. DNA primase is a heterodimer of large (p60) and small (p50) subunits in eukaryotes. This family represents sequences of the small subunit and the DNA primase sequences of the Archaea [MEDLINE:20007889]. No sequence similarity can be detected between the eukaryotic p50 and p60 subunits and the primases purified from bacteriophage and bacteria, IPR006295.

\ \ DNA primase activity ; GO:0003896 \N DNA replication, priming ; GO:0006269 21358 IPR002752 These proteins of unknown function are found in bacteria and archaebacteria.\ \N \N \N 21359 IPR002753 These archaebacterial proteins have no known function. Members ofthe family are about 90-105 amino acid residues long.\ \ \N \N \N 21357 IPR002751 This integral membrane protein is involved in cobalamin synthesis [MEDLINE:93273696]. Two pathways for corrin ring formation have been found-an aerobic pathway (in Pseudomonas denitrificans) and an anaerobic pathway (in Propionibacterium freudenreichii subsp. shermanii and Salmonella typhimurium)-that differ in the point of cobalt insertion. Analysis of B12 transport in Escherichia coli reveals two systems: one (with two proteins) for the outer membrane, and one (with three proteins) for the inner membrane [MEDLINE:97061032].\ \N \N vitamin B12 biosynthesis ; GO:0009236 21355 IPR002749 These proteins of unknown function are found in archaebacteria and areprobably transmembrane proteins.\ \ \N \N \N 21356 IPR002750 Members of this family are involved in cobalamin synthesis.The gene encoded by P72862 has been designated cbiH but\ in fact represents a fusion between cbiH and cbiG. As other\ multi-functional proteins involved in cobalamin biosynthesis\ catalyse adjacent steps in the pathway, including CysG,\ CobL (CbiET), CobIJ and CobA-HemD, it is therefore possible\ that CbiG catalyses a reaction step adjacent to CbiH. In the\ anaerobic pathway such a step could be the formation of a\ gamma lactone, which is thought to help to mediate the\ anaerobic ring contraction process [MEDLINE:98416126].\ \ \N \N vitamin B12 biosynthesis ; GO:0009236 21352 IPR002746 Protein found in Archaebacteria. These proteins have no known function.\ \N \N \N 21353 IPR002747 Protein found in Archaebacteria and Bacteria. These proteins have no known function.\ \N \N \N 21354 IPR002748 CbiD is essential for cobalamin biosynthesis in bothS. typhimurium and B. megaterium, no functional role\ has been ascribed to the protein. The CbiD protein\ has a putative S-AdoMet binding site. It is possible that\ CbiD might have the same role as CobF in undertaking\ the C-1 methylation and deacylation reactions required\ during the ring contraction process [MEDLINE:98416126].\ \ \N \N vitamin B12 biosynthesis ; GO:0009236 21329 IPR002720 Retinoblastoma-like and retinoblastoma-associated proteins may have a function in cell cycle regulation. They form a complex with adenovirus E1A and SV40 large T antigen, and may bind and modulate the function of certain cellular proteins with which T and E1A compete for pocket binding. The proteins may act as tumor suppressors, and are potent inhibitors of E2F-mediated trans-activation. This domain has the cyclin fold [MEDLINE:94203808].\ \

The crystal structure of the Rb pocket bound to a nine-residue E7 peptide containing the LxCxE motif, shared by other Rb-binding viral and cellular proteins, shows that the LxCxE peptide binds a highly conserved groove on the B-box portion of the pocket; the A-box portion appears to be required for the stable folding of the B box (see IPR002719.

\ \

The A and B boxes are found at the C-terminal end of the protein; the A-box is on N-terminal side of the B-box.

\ \ \N \N \N 21340 IPR002733 The human protein coded for by the AMMECR1 gene is absent in the Alport syndrome (A), mental retardation (M), midface hypoplasia (M), and elliptocytosis (E) contiguous gene deletion syndrome (AMME). The protein may be a regulatory factor potentially involved in the development of AMME contiguous gene deletion syndrome [MEDLINE:99168904]. This gene is conserved in several species ranging from Caenorhabditis elegans and yeast to plants and micro-organisms although no function has yet been ascribed to the other proteins in this family.\ \N \N \N 21341 IPR002734 This domain isfound in the C-terminus of the bifunctional deaminase-reductase of Escherichia coli, Bacillus subtilis and other bacteria in combination with IPR002125.\ \ \ 5-amino-6-(5-phosphoribosylamino)uracil reductase activity ; GO:0008703\ \N \N vitamin B2 biosynthesis ; GO:0009231 21339 IPR002732

This family of archaebacterial proteins are holliday junction resolvases (hjc gene) [MEDLINE:99362678]. The Holliday junction is an essential intermediate of homologous recombination. Holliday junctions are four-stranded DNA complexes that are formed during recombination and related DNA repair events. In the presence of divalent cations, these junctions exist predominantly as the stacked-X form inwhich the double-helical segments are coaxially stacked and twisted by 60 degrees in a right-handed direction across the junction cross-over. In this structure,\ the stacked arms resemble two adjacent double-helices, but are linked at the junction by two common strands that cross-over between the duplexes [MEDLINE:22125955] ]. During homologous recombination, genetic information is physically exchanged between parental DNAs via crossing single\ strands of the same polarity within the four-way Holliday structure. This process is terminated by the\ endonucleolytic activity of resolvases, which convert the four-way DNA back to two double strands.

\ \ \N \N \N 21336 IPR002729 This family of proteins are found in archaea and bacteria and are, as yet, functionally uncharacterised.\ \N \N \N 21337 IPR002730

Proteins that belong to this family have no known function although one, Rpp29, is a subunit of human ribonuclease P.

\ \N \N \N 21338 IPR002731 This family includes the BadF O07462proteins that are two subunits of Benzoyl-CoA reductase, that may\ be involved in ATP hydrolysis.\ The family also includes an activase subunit from the enzyme\ 2-hydroxyglutaryl-CoA dehydratase O07462/>. The protein\ O66634 contains two copies of this region suggesting that\ the family may form structurally dimerise.\ \ \N \N \N 21335 IPR002728 Members of this family include Q16439, and DPH2 fromyeast Q16439/>\ \ \ \ [MEDLINE:94010339], which confers resistance to diphtheria toxin and\ has been found to be involved in diphthamide synthesis. Diphtheria\ toxin inhibits eukaryotic protein synthesis by ADP-ribosylating\ diphthamide, a posttranslationally modified histidine residue present\ in EF2. The exact function of the members of this family is\ unknown.\ \ \N \N \N 21333 IPR002726 This archaebacterial protein has no known function. Itcontains several predicted transmembrane regions,\ suggesting it is an integral membrane protein.\ \ \N \N \N 21334 IPR002727 This family includes prokaryotic proteins of unknown function, as well as a protein annotated as the pit accessory protein from Sinorhizobium meliloti\ \ \ O30498.\ \ \N \N \N 21332 IPR002725 Members of this family are found in some archaebacteria, as well as Helicobacter pylori. The proteins are 190-240 amino acids long, with the C terminus being the most conserved region, containing three conserved histidines.\ \N \N \N 21331 IPR002724 This family includes archaebacterial proteins of unknownfunction. All the members are 350-400 amino acids long.\ Archaeoglobus fulgidus contains three copies of this\ 80 residue domain.\ \ \N \N \N 21330 IPR002723

This family of prokaryotic proteins have not been characterized. All the members are 350-400 amino acids long.

\ \N \N \N 21318 IPR002708

This domain is about 320 residues long and is found in proteins that have two C-terminal IPR000644domains. The function of DUF39 is unknown. The\ protein IPR000644/> has been misannotated as an inosine\ monophosphate dehydrogenase based on the similarity to the\ CBS domains.

\ \ \N \N \N 21319 IPR002710 Dilute encodes a novel type of myosin heavy chain, with a tail, or C-terminal, region that has elements of both type II (

-helical coiled-coil) and type I (non-coiled-coil) myosin heavy chains. The DIL non

-helical domain is found in dilute myosin heavy chain proteins and other myosins. In mouse the dilute protein may play a role in the elaboration, maintenance, or function of cellular processes of melanocytes and neurons [MEDLINE:91141583].\ The MYO2 protein of Saccharomyces cerevisiae is implicated in vectorial vesicle transport and is homologous to the dilute protein over practically its entire length [MEDLINE:91201404].\ \ \N \N \N 21320 IPR002711 HNH endonuclease is found in bacteria and viruses [MEDLINE:98026854], [MEDLINE:95004046], [MEDLINE:95117127]. This family includes pyocins, colicins and anaredoxins.\ endonuclease activity ; GO:0004519 \N \N 21321 IPR002712 CcdB protein is a topoisomerase poison from E. coli\ \ \ [MEDLINE:99141409].\ It is responsible for killing plasmid-free segregants, and interferes with the activity of DNA gyrase. It acts to inhibit partitioning of the chromosomal DNA.\ \ \N \N \N 21322 IPR002713 The FF domain may be involved in protein-protein interaction [MEDLINE:99322199]. It often occurs as multiple copies and often accompanies WW domains IPR001202.\ \N \N \N 21323 IPR002714 VHL forms a ternary complex with the elonginB O44226 mRNA.\ \N \N \N 21324 IPR002715

Nascent polypeptide-associated complex (NAC) is among the first ribosome-associated entities to bind the nascent polypeptide after peptide bond formation. The nascent polypeptide-associated complex (NAC) of yeast functions in the targeting process of ribosomes to the ER membrane [MEDLINE:99448377]. NAC may prevent binding of ribosome nascent chains (RNCs) without a signal sequence to yeast membranes.

\ \N \N \N 21325 IPR002716

The PilT protein, N-terminal domain (PIN) is a compact domain of about 100 amino acids. The domain has two nearly invariant aspartates and forms a coiled-coil with other monomer units to polymerize a pilus fibre [MEDLINE:99232500]. The function of the PIN domain is unknown but a role in signaling appears likely given the presence of this domain in some bacterial plasmid stability proteins and Dis3 from yeast that is implicated in mitotic control [MEDLINE:97051818].

\ \N \N \N 21326 IPR002717

Moz is a monocytic leukemia Zn_finger protein and the SAS protein from Saccharomyces cerevisiae is involved in silencing the Hmr locus. These proteins were reported to be homologous to acetyltransferases [MEDLINE:96182937] but this similarity is not supported by standard sequence analysis.

\ \N \N \N 21327 IPR002718 This family seems confined to Helicobacter pylori. It is predicted to be an outer membrane protein based on its pattern of alternating hydrophobic amino acids similar to porins [MEDLINE:97394467].\ \N \N \N 21328 IPR002719 Retinoblastoma-like and retinoblastoma-associated proteins may have a function in cell cycle regulation. They form a complex with adenovirus E1A and SV40 large T antigen, and may bind and modulate the function of certain cellular proteins with which T and E1A compete for pocket binding. The proteins may act as tumor suppressors, and are potent inhibitors of E2F-mediated trans-activation. This domain has the cyclin fold [MEDLINE:94203808].\ \

\ \

The A and B boxes are found at the C-terminal end of the protein; the B-box is on C-terminal side of the A-box.

\ \ \N \N \N 21314 IPR002703 The Levivirus coat protein forms the bacteriophage coat that encapsidates the viral RNA. 180 copies of this protein form the virion shell. The MS2 bacteriophage coat protein controls M two distinct processes: sequence-specific RNA encapsidation and repression of replicase translation-by binding to an RNAstem-loop structure of 19 nucleotides containing the initiation codon of the replicase gene. The binding of a coat protein dimer to this hairpin shuts off synthesis of the viral replicase, switching the viral replication cycle to virion assembly rather than continued replication [MEDLINE:95021717].\ \ structural molecule activity ; GO:0005198 viral capsid ; GO:0019028 \N 21315 IPR002704

\ Peptidase C7 family is found in fungi and viruses (hypoviridae). They are involved in transmissible hypovirulence and may indicate the possible origins of hypovirulence-associated dsRNAs [MEDLINE:91184117].\ \ cysteine-type endopeptidase activity ; GO:0004197 \N proteolysis and peptidolysis ; GO:0006508 21317 IPR002706

DNA-repair protein Xrcc1 functions in the repair of single-strand DNA breaks in mammalian cells and forms a repair complex with -Pol, ligase III and PARP [MEDLINE:99396729]. The NMR solution structure of the Xrcc1 N-terminal domain (Xrcc1 NTD) shows that the structural core is a -sandwich with -strands connected by loops, three helices and two short two-stranded -sheets at each connection side. The Xrcc1 NTD specifically binds single-strand break DNA (gapped and nicked) and a gapped DNA--Pol complex [MEDLINE:99396744].

\ damaged DNA binding activity ; GO:0003684 nucleus ; GO:0005634 single-strand break repair ; GO:0000012 21316 IPR002705

Peptidase C16 family is found in viruses such as Coronaviridae. This is often found as part of a multifunctional protein with RNA-directed RNA polymerase activity.

\ \ cysteine-type peptidase activity ; GO:0008234 \N proteolysis and peptidolysis ; GO:0006508 21311 IPR002699

\ \

\ \ \ \ \ \ \

The CF(0) D subunit may be an integral part of the catalytic sector of the V-ATPase [MEDLINE:95132627]. Proteins in this family include V-type H⁺ transporting and Na⁺ dependent ATPases.

\ \ hydrogen-transporting two-sector ATPase activity ; GO:0003936 \N proton transport ; GO:0015992 21313 IPR002702 The translational regulator protein regA is encoded by the T4 bacteriophage and binds to a region of messenger RNA (mRNA) that includes the initiator codon. RegA is unusual in that it represses the translation of about 35 early T4 mRNAs but does not affect nearly 200 other mRNAs [MEDLINE:95281996].\ RNA binding activity ; GO:0003723 \N regulation of translation ; GO:0006445 21312 IPR002701

Chorismate mutase, EC: 5.4.99.5, catalyses the conversion of chorismate to prephenate in the pathway of tyrosine and phenylalanine biosynthesis. This enzyme is negatively regulated by tyrosine, tryptophan and phenylalanine [MEDLINE:98307941], [MEDLINE:98165805]. Prephenate dehydratase (IPR001086.

\ chorismate mutase activity ; GO:0004106 \N aromatic amino acid family biosynthesis ; GO:0009073 21301 IPR002687 This domain is present in various pre-mRNA processing ribonucleoproteins. The function of the domain is unknown however it may be a common RNA or snoRNA or Nop1p binding domain.

Proteins have been implicated in an expanding variety of functions during\ pre-mRNA splicing. Molecular cloning has identified genes encoding spliceosomal proteins that potentially act as novel RNA helicases, GTPases, or protein isomerases. Novel protein-protein and protein-RNA interactions that are required for functional spliceosome formation have also been described. Finally, growing evidence suggests that proteins may contribute directly to the spliceosome's active sites [MEDLINE:97303139].

\ \ \N \N \N 21302 IPR002689 Glycoprotein L from cytomegalovirus serves a chaperone for the correct folding and surface expression of glycoprotein H (gH) [MEDLINE:95053910]. Glycoprotein L is a member of the heterotrimeric gCIII complex of glycoprotein which also includes gH and gO and has an essential role in viral fusion [MEDLINE:99214326].\ \N \N \N 21303 IPR002690 This family consist of various capsid proteins from members of the herpesviridae. The capsid protein VP23 in herpes simplex virus forms a triplex together with VP19C these fit between and link together adjacent capsomers as formed by VP5 and VP26 [MEDLINE:99329207]. VP3 along with the scaffolding proteins helps to form normal capsids by defining the curvature of the shell and size of the particle [MEDLINE:99329207].\ structural molecule activity ; GO:0005198 viral capsid ; GO:0019028 \N 21304 IPR002691 The LIM-domain binding protein, binds to the LIM domain IPR001781.\ transcription cofactor activity ; GO:0003712 nucleus ; GO:0005634 development ; GO:0007275 21305 IPR002692 Penicillin amidase or penicillin acylase EC: 3.5.1.11 catalyses the hydrolysis of benzylpenicillin to phenylacetic acid and 6-aminopenicillanic acid (6-APA) a key intermediate in the the synthesis of penicillins [MEDLINE:97438505].\ hydrolase activity ; GO:0016787 \N antibiotic biosynthesis ; GO:0017000 21306 IPR002693 This family consists of paramyxovirus P phosphoprotein from sendai virus and human and bovine parainfluenza viruses. The P protein is an essential part of the viral RNA polymerase complex formed form the P and L proteins [MEDLINE:99329169]. The exact role of the P protein in this complex in unknown but it is involved in multiple protein-protein interactions and binding the polymerase complex to the nucleocapsid or ribonucleoprotein template [MEDLINE:99329169]. It also appears to be important for the proper folding of the L protein [MEDLINE:99329169]. The paramyxoviruses have a negative sense ssRNA genome\ \ \ [MEDLINE:99329169].\ \ RNA-directed RNA polymerase activity ; GO:0003968 \N transcription ; GO:0006350 21307 IPR002694 Zinc fingers are found in a wide variety of proteins, and are associated with DNA binding. There are several different types, and this family contains the CHC2-type zinc finger, which is found in bacteria and viruses.\ DNA primase activity ; GO:0003896 \N DNA replication ; GO:0006260 21308 IPR002695 This is a family of bifunctional enzymes catalysing the last two steps in de novo purine biosynthesis. The bifunctional enzyme is found in both prokaryotes and eukaryotes. The second last step is catalysed by 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase EC: 2.1.2.3 (AICARFT), this enzyme catalyses the formylation of AICAR with 10-formyl-tetrahydrofolate to yield FAICAR and tetrahydrofolate [MEDLINE:97473523]. The last step is catalysed by IMP (Inosine monophosphate) cyclohydrolase EC: 3.5.4.10 (IMPCHase), cyclizing FAICAR (5-formylaminoimidazole-4-carboxamide ribonucleotide) to IMP [MEDLINE:97473523].\ phosphoribosylaminoimidazole-carboxamide formyltransferase activity ; GO:0004643 \N purine nucleotide biosynthesis ; GO:0006164 21309 IPR002696 This is a family of short (70 amino acid) hypotheticalproteins from various bacteria. They contain three conserved \ cysteine residues. Q44066 has\ been found to have hemolytic activity (unpublished).\ \ \N \N \N 21310 IPR002698 5-formyltetrahydrofolate cyclo-ligase or methenyl-THF synthetase EC: 6.3.3.2 catalyses the interchange of 5-formyltetrahydrofolate (5-FTHF) to 5-10-methenyltetrahydrofolate, this requires ATP and Mg²⁺ [MEDLINE:96096540]. 5-FTHF is used in chemotherapy where it is clinically known as Leucovorin [MEDLINE:94308074].\ enzyme activity ; GO:0003824 \N metabolism ; GO:0008152 21297 IPR002683

This family consists of the 23 kDa subunit of oxygen evolving system of photosystem II or PsbP from various plants (where it is encoded by the nuclear genome) and Cyanobacteria. The 23 kDa PsbP protein is required for PSII to be fully operational in vivo, it increases the affinity of the water oxidation site for Cl^- and provides the conditions required for high affinity binding of Ca²⁺ [MEDLINE:97191538].

\ \N \N \N 21298 IPR002684

Biotin synthase EC: 2.8.1.6 works with flavodoxin, S-adenosylmethionine, and possibly cysteine to catalyze the last step of the biotin biosynthetic pathway. The reaction consists of the introduction of a sulphur atom intodethiobiotin, thus requiring activation of C-H bonds [MEDLINE:96312354]. Biotin (vitamin H) is a prosthetic group in enzymes catalysing carboxylation and transcarboxylation reactions [MEDLINE:97074643].

Biotin synthase from Escherichia coli is a homodimer of 76 kDa, with each polypeptide\ chain carrying an oxygen-sensitive (4Fe-4S) cluster, probably ligated by three cysteines of a CXXXCXXC box conserved among all known BioB sequences\ and a fourth still not identified ligand. BioB displays a pyridoxal phosphate-dependent cysteine desulphurase activity, which allows mobilization of the\ sulphur atom from free cysteine [MEDLINE:22114344].

\ \ biotin synthase activity ; GO:0004076 \N biotin biosynthesis ; GO:0009102 21299 IPR002685

Glycosyltransferase family 15 CAZY:GT_15.

\ \ glycolipid 2-alpha-mannosyltransferase activity ; GO:0004377 membrane ; GO:0016020 protein amino acid glycosylation ; GO:0006486 21300 IPR002686 Transposases are needed for efficient transposition of the insertion sequence or transposon DNA. This family includes transposases for IS200 from Escherichia coli.\ \N \N \N 21292 IPR002678 One member of this family NIF3 (NGG1p interacting factor 3) interacts with the yeast transcriptional coactivator NGG1p which is part of the ADA\ complex the exact function of this interaction is unknown [MEDLINE:96279124].\ \ \N \N \N 21293 IPR002679 This family consist of coat proteins from closteroviruses a member of the closteroviridae. The viral coat protein encapsulates and protects the viral genome. Both the large cp1 and smaller cp2 coat protein originate from the same primary transcript [MEDLINE:91237334]. Members of the closteroviridae include Sugar beet yellow virus and Grapevine leafroll-associated virus, closteroviruses have a positive strand ssRNA genome with no DNA stage during replication.\ structural molecule activity ; GO:0005198 viral capsid ; GO:0019028 \N 21294 IPR002680 The alternative oxidase is used as a second terminal oxidase in the mitochondria, electrons are transferred directly from reduced ubiquinol to oxygen forming water [MEDLINE:96366413]. This is not coupled to ATP synthesis and is not inhibited by cyanide, this pathway is a single step process [MEDLINE:98086211]. In rice the transcript levels of the alternative oxidase are increased by low temperature [MEDLINE:98086211]. It has been predicted to contain a coupled diiron center on the basis of a conserved sequence motif consisting of the proposed iron ligands, four Glu and two His residues [MEDLINE:20560609]. The EPR study of Arabidopsis thalianaalternative oxidase AOX1a shows that the enzyme contains a\ hydroxo-bridged mixed-valent Fe(II)/Fe(III) binuclear iron center [MEDLINE:22313530]. A catalytic cycle has been proposed that involves diiron center and at least one transient protein-derived radical, most probably an invariant Tyr residue [MEDLINE:21659531].\ \ \ \ \N mitochondrial membrane ; GO:0005740 respiratory gaseous exchange ; GO:0007585 21295 IPR002681 This family consists of various coat proteins from the ilarviruses part of the Bromoviridae, members include apple mosaic virus and prune dwarf virus. The ilarvirus coat protein is required to initiate replication of the viral genome in host plants [MEDLINE:95248275]. Members of the Bromoviridae have a positive stand ssRNA genome with no DNA stage in their replication.\ structural molecule activity ; GO:0005198 viral capsid ; GO:0019028 \N 21296 IPR002682 This family consists of the photosystem II reaction center protein PsbJ from plants and Cyanobacteria. In Synechocystis sp. PCC 6803 PsbJ regulates the number of photosystem II centers in thylakoid membranes, it is a predicted 4kDa protein with one membrane spanning domain [MEDLINE:93131892].\ \N \N \N 21289 IPR002675

\ \ \

Ribosomal protein L38e forms part of the 60S ribosomal subunit [MEDLINE:91207349]. This family is found in eukaryotes.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 21290 IPR002676

The RimM protein is essential for efficient processing of 16S rRNA [MEDLINE:98083058]. The RimM protein was shown to have affinity for free ribosomal 30S subunits but not for 30S subunits in the 70S ribosomes [MEDLINE:98083058].

\ \N \N ribosome biogenesis ; GO:0007046 21291 IPR002677

\ \ \

Ribosomal protein L32p is part of the 50 S ribosomal subunit. This family is found in both prokaryotes and eukaryotes. Ribosomal protein L32 of yeast binds to and regulates the splicing and the translation of the transcript of its own gene [MEDLINE:97219985]}.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 21286 IPR002672

\ \ \

Ribosomal protein L28e forms part of the 60S ribosomal subunit [MEDLINE:91207349]. This family is found in eukaryotes. In rat there are 9 or 10 copies of the L28 gene. The L28 protein contains a possible internal duplication of 9 residues [MEDLINE:91002678].

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 21288 IPR002674

\ \ \

This ribosomal protein is found in archaebacteria and eukaryotes [MEDLINE:89325328]. Ribosomal protein L37 has a single zinc finger-like motif of the C2-C2 type [MEDLINE:93249430].

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 21287 IPR002673

\ \ \

Ribosomal protein L29e forms part of the 60S ribosomal subunit [MEDLINE:91207349]. This family is found in eukaryotes. There are there are 20 to 22 copies of the L29 gene in rat. Rat L29 is related to yeast ribosomal protein YL43 [MEDLINE:93249429].

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 21280 IPR002666 The reduced folate carrier (a transmembrane glycoprotein) transports reduced folate into mammalian cells via the carrier mediated mechanism (as opposed to the receptor mediated mechanism) it also transports cytotoxic folate analogues used in chemotherapy [MEDLINE:97305137], such as methotrexate (MTX). Mammalian cells have an absolute requirement for exogenous folates which are needed for growth, and biosynthesis of macromolecules [MEDLINE:97305137].\ reduced folate carrier activity ; GO:0008518 membrane ; GO:0016020 transport ; GO:0006810 21281 IPR002667 Isopentenyl-diphosphate delta-isomerase or IPP isomerase EC: 5.3.3.2 catalyses the interconversion of isopentenyl diphosphate and dimethylallyl diphosphate. Dimethylallyl phosphate is the initial substrate for the biosynthesis of carotenoids and other long chain isoprenoids [MEDLINE:98409684].\ isopentenyl-diphosphate delta-isomerase activity ; GO:0004452 \N isoprenoid biosynthesis ; GO:0008299 21282 IPR002668 The sodium-requiring nucleoside transport proteins include permeases and other membrane proteins responsible for the transport of specific nucleosides across the membrane, using proton motive force.\ nucleoside:sodium symporter activity ; GO:0005415 membrane ; GO:0016020 transport ; GO:0006810 21283 IPR002669 UreD is a urease accessory protein. Urease IPR005848.\ nickel ion binding activity ; GO:0016151 \N nitrogen metabolism ; GO:0006807 21284 IPR002670

\ \ \

Ribosomal protein L18ae forms part of the 60S ribosomal subunit [MEDLINE:91207349]. This family is found in eukaryotes. Rat ribosomal protein L18 is homologous to Xenopus laevis L14 [MEDLINE:88224560].

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 21266 IPR002651 This entry represents a group of hypothetical Caenorhabditis elegans proteins with unknown function. The aligned\ region is approximately 160 amino acids long.\ \ \N \N \N 21267 IPR002652 This family consists of the importin

(karyopherin

), importin

(karyopherin

) binding domain. The domain mediates formation of the importin

complex; required for classical NLS import of proteins into the nucleus, through the nuclear pore complex and across the nuclear envelope. Also in the alignment is the NLS of importin

which overlaps with the IBB domain [MEDLINE:96270582].\ protein transporter activity ; GO:0008565 \N intracellular protein transport ; GO:0006886 21260 IPR002644 This family consists of the hypothetical protein product of the YCF9 gene from chloroplasts and cyanobacteria. A small conserved open reading frame in the plastid genome, ycf9, encodes a putative membrane protein of 62 amino acids. The protein may be protein as a novel architectural component of the light-harvesting antenna [MEDLINE:20231888].\ \N \N \N 21261 IPR002645 The STAS (after Sulphate Transporter and AntiSigma factor antagonist) domain is found in the C terminal region of sulphate transporters and bacterial anti-sigma factor antagonists. It has been suggested that this domain may have a general NTP binding function. The establishment of differential gene expression in sporulating Bacillus subtilis involves four protein components one of which is SpoIIAA P10727. The STAS domain is found in the anti-sigma factor antagonist SpoIIAA.\ \N \N \N 21262 IPR002646

This family includes nucleic acid independent RNA polymerases, such as polynucleotide adenylyltransferase (EC: 2.7.7.19), which adds the poly (A) tail to mRNA. This family also includes the tRNA nucleotidyltransferase that adds the CCA to the 3' of the tRNA EC: 2.7.7.25.

\ RNA binding activity ; GO:0003723 \N RNA processing ; GO:0006396 21263 IPR002648 Isopentenyl transferase / dimethylallyl transferase synthesizes isopentenyladensosine 5'-monophosphate, a cytokinin that induces shoot formation on host plants infected with the Ti plasmid [MEDLINE:93101133].\ dimethylallyltransferase activity ; GO:0004161 \N biosynthesis ; GO:0009058 21264 IPR002649

In transfer RNA many different modified nucleosides are found, especially in the anticodon region.tRNA (guanine-N1-)-methyltransferase EC: 2.1.1.31 is one of several nucleases operating together with the tRNA-modifying enzymes before the formation of the mature tRNA. It catalyses the reaction:\

\
S-adenosyl-L-methionine + tRNA -> S-adenosyl-L-homocysteine + tRNA containing\
                 N1-methylguanine

\ \ methylating guanosine(G) to N1-methylguanine (1-methylguanosine (m1G)) at position 37 of tRNAs that read CUN (leucine), CCN(proline), and CGG (arginine) codons. The presence of m1G improves the cellular growth rate and the polypeptide steptime and also prevents the tRNA from shifting the reading frame [MEDLINE:91002655].

The mechanism of the trmD3-induced frameshift involving mutant tRNA(Pro) and tRNA(Leu) species has been investigated [MEDLINE:93360265]. It has been suggested that the conformation of the anticodon loop may be a major determining element for the formation of m1G37 in vivo [MEDLINE:97199387].

\ \ tRNA methyltransferase activity ; GO:0008175 \N tRNA processing ; GO:0008033 21265 IPR002650 This family consists of ATP-sulfurylase or sulfate adenylyltransferase EC: 2.7.7.4 some of which are part of a bifunctional polypeptide chain associated with adenosyl phosphosulphate (APS) kinase IPR002891.\ sulfate adenylyltransferase (ATP) activity ; GO:0004781 \N sulfate assimilation ; GO:0000103 21285 IPR002671

\ \ \

Ribosomal protein L22e forms part of the 60S ribosomal subunit [MEDLINE:91207349]. This family is found in eukaryotes. Rat L22 is related to ribosomal proteins from other eukaryotes and is identical in amino acid sequence to human EAP, the EBER 1 (Epstein-Barr virus encoded RNA) associated protein [MEDLINE:95092785].

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 21278 IPR002663 VP3 is a minor structural component of the virus. The large RNA segment of birnaviruses codes for a polyprotein (N-VP2-VP4-VP3-C) [MEDLINE:88119196].\ structural molecule activity ; GO:0005198 \N \N 21279 IPR002664 VP4 is a viral protease [MEDLINE:88119196]. The large RNA segment of birnaviruses codes for a polyprotein (N-VP2-VP4-VP3-C) [MEDLINE:88119196].\ \N \N \N 21276 IPR002661

The ribosome recycling factor or ribosome release factor (RRF) dissociates ribosomes from mRNA after termination of translation, and is essential for bacterial growth [MEDLINE:94240115]. Thus ribosomes are 'recycled' and ready for another round of protein synthesis.

\ \ \N \N protein biosynthesis ; GO:0006412 21277 IPR002662 VP2 is the major structural protein of birnaviruses\ \ \ [MEDLINE:96095222]. The large RNA segment of birnaviruses codes for a polyprotein (N-VP2-VP4-VP3-C) [MEDLINE:88119196].\ \ structural molecule activity ; GO:0005198 \N \N 21275 IPR002660 This family consists of various proteins from the herpesviridae that are similar to herpes simplex virus type I UL6 virion protein. UL6 is essential for cleavage and packaging of the viral genome [MEDLINE:97124665].\ \N \N DNA packaging ; GO:0006323 21274 IPR002659

Glycosyltransferase family 31 (CAZY:GH_31) comprises\ enzymes with a number of known activities; N-acetyllactosaminide -1,3-N-acetylglucosaminyltransferase (EC: 2.4.1.149); -1,3-galactosyltransferase (EC: 2.4.1.-); fucose-specific -1,3-N-acetylglucosaminyltransferase (EC: 2.4.1.-); globotriosylceramide -1,3-GalNAc transferase (EC: 2.4.1.79) PUB00007032, [MEDLINE:98079027].

\ \ galactosyltransferase activity ; GO:0008378 membrane ; GO:0016020 protein amino acid glycosylation ; GO:0006486 21272 IPR002657 This family of proteins are found both in prokaryotes and eukaryotes. They are related to the human bile acid:sodium symporters, which are transmembrane proteins functioning in the liver in the uptake of bile acids from portal blood plasma, a process mediated by the co-transport of Na⁺ [MEDLINE:92073340].\ bile acid:sodium symporter activity ; GO:0008508 membrane ; GO:0016020 sodium ion transport ; GO:0006814 21273 IPR002658 The 3-dehydroquinate synthase EC: 4.6.1.3 domain is present in isolation in various bacterial 3-dehydroquinate synthases and also present as a domain in the pentafunctional AROM polypeptide P07547\ \ \ [MEDLINE:96048023]. 3-dehydroquinate (DHQ) synthase catalyses the formation of dehydroquinate (DHQ) and orthophosphate from 3-deoxy-D-arabino heptulosonic 7 phosphate [MEDLINE:98273626]. This reaction is part of the shikimate pathway which is involved in the biosynthesis of aromatic amino acids.\ \ \ 3-dehydroquinate synthase activity ; GO:0003856\ \N \N aromatic amino acid family biosynthesis ; GO:0009073 21271 IPR002656 This family includes a range of acyltransferase enzymes as well as yet uncharacterised proteins from C. elegans.\ transferase activity, transferring groups other than amino-acyl groups ; GO:0016747 \N \N 21270 IPR002655 This is a family of Acyl-CoA oxidases EC: 1.3.3.6. Acyl-coA oxidase converts acyl-CoA into trans-2-enoyl-CoA [MEDLINE:98192624].\ acyl-CoA oxidase activity ; GO:0003997 peroxisome ; GO:0005777 fatty acid beta-oxidation ; GO:0006635 21268 IPR002653 A20 (an inhibitor of cell death)-like zinc fingers are believed to mediate self-association in A20. These fingers also mediate IL-1-induced NF-kappa B activation.\ zinc ion binding activity ; GO:0008270 \N \N 21269 IPR002654

Glycosyltransferase family 25 CAZY:GT_25.

\ \ \N \N lipopolysaccharide biosynthesis ; GO:0009103 21250 IPR002635 This family consists of the chorion superfamily proteins classes A, B, CA, CB and high-cysteine HCB from silk, gypsy and polyphemus moths. The chorion proteins make up the moths egg shell a complex extracellular structure [MEDLINE:86313609].\ \N \N \N 21251 IPR002636 This family consists of various hypothetical proteinsfrom cyanobacteria, none of which are functionally\ described. The aligned region is approximately 120-140\ amino acids long corresponding to almost the entire\ length of the proteins in the family.\ \ \N \N \N 21252 IPR002637

This family consists of the Ham1 protein P47119\ \ \ P47119/>\ \ \ \ [MEDLINE:96381244]. The Ham1 protein protects the cell from HAP, either on the level of deoxynucleoside triphosphate or the DNA level by a yet unidentified set of reactions [MEDLINE:96381244].

\ \ \N \N \N 21253 IPR002638 Quinolinate phosphoribosyl transferase (QPRTase) or nicotinate-nucleotide pyrophosphorylase EC: 2.4.2.19 is involved in the de novo synthesis of NAD in both prokaryotes and eukaryotes. It catalyses the reaction of quinolinic acid with 5-phosphoribosyl-1-pyrophosphate (PRPP) in the presence of Mg²⁺ to give rise to nicotinic acid mononucleotide (NaMN), pyrophosphate and carbon dioxide [MEDLINE:97169443], [MEDLINE:96139309]. Unlike IPR004393, this family also includes the molybdenum transport system protein ModD.\ nicotinate-nucleotide pyrophosphorylase (carboxylating) activity ; GO:0004514 \N nicotinamide adenine dinucleotide biosynthesis ; GO:0009435 21254 IPR002638 Quinolinate phosphoribosyl transferase (QPRTase) or nicotinate-nucleotide pyrophosphorylase EC: 2.4.2.19 is involved in the de novo synthesis of NAD in both prokaryotes and eukaryotes. It catalyses the reaction of quinolinic acid with 5-phosphoribosyl-1-pyrophosphate (PRPP) in the presence of Mg²⁺ to give rise to nicotinic acid mononucleotide (NaMN), pyrophosphate and carbon dioxide [MEDLINE:97169443], [MEDLINE:96139309]. Unlike IPR004393, this family also includes the molybdenum transport system protein ModD.\ nicotinate-nucleotide pyrophosphorylase (carboxylating) activity ; GO:0004514 \N nicotinamide adenine dinucleotide biosynthesis ; GO:0009435 21255 IPR002639 This family consists of the Urease accessory protein UreF. The urease enzyme (urea amidohydrolase) hydrolyses urea into ammonia and carbamic acid [MEDLINE:96146510]. UreF is proposed to modulate the activation process of urease by eliminating the binding of nickel irons to noncarbamylated protein [MEDLINE:96404789].\ nickel ion binding activity ; GO:0016151 \N nitrogen metabolism ; GO:0006807 21256 IPR002640 This family consists of arylesterases (Also known as serum paraoxonase) EC: 3.1.1.2. These enzymes hydrolyse organophosphorus esters such as paraoxon and are found in the liver and blood. They confer resistance to organophosphate toxicity [MEDLINE:97184641]. Human arylesterase (PON1) P27169.\ arylesterase activity ; GO:0004064 \N \N 21257 IPR002641 This family consists of various patatin glycoproteins from the total soluble protein in potato tubers [MEDLINE:88226014]. Patatin is a storage protein but it also has the enzymatic activity of lipid acyl hydrolase, catalysing the cleavage of fatty acids from membrane lipids [MEDLINE:88226014].\ nutrient reservoir activity ; GO:0045735 \N \N 21258 IPR002642 This family consists of lysophospholipase / phospholipase B EC: 3.1.1.5 and cytosolic phospholipase A2 which also has a C2 domain IPR000008.\ phospholipase activity ; GO:0004620 \N phospholipid catabolism ; GO:0009395 21259 IPR002643 This family consists of the DNA-binding protein or agnoprotein from various polyomaviruses. This protein is highly basic and can bind single stranded and double stranded DNA [MEDLINE:81197675]. Mutations in the agnoprotein produce smaller viral plaques, hence its function is not essential for growth in tissue culture cells but something has slowed in the normal replication cycle [MEDLINE:87113010]. There is also evidence suggesting that the agnogene and agnoprotein act as regulators of structural protein synthesis [MEDLINE:87113010].\ DNA binding activity ; GO:0003677 \N \N 21236 IPR002619 This domain has no known function. It is found in several Caenorhabditis elegans proteins. The domain contains 6 conserved cysteines that probably form three disulphide bridges.\ \N \N \N 21237 IPR002620 The alphaviruses produce two mRNAs after infection: the genomic (49S) RNA which is translated into the nonstructural (replicase) proteins and the subgenomic (26S) RNA which serves as the mRNA for the virion structural proteins. The long polyprotein comprises individual nonstructural proteins that are formed by a proteolytic processing steps to give nsPl, nsP2, nsP3 and nsP4 [MEDLINE:86286581].\ \N \N \N 21238 IPR002621 Protein from geminiviruses infecting monocotyledons.\ \N \N \N 21239 IPR002622 Transposase proteins are necessary for efficient DNA transposition.This family includes insertion sequences from Synechocystis PCC 6803 three of which are characterised as homologous to bacterial IS5- and IS4- and to several members of the IS630-Tc1-mariner superfamily [MEDLINE:97449302].\ \ \N \N \N 21240 IPR002624 This family consists of various deoxynucleoside kinases including cytidine EC: 2.7.1.74, guanosine EC: 2.7.1.113, adenosine EC: 2.7.1.76 and thymidine kinase EC: 2.7.1.21 (which also phosphorylates deoxyuridine and deoxycytosine). These enzymes catalyse the production of deoxynucleotide 5'-monophosphate from a deoxynucleoside, using ATP and yielding ADP in the process.\ phosphotransferase activity, alcohol group as acceptor ; GO:0016773 \N nucleobase, nucleoside, nucleotide and nucleic acid metabolism ; GO:0006139 21241 IPR002625 This family includes the Smr (Small MutS Related) proteins,and the C-terminal region of the MutS2 protein. It has been suggested that this domain interacts with the MutS1 P23909\ \ \ \ [MEDLINE:99362780].\ \ ATP binding activity ; GO:0005524 \N mismatch repair ; GO:0006298 21242 IPR002626 This family consists of plant virus movement proteins from the caulimovirus family. These proteins are required for transmission of the virus from cell to cell. It has been suggested in cauliflower mosaic virus that these proteins mediated viral movement by modifying plasmodesmata and forming tubules in the channel that can accommodate the virus particles [MEDLINE:97081199] and references therein. The aligned region comprises almost the entire length of the caulimovirus sequences. Also in this family is ORF1 Q66275; here the 300 amino acids occupy only part of a longer polyprotein.\ DNA binding activity ; GO:0003677 \N \N 21243 IPR002627 tRNA isopentenyltransferases EC: 2.5.1.8 also known as tRNA delta(2)-isopentenylpyrophosphate transferases or IPP transferases. These enzymes modify both cytoplasmic and mitochondrial tRNAs at A(37) to give isopentenyl A(37) [MEDLINE:94187700].\ ATP binding activity ; GO:0005524 \N tRNA processing ; GO:0008033 21244 IPR002628 This family consists of the 33 KDa photosystem II polypeptide from the oxygen evolving complex (OEC) of plants and cyanobacteria. The protein is also known as the manganese-stabilizing protein as it is associated with the manganese complex of the OEC and may provide the ligands for the complex [MEDLINE:88334494].\ \N \N \N 21245 IPR002629 This is a family of vitamin-B12 independent methionine synthases or 5-methyltetrahydropteroyltriglutamate--homocysteine methyltransferases, EC: 2.1.1.14 from bacteria and plants. Plants are the only higher eukaryotes that have the required enzymes for methionine synthesis [MEDLINE:98301657]. This enzyme catalyses the last step in the production of methionine by transferring a methyl group from 5-methyltetrahydrofolate to homocysteine [MEDLINE:98301657]. The aligned region makes up the carboxy region of the approximately 750 amino acid protein except in some hypothetical archaeal proteins present in the family, where this region corresponds to the entire length.\ \ 5-methyltetrahydropteroyltriglutamate-homocysteine S-methyltransferase activity ; GO:0003871\ \N \N methionine biosynthesis ; GO:0009086 21246 IPR002630 This family consists of orbivirus non-structural protein NS1, or hydrophobic tubular protein. NS1 has no specific function in virus replication, it is however thought to play a role in transport of mature virus particles from virus inclusion bodies to the cell membrane [MEDLINE:97296956]. Orbivirus are part of the larger reoviridae which have a dsRNA genome of at least 10 segments encoding at least 10 viral proteins [MEDLINE:97296956]; orbivirus found in this family include bluetongue virus, and african horsesickness virus.\ \N \N \N 21223 IPR002603 This domain has no known function. It is found in severalC. elegans proteins. The domain contains 8-10 conserved\ cysteines that probably form 4-5 disulphide bridges. By\ inspection of the conservation of cysteines it looks like\ cysteines 1,2,3,4,9 and 10 are always present and that\ sometimes the pair 5 and 8 or the pair 6 and 7 are missing.\ This suggests that cysteines 5/8 and 6/7 make disulphide\ bridges.\ \ \N \N \N 21224 IPR002605 This family consists of various adenovirus penton baseproteins, from both the Mastadenoviridae having mammalian hosts\ and the Aviadenoviridae having avian hosts. The penton base is a \ major structural protein forming part of the penton which consists\ of a base and a fiber, the pentons hold a morphologically prominent \ position at the vertex capsomer in the adenovirus particle [MEDLINE:92263795]. \ In mammalian adenovirus there is only one tail on each base where as \ in avian adenovirus there are two [MEDLINE:92263795].\ \ structural molecule activity ; GO:0005198 \N \N 21225 IPR002606 This family consists of part of the bifunctional enzyme riboflavin kinase / FAD synthetase. These enzymes have both ATP:riboflavin \ 5'-phospho transferase and ATP:FMN-adenylyltransferase activities [MEDLINE:87057286].\ They catalyse the 5'-phosphorylation of riboflavin to FMN and the \ adenylylation of FMN to FAD [MEDLINE:87057286]. A domain has been identified in the N-terminal region that is well conserved in all the bacterial FAD synthetases.This domain has remote similarity to nucleotidyl transferases and, hence, it may be involved in the adenylylation reaction of FAD synthetases [MEDLINE:22406498].\ \ riboflavin kinase activity ; GO:0008531 \N vitamin B2 biosynthesis ; GO:0009231 21226 IPR002607 This family consist of various hydratases and 4-oxalocrotonate decarboxylases which are involved in the bacterial meta-cleavage \ pathways for degradation of aromatic compounds.\ 2-hydroxypentadienoic acid hydratase encoded by mhpD in Escherichia coli\ \ \ \ P77608 is involved in the phenylpropionic acid pathway of\ E. coli and catalyses the conversion of 2-hydroxy pentadienoate to\ 4-hydroxy-2-keto-pentanoate and uses a Mn²⁺ co-factor [MEDLINE:98151237].\ OHED hydratase encoded by hpcG in E. coli P77608/> is involved \ in the homoprotocatechuic acid (HPC) catabolism [MEDLINE:95255666].\ XylI in Pseudomonas putida\ \ \ \ P49155.\ \ lyase activity ; GO:0016829 \N aromatic compound metabolism ; GO:0006725 21227 IPR002608

This family consist of the C proteins (C', C, Y1, Y2) found in paramyxovirus ; human parainfluenza virus 3 , and sendai virus. The C proteins effect viral RNA synthesis having both a positive and negative effect during the course of infection [MEDLINE:98285759].Paramyxovirus have a negative-strand ssRNA genome of 15.3 kb from which six mRNAs are transcribed, five of these are monocistronic. \ The P/C mRNA is polycistronic and has two overlapping open reading frames P and C, C encodes the nested C proteins C', C, Y1 and Y2 [MEDLINE:89251580].

\ \ \N \N \N 21249 IPR002634 This family consist of the morpho-protein BolA from Escherichia coli and its various homologs. In E. coli, over-expression of this protein causes round morphology and may be involved in switching the cell between elongation and septation systems during cell division [MEDLINE:99291046]. The expression of BolA is growth rate regulated and is induced during the transition into the the stationary phase [MEDLINE:99291046]. BolA is also induced by stress during early stages of growth [MEDLINE:99291046] and may have a general role in stress response. It has also been suggested that BolA can induce the transcription of penicillin binding proteins 6 and 5 [MEDLINE:90059998], [MEDLINE:99291046].\ transcription regulator activity ; GO:0030528 \N \N 21247 IPR002631 This family consists of various bacterial plasmid replication (Rep) proteins. These proteins are essential for replication of plasmids, the Rep proteins are topoisomerases that nick the positive stand at the plus origin of replication and also at the single-strand conversion sequence [MEDLINE:90152374].\ DNA topoisomerase activity ; GO:0003916 extrachromosomal circular DNA ; GO:0005727 DNA replication ; GO:0006260 21248 IPR002633 The bacteriocins are small peptides that inhibit the growth of various bacteria. Bacteriocins of lactic acid bacteria may inhibit their target cells by permeabilizing the cell membrane [MEDLINE:98274743].\ bacteriocin activity ; GO:0015470 extracellular ; GO:0005576 \N 21235 IPR002618 This family consists of UTP--glucose-1-phosphate uridylyltransferases, EC: 2.7.7.9. Also known as UDP-glucose pyrophosphorylase (UDPGP) and Glucose-1-phosphate uridylyltransferase. UTP--glucose-1-phosphate uridylyltransferase catalyses the interconversion of MgUTP + glucose-1-phosphate and UDP-glucose + MgPP_i [MEDLINE:96202932]. UDP-glucose is an important intermediate in mammalian carbohydrate interconversion involved in various metabolic roles depending on tissue type [MEDLINE:96202932]. In Dictyostelium (slime mold) mutants in this enzyme abort the development cycle [MEDLINE:87231075]. Also within the family is UDP-N-acetylglucosamine Q16222\ \ \ Q16222/> and O51036.\ \ nucleotidyltransferase activity ; GO:0016779 \N metabolism ; GO:0008152 21234 IPR002616 This is a family of queuine and general tRNA-ribosyltransferases EC: 2.4.2.29, also known as tRNA-guanine transglycosylase and guanine insertion enzyme. Queuine tRNA-ribosyltransferase modifies tRNAs for asparagine, aspartic acid, histidine and tyrosine with queuine. It catalyses the exchange of guanine-34 at the wobble position with 7-aminomethyl-7-deazaguanine, and the addition of a cyclopentenediol moiety to 7-aminomethyl-7-deazaguanine-34 tRNA; giving a hypermodified base queuine in the wobble position [MEDLINE:96256303], [MEDLINE:93287116]. The aligned region contains a zinc binding motif C-x-C-x2-C-x29-H, and important tRNA and 7-aminomethyl-7deazaguanine binding residues [MEDLINE:96256303].\ queuine tRNA-ribosyltransferase activity ; GO:0008479 \N queuosine biosynthesis ; GO:0008616 21233 IPR002615 This family consists of the photosystem I reaction centre subunit IX or PsaJ from various organisms including Synechocystis sp. (strain pcc 6803), Pinus thunbergii (green pine) and Zea mays (maize).PsaJ P19443.\ \ \N \N \N 21232 IPR002614 The orbivirus VP3 protein is part of the virus core and makes a 'subcore' shell made up of 120 copies of the 100K protein [MEDLINE:98445087]. VP3 particles can also bind RNA and are fundamental in the early stages of viral core formation [MEDLINE:98445087].\ Also found in the family is structural core protein VP2 from broadhaven virus which is similar to VP3 in bluetongue virus\ \ \ \ [MEDLINE:93019012].\ Orbivirus are part of the larger reoviridae which have a dsRNA genome of 10-12 linear segments [MEDLINE:98445087]; orbivirus found in this family include bluetongue virus and epizootic hemorrhagic disease virus.\ \ structural molecule activity ; GO:0005198 \N \N 21231 IPR002612

This family consists of adenovirus E1B 55 kDa protein or large t-antigen. E1B 55 kDa binds p53 the tumor suppressor protein converting it from a transcriptional activator which responds to damaged DNA in to an unregulated repressor of genes with a p53 binding site [MEDLINE:99223569]. This protects the virus against p53 induced host antiviral responses and prevents apoptosis as induced by the adenovirus E1A protein [MEDLINE:99223569].The E1B region of adenovirus encodes two proteins E1B 55 kDa, the large t-antigen as found in this family and E1B 19 kDa IPR002924, the small t-antigen. Both of these proteins inhibit E1A induced apoptosis.

\ \ \N \N \N 21230 IPR002611 These proteins contain an ATP/GTP binding P-loop motif. They are found associated with IS21 family insertion sequences [MEDLINE:95212933]. Functionally they have not been characterized, but they may be involved in transposition [MEDLINE:97286520].\ \ \N \N \N 21228 IPR002609 This family consists of various caulimovirus viroplasminproteins. The viroplasmin protein is encoded by gene VI \ and is the main component of viral inclusion bodies or viroplasms .\ Inclusions are the site of viral assembly, DNA synthesis and \ accumulation P. Two domains exist within gene VI corr\ esponding \ approximately to the 5' third and middle third of gene VI, these influence\ systemic infection in a light-dependent manner P.\ \ \N inclusion body ; GO:0016234 regulation of translation ; GO:0006445 21229 IPR002610 This family contains integral membrane proteins that arerelated to Drosophila rhomboid protein P20350. Members\ of this family are found in bacteria and eukaryotes. These\ proteins contain three strongly conserved histidines in the\ putative transmembrane regions that may be involved in the\ as yet unknown function of these proteins.\ \ \N \N \N 21222 IPR002602 This domain has no known function. It is found in severalCaenorhabditis elegans proteins. The domain contains 12 conserved\ cysteines that probably form six disulphide bridges.\ This domain is found associated with ig IPR003006 and\ fn3 IPR003006/> domains, as well as in some lipases IPR001087.\ \ \N \N \N 21221 IPR002601

This domain of unknown function is found at the C-terminus in a number of Caenorhabditis elegans proteins. It may be an extracellular domain. The C6domain contains six conserved cysteine residues in most copies of the\ domain. However some copies of the domain are missing cysteine residues\ 1 and 3 suggesting that these form a disulphide bridge. In Q19522 there are 18 copies of the domain.

\ \ \N \N \N 21219 IPR002597 This family consists of probable major envelope glycoproteinsfrom members of the herpesviridae including herpes simplex \ virus, human cytomegalovirus and varicella-zoster virus.\ Members of the herpesviridae have a dsDNA genome and do\ not have a RNA stage during there replication.\ \ \N viral envelope ; GO:0019031 \N 21220 IPR002600 This family consists of various functionally undefined proteinsfrom the herpesviridae and UL7 from bovine herpes virus\ \ \ \ [MEDLINE:96135223], [MEDLINE:95313343].\ UL7 is not essential for virus replication in\ cell culture, and is found localized in the cytoplasm of\ infected cells accumulated around the nucleus\ but could not be detected in purified virions [MEDLINE:96135223]. \ Members of the herpesviridae have a dsDNA genome and do\ not have a RNA stage during there replication.\ \ \N \N \N 21218 IPR002596 This family consists of conserved hypothetical proteins fromBorrelia burgdorferi the lyme disease spirochaete, some of which\ are putative plasmid partition proteins [MEDLINE:98361033].\ \ \N \N \N 21217 IPR002595 The multigene family 360 protein are found within the African swine fever virus (ASF) genome which consist of\ dsDNA and has similar structural features to the \ poxviruses\ \ \ \ [MEDLINE:90219205]. The biological function of this family is \ not known [MEDLINE:90219205], although Q65137 is a major structural \ protein [MEDLINE:95159428].\ \ \N \N \N 21215 IPR002593 This domain has no known function. It is found in severalCaenorhabditis elegans proteins. The domain contains 6 conserved\ cysteines that probably form three disulphide bridges.\ \ \N \N \N 21216 IPR002594

Glycoside hydrolase family 12 CAZY:GH_12); xyloglucan hydrolase (EC not defined). These enzymes were formerly known as cellulase family H.

\ \ cellulase activity ; GO:0008810 \N polysaccharide catabolism ; GO:0000272 21212 IPR002589

This domain is found in a number of otherwise unrelated proteins.This domain is found at the C-terminal of the macro-H2A histone\ protein Q02874, in the non-structural\ proteins of several types of ssRNA viruses such as NSP2 from\ alphaviruses\ \ \ \ Q02874/>. It is also found on its own\ in a family of proteins from bacteria P75918\ \ \ \ P75918/> and eukaryotes Q17432, suggesting that it is\ involved in an important and ubiquitous cellular process.

\ \ \N \N \N 21213 IPR002591 This family consists of phosphodiesterases, including humanplasma-cell membrane glycoprotein PC-1 / alkaline phosphodiesterase I\ / nucleotide pyrophosphatase (nppase). These enzymes catalyse the\ cleavage of phosphodiester and phosphosulfate bonds in NAD, \ deoxynucleotides and nucleotide sugars [MEDLINE:98008933]. Another member of this family is\ ATX an autotaxin, tumor cell motility-stimulating protein which \ exhibits type I phosphodiesterases activity [MEDLINE:95074054].\ The alignment encompasses the active site [MEDLINE:95247775], [MEDLINE:95074054].\ Also present with in this family is 60 kDa Ca²⁺-ATPase from \ Myroides odoratus\ \ \ \ [MEDLINE:96214941].\ \ hydrolase activity ; GO:0016787 \N nucleotide metabolism ; GO:0009117 21214 IPR002592 This family consists of the reovirus sigma 1 hemagglutinin,cell attachment protein. This glycoprotein is a minor capsid \ protein and also determines the serotype-specific humoral immune response.\ Sigma 1 consist of a fibrous tail and a globular head. The head has\ important roles in the cell attachment function of sigma 1 \ and determinant of the type-specific humoral immune response [MEDLINE:90376438].\ Reovirus is part of the orthoreovirus group of reoviridae with,\ a dsRNA genome. Also present in this family is bacteriophage SF6 \ lysozyme P21270.\ \ \N \N cell adhesion ; GO:0007155 21211 IPR002588 This RNA methyltransferase domain [MEDLINE:99294905] is found in a wide range of ssRNA viruses, including Hordei-, Tobra-, Tobamo-, Bromo-,\ Clostero- and Caliciviruses. This methyltransferase is involved\ in mRNA capping. Capping of mRNA enhances its stability. This usually\ occurs in the nucleus. Therefore, many viruses that replicate\ in the cytoplasm encode their own [MEDLINE:99294905].\ \ mRNA methyltransferase activity ; GO:0008174 \N RNA processing ; GO:0006396 21210 IPR002587 1L-myo-Inositol-1-phosphate synthase (EC: 5.5.1.4) catalyzes the conversion of D-glucose 6-phosphate to 1L-myo-inositol-1-phosphate, the first committed step in the production of all inositol-containing compounds, including phospholipids, either directly or by salvage. The enzyme exists in a cytoplasmic form in a wide range of plants, animals, and fungi. It has also been detected in several bacteria and a chloroplast form is observed in alga and higher plants. Inositol phosphates play an important role in signal transduction.

In baker's yeast, Saccharomyces cerevisiae, the transcriptional regulation of the INO1 gene has been studied in detail [MEDLINE:95066381] and its expression is sensitive to the availability of phospholipid precursors as well as growth phase. The regulation of the structural gene encoding 1L-myo-inositol-1-phosphate synthase has also been analyzed at the transcriptional level in the aquatic angiosperm, Spirodela polyrrhiza and the halophyte, Mesembryanthemum crystallinum\ \ \ \ [MEDLINE:98036106].

\ \ inositol-3-phosphate synthase activity ; GO:0004512 \N phospholipid biosynthesis ; GO:0008654 21198 IPR002574 This family consists of various coronavirus matrix proteins which are transmembrane glycoproteins. The M protein or E1 glycoprotein is\ The coronavirus M protein is implicated in virus assembly [MEDLINE:84191468].\ The E1 viral membrane protein is required for formation of the viral \ envelope and is transported via the Golgi complex [MEDLINE:90163229].\ \ \N \N viral infectious cycle ; GO:0019058 21199 IPR002575 This family consists of bacterial antibiotic resistance proteins, which confer resistance to various aminoglycosides they include:-\ aminoglycoside 3'-phosphotransferase or kanamycin kinase / \ neomycin-kanamycin phosphotransferase and streptomycin 3''-kinase\ or streptomycin 3''-phosphotransferase. The aminoglycoside \ phosphotransferases inactivate aminoglycoside antibiotics via \ phosphorylation [MEDLINE:90356422].\ \ \N \N \N 21209 IPR002586 This family consists of various cobyrinic acid a,c-diamide synthases. These include CbiA and CbiP from \ S.typhimurium\ \ \ \ [MEDLINE:95362677]., and CobQ from R. capsulatus\ \ \ \ [MEDLINE:93273696].\ These amidases catalyse amidations to various side chains of \ hydrogenobyrinic acid or cobyrinic acid a,c-diamide in the biosynthesis \ of cobalamin (vitamin B12) from uroporphyrinogen III.\ Vitamin B12 is an important cofactor and an essential nutrient for many \ plants and animals and is primarily produced by bacteria [MEDLINE:95362677].\ \ cobyrinic acid a,c-diamide synthase activity ; GO:0042242 \N vitamin B12 biosynthesis ; GO:0009236 21208 IPR002585 These proteins are cytochrome bd type terminal oxidases that catalyse quinol dependent, Na⁺ independent oxygen uptake [MEDLINE:96198179]. Members of this family are integral membrane proteins and contain a protoheame IX center B558.

Cytochrome bd may play an important role in microaerobic nitrogen fixation in the enteric bacterium Klebsiella pneumoniae, where it is expressed under all conditions that permit diazotrophy [MEDLINE:97419506]. Subunit I binds a single b-haem, through ligands at His186 and Met393 (using SW:P11026 numbering). In addition His19 is a ligand for the haem b found in subunit II (IPR003317).

\ \ oxidoreductase activity ; GO:0016491 membrane ; GO:0016020 electron transport ; GO:0006118 21207 IPR002584 RepA is an E.coli protein involved in plasmid replication. The RepA protein binds to DNA repeats that flanks the repA\ gene [MEDLINE:93308080], [MEDLINE:86140142]. A similar RepA family of proteins with wider distribution are the bacterial plasmid DNA replication initiator proteins (see IPR004322).\ \ DNA binding activity ; GO:0003677 extrachromosomal circular DNA ; GO:0005727 DNA replication ; GO:0006260 21190 IPR002565 The function of this Orbivirus non structural protein isuncertain. However it may play a role in release of the\ virus from infected cells [MEDLINE:91374028].\ \ \N \N \N 21191 IPR002566 This family includes a number of bacterial surface antigens expressed on the surface of pathogens. The Anaplasma marginale surface proteins are targets of protective immune responses but are antigenically polymorphic [MEDLINE:94341886], [MEDLINE:94124017].\ \N \N \N 21192 IPR002567 Herpes simplex virus type 1 glycoprotein K (gK) plays an essential role in viral replication and cell fusion. gK is a very hydrophobic membrane protein that contains a signal sequence and several hydrophobic regions. gK contains three transmembrane domains (amino acids 125-139, 226-239, and 311-325) and another hydrophobic domain (amino acids 241-265), which is relatively less hydrophobic and much longer compared with the transmembrane sequences located in the extracellular loop. The domains may interact with each other to form a complex tertiary structure that is critical for the biological function of gK [MEDLINE:98070539].\ \N membrane ; GO:0016020 cell adhesion ; GO:0007155 21193 IPR002568 This family of carlavirus nucleic acid binding proteins includes a motif for a potential C-4 type zinc finger this has four highly conserved \ cysteine residues and is a conserved feature of the carlaviruses 3' \ terminal ORF [MEDLINE:91092429].\ These proteins may function as viral transcriptional regulators. \ The carlavirus family includes garlic latent virus and potato virus S \ and M, these viruses are positive strand, ssRNA with no DNA stage.\ \ nucleic acid binding activity ; GO:0003676 \N regulation of transcription, DNA-dependent ; GO:0006355 21194 IPR002569 The major mechanism for dealing with oxidative damage to

-type small, acid-soluble spore proteins (SASP) is DNA binding, which protects the protein's methionine residues from oxidation both in vitro and in vivo. This may be important in vivo since

-type SASP containing oxidized methionine residues no longer bind DNA well and

-type SASP-DNA binding is essential for long-term spore survival [MEDLINE:98241532].

Peptide methionine sulfoxide reductase reverses the inactivation of many proteins due to the oxidation of critical methionine residues by reducing methionine sulfoxide, Met(O), to methionine [MEDLINE:20300923].

\ \ protein-methionine-S-oxide reductase activity ; GO:0008113 \N protein modification ; GO:0006464 21205 IPR002582 Holo-acyl carrier protein synthase (ACPS) transfers the 4'-phosphopantetheine (4'-PP) moiety from coenzyme A (CoA) to Ser-36\ of acyl carrier protein (ACP) in Escherichia coli.\ This post-translational modification renders holo-ACP capable of\ acyl group activation via thioesterification of the cysteamine thiol\ of 4'-PP [MEDLINE:96027548].\ \ transferase activity ; GO:0016740 \N metabolism ; GO:0008152 21206 IPR002583

\ \ \

Bacterial ribosomal protein S20 forms part of the 30S ribosomal subunit, and interacts with 16S rRNA [MEDLINE:88230452]. This family is found in eubacteria and eukaryotes.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 21204 IPR002581 This family consists of morbillivirus RNA polymerase

subunit and non structural protein V. The P gene of morbillivirus is \ cotranscriptionally edited leading to the N-terminal \ half of the P protein being appended to the C-terminal of the P protein, \ and a cysteine rich region in the V fusion protein which has been \ shown to bind zinc [MEDLINE:92341068].\ Morbilliviruses are negative strand ssRNA viruses and a part of the\ paramyxoviridae family, members include measles virus and phocine \ distemper virus.\ \ RNA-directed RNA polymerase activity ; GO:0003968 \N transcription ; GO:0006350 21202 IPR002579 This domain has no known function. It is found associatedwith the peptide methionine sulfoxide reductase enzymatic\ domain IPR002569. The domain has two conserved cysteine\ and histidine residues that could suggest a zinc binding site.\ The final cysteine is found to be replaced by the rare amino\ acid selenocysteine in some proteins [MEDLINE:20076492].\ \ \N \N \N 21203 IPR002580 This family consists of various herpes virus proteins; the gene 20 product, U49 protein, UL24 protein and BXRF1.\ The UL24 gene (product of the 24th ORF) is not essential for virus \ replication, mutants with lesions in UL24 show a reduced ability to \ replicate in tissue culture and have reduced thymidine kinase activity\ as the UL24 gene overlaps with thymidine kinase [MEDLINE:98162578].\ \ \N \N \N 21200 IPR002576 This family contains a conserved P-loop motif that is involved in binding ATP. This family is only found in\ archaebacteria and particularly in Methanococcus jannaschii\ that encodes sixteen members of this family.\ \ \N \N \N 21201 IPR002577 Proteins belonging to this family are found in archaebacteria and eubacteria. The function of members of this family is unknown.\ \N \N \N 21195 IPR002571 In response to elevated temperature, both prokaryotic and eukaryotic cells increase expression of a small family of chaperones. The regulatory network that functions to control the transcription of the heat shock genes in bacteria includes unique structural motifs in the promoter region of these genes and the expression of alternate sigma factors. One of the conserved structural motifs, the inverted repeat CIRCE element, is found in the 5' region of many heat shock operons [MEDLINE:96178944].

For Bacillus subtilis three classes of heat shock genes regulated by different mechanisms have been described. Regulation of class I heat shock genes (dnaK and groE operons) involves an inverted repeat (CIRCE element) which most probably serves as an operator for a repressor [MEDLINE:96165263].

\ \ \N \N regulation of transcription, DNA-dependent ; GO:0006355 21196 IPR002572 This domain is found in 1 to 3 copies in archaebacterial proteins. The function of the domain is unknown. This\ family appears to be expanded in Archaeoglobus fulgidus.\ \ \N \N \N 21197 IPR002573 Choline kinase, (ATP:choline phosphotransferase, EC: 2.7.1.32) catalyses the committed step in the synthesis of phosphatidylcholine by the CDP-choline pathway [MEDLINE:98175949].\ \ \N \N \N 21184 IPR002558 I/LWEQ domains bind to actin. It has been shown that the I/LWEQdomains from mouse talin P26039 and yeast Sla2p\ P26039/> interact with F-actin [MEDLINE:97303189]. \ The domain has four conserved blocks, the name of the domain is derived from the initial conserved amino acid of\ each of the four blocks [MEDLINE:97303189]. I/LWEQ domains can be\ placed into four major groups based on sequence similarity:\

Metazoan talin.
Dictyostelium TalA/TalB P54633 and SLA110.
Metazoan Hip1p P54633/>.
Yeast Sla2p P33338.

\ \ actin binding activity ; GO:0003779 \N \N 21189 IPR002563 NAD(P)H-flavin oxidoreductases (flavin reductases (FR)) are a class of enzymes capable of producing reduced flavin for bacterial bioluminescence and other\ biological processes.\ The family consists of enzymes \ known to be flavin reductases as well as various oxidoreductase and\ monooxygenase enzymes [MEDLINE:95394837].\

A crystal structure is known for the protein from Methanobacterium thermoautotrophicum\ \ \ \ [MEDLINE:20473232].

\ \ oxidoreductase activity ; GO:0016491 \N electron transport ; GO:0006118 21188 IPR002562

This domain is responsible for the 3'-5' exonuclease proofreadingactivity of Escherichia coli DNA polymerase I (polI) and other enzymes, \ it catalyses the hydrolysis of unpaired or mismatched nucleotides. \ This domain consists of the amino-terminal half of the Klenow fragment \ in E. coli polI it is also found in the Werner syndrome helicase \ (WRN), focus forming activity 1 protein (FFA-1) and ribonuclease D\ (RNase D).

\ \ \ 3'-5' exonuclease activity ; GO:0008408\ nucleic acid binding activity ; GO:0003676 intracellular ; GO:0005622 \N 21187 IPR002561 This family includes an extracellular region from theenvelope glycoprotein of Ebola and Marburg viruses.\ This region is also produced as a separate transcript\ that gives rise to a non-structural, secreted glycoprotein,\ which is produced in large amounts and has an unknown function [MEDLINE:98245155].\ Processing of this protein may be involved in viral\ pathogenicity [MEDLINE:96195018].\ \ \N \N \N 21186 IPR002560 Autonomous mobile genetic elements such as transposon or insertion sequences (IS)encode an enzyme, transposase, that is required for excising and inserting\ the mobile element. Transposases have been grouped into various families [MEDLINE:94316508], [MEDLINE:92149305], [MEDLINE:92039004]. This family\ includes the IS204 [MEDLINE:94254729], IS1001 [MEDLINE:93106948], IS1096 [MEDLINE:92078082] and IS1165 [MEDLINE:92383311] transposases.\ \ transposase activity ; GO:0004803 \N DNA recombination ; GO:0006310 21185 IPR002559 Autonomous mobile genetic elements such as transposon or insertion sequences (IS)encode an enzyme, transposase, that is required for excising and inserting\ the mobile element. Transposases have been grouped into various families [MEDLINE:94316508], [MEDLINE:92149305], [MEDLINE:92039004]. This family includes the IS4 transposase.\ \ \N \N \N 21182 IPR002556 This family consists of viral envelope proteins from thearterivirus genus; this includes porcine reproductive and \ respiratory virus (PRRSV) envelope protein GP3 and lactate \ dehydrogenase elevating virus (LDV) structural glycoprotein.\ Arteriviruses consists of positive ssRNA and do not have a DNA\ stage.\ \ \N viral envelope ; GO:0019031 \N 21183 IPR002557

The Peritrophin-A domain is found in chitin binding proteins, particularly the peritrophic matrix proteins of insects and animal chitinases [MEDLINE:98316335], [MEDLINE:96224111], [MEDLINE:97404326]. Copies of the domain are also found in some baculoviruses . It is an extracellular domain that contains six\ conserved cysteines that probably form three disulphide bridges. Chitin binding has been demonstrated for a\ protein containing only two of these domains [MEDLINE:98316335].

\ \ chitin binding activity ; GO:0008061 extracellular ; GO:0005576 chitin metabolism ; GO:0006030 21175 IPR002548 E1 forms a heterodimer with E2 (IPR000936). The virus spikes are madeup of 80 trimers of these heterodimers (sindbis virus) [MEDLINE:97151146].\ \ \N \N \N 21176 IPR002549

This is a family of hypothetical proteins. A number of the sequence records state they are transmembrane proteins or putative permeases. It is not clear what source suggested that these proteins might be permeases and this information should be treated with caution.

\ \ \ \N \N \N 21177 IPR002550 This transmembrane region has no known function. Many of the sequences in this family are annotated as hemolysins, however this is due to a similarity to Q54318).\ \N \N \N 21178 IPR002551 The type I glycoprotein S of coronavirus, trimers of which constitute the typical viral spikes, is assembled into virions through noncovalent interactions with the M protein. The spike glycoprotein is translatedas a large polypeptide that is subsequently cleaved to S1 and S2 IPR002552\ \ \ \ [MEDLINE:85159540]. Both chimeric S proteins appeared to cause cell fusion when expressed individually, suggesting that they were biologically fully active [MEDLINE:20094947]. The spike is a type I membrane glycoprotein that possesses a conserved transmembrane anchor and an unusual cysteine-rich (cys) domain that bridges the putative junction of the anchor and the cytoplasmic tail [MEDLINE:20192177].\ \ \N \N \N 21179 IPR002552 The type I glycoprotein S of coronavirus, trimers of which constitute the typical viral spikes, is assembled into virions through noncovalent interactions with the M protein. The spike glycoprotein is translatedas a large polypeptide that is subsequently cleaved to S1 IPR002551.\ \ \N \N \N 21180 IPR002553 This domain is the N-terminal region of various

and gamma subunits of the AP-1, AP-2 and AP-3 adaptorprotein complexes. The adaptor protein (AP) complexes are involved in\ the formation of clathrin-coated pits and vesicles [MEDLINE:97409270].\ The N-terminal region of the various adaptor proteins (APs) is constant\ by comparison to the C-terminal which is variable within members of the\ AP-2 family [MEDLINE:89202379]; and it has been proposed that this constant region\ interacts with another uniform component of the coated vesicles [MEDLINE:89202379].\ \ \N \N \N 21181 IPR002554 Protein phosphatase 2A (PP2A) is a major intracellular proteinphosphatase that regulates multiple aspects of cell growth and metabolism.\ The ability of this widely distributed heterotrimeric enzyme to act on a\ diverse array of substrates is largely controlled by the nature of its\ regulatory B subunit. There are multiple families of B subunits, this family is called the B56 family [MEDLINE:96064678].\ \ protein phosphatase type 2A, regulator activity ; GO:0008601 protein phosphatase type 2A complex ; GO:0000159 signal transduction ; GO:0007165 21169 IPR002542 This domain has no known function. It is found in one or two copies in several Caenorhabditis elegans proteins. It is\ roughly 130 amino acids and contains 12 conserved\ cysteines.\ \ \N \N \N 21170 IPR002543

The FtsK/SpoIIIE domain is found extensively in a wide variety of proteins from prokaryotes and plasmids [MEDLINE:96042098] some of which contain up to three copies.The domain contains a putative ATP binding P-loop motif. A mutation in FtsK causes a temperature sensitive block in cell\ division and it is involved in peptidoglycan synthesis or modification [MEDLINE:96042098]. The SpoIIIE protein is implicated in intercellular chromosomal DNA transfer [MEDLINE:96042098].

\ \ \N \N \N 21171 IPR002544 The neuropeptide Phe-Met-Arg-Phe-NH2 (FMRFamide) is a potent cardioactive neuropeptide in Lymnaea stagnalis\ \ \ [MEDLINE:90155411]. FMRFamide (Phe-Met-Arg-Phe-NH2) was first demonstrated to be cardioactive in several molluscan species. FMRFamide is now known to be cardioexcitatory in mammals, to inhibit morphine-induced antinociception, and to block morphine-, defeat-, and deprivation-induced feeding [MEDLINE:89145036]. \

Thirteen neuropeptides varying in length from 7 to 11 residues and ending C-terminally in -Phe-Met-Arg-Phe-NH2 (calliFMRFamides 1-13) and one dodecapeptide ending in -Met-Ile-Arg-Phe-NH2 (calliMIRFamide 1) have been isolated from thoracic ganglia of the blowfly Calliphora vomitoria. Results indicate that the N terminus (in addition to the C terminus as previously found for FMRFamides of other organisms) is crucial for at least some biological activities [MEDLINE:92196111].

\ \ \N \N neuropeptide signaling pathway ; GO:0007218 21172 IPR002545 CheW proteins are part of the chemotaxis signalingmechanism in bacteria. CheW interacts with the methyl\ accepting chemotaxis proteins (MCPs) and relays signals\ to CheY, which affects flageller rotation. This family\ includes CheW and other related proteins that are\ involved in chemotaxis. The CheW-like regulatory domain\ in CheA [MEDLINE:99142610] binds to CheW, suggesting that these domains can\ interact with each other.\ \ signal transducer activity ; GO:0004871 intracellular ; GO:0005622 signal transduction ; GO:0007165 21173 IPR002546 This basic domain is found in the MyoD family of muscle specific proteins that control muscle development. The bHLH region of the MyoD family\ includes the basic domain and the Helix-loop-helix (HLH) motif.\ The bHLH region mediates specific DNA binding [MEDLINE:98001585]. With 12 residues\ of the basic domain involved in DNA binding [MEDLINE:96382471]. The basic domain\ forms an extended

helix in the structure.\ \ DNA binding activity ; GO:0003677 nucleus ; GO:0005634 muscle development ; GO:0007517 21168 IPR002541 This family consists of various proteins involved in cytochrome cassembly from mitochondria and bacteria; CycK from Rhizobium\ \ \ \ [MEDLINE:95394794], \ CcmC from E. coli and Paracoccus denitrificans\ \ \ \ [MEDLINE:95362656], [MEDLINE:97195802]\ and orf240 from wheat mitochondria [MEDLINE:95124303]. \ The members of this family are probably integral membrane proteins\ with six predicted transmembrane helices that may comprise the membrane component of an \ ABC (ATP binding cassette) transporter complex. This transporter may be necessary for transport of some component \ needed for cytochrome c assembly. \

One member CycK contains a putative heme-binding motif [MEDLINE:95394794],\ orf240 also contains a putative heme-binding motif and is a proposed \ ABC transporter with c-type heme as its proposed substrate [MEDLINE:95124303].\ However it seems unlikely that all members of this family transport\ heme nor c-type apocytochromes because CcmC in the putative CcmABC\ transporter transports neither [MEDLINE:97195802].

\ \ \N membrane ; GO:0016020 cytochrome c oxidase biogenesis ; GO:0008535 21174 IPR002547 This domain is found in prokaryotic methionyl-tRNA synthetases, prokaryotic phenylalanyl tRNA synthetases the yeast GU4 nucleic-binding \ protein (G4p1 or p42, ARC1) [MEDLINE:97050848], human tyrosyl-tRNA synthetase [MEDLINE:97306356],\ and endothelial-monocyte activating polypeptide II. \ G4p1 binds specifically to tRNA form a complex with methionyl-tRNA \ synthetases [MEDLINE:97050848]. In human tyrosyl-tRNA synthetase this domain may direct\ tRNA to the active site of the enzyme [MEDLINE:97050848]. This domain may perform a\ common function in tRNA aminoacylation [MEDLINE:97306356].\ \ tRNA binding activity ; GO:0000049 \N \N 21154 IPR002524

Members of this family are integral membrane proteins, thatare found to increase tolerance to divalent metal ions such\ as cadmium, zinc, and cobalt. These proteins are considered to\ be efflux pumps that remove these ions from cells [MEDLINE:98361887], [MEDLINE:96219090], however others are implicated in ion uptake [MEDLINE:92375034]. The\ family has six predicted transmembrane domains. Members of the family are variable\ in length because of variably sized inserts, often containing low-complexity sequence.

\ \ cation transporter activity ; GO:0008324 membrane ; GO:0016020 cation transport ; GO:0006812 21155 IPR002525

Transposase proteins are necessary for efficient DNA transposition.This family includes an amino-terminal region of the pilin gene inverting\ protein (PIVML) and members of the IS111A/IS1328/IS1533 family of\ transposases.

\ \ transposase activity ; GO:0004803 \N DNA recombination ; GO:0006310 21156 IPR002527 Poliovirus infection leads to drastic alterations in membranepermeability late during infection. Proteins 2B and 2BC enhance\ membrane permeability [MEDLINE:97361833], [MEDLINE:96394400].\ \ \N \N \N 21157 IPR002528

Characterised members of the Multi Antimicrobial Extrusion (MATE) family (TC:2.A.66.1) function as drug/sodium antiporters. These proteins mediate resistance to a wide range of cationic dyes, fluroquinolones, aminoglycosides and other structurally diverse antibodies and drugs. MATE proteins are found in bacteria, archaea and eukaryotes. These proteins are predicted to have 12 -helical transmembrane regions, some of the animal proteins may have an additional C-terminal helix.

\ antiporter activity ; GO:0015297 membrane ; GO:0016020 multidrug transport ; GO:0006855 21158 IPR002529 This family consists of fumarylacetoacetase (FAA), or fumarylacetoacetate hydrolase (FAH) and it also includes \ HHDD isomerase EC: 5.3.3.-/OPET decarboxylase EC: 4.1.1.- from E. coli strain W.\ \ enzyme activity ; GO:0003824 \N metabolism ; GO:0008152 21159 IPR002530

Alpha-prolamins are the major seed storage proteins of species of the grass tribe Andropogonea. They are unusually rich in glutamine, proline, alanine, and leucine residues and their sequences show a series of tandem repeats presumed to be the result of multiple intragenic duplication [MEDLINE:93197294]. In Zea mays, the 22 kDa and 19 kDa zeins are encoded by a large multigene family and are the major seed storage proteins accounting for 70% of the total zein fraction. Structurally the 22 kDa and 19 kDa zeins are composed of nine adjacent, topologically antiparallel helices clustered within a distorted cylinder. The 22 kDa -zeins are encoded by 23 genes [MEDLINE:21549079]; twenty-two of the members are found in a roughly tandem array forming a dense gene cluster. The expressed genes in the cluster are interspersed with nonexpressed genes. Interestingly, some of the expressed genes differ in their transcriptional regulation. Gene amplification appears to be in blocks of genes explaining the rapid and compact expansion of the cluster during the evolution of maize.

\ nutrient reservoir activity ; GO:0045735 \N \N 21152 IPR002522

The Hepatitis C virus has a ssRNA genome. The virion is a nucleocapsid covered by a lipoprotein envelope consisting of two proteins, protein M and glycoprotein E. The nucleocapsid is a complex of protein C and mRNA.

\ structural molecule activity ; GO:0005198 viral capsid ; GO:0019028 \N 21153 IPR002523 The CorA transport system is the primary Mg²⁺ influx system of Salmonellatyphimurium and Escherichia coli\ \ \ \ [MEDLINE:98448512], [MEDLINE:99003207]. CorA is virtually ubiquitous in the\ Bacteria and Archaea. There are also eukaryotic relatives of this protein\ \ heavy metal ion porter activity ; GO:0005373 membrane ; GO:0016020 heavy metal ion transport ; GO:0006823 21165 IPR002538 Members of this family assemble into long tubular structures at the surface of the infected protoplast. Theseproteins aid the infection of the virus\ \ \ \ [MEDLINE:97410297], [MEDLINE:98190358].\ \ \N \N \N 21166 IPR002539 The C terminus of the MaoC protein is found to share similarity witha wide variety of enzymes. All these enzymes contain multiple domains.\ This domain is found in parts of two enzymes that have been assigned\ dehydratase activities.\ A deletion mutant of the C-terminal 271 amino acids in Q02207\ abolished its 2-enoyl-CoA hydratase activity, suggesting that this\ region may be a hydratase enzyme [MEDLINE:99108114].\ The maoC gene is part of a operon with maoA which is involved\ in the synthesis of monoamine oxidase [MEDLINE:92210491].\ \ oxidoreductase activity ; GO:0016491 \N metabolism ; GO:0008152 21167 IPR002540

The potyviridae are a family of positive strand RNA viruses, members of which include zucchini yellow mosaic virus,and turnip mosaic viruses which cause considerable losses of crops \ worldwide.

This family consists of a C-terminal region from various plant\ potyvirus P1 proteins (found at the N terminus of the polyprotein).\ The C terminus of P1 is a serine-type protease responsible for \ autocatalytic cleavage between P1 and the helper component protease IPR001456\ \ \ \ [MEDLINE:95146958], [MEDLINE:92410606]. The entire P1 protein may be involved in virus-host interactions [MEDLINE:95146958].

\ \ cysteine-type endopeptidase activity ; GO:0004197 \N proteolysis and peptidolysis ; GO:0006508 21164 IPR002535 The flaviviruses are small enveloped animal viruses containing a singlepositive strand genomic RNA\ \ \ \ [MEDLINE:91069238]. The genome encodes one large ORF a\ polyprotein which undergos proteolytic processing into mature viral \ peptide chains.\ This family consists of a propeptide region of approximately 90 amino\ acid length.\ \ \N \N \N 21163 IPR002534 The medium (M) genome segment of hantaviruses (family Bunyaviridae)encodes the two virion glycoproteins [MEDLINE:87316891]. G1 and G2, as a precursor\ protein in the complementary sense RNA.\ \ \N \N \N 21162 IPR002533 If the trimeric spike complex (E1, E2, E3)3 is represented as a triangle, E2 extends from the centre to the vertices and E1 fills in between the ridges of E2 to form the edges of the triangle while E3 is at the distal end of the spike, interacting primarily with E2 [MEDLINE:98105802], [MEDLINE:94149759].\ \N \N \N 21160 IPR002531 The hypervariable region of the E2/NS1 region of hepatitis C virusvaries greatly between viral isolates. E2 is thought to encode a\ structurally unconstrained envelope protein [MEDLINE:98085910].\ \ \N \N \N 21161 IPR002532 The medium (M) genome segment of hantaviruses (family Bunyaviridae)encodes the two virion glycoproteins [MEDLINE:87316891]. G1 and G2, as a precursor\ protein in the complementary sense RNA.\ \ \N \N \N 21148 IPR002518 The viral genome is translated into a single polyprotein ofabout 3000 amino acids. Generation of the mature non-structural proteins\ relies on the activity of viral proteases. Cleavage at the\ NS2/NS3 junction is accomplished by a metal-dependent autoprotease\ encoded within NS2 and the N-terminus of NS3 [MEDLINE:97368158], [MEDLINE:97404642].\ \ \N \N \N 21149 IPR002519 Hepatitis C virus envelope glycoprotein E1 is contained within the genome polyprotein that contains: capsid protein C; the envelope glycoprotein E1; envelope glycoprotein E2; nonstructural proteins NS2, NS3, NS4A, NS4B, NS5A and NS5B. The virion of the virus is covered by a lipoprotein envelope that consists of two proteins: protein M and glycoprotein E.\ \N viral envelope ; GO:0019031 \N 21150 IPR002520 This family consists of the p50 and variable adherence-associated antigen(Vaa) adhesins from Mycoplasma hominis. M. hominis is a mycoplasma associated with human urogenital diseases, pneumonia, and septic\ arthritis [MEDLINE:96294788].\ An adhesin is a cell surface molecule that mediates adhesion to other\ cells or to the surrounding surface or substrate.\ The Vaa antigen is a 50-kDa surface lipoprotein that has four tandem\ repetitive DNA sequences encoding a periodic peptide structure, and is\ highly immunogenic in the human host [MEDLINE:96294788]. p50 is also a 50-kDa\ lipoprotein, having three repeats A,B and C, that may be a tetramer of\ 191-kDa in its native environment [MEDLINE:97047675].\ \ \N \N cell adhesion ; GO:0007155 21151 IPR002521 The viral core protein forms the internal viral coat thatencapsidates the genomic RNA and is enveloped in a host\ cell-derived lipid membrane. The core protein has been shown,\ by yeast two-hybrid assay to interact with cellular DEAD box\ helicases [MEDLINE:99263161]. The N terminus of the core protein is\ involved in transcriptional repression [MEDLINE:99180429].\ \ structural molecule activity ; GO:0005198 \N \N 21141 IPR002511 Disruption of the V1 gene in Tomato yellow leaf curl virus (TYLCV)stopped its ability to systemically infect tomato plants, suggesting\ that the V1 gene product is required for successful infection\ of the host [MEDLINE:97223325].\ \ \N \N \N 21142 IPR002512 Rotaviruses are dsRNA viruses that appear to infect a wide range of mammals. Gene 11 product is a non-structural phosphoprotein designated as NS26 [MEDLINE:89342638].\ \N \N \N 21143 IPR002513 This family includes transposases of Tn3, Tn21, Tn1721,Tn2501, Tn3926 transposons from E. coli. The specific binding of the Tn3 transposase to DNA has been demonstrated.\ Sequence analysis has suggested that the invariant triad of Asp689, Asp765, Glu895 (numbering as in Tn3) may correspond to the D-D-35-E motif previously implicated in the catalysis of numerous transposases [MEDLINE:97086320].\ \ \N \N \N 21144 IPR002514 Transposase proteins are necessary for efficient DNA transposition.This family consists of various E. coli insertion elements and other\ bacterial transposases some of which are members of the IS3 family.\ This region includes a helix-turn-helix motif (HTH) at the N-terminus\ followed by a leucine zipper (LZ) motif. The LZ motif has been shown\ to mediate oligomerisation of the transposase components in IS911 [MEDLINE:98437368].\ \ \N \N \N 21145 IPR002515 Zinc fingers are found in a wide variety of proteins, and are associated with DNA binding. There are several different types, and this family contains the C2HC-type zinc finger, which is found in eukaryotes.\ transcription factor activity ; GO:0003700 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 21146 IPR002516

Glycosyltransferase family 11 CAZY:GT_11).

\ \

Some of the proteins in this group are responsible for the molecular basis of the blood group antigens, surface markers on the outside of the red blood cell membrane. Most of these markers are proteins, but some are carbohydrates attached to lipids or proteins [Reid M.E., Lomas-Francis C. The Blood Group Antigen FactsBook Academic Press, London / San Diego, (1997)]. Galactoside 2-L-fucosyltransferase 1 (EC: 2.4.1.69) and Galactoside 2-L-fucosyltransferase 2 (EC: 2.4.1.69) belong to the Hh blood group system and are associated with H/h and Se/se antigens.

\ \ galactoside 2-alpha-L-fucosyltransferase activity ; GO:0008107 membrane ; GO:0016020 carbohydrate metabolism ; GO:0005975 21139 IPR002509 This domain is found in polysaccharide deacetylase. This family ofpolysaccharide deacetylases includes NodB (nodulation protein B from \ Rhizobium) which is a chitooligosaccharide deacetylase [MEDLINE:97305956].\ It also includes chitin deacetylase from yeast [MEDLINE:97279228],\ and endoxylanases which hydrolyses glucosidic bonds in xylan [MEDLINE:94224155].\ \ hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds ; GO:0016810 \N carbohydrate metabolism ; GO:0005975 21140 IPR002510

The letA (ccdA) and letD (ccdB) genes of the F plasmid, located just outside the sequence essential for replication, contribute to stable maintenance of the plasmid in Escherichia coli cells. The letD gene product acts to inhibit partitioning of chromosomal DNA and cell\ division by inhibiting DNA gyrase activity, whereas the letA gene product acts to reverse the\ inhibitory activity of the letD gene product [MEDLINE:96177756]. It has also\ been suggested that PmbA may be involved in secretion [MEDLINE:91186828].

\ \ \N \N \N 21147 IPR002517 The tospovirus genome consists of three linear ssRNA segments,denoted L, M and S complexed with the nucleocapsid protein.\ The S RNA encodes the nucleocapsid protein and another\ non-structural protein [MEDLINE:93155639].\ \ \N viral nucleocapsid ; GO:0019013 \N 21132 IPR002501 Members of this family are involved in modifying bases in RNAmolecules. They carry out the conversion of uracil bases to\ pseudouridine. This family includes TruB, a pseudouridylate synthase\ that specifically converts uracil 55 to pseudouridine in most tRNAs.\ This family also includes Cbf5p that modifies rRNA [MEDLINE:98139521].\ \ pseudouridylate synthase activity ; GO:0004730 \N RNA processing ; GO:0006396 21133 IPR002502 This family includes zinc amidases that have N-acetylmuramoyl-L-alanineamidase activity EC: 3.5.1.28 This enzyme domain cleaves the amide bond\ between N-acetylmuramoyl and L-amino acids in bacterial cell walls\ (preferentially: D-lactyl-L-Ala). The structure is known for the\ bacteriophage T7 structure and shows that two of the conserved histidines\ are zinc binding.\ \ N-acetylmuramoyl-L-alanine amidase activity ; GO:0008745 \N peptidoglycan catabolism ; GO:0009253 21134 IPR002504 Members of this family are ATP-NAD kinases EC: 2.7.1.23. The enzymes catalyse the phosphorylation of NAD to NADP utilizing ATP and other nucleoside triphosphates as well as inorganic polyphosphate as a source of phosphorus.\ \ \N \N \N 21135 IPR002505

This family contains both phosphate acetyltransferase EC: 2.3.1.8:\

Acetyl-CoA\
   +  phosphate\
  =\
      CoA\
   +  acetyl phosphate\

\ and\ phosphate butaryltransferase EC: 2.3.1.19:

\ \

\
   Butanoyl-CoA\
   +  phosphate\
  =\
      CoA\
   +  butanoyl phosphate\

\ \

These enzymes catalyse the\ transfer of an acetyl or butaryl group to orthophosphate.

\ \ acyltransferase activity ; GO:0008415 \N metabolism ; GO:0008152 21136 IPR002506 The hepatitis delta virus (HDV) encodes a single protein, thehepatitis delta antigen (HDAg). The central region of this protein\ has been shown to bind RNA [MEDLINE:94065676]. Several interactions are also\ mediated by a coiled-coil region at the N terminus of the protein [MEDLINE:98362586].\ \ RNA binding activity ; GO:0003723 host cell nucleus ; GO:0042025 \N 21137 IPR002507 Reovirus nonstructural protein sigma NS exhibits a ssRNA-binding activity and is thought to be involved in assembling the reovirus mRNAs for genome replication and virion morphogenesis. Various studies have been carried out to localize the RNA-binding site [MEDLINE:98001332]. They suggest that the first 11 amino acids of sigma NS, which are predicted to form an amphipathic

-helix, are important for both ssRNA binding and formation of complexes larger than 7-9 S.

A number of other studies have attempted to identify and characterise the RNA-binding activities of sigma NS. A study of the avian reovirus sigma NS protein suggests that it binds to single-stranded RNA in a nucleotide sequence non-specific manner and is functionally similar to its counterpart specified by mammalian reovirus [MEDLINE:98295840].

\ \ RNA-directed RNA polymerase activity ; GO:0003968 \N \N 21138 IPR002508

The cell wall envelope of gram-positive bacteria is a macromolecular, exoskeletal organelle that is assembled and turned over at designated sites. The cell wall also functions as a surface organelle that allows gram-positive pathogens to interact with their environment, in particular the tissues of the infected host. All of these functions require that surface proteins and enzymes be properly targeted to the cell wall envelope. Two basic mechanisms, cell wall sorting and targeting, have been identified. Cell well sorting is the covalent attachment of surface proteins to the peptidoglycan via a C-terminal sorting signal that contains a consensus LPXTG sequence. More than 100 proteins that possess cell wall-sorting signals, including the M proteins of Streptococcus pyogenes, protein A of Staphylococcus aureus, and several internalins of Listeria monocytogenes, have been identified. Cell wall targeting involves the noncovalent attachment of proteins to the cell surface via specialized binding domains. Several of these wall-binding domains appear to interact with secondary wall polymers that are associated with the peptidoglycan, for example teichoic acids and polysaccharides. Proteins that are targeted to the cell surface include muralytic enzymes such as autolysins, lysostaphin, and phage lytic enzymes. Other examples for targeted proteins are the surface S-layer proteins of bacilli and clostridia, as well as virulence factors required for the pathogenesis of L. monocytogenes (internalin B) and Streptococcus pneumoniae (PspA) infections [MEDLINE:99167688].

Autolysin EC: 3.5.1.28 hydrolyzes the link between N-acetylmuramoyl residues and L-amino acid residues in certain bacterial cell wall glycopeptides.

\ \ N-acetylmuramoyl-L-alanine amidase activity ; GO:0008745 \N peptidoglycan catabolism ; GO:0009253 21125 IPR002493 The herpesvirus UL25 gene product is a virion component involved in viruspenetration [MEDLINE:96187818] and capsid assembly. The product of the UL25 gene is\ required for packaging but not cleavage of replicated viral DNA [MEDLINE:96187818].\ This family includes a number of herpesvirus proteins: EHV-1 36, EBV BVRF1\ P03233 gene\ 34 P03233/>.\ \ \N \N \N 21126 IPR002494 High sulfur proteins are cysteine-rich proteins synthesizedduring the differentiation of hair matrix cells, and form hair\ fibers in association with hair keratin intermediate filaments [MEDLINE:98201605].\ This family has been divided up into four regions, with the second\ region containing 8 copies of a short repeat [MEDLINE:98201605]. This family is\ also known as B2 or KAP1.\ \ \N \N \N 21127 IPR002495

Glycosyltransferase family 8 CAZY:GT_8), lipopolysaccharide\ glucosyltransferase 1 (EC: 2.4.1.58), glycogenin glucosyltransferase (EC: 2.4.1.186), inositol 1--galactosyltransferase (EC: 2.4.1.123). These enzymes have a distant similarity to family GT24.

\ \ transferase activity, transferring hexosyl groups ; GO:0016758 \N carbohydrate biosynthesis ; GO:0016051 21128 IPR002496 Phosphoribosyl-AMP cyclohydrolase EC: 3.5.4.19 catalyses the third step in the histidine biosynthetic pathway:

\
5-phosphoribosyl-AMP + H₂O = 5-(5-phospho-D-ribosylaminoformimino)-1-(5-phospho-ribosyl) imidazole-4-carboxamide\

\ It requires Zn²⁺ ions for activity [MEDLINE:99129952].\ \ phosphoribosyl-AMP cyclohydrolase activity ; GO:0004635 \N histidine biosynthesis ; GO:0000105 21124 IPR002492 Transposase proteins are necessary for efficient DNA transposition.This family includes the amino-terminal region of Tc1, Tc1A, Tc1B and Tc2B transposases of Caenorhabditis elegans. The region encompasses the specific DNA binding and second DNA recognition domains as well as an amino-terminal region of the catalytic domain of Tc3 as described in [MEDLINE:97459988]. Tc3 is a member of the Tc1/mariner family of transposable elements.\ \ transposase activity ; GO:0004803 nucleus ; GO:0005634 DNA integration ; GO:0015074 21131 IPR002500 This domain is found in phosphoadenosine phosphosulfate (PAPS) reductaseenzymes or PAPS sulfotransferase. PAPS reductase is part of the adenine \ nucleotide

hydrolases superfamily also including N type ATP PPases\ and ATP sulphurylases [MEDLINE:97411695]. The enzyme uses thioredoxin as an electron \ donor for the reduction of PAPS to phospho-adenosine-phosphate (PAP) [MEDLINE:97411695], [MEDLINE:96061968].\ It is also found in NodP nodulation protein P from Rhizobium which has ATP\ sulfurylase activity (sulfate adenylate transferase) [MEDLINE:91066949].\ \ transferase activity ; GO:0016740 \N metabolism ; GO:0008152 21130 IPR002499

Vaults are the largest ribonucleoprotein particles known having a mass of approximately 13 MDa. Their function has not been determined [MEDLINE:99216533]. This family corresponds to a repeat found in the amino terminal half of the major vault protein (MVP or Lung resistance-related protein) which has a mass of 100 kDa.

The 13 MDa mammalian vault structure is highly regular and consists of approximately 96 molecules of the 100 kDa major vault protein (MVP), 2 molecules of the 240 kDa minor vault protein TEP1, 8 molecules of the 193 kDa minor vault protein VPARP and at least 6 copies of a small untranslated RNA of 88141 bases. The MVP molecules form the core of the complex, which is a barrel-like structure with an invaginated waist and two protruding caps. The complex can unfold into two symmetrical flower-like structures with 8 petals each supposedly consisting of 6 MVP molecules [MEDLINE:99216533].

\ \

Although all vault components have been identified and characterized, and a model of the vault complex has been determined to 31-Angstrom [MEDLINE:99216533], not much is known about vault assembly. MVP molecules interact with each other via their coiled coil domain. Purified MVP is able to bind calcium as it contains typical calcium-binding EF-hands. No interactions have been demonstrated between TEP1 and other vault proteins. However, the N-terminal half of MVP binds to a specific domain in the C terminus of VPARP. Furthermore, VPARP (e.g. Q9UKK3. MVP (Lung resistance-related protein) is overexpressed in many multidrug-resistant cancer cells.

\ \

TEP1 (e.g. Q9UKK3/>) has a mass of 240 kDa and in addition to being a vault component it is also a telomerase-associated component. The presence of a large number of WD40 repeats, IPR001680, in the C terminus of the TEP1 protein is a convenient number for this protein to serve a structural or organizing role in the vault. The sharing of the TEP1 protein between vaults and telomerase suggests that TEP1 may play a common role in some aspect of ribonucleoprotein structure, function or assembly.

\ \ \N \N \N 21129 IPR002498 This family contains a region from the common kinase core found in the typeI phosphatidylinositol-4-phosphate 5-kinase (PIP5K) family as described in\ [MEDLINE:98204859]. The family consists of various type I, II and III PIP5K enzymes.\ PIP5K catalyses the formation of phosphoinositol-4,5-bisphosphate via the \ phosphorylation of phosphatidylinositol-4-phosphate a precursor in the \ phosphinositide signaling pathway.\ \ \ 1-phosphatidylinositol-4-phosphate 5-kinase activity ; GO:0016308\ \N \N \N 21115 IPR002483

The PWI domain, found only in eukaryotic proteins, contains a conserved PWI motif at its N terminus. The presence ofPWI motifs in known splicing factors suggests that it may be important for\ multiple interactions within splicing complexes [MEDLINE:99257313].

\ \ \N \N mRNA splicing ; GO:0006371 21116 IPR002484 Arterivirus are ssRNA positive-strand viruses with no DNA stage in their replication cycle. The viral nucleocapsid protein encapsidates the viral ssRNA.\ \N viral nucleocapsid ; GO:0019013 \N 21117 IPR002485 This domain is found in nematode proteins. It is currentlyof unknown function.\ \ \N \N \N 21118 IPR002486 The function of this domain is unknown. It is found in the N-terminalregion of nematode cuticle collagens, see IPR008160. Cuticle is a tough\ elastic structure secreted by hypodermal cells and is primarily composed of\ collagen proteins [MEDLINE:89326131], [MEDLINE:95129867].\ \ \N \N \N 21119 IPR002487 The K-box region is commonly found associated with SRF-typetranscription factors see IPR002100. The K-box is a possible\ coiled-coil structure [MEDLINE:91233366]. Possible role in multimer formation [MEDLINE:95047314].\ \ transcription factor activity ; GO:0003700 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 21120 IPR002488 This family consists of the N terminal region of geminivirusC4 or AC4 proteins. In Tomato yellow leaf curl geminivirus\ (TYLCV) the C4 protein is necessary for efficient spreading of\ the virus in tomato plants [MEDLINE:94378537].\ \ \N \N \N 21121 IPR002489

This domain is found in glutamate synthase, tungsten formylmethanofuran dehydrogenase subunit c (FwdC) and molybdenum formylmethanofuran\ dehydrogenase subunit c (FmdC). It has no known function.

\ \ \N \N \N 21122 IPR002490 This family consists of the 116kDa V-type ATPase (vacuolar (H⁺)-ATPases)subunits, as well as V-type ATP synthase subunit i. \ The V-type ATPases family are proton pumps that acidify intracellular\ compartments in eukaryotic cells for example yeast central vacuoles,\ clathrin-coated and synaptic vesicles. They have important roles in\ membrane trafficking processes [MEDLINE:99240666]. \ The 116kDa subunit (subunit a) in the V-type ATPase is part of the V0\ functional domain responsible for proton transport. The a subunit is a\ transmembrane glycoprotein with multiple putative transmembrane helices \ it has a hydrophilic amino terminal and a hydrophobic carboxy \ terminal [MEDLINE:99240666], [MEDLINE:99270697]. It has roles in proton transport and assembly of the\ V-type ATPase complex [MEDLINE:99240666], [MEDLINE:99270697]. \ This subunit is encoded by two homologous gene in yeast VPH1 and STV1 [MEDLINE:99270697].\ \ hydrogen-transporting two-sector ATPase activity ; GO:0003936 membrane ; GO:0016020 proton transport ; GO:0015992 21123 IPR002491 Most high-affinity systems for iron uptake in Gram-negative bacteria are thought to employ periplasmic-binding-protein-dependent transport. In Escherichia coli, FepB is a periplasmic protein required for uptake of iron complexed to its endogenously-synthesized siderophore enterobactin (Ent) [MEDLINE:96004464].

In planta expression of a high-affinity iron-uptake system involving the siderophore chrysobactin in Erwinia chrysanthemi 3937 contributes greatly to invasive growth of this pathogen on its natural host, African violets [MEDLINE:96154939].

\ \ iron ion transporter activity ; GO:0005381 \N high affinity iron ion transport ; GO:0006827 21111 IPR002479 This repeat is found in multiple tandem copies in severalproteins. The repeat is 20 amino acid residues long. \ It has been suggested that these repeats in P15057\ might be responsible for the specific recognition of\ choline-containing cell walls [MEDLINE:88124951]. Glucan binding for\ these repeats has been shown [MEDLINE:91123227]. Similar repeats are found in the glucosyltransferases and glucan-binding protein of\ oral streptococci, dextransucrases of Leuconostoc mesenteroides as well as toxins of Clostridium difficile.\ \ \N \N \N 21112 IPR002480 Members of the 3-deoxy-D-arabino-heptulosonate 7-phosphate (DAHP) synthetase family EC: 4.1.2.15 catalyse the first step in aromatic amino acid biosynthesis from chorismate. Class I (see IPR006218.

\ \ \ 2-dehydro-3-deoxyphosphoheptonate aldolase activity ; GO:0003849\ \N \N aromatic amino acid family biosynthesis ; GO:0009073 21113 IPR002481

The Ferric uptake regulator or FUR family includes metal ion uptake regulator proteins,which bind to the operator DNA and control the transcription\ of metal ion-responsive genes.

\ \ transcription factor activity ; GO:0003700 \N regulation of transcription, DNA-dependent ; GO:0006355 21114 IPR002482 This domain is about 40 residues long and is found in a varietyof enzymes involved in bacterial cell wall degradation [MEDLINE:92324582]. This\ domain may have a general peptidoglycan binding function.\ \ \N \N cell wall catabolism ; GO:0016998 21107 IPR002474 The carbamoyl-phosphate synthase domain is in the amino terminus of the protein.\ Carbamoyl-phosphate synthase catalyses the ATP-dependent synthesis of\ carbamoyl-phosphate from glutamine or ammonia and bicarbonate. This \ important enzyme initiates both the urea cycle and the biosynthesis \ of arginine and/or pyrimidines [MEDLINE:90285162].\ The carbamoyl-phosphate synthase (CPS) enzyme in prokaryotes is a \ heterodimer of a small and large chain. The small chain promotes\ the hydrolysis of glutamine to ammonia, which is used by the large\ chain to synthesize carbamoyl phosphate.\ \ ATP binding activity ; GO:0005524 \N nitrogen metabolism ; GO:0006807 21108 IPR002475 Active cell suicide (apoptosis) is induced by events such as growth factor withdrawal and toxins.It is controlled by regulators, which have either an inhibitory effect on programmed cell death\ (anti-apoptotic) or block the protective effect of inhibitors (pro-apoptotic) PUB00001030,\ PUB00001030. Many viruses have found a way of countering defensive apoptosis by encoding their own\ anti-apoptosis genes preventing their target-cells from dying too soon. All proteins belonging to\ the Bcl-2 family [MEDLINE:97067261] contain either a BH1, BH2, BH3, or BH4 domain. All anti-apoptotic\ proteins contain BH1 and BH2 domains, some of them contain an additional N-terminal BH4 domain\ (Bcl-2, Bcl-x(L), Bcl-w), which is never seen in pro-apoptotic proteins, except for Bcl-x(S). On the\ other hand, all pro-apoptotic proteins contain a BH3 domain (except for Bad) necessary for\ dimerization with other proteins of Bcl-2 family and crucial for their killing activity, some of them\ also contain BH1 and BH2 domains (Bax, Bak). The BH3 domain is also present in some anti-apoptotic\ protein, such as Bcl-2 or Bcl-x(L). This profile is found in all these proteins, as well as E1B 19K protein (small t-antigen), which inhibits E1A induced\ apoptosis and hence prolongs the viability of the host cell.\ \ apoptosis regulator activity ; GO:0016329 \N apoptosis ; GO:0006915 21109 IPR002477 PBSX is a phage-like bacteriocin (phibacin) of Bacillus subtilis 168. Bacteria carrying the PBSX genome are induced by DNA-damaging agents to lyse and\ produce PBSX particles. Four genes of the Bacillus subtilis identified within the late operon of PBSX show characteristics expected of a host cell lysis system; they are xepA, encoding an exported protein; xhlA, encoding a putative membrane-associated protein; xhlB, encoding a putative holin; and xlyA, encoding a putative endolysin. Expression of xhlB (encoding the putative holin)\ together with xlyA (encoding the endolysin) cannot effect cell lysis indicating that it is probable that PBSX encodes a second endolysin activity which also uses XhlA and XhlB for export from the cell [MEDLINE:98215178].\

The putative peptidoglycan binding domain 1 is composed of three helices and is found at the N or C terminus of a variety of enzymes involved\ in bacterial cell wall degradation [MEDLINE:83012968], [MEDLINE:92065258]. This domain may have a\ general peptidoglycan binding function.

\ \ \N \N peptidoglycan metabolism ; GO:0000270 21110 IPR002478 The PUA domain named after PseudoUridine synthase and Archaeosinetransglycosylase, was detected in archaeal and eukaryotic pseudouridine\ synthases, archaeal archaeosine synthases, a family of predicted ATPases\ that may be involved in RNA modification, a family of predicted archaeal\ and bacterial rRNA methylases. Additionally, the PUA domain was detected\ in a family of eukaryotic proteins that also contain a domain homologous\ to the translation initiation factor eIF1/SUI1; these proteins may\ comprise a novel type of translation factors. Unexpectedly, the PUA\ domain was detected also in bacterial and yeast glutamate kinases; this\ is compatible with the demonstrated role of these enzymes in the\ regulation of the expression of other genes [MEDLINE:99193178]. It is predicted that\ the PUA domain is an RNA binding domain.\ \ RNA binding activity ; GO:0003723 \N \N 21104 IPR002471

Prolyl endopeptidase, also called post-proline cleaving enzyme, is an enzyme that cleaves peptide bonds on the C-terminal side of prolyl residues. This C-terminus signature is often found with IPR002469.

\ \

Many proteins in this group are CD26 (EC: 3.4.14.5) also called adenosine deaminase-binding protein (ADA-binding protein) or dipeptidylpeptidase IV (DPP IV ectoenzyme). The exopeptidase cleaves off N-terminal X-Pro or X-Ala dipeptides from polypeptides (dipeptidyl peptidase IV activity). CD26 serves as the costimulatory molecule in T cell activation and is an associated marker of autoimmune diseases, adenosine deaminase-deficiency and HIV pathogenesis.

\ \

CD molecules are leucocyte antigens on cell surfaces. CD antigens nomenclature is updated at http://www.ncbi.nlm.nih.gov/PROW/guide/45277084.htm \

\ \ \ prolyl oligopeptidase activity ; GO:0004287 \N proteolysis and peptidolysis ; GO:0006508 21105 IPR002472 Neuronal ceroid lipofuscinoses (NCL) represent a group of encephalopathies that occur in 1 in 12,500 children . Mutations in the palmitoyl protein thioesterase gene causing infantile neuronal\ ceroid lipofuscinosis [MEDLINE:95364950]. \ \ The most common mutation results in intracellular\ accumulation of the polypeptide and undetectable enzyme activity in\ the brain.\ Direct sequencing of cDNAs derived from brain RNA of INCL patients has\ shown a mis-sense transversion of A to T at nucleotide position 364, which\ results in substitution of Trp for Arg at position 122 in the protein - \ Arg 122 is immediately adjacent to a lipase consensus sequence that \ contains the putative active site Ser of PPT. The occurrence of this and\ two other independent mutations in the PPT gene strongly suggests that\ defects in this gene cause INCL .\ \ palmitoyl-protein hydrolase activity ; GO:0008474 lysosome ; GO:0005764 protein modification ; GO:0006464 21106 IPR002473 Most members of this family of low-molecular weight proteins seem to havemitogenic, chemotactic or inflammatory activities. They are released by phagocytes,\ mesenchymal cells and a wide variety of tissue cells, upon exposure to inflammation\ [MEDLINE:92347562]. These small cytokines are also called intercrines or chemokines. They\ are cationic proteins of 70 to 100 amino acid residues that share four conserved\ cysteine residues involved in two disulfide bonds.\ \

The family can be split into two groups, depending on the spacing of two N-terminal\ Cys residues: in one group (CxC), the cysteines are separated by a\ single amino acid; in the second (CC), they are adjacent [MEDLINE:89231715]. The CxC\ group includes such factors as interleukin-8, platelet factor 4, melanoma growth\ stimulatory activity protein, macrophage inflammatory protein 2, platelet basic\ protein, and several others. The 'C-C' group includes the monocyte chemotactic\ proteins, macrophage inflammatory proteins and others.

The accumulation of neutrophil leukocytes in tissues is a major event in \ inflammation, a defensive reaction in response to injury or infection [MEDLINE:92347562].\ Neutrophils are drawn in from the blood by chemotactic signals that\ direct their migration to the affected site . Interleukin-8 (IL8) is one\ such chemotactic protein: it is released by phagocytes, mesenchymal cells\ and a wide variety of tissue cells, upon exposure to inflammation ; and\ it acts as a neutrophil-activating cytokine, inducing chemotaxis, exo-\ cytosis, and the respiratory burst .

\ \ cytokine activity ; GO:0005125 extracellular ; GO:0005576 immune response ; GO:0006955 21102 IPR002469

CD26 (EC: 3.4.14.5) is also called adenosine deaminase-binding protein (ADA-binding protein) or dipeptidylpeptidase IV (DPP IV ectoenzyme). The exopeptidase cleaves off N-terminal X-Pro or X-Ala dipeptides from polypeptides (dipeptidyl peptidase IV activity). CD26 serves as the costimulatory molecule in T cell activation and is an associated marker of autoimmune diseases, adenosine deaminase-deficiency and HIV pathogenesis.

Dipeptidyl peptidase IV (DPP IV) is responsible for the removal of N-terminal dipeptides sequentially from polypeptides having unsubstituted N termini, provided that the penultimate residue is proline. The enzyme catalyses the reaction:\

Dipeptidyl-Polypeptide + H₍₂₎O = Dipeptide + Polypeptide

\ It is a type II membrane protein that forms a homodimer. This domain is an alignment of the region to the N-terminal side of the active site. It is often found with IPR002471.

\ \

CD molecules are leucocyte antigens on cell surfaces. CD antigens nomenclature is updated at http://www.ncbi.nlm.nih.gov/PROW/guide/45277084.htm \

\ \ \ dipeptidyl-peptidase IV activity ; GO:0004274 membrane ; GO:0016020 proteolysis and peptidolysis ; GO:0006508 21103 IPR002470

Prolyl oligopeptidases belong to the S9A subfamily of the carboxypeptidase SC clan [MEDLINE:95147689], see Protease database http://merops.sanger.ac.uk/merops.htm]. The active site of members of this clan consists of a linear\ arrangment of serine, histidine and threonine catalytic residues [MEDLINE:95147689]. Prolyl\ oligopeptidases are either located in the cytosol or they are membrane bound,\ where they cleave peptide bonds with prolyl P1 specificities (but cleavage\ of alanyl bonds has been detected). The proline must adopt a trans configuration\ within the chain. Peptides of up to 30 residues are cleaved [MEDLINE:95147689].

\ \ \ prolyl oligopeptidase activity ; GO:0004287 \N proteolysis and peptidolysis ; GO:0006508 21097 IPR002463 Ornatin is a potent glycoprotein IIb-IIIa (GP IIb-IIIa) antagonist andplatelet aggregation inhibitor [MEDLINE:92111479]. The protein is 41-52 residues in length\ and contains the RGD recognition motif common in adhesion proteins, and\ 6 conserved cysteine residues. The sequences of ornatin isoforms B, C, D \ and E are highly similar, while isoforms A2 and A3 are less similar, lacking\ the N-terminal 9 residues. Ornatins share ~40% identity with decorsin,\ a GP IIb-IIIa antagonist isolated from the leech Macrobdella decora\ \ \ \ [MEDLINE:92111479].\ \ \N \N \N 21098 IPR002464

A number of eukaryotic and prokaryotic proteins have been characterized [MEDLINE:92203994], [MEDLINE:89097246], [MEDLINE:91125473] on the basis of their structural similarity. They all seem to be involved in ATP-dependent, nucleic-acid unwinding. There are two subfamilies of such proteins, the D-E-A-D-box and D-E-A-H-box families.\ Proteins that belong to the subfamily which have His instead of the second\ Asp are said to be 'D-E-A-H-box' proteins [MEDLINE:91125473], [MEDLINE:92066492], [MEDLINE:92341083].

Proteins currently known to belong to this subfamily include\ yeast PRP2, PRP16, PRP22 and PRP43, involved in\ various ATP-requiring steps of the pre-mRNA splicing process; fission yeast prh1, which my be involved in pre-mRNA splicing; Drosophila male-less (mle) protein required in males for dosage compensation of X chromosome linked genes; yeast RAD3, a DNA helicase involved in excision repair of DNA\ damaged by UV light, bulky adducts or cross-linking agents; fission\ yeast rad15 (rhp3) and mammalian DNA excision repair protein XPD (ERCC-2);\ yeast CHL1 (or CTF1), which is important for chromosome transmission and\ normal cell cycle progression in G(2)/M; Yeast TPS1, Caenorhabditis elegans hypothetical proteins C06E1.10 and K03H1.2; Poxviruses' early transcription factor 70 kD subunit which acts with RNA polymerase to initiate transcription from early gene promoters; vaccinia virus putative helicase I8; and Escherichia coli putative RNA helicase hrpA.\ All these proteins share a number of conserved sequence motifs. Some of them\ are specific to this family while others are shared by other ATP-binding\ proteins or by proteins belonging to the helicases 'superfamily' [MEDLINE:88202097].

\ \ ATP dependent helicase activity ; GO:0008026 \N \N 21099 IPR002466 Editase (EC: 3.5.-.-"/) are enzymes that alter mRNA by catalyzing thesite-selective deamination of adenosine residue into inosine residue.\ The editase domain contains the active site and binds three Zn atoms [MEDLINE:97303142].\ \ Several editases share a common global arrangement of domains: two\ DRADA_REP domains (PS50139) involved in DNA binding, followed by\ three DSRBD domains (PS50137) involved in RNA binding, followed by\ the editase domain are found from N to C-terminus. Other editases have a simplified domains structure with no\ DRADA_REP and possibly fewer DSRBD domains. Editase that deaminate cytidine are not detected by this signature.\ \ adenosine deaminase activity ; GO:0004000 \N RNA processing ; GO:0006396 21100 IPR002467 Methionine aminopeptidase (EC: 3.4.11.18) (MAP) is responsible for the removal of the amino-terminal (initiator) methionine from nascent eukaryotic cytosolic\ and cytoplasmic prokaryotic proteins if the penultimate amino acid is small\ and uncharged. All MAP studied to date are monomeric proteins that require\ cobalt ions for activity. Two subfamilies of MAP enzymes are known to exist [MEDLINE:95372350], [MEDLINE:96368275]. While being\ evolutionary related, they only share a limited amount of sequence similarity\ mostly clustered around the residues shown, in the Escherichia coli MAP [MEDLINE:93229487],\ to be involved in cobalt-binding. The first family consists of enzymes from prokaryotes as well as eukaryotic MAP-1, while the second group is made up of archebacterial MAP and eukaryotic MAP-2. This entry is for family 1.\ \ methionyl aminopeptidase activity ; GO:0004239 \N proteolysis and peptidolysis ; GO:0006508 21101 IPR002468 Methionine aminopeptidase (EC: 3.4.11.18) (MAP) is responsible for the removal of the amino-terminal (initiator) methionine from nascent eukaryotic cytosolic\ and cytoplasmic prokaryotic proteins if the penultimate amino acid is small\ and uncharged. All MAP studied to date are monomeric proteins that require\ cobalt ions for activity. Two subfamilies of MAP enzymes are known to exist [MEDLINE:95372350], [MEDLINE:96368275]. While being\ evolutionary related, they only share a limited amount of sequence similarity\ mostly clustered around the residues shown, in the Escherichia coli MAP [MEDLINE:93229487],\ to be involved in cobalt-binding. The first family consists of enzymes from prokaryotes as well as eukaryotic MAP-1, while the second group is made up of archebacterial MAP and eukaryotic MAP-2. The second subfamily also includes proteins which do not seem to be\ MAP, but that are clearly evolutionary related such as mouse proliferation-associated protein 1 and fission yeast curved DNA-binding protein.\ \ methionyl aminopeptidase activity ; GO:0004239 \N proteolysis and peptidolysis ; GO:0006508 21096 IPR002462

Synucleins are small, soluble proteins expressed primarily in neural tissue and in certain tumors [MEDLINE:98424410], [MEDLINE:21666014]. The family includes three known proteins: -synuclein, -synuclein, and gamma-synuclein. All synucleins have in common a highly conserved -helical lipid-binding motif with similarity to the class-A2 lipid-binding domains of the exchangeable apolipoproteins [MEDLINE:20507884].

Synuclein family members are not found outside vertebrates, although they have some conserved structural similarity with plant 'late-embryo-abundant' proteins. The - and -synuclein proteins are found primarily in brain tissue, where they are seen mainly in presynaptic terminals [MEDLINE:95161076], [MEDLINE:95182823]. The gamma-synuclein protein is found primarily in the peripheral nervous system and retina, but its expression in breast tumors is a marker for tumor progression [MEDLINE:97178957].\ Normal cellular functions have not been determined for any of the synuclein proteins,\ although some data suggest a role in the regulation of membrane stability and/or turnover.\ Mutations in -synuclein are associated with rare familial cases of early-onset Parkinson's\ disease, and the protein accumulates abnormally in Parkinson's disease, Alzheimer's disease,\ and several other neurodegenerative illnesses [MEDLINE:21326551].

As with other synucleins, gamma-synuclein, or persyn, is believed to be\ involved in the pathogenesis of human neurodegenerative diseases [MEDLINE:98367030]. Persyn influences neurofilament network integrity [MEDLINE:99211026].

\ \ \N \N \N 21095 IPR002461

Beta-synuclein, also known as PNP 14, is expressed in the brain, specifically in synapses around\ neurons, but not in glial cells. The protein, which has been designated\ a phosphoneuroprotein, has been found to be phosphorylated in vitro and in\ vivo [MEDLINE:94039126]. It is believed that the physiological functions of -synuclein may be controlled by the phosphorylation reaction.

\ \ \N \N \N 21094 IPR002460

Synucleins are small, soluble proteins expressed primarily in neural tissue and in certain tumors [MEDLINE:98424410], [MEDLINE:21666014] ]. The family includes three known proteins: -synuclein, -synuclein, and gamma-synuclein. All synucleins have in common a highly conserved -helical lipid-binding motif with similarity to the class-A2 lipid-binding domains of the exchangeable apolipoproteins [MEDLINE:20507884].

Synelfin from the zebra finch is a homolog of the human -synuclein and may serve a novel function critical to the regulation of vertebrate neural plasticity [MEDLINE:95374791]. It is regulated during the critical period for song learning.

\ \ \N \N \N 21092 IPR002456

GABA is the principal inhibitory neurotransmitter\ in the brain, and signals through ionotropic (GABA(A)/GABA(C)) and\ metabotropic (GABA(B)) receptor systems. The GABA(B) receptors have\ been cloned, and photoaffinity labelling experiments suggest that they\ correspond to two highly conserved receptor forms in the vertebrate nervous\ system [MEDLINE:97222131].

GABA(B) receptors are involved in the fine tuning of inhibitory synaptic\ transmission [MEDLINE:99061981]. Presynaptic receptors inhibit neurotransmitter release by\ down-regulating high-voltage activated Ca²⁺ channels, while postsynaptic\ receptors decrease neuronal excitability by activating a prominent inwardly\ rectifying K⁺ (Kir) conductance that underlies the late inhibitory postsynaptic potentials [MEDLINE:99061981]. GABA(B) receptors negatively couple to adenylyl\ cyclase and show sequence similarity to the metabotropic receptors for the\ excitatory neurotransmitter L-glutamate.

Neurophysiological and pharmacological studies point to a major role of the\ GABA(B) receptor in the epileptogenesis of absence seizures PUB00006086. Using in\ situ hybridisation, the gene encoding the human GABA(B) type 1 receptor has\ been mapped to chromosome 6p21.3, in the vicinity of a susceptibility locus\ (EJM1) for idiopathic generalised epilepsies, identifying a candidate gene\ for inherited forms of epilepsy PUB00006086, PUB00006086.

\ \ GABA-B receptor activity ; GO:0004965 membrane ; GO:0016020 \N 21093 IPR002457

A new subtype of the GABA(B) receptor (GABA(B)R2) has been identified by\ EST database mining [MEDLINE:99087321]. Yeast two-hybrid screening has shown that the new\ subtype forms heterodimers with GABA(B)R1 via an interaction at their\ intracellular C-terminal tails. On expression with GABA(B)R2 in HEK293T\ cells, GABA(B)R1 is terminally glycosylated and expressed at the cell\ surface. Co-expression of the receptors produces a fully functional GABA(B)\ receptor at the cell surface; this receptor binds GABA with a high affinity\ equivalent to that of the endogenous brain receptor [MEDLINE:99087321]. Such results\ indicate that, in vivo, functional brain GABA(B) receptors may be heterodimers of GABA(B)R1 and GABA(B)R2.

\ \ GABA-B receptor activity ; GO:0004965 membrane ; GO:0016020 \N 21090 IPR002454 Microtubules are polymers of tubulin, a dimer of two 55 kD subunits, designated

and

[MEDLINE:85277991], [MEDLINE:90304955]. Within the microtubule lattice,

heterodimers associate in a head-to-tail fashion, giving rise to microtubule \ polarity. Fluorescent labelling studies have suggested that tubulin is\ oriented in microtubules with

Most species, excepting simple eukaryotes, express a variety of closely \ related - and -isotypes. A third family member, gamma tubulin, has\ also been identified in a number of species [MEDLINE:94099776], [MEDLINE:91249388]. \ Gamma-tubulins constitute a ubiquitous and highly conserved subfamily of \ the tubulin family. The protein is found at microtubule-organising centres, \ such as the spindle poles or the centrosome. It remains associated with the \ centrosome when microtubules are depolymerised, suggesting that it is \ an integral component that might play a role in minus-end nucleation of \ microtubule assembly [MEDLINE:94099776], [MEDLINE:91249388].

\ \ \ structural molecule activity ; GO:0005198 microtubule ; GO:0005874 microtubule-based movement ; GO:0007018 21091 IPR002455

\ \ GABA-B receptor activity ; GO:0004965 membrane ; GO:0016020 \N 21089 IPR002453 Microtubules are polymers of tubulin, a dimer of two 55 kD subunits, designated

and

[MEDLINE:85277991], [MEDLINE:90304955]. Within the microtubule lattice,

heterodimers associate in a head-to-tail fashion, giving rise to microtubule \ polarity. Fluorescent labelling studies have suggested that tubulin is\ oriented in microtubules with

Most species, excepting simple eukaryotes, express a variety of closely \ related - and -isotypes. A third family member, gamma tubulin, has\ also been identified in a number of species [MEDLINE:94099776].\ British type familial amyloidosis is an autosomal dominant disease \ characterised by progressive dementia, spastic paralysis and ataxia. \ Amyloid deposits from the brain tissue of an individual who died with this \ disease have been characterised. Trypsin digestion and subsequent N-terminal\ sequence analysis yielded a number of short sequences, all of which are\ tryptic fragments of the C-termini of human - and -tubulin. \ Consistent with the definition of amyloid, synthetic peptides based on the \ sequences of these fragments formed fibrils in vitro, suggesting that the\ C-termini of both - and -tubulin are closely associated with the\ amyloid deposits of this type of amyloidosis [MEDLINE:96190699]. \ The amino acid sequences encoded by tubulin genes have revealed a high \ level of overall similarity, but significant divergence between their\ C-termini [MEDLINE:85210890]. The pattern of expression of the -tubulin genes has been \ studied in several different human cell lines and has revealed varying \ levels of and differential expression in different cell lines. It\ appears that distinct human -tubulin isotypes are encoded by genes\ whose exon size and number has been conserved evolutionarily, but whose \ pattern of expression may be regulated either co-ordinately or uniquely [MEDLINE:85210890].

\ \ \ structural molecule activity ; GO:0005198 microtubule ; GO:0005874 microtubule-based movement ; GO:0007018 21088 IPR002452 Microtubules are polymers of tubulin, a dimer of two 55 kD subunits, designated

and

[MEDLINE:85277991], [MEDLINE:90304955]. Within the microtubule lattice,

heterodimers associate in a head-to-tail fashion, giving rise to microtubule \ polarity. Fluorescent labelling studies have suggested that tubulin is\ oriented in microtubules with

Most species, excepting simple eukaryotes, express a variety of closely \ related - and -isotypes. A third family member, gamma tubulin, has\ also been identified in a number of species [MEDLINE:94099776].\ British type familial amyloidosis is an autosomal dominant disease \ characterised by progressive dementia, spastic paralysis and ataxia. \ Amyloid deposits from the brain tissue of an individual who died with this \ disease have been characterised. Trypsin digestion and subsequent N-terminal\ sequence analysis yielded a number of short sequences, all of which are\ tryptic fragments of the C-termini of human - and -tubulin. \ Consistent with the definition of amyloid, synthetic peptides based on the \ sequences of these fragments formed fibrils in vitro, suggesting that the\ C-termini of both - and -tubulin are closely associated with the\ amyloid deposits of this type of amyloidosis [MEDLINE:96190699]. \ Several -tubulin isotypes have been described, each distinguished by \ the presence of unique amino acid substitutions within the coding region. \ Most of these isotype-specific amino acids are clustered at the C-terminus.\ Patterns of developmental expression of the various -tubulin isotypes\ have been studied. Results suggest that individual tubulin isotypes \ confer functional specificity on different kinds of microtubules [MEDLINE:87064538].

\ \ \ structural molecule activity ; GO:0005198 microtubule ; GO:0005874 microtubule-based movement ; GO:0007018 21087 IPR002450

Von Ebner's gland protein (VEGP), a protein highly expressed by the small acinar von Ebner's salivary glands of the tongue, but not in the secretory \ duct, undertakes the selective binding of sapid chemicals and their transport \ to taste receptors [MEDLINE:90136923] in salivary secretions. VEGP can help to clear the \ bitter-tasting compound denatonium benzoate in vivo [MEDLINE:95183580], suggesting a \ possible clearance function in taste reception, although it fails to bind\ other bitter compounds [MEDLINE:94221911]. VEGP is also secreted by the lachrymal gland \ into tear fluid, where, historically, it has been called tear prealbumin [MEDLINE:93015903].\ Together with lysozyme and lactoferrin, VEGP forms 70-80% of total tear \ protein, although diseases affecting the lachrymal gland decrease this. Tear\ VEGP has been suggested to enhance the bactericial activity of lysozyme and\ to have an anti-microbial function, perhaps through transported compounds\ with anti-bacterial properties [MEDLINE:95376965]. VEGP has been shown to bind retinol [MEDLINE:93015903],\ and can be co-extracted with fatty acids, particularly stearate and \ palmitate, phospholipids, glycolipids and fatty alcohols (including \ cholesterol) [MEDLINE:95376965]. VEGP may act as a transporter of lipids, synthesised in \ the dorsal, or meibomian, glands of the eyelid, to the thin film they form \ at the tear-fluid/air interface. \ Recently, two lipocalins, specifically expressed in the posterior and\ vomeronasal glands of the mouse nasal septum, have been identified and were\ suggested to act in the chemoreception of, as yet-unidentified, small \ lipophilic pheromones [MEDLINE:95112792]. One of these proteins was immunolocalised on the\ vomeronasal sensory epithelium, the site of primary pheromone reception, and\ the immunoreactivity was greatest during periods when contact between \ animals plays an important role in modulating behaviour.\ Canis familiaris allergen 1 (Can f1) is the major allergen present in dog\ dander and is produced by tongue epithelial tissue [MEDLINE:98158930].

\ \

The allergens in this family include allergens with the following designations: Bos d 2 and Can f 2.

\ \ \ transporter activity ; GO:0005215 \N transport ; GO:0006810 21086 IPR002449

The crystal structures of several lipocalins have been solved and show a \ novel 8-stranded anti-parallel -barrel fold well conserved within the\ family. Sequence similarity within the family is at a much lower level and\ would seem to be restricted to conserved disulphides and 3 motifs, which\ form a juxtaposed cluster that may act as a common cell surface receptor\ site [MEDLINE:96358478]. By contrast, at the more variable end of the fold are found an \ internal ligand binding site and a putative surface for the formation of \ macromolecular complexes PUB00003448. The anti-parallel -barrel fold is also\ exploited by the fatty acid-binding proteins (which function similarly by\ binding small hydrophobic molecules), by avidin and the closely related\ metalloprotease inhibitors, and by triabin. Similarity at the sequence \ level, however, is less obvious, being confined to a single short \ N-terminal motif.\ The lipocalin family can be subdivided into kernal and outlier sets. The\ kernal lipocalins form the largest self consistent group, comprising the subfamily of retinol-binding proteins. The outlier lipocalins form several smaller distinct subgroups: \ the OBPs, the von Ebner's gland proteins, -1-acid glycoproteins, \ tick histamine binding proteins and the nitrophorins.

Serum Retinol Binding Protein (RBP) PUB00003448 is virtually the sole retinol\ transporter in plasma, binding a single all-trans-retinol molecule as its\ physiological ligand. RBP is synthesised in hepatic parenchymal cells, where\ the apoprotein is loaded with retinol, triggering its release into general\ circulation. 85-90% of plasma RBP carries bound retinol, while about 96% is\ complexed to transthyretin. Transthyretin has a higher affinity for halo-RBP \ than apo RBP, and its interaction with RBP is also sensitive to both ionic\ strength and pH; the complex dissociates at low ionic strength and is only \ stable between pH 5.0 and 9.0. The RBP-transthyretin complex is larger than \ RBP, preventing its loss by filtration through the kidney glomeruli. RBP-mediated retinol transport facilitates the transfer of insoluble retinol \ from storage sites to peripheral tissues. RBP also protects bound retinol\ from oxidation. The synthesis of RBP regulates retinol release from the \ liver and controls the specificity of its uptake by target cells. RBP-target-cell interaction is crucial to its biological function: RBP is \ recognised by a cell-surface receptor, releasing retinol, and losing its \ affinity for transthyretin. The resulting apo-RBP is filtered by the kidney,\ reabsorbed and catabolised. RBP carries only one retinol molecule before\ being degraded.\ It seems that retinol is taken up by target cells through a specific cell-surface receptor that recognises RBP. Using mutagenesis, Sivaprasadarao has\ shown that specific amino acids within the open-end loop scaffold are\ responsible for binding to the RBP receptor [MEDLINE:94040302], and proposes that RBP \ remains external to the cell, with only retinol being internalised by the \ RBP receptor in a manner not involving receptor-mediated endocytosis. By \ contrast, Noy and co-workers have suggested that retinol dissociates\ spontaneously from RBP outside the cell and undergoes passive transfer\ through the plasma membrane to be bound by high-affinity sites in the \ cytoplasm [MEDLINE:91274285].

\ \ retinoid binding activity ; GO:0005501 \N transport ; GO:0006810 21085 IPR002448

The crystal structures of several lipocalins have been solved and show a \ novel 8-stranded anti-parallel -barrel fold well conserved within the\ family. Sequence similarity within the family is at a much lower level and\ would seem to be restricted to conserved disulphides and 3 motifs, which\ form a juxtaposed cluster that may act as a common cell surface receptor\ site [MEDLINE:96358478]. By contrast, at the more variable end of the fold are found an \ internal ligand binding site and a putative surface for the formation of \ macromolecular complexes PUB00003448. The anti-parallel -barrel fold is also\ exploited by the fatty acid-binding proteins (which function similarly by\ binding small hydrophobic molecules), by avidin and the closely related\ metalloprotease inhibitors, and by triabin. Similarity at the sequence \ level, however, is less obvious, being confined to a single short \ N-terminal motif.\ The lipocalin family can be subdivided into kernal and outlier sets. The\ kernal lipocalins form the largest self consistent group, comprising the subfamily of odour-binding proteins. The outlier lipocalins form several smaller distinct subgroups: \ the OBPs, the von Ebner's gland proteins, -1-acid glycoproteins, \ tick histamine binding proteins and the nitrophorins.

Odour Binding Proteins (OBPs) PUB00003448 are associated with olfactory tissue, \ and seem able to bind odorant molecules with high specificity. Rat OBP is localised to the lateral\ nasal, or Sterno's, gland, the largest of the 20 discrete nasal glands of \ the rat. A similar protein from the olfactory tissue of the frog Rana\ pipiens, which was named protein BG (Bowman's gland), has been identified,\ cloned and sequenced. It is thought that the OBPs\ may function by concentrating and delivering odorant molecules to their \ receptors.\ Aphrodisin [MEDLINE:99085042] is the major macromolecular component of hamster vaginal\ discharge, and is secreted by vaginal tissue and the Bartholin's gland. \ These secretions, acting via the vomeronasal organ, are known to elicit a\ copulatory response in male hamsters. If applied to the hind parts of an\ unconscious male hamster and another male hamster is encouraged to nuzzle \ the treated area with its snout, the latter will reproducibly attempt an \ abortive copulation. Aphrodisin is responsible for\ these effects, suggesting it is a mammalian proteinaceous pheromone. \ Probasin [MEDLINE:94224242] is a lipocalin originally isolated from the nuclei of rat \ dorsolateral prostate epithelial cells. Probasin mRNA expression, which is\ regulated by androgens, gives rise to both a secreted and a nuclear form of\ probasin, the relative abundance of the two forms being correlated with cell\ type. Probasin concentration also seems to be closely linked with cell age\ and state of differentiation.\ Bovine lipocalin allergen Bos d 2 is found in the secretory cells of skin\ apocrine sweat glands and the basement membranes of the epithelium and hair\ follicles. Immunohistochemistry with a monoclonal anti-Bos d 2 antibody has\ confirmed that skin is the only tissue where mRNA encoding Bos d 2 is \ detected. This suggest that Bos d 2 is produced in sweat glands and\ transported to the skin surface as a carrier of a pheromone. Because dander \ allergens of several mammalian species are lipocalins, the biological \ function of pheromone transport appears to be a common feature of an\ important group of aeroallergens [MEDLINE:99107890].

\ \ \ odorant binding activity ; GO:0005549 \N transport ; GO:0006810 21084 IPR002447 The lipocalins are a diverse, interesting, yet poorly understood family of proteins composed, in the main, of extracellular ligand-binding proteins\ displaying high specificity for small hydrophobic molecules [MEDLINE:85168267], [MEDLINE:96358478]. Functions\ of these proteins include transport of nutrients, control of cell regulation, pheromone transport, cryptic colouration and the enzymatic synthesis\ of prostaglandins.\

\ The crystal structures of several lipocalins have been solved and show a \ novel 8-stranded anti-parallel -barrel fold well conserved within the\ family. Sequence similarity within the family is at a much lower level and\ would seem to be restricted to conserved disulphides and 3 motifs, which\ form a juxtaposed cluster that may act as a common cell surface receptor\ site [MEDLINE:96358478]. By contrast, at the more variable end of the fold are found an \ internal ligand binding site and a putative surface for the formation of \ macromolecular complexes PUB00003448. The anti-parallel -barrel fold is also\ exploited by the fatty acid-binding proteins (which function similarly by\ binding small hydrophobic molecules), by avidin and the closely related\ metalloprotease inhibitors, and by triabin. Similarity at the sequence \ level, however, is less obvious, being confined to a single short \ N-terminal motif.\ The lipocalin family can be subdivided into kernal and outlier sets. The\ kernal lipocalins form the largest self consistent group, comprising the subfamily of -lactoglobulins. The outlier lipocalins form several smaller distinct subgroups: the OBPs, the von Ebner's gland proteins, -1-acid glycoproteins, tick histamine binding proteins and the nitrophorins.

\ Beta-lactoglobulin (Blg) is the major protein component of milk from a wide \ range of species but not human\ \ \ \ PUB00003448. Glycodelin or PP14 protein is the human \ equivalent of Blg and is secreted into the endometrium. Blg binds a wide \ variety of hydrophobic ligands but its function remains unknown. The crystal\ structure of Blg has been solved [MEDLINE:97277234], confirming membership of the lipocalin\ protein family.

\ \ \ \N \N transport ; GO:0006810 21083 IPR002446 The lipocalins are a diverse, interesting, yet poorly understood family of proteins composed, in the main, of extracellular ligand-binding proteins\ displaying high specificity for small hydrophobic molecules [MEDLINE:85168267], [MEDLINE:96358478]. Functions\ of these proteins include transport of nutrients, control of cell regulation, pheromone transport, cryptic colouration, and the enzymatic synthesis\ of prostaglandins.\ \

The crystal structures of several lipocalins have been solved and show a \ novel 8-stranded anti-parallel -barrel fold well conserved within the\ family. Sequence similarity within the family is at a much lower level and\ would seem to be restricted to conserved disulphides and 3 motifs, which\ form a juxtaposed cluster that may act as a common cell surface receptor\ site [MEDLINE:96358478]. By contrast, at the more variable end of the fold are found an internal ligand binding site and a putative surface for the formation of macromolecular complexes PUB00003448. The anti-parallel -barrel fold is also\ exploited by the fatty acid-binding proteins (which function similarly by\ binding small hydrophobic molecules), by avidin and the closely related\ metalloprotease inhibitors, and by triabin. Similarity at the sequence \ level, however, is less obvious, being confined to a single short \ N-terminal motif.\ The lipocalin family can be subdivided into kernal and outlier sets. The\ kernal lipocalins form the largest self consistent group (see IPR002345). The outlier lipocalins form several smaller distinct subgroups: \ the OBPs, the von Ebner's gland proteins, -1-acid glycoproteins, \ tick histamine binding proteins and the nitrophorins.

Relatively recently, bacterial lipocalins have been described for the \ first time PUB00003448, [MEDLINE:96032747], [MEDLINE:97346032]. These are lipoproteins anchored to the outer membrane \ of Gram-negative bacteria such as Escherichia coli. Their promoters are activated at \ the transition between exponential and stationary growth phases. Bacterial\ lipocalin sequences are quite closely related to apolipoprotein D and may\ serve a starvation response function in bacteria. Overexpression, membrane\ fractionation, and metabolic labelling with tritiated palmitate showed \ bacterial lipocalins to be globomycin-sensitive outer membrane proteins.\ The bacterial lipocalins have been found in a small number of species, \ raising the possibility that they originated by horizontal transfer. \ Estimates of the G+C content in the first and third codon positions of \ these genes have been calculated. A biased %G+C in the 1st and 3rd codon\ positions would suggest horizontal transfer. None of the computed G+C \ contents of the bacterial lipocalin genes were outside of the expected \ limits (between the first and third quartiles). These data provide no \ support for a hypothesis in which bacterial lipocalins were recently \ acquired through horizontal transfer. Further evidence against horizontal \ transfer will come from finding more lipocalins in different species, \ thus making the gene transfer hypothesis more unlikely.

\ \ \N \N transport ; GO:0006810 21082 IPR002445

Recent molecular studies have identified two distinct isoforms: one fromCl^- secretory epithelia, NKCC1; and another, NKCC2, found specifically in\ the diluting segment of the vertebrate kidney, a Cl^- absorptive epithelium\ [MEDLINE:96002877]. They show lowish amino acid sequence identity (~58%); nevertheless,\ they have rather similar hydropathy profiles, with hydrophilic N- and\ C-termini, flanking a central hydrophobic domain. Their N-termini show\ considerable variation, unlike the central domain (containing the 12\ putative transmembrane (TM) domains) and their C-termini, which are well\ conserved (~70%). Both isoforms are known to be glycosylated and, consistent\ with this, consensus sites for N-linked glycosylation are located within the\ large hydrophilic loop between presumed TM domains 7 and 8. Sequence\ comparisons with other cloned ion co-transporters reveals that Na-K-Cl\ co-transporters belong to a superfamily of electroneutral cation-chloride\ co-transporters, which includes the K-Cl co-transporter IPR000076) and the\ thiazide-sensitive Na-Cl co-transporter. All share a similar predicted\ membrane topology of 12 TM regions in a central hydrophobic domain,\ together with hydrophilic N- and C-termini that are likely cytoplasmic.

\ \

Mutations in the gene encoding the renal-specific isoform of the Na-K-Cl\ co-transporter (NKCC2) give rise to Bartter's Syndrome Type 1, an inherited\ kidney disease characterised by hypokalaemia, metabolic alkalosis,\ salt-wasting and hypotension [MEDLINE:98386333].

\ \

NKCC2 (also called BSC1) is an apical absorptive Na-K-Cl co-transporter\ isoform. In contrast to the wide tissue distribution of NKCC1, expression\ of the NKCC2 isoform is restricted to the vertebrate kidney, where it is\ involved in urinary concentration [MEDLINE:94292537]. Subsequent studies revealed that\ three variants exist, differing by 31 amino acids, which are generated\ by alternatively splicing. They show differential distributions within\ the kidney, suggesting they may subserve varying functions [MEDLINE:94240172]. NKCC2\ consists of 1099 amino acid residues (human isoform) and, as mentioned\ above, has been found to be responsible for a heritable kidney disorder,\ Bartter's syndrome type 1, an autosomal recessive disorder. To date, at\ least six different mutations have been found that result in loss of\ NKCC2 function; this markedly reduces salt reabsorption by the thick\ ascending limb of Henle's loop, thereby leading to salt wasting,\ hypovolaemia, and hypotension [MEDLINE:98386333].

\ \ transporter activity ; GO:0005215 membrane ; GO:0016020 ion transport ; GO:0006811 21080 IPR002443

The Na-K-Cl co-transporters are a family of integral membrane proteins thatare ubiquitously expressed in animal tissues, serving a variety of\ functions. In cells of Cl^- absorptive and Cl^- secretory epithelia, Na-K-Cl\ co-transport serves as the major Cl^- entry pathway, and functions in\ concert with other membrane ion channels and pumps to carry out net\ transepithelial movement of salt. This vectorial transport of Cl^- across\ epithelia is involved in the reabsorption of salt in the vertebrate kidney\ (which is crucial for urinary concentration), and in the secretion of salt\ in such tissues as the mammalian intestine and trachea. In addition,\ Na-K-Cl co-transport is known to play a role in cell volume regulation in\ most mammalian cell types. The proteins mediate the coupled, electroneutral\ transport of sodium, potassium and chloride ions across the plasma membrane\ of cells (with a stoichiometry of 1:1:2, respectively). Co-transport of all\ three ions is obligatory, since absence of one is sufficient to prevent ion\ movement. Their transport activity does not alter the cell's membrane\ potential, thus the driving force for the transport is determined solely\ by the chemical gradients of the three transported ions; hence, under\ normal physiological conditions, the direction will be inward.

\ \

Recent molecular studies have identified two distinct isoforms: one from\ Cl^- secretory epithelia, NKCC1; and another, NKCC2, found specifically in\ the diluting segment of the vertebrate kidney, a Cl^- absorptive epithelium\ [MEDLINE:96002877]. They show lowish amino acid sequence identity (~58%); nevertheless,\ they have rather similar hydropathy profiles, with hydrophilic N- and\ C-termini, flanking a central hydrophobic domain. Their N-termini show\ considerable variation, unlike the central domain (containing the 12\ putative transmembrane (TM) domains) and their C-termini, which are well\ conserved (~70%). Both isoforms are known to be glycosylated and, consistent\ with this, consensus sites for N-linked glycosylation are located within the\ large hydrophilic loop between presumed TM domains 7 and 8. Sequence\ comparisons with other cloned ion co-transporters reveals that Na-K-Cl\ co-transporters belong to a superfamily of electroneutral cation-chloride\ co-transporters, which includes the K-Cl co-transporter (IPR000076) and the\ thiazide-sensitive Na-Cl co-transporter. All share a similar predicted\ membrane topology of 12 TM regions in a central hydrophobic domain,\ together with hydrophilic N- and C-termini that are likely cytoplasmic.

\ \

\ \ transporter activity ; GO:0005215 membrane ; GO:0016020 ion transport ; GO:0006811 21081 IPR002444

\ \

Recent molecular studies have identified two distinct isoforms: one from\ Cl^- secretory epithelia, NKCC1; and another, NKCC2, found specifically in\ the diluting segment of the vertebrate kidney, a Cl^- absorptive epithelium\ [MEDLINE:96002877]. They show lowish amino acid sequence identity (~58%); nevertheless,\ they have rather similar hydropathy profiles, with hydrophilic N- and\ C-termini, flanking a central hydrophobic domain. Their N-termini show\ considerable variation, unlike the central domain (containing the 12\ putative transmembrane (TM) domains) and their C-termini, which are well\ conserved (~70%). Both isoforms are known to be glycosylated and, consistent\ with this, consensus sites for N-linked glycosylation are located within the\ large hydrophilic loop between presumed TM domains 7 and 8. Sequence\ comparisons with other cloned ion co-transporters reveals that Na-K-Cl\ co-transporters belong to a superfamily of electroneutral cation-chloride\ co-transporters, which includes the K-Cl co-transporter IPR000076) and the\ thiazide-sensitive Na-Cl co-transporter. All share a similar predicted\ membrane topology of 12 TM regions in a central hydrophobic domain,\ together with hydrophilic N- and C-termini that are likely cytoplasmic.

\ \

NKCC1 (also called BSC2) was first cloned from the shark rectal gland, a\ model secretory epithelium [MEDLINE:94181560]. Subsequently, mammalian homologues were\ cloned from mouse and human tissues. NKCC1 has a wide distribution and is\ a basolateral secretory isoform, likely involved in salt secretion in a\ diverse range of tissues. Its broad distribution also suggests that it\ may be involved in cell volume regulation and ionic homeostasis [MEDLINE:95355397], [MEDLINE:95014374].\ The human isoform consists of 1212 amino acid residues and shares ~90\ identity with the mouse homologue. It shows lower identity to other members\ of the cation-chloride co-transporter superfamily, being ~40% identical to\ the thiazide-sensitive Na-Cl co-transporter.

\ \ transporter activity ; GO:0005215 membrane ; GO:0016020 ion transport ; GO:0006811 21079 IPR002442

GLUT5 exhibits the weakest inter-isoform similarity of any of the members\ of the GLUT family. This is consistent with its identity as a fructose\ rather than a glucose transporter [MEDLINE:92340476]. It is expressed abundantly in the\ upper small intestine, where it is located in the epithelial brush border.\ Here it likely forms the principal route for dietary fructose uptake. It\ is also found in high levels in the plasma membrane of spermatozoa,\ consistent with their ability to utilise the fructose in seminal fluid as\ an energy source. GLUT5 has also been found in the brain endothelium,\ muscle and fat cells, although its function in these locations is unknown.\ It consists of 501 amino acids (human isoform) and shares ~40% amino acid\ identity with the other isoforms.

\ \ fructose transporter activity ; GO:0005353 membrane ; GO:0016020 transport ; GO:0006810 21078 IPR002441

GLUT4 is thought to be an insulin-responsive glucose transporter, expressed in the membranes of the cells and organelles of skeletal muscle, heart and fat. These tissues\ are insulin-sensitive and respond to increased blood insulin\ levels by a rapid and reversible 20-30 fold increase in glucose transport.\ This is thought to be brought about (at least partially) by the\ translocation of a latent pool of glucose transporters from an intracellular\ site to the plasma membrane. On entry into the endosomal system, GLUT4 is\ selectively retained at the expense of other recycling\ transport that constitutively moves betwwen the endosomes and the cell surface. This retention mechanism might predispose GLUT4 for sorting into transport\ vesicles that bud slowly from the endosome and that are targeted to the trans-Golgi network (TGN).\ GLUT4 is sorted into a secretory pathway in the TGN. This probably\ involves a specialized population of secretory vesicles that excludes other\ secretory cargo, and that does not fuse constitutively with the plasma membrane.\ In the absence of insulin, GLUT4 storage vesicles might\ slowly fuse with endosomes, thereby accounting for the presence of a significant\ but small pool of GLUT4 in endosomes, even in the absence of insulin. Insulin\ would then shift GLUT4 from this TGNendosome cycle to a pathway that takes\ GLUT4 directly to the cell surface. [Bryant NJ et al. Nature Reviews Molecular Cell Biology 3, 267-277 (2002)]

\ \

GLUT4 consists of 509 amino acids (human isoform) and shows ~60% amino acid\ identity to the GLUT1-3 isoforms, being most similar to GLUT1. Both the N- and C-terminal portions of the molecule having been reported to be\ involved in the targeting (3).

\ \ glucose transporter activity ; GO:0005355 membrane ; GO:0016020 transport ; GO:0006810 21077 IPR002440

GLUT2 is the major glucose transporter isoform expressed in hepatocytes,\ insulin-secreting pancreatic cells, and absorptive epithelial cells\ of the intestinal mucosa and kidney. It functions as a low affinity,\ high-turnover transport system; together with the enzyme glucokinase, it\ is thought to act as a glucose-sensing apparatus that plays a role in blood\ glucose homeostasis, by responding to changes in blood glucose concentration\ (such as might occur following a meal) and altering the rate of glucose\ uptake into liver cells, where it can be stored as glycogen. It consists of\ 524 amino acids (human isoform) and is ~55% identical to GLUT1 at the amino\ acid level. GLUT2 has received attention as a molecule that could be\ involved in the pathogenesis of diabetes mellitus. Reductions in pancreatic cell GLUT2 levels have been observed in several animal models of\ diabetes, as well as human patients; whether this is causative, or an\ epiphenomenon remains to be resolved.

\ \ glucose transporter activity ; GO:0005355 membrane ; GO:0016020 transport ; GO:0006810 21076 IPR002439

GLUT1 (also called HepG2) is the most ubiquitously distributed of the\ glucose transporter isoforms. It is expressed in many foetal and adult\ mammalian tissues, and cell lines, although frequently at low levels,\ and in conjunction with other glucose transporter isoforms that show a\ more limited expression pattern. The highest levels are found in foetal\ tissues, and in adult tissues, brain microvessels containing the highest\ levels. To date, it is the most extensively-studied glucose transporter,\ and was initially biochemically characterised as the facilitated\ transporter of human erythrocytes, prior to its cloning. It consists of 492\ amino acid residues (human isoform), which are highly conserved between\ species (98% amino acid identity, human vs. rat). It is thought to provide\ glucose transport in various cells that form barriers between body tissues\ and the blood supply. Thus it is found in epithelial and endothelial barrier\ cells, such as those that constitute the blood-brain barrier, and also in\ the placenta.

\ \ glucose transporter activity ; GO:0005355 membrane ; GO:0016020 transport ; GO:0006810 21074 IPR002437

The 5-HT neurotransmitter transporter is known to be expressed in the brain\ and also in the periphery: on platelet, placental and pulmonary cell\ membranes. The brain 5-HT transporter is thought to be the principal site\ of action of therapeutic anti-depressants (which inhibit this transporter),\ and it may also mediate the behavioural effects of cocaine and amphetamines\ [MEDLINE:93211998]. The human form (630 amino acids) is 92% identical to the rat brain\ 5-HT transporter, and shares the same predicted topology and conserved sites\ for post-translational modification.

\ \ serotonin:sodium symporter activity ; GO:0005335 membrane ; GO:0016020 neurotransmitter transport ; GO:0006836 21075 IPR002438

The orphan transporters are an expanding group of putative\ transporters that have been cloned, but as yet have uncharacterised\ substrate(s) for transport. They include NTT4 and NTT73, which were cloned\ from rat brain tissues [MEDLINE:93114444], and a family of alternatively-spliced variants\ from kidney [MEDLINE:99131080]. Sequence analysis strongly suggests that these indeed are\ Na⁺ and Cl^- -coupled cell membrane transporters, since they show significant\ identity, and similar predicted topology, to the functionally-characterised\ members of this superfamily.

\ \ neurotransmitter:sodium symporter activity ; GO:0005328 membrane ; GO:0016020 neurotransmitter transport ; GO:0006836 21073 IPR002436

In the mammalian brain, the dopamine system is thought to be involved in\ the control of locomotion, cognition and endocrine function. The dopamine\ transporter is critical for the removal of dopamine from the extracellular\ space, following its release, and is the principal site of action for\ psycho-stimulant drugs, such as cocaine and amphetamines, which inhibit\ the transporter's activity. A single form of dopamine transporter\ (containing ~620 amino acids) has been isolated from humans and other\ mammals. Studies of its brain distribution show transcripts to be present\ in areas previously established to possess dopaminergic systems, such as\ the substantia nigra and ventral tegmental area, which regions are known\ to contain dopaminergic cell bodies [MEDLINE:93024326]. Targeted gene disruption of the\ dopamine transporter has confirmed its importance in maintaining low\ extracellular dopamine levels. Mice lacking the transporter show profound\ alterations in the homeostasis of the nigrostriatal dopamine system of the\ brain. Extracellular levels of dopamine are elevated and removal of\ released dopamine is ~300 times slower then in control mice. Additionally,\ the rather stereotyped behavioural responses observed in response to\ administration of cocaine or amphetamine are greatly attenuated [MEDLINE:99364054].

\ \ dopamine:sodium symporter activity ; GO:0005330 membrane ; GO:0016020 neurotransmitter transport ; GO:0006836 21072 IPR002435

The human noradrenaline transporter is the primary target for\ widely-used tricyclic antidepressant drugs, such as desipramine. Cloning studies\ have revealed a single noradrenaline transporter isoform. The cDNA sequence\ predicts a protein of ~617 amino acids, with 12-13 highly hydrophobic\ regions, as would be expected for a member of the Na⁺ and Cl^- -coupled\ neurotransmitter superfamily [MEDLINE:91179515]. Related noradrenaline transporter species\ have been identified in both Drosophila and bullfrog. In mammalian species,\ mRNA for the transporter is localised to the brainstem and the adrenal\ glands. Chromosome mapping has placed the encoding gene to chromosome\ 16q12.2 in humans [MEDLINE:93239190]. Recently, a bovine noradrenaline transporter variant\ has been identified that shows altered targeting to the plasma membrane.\ This has implicated the cytoplasmic facing C-terminus in the intracellular\ trafficking of this protein [MEDLINE:98149771].

\ \ neurotransmitter:sodium symporter activity ; GO:0005328 membrane ; GO:0016020 neurotransmitter transport ; GO:0006836 21071 IPR002434

Cells regulate their volume and adapt to alterations in the tonicity of\ their local environment by adjusting their solute content accordingly.\ Resultant water movements rapidly establish osmotic balance. Solutes\ utilised in this manner are referred to as osmolytes and include:\ glycerophosphorylcholine, betaine, myo-inositol, sorbitol and taurine [MEDLINE:95162643].\ Cell membrane transporters for betaine and taurine have been cloned, and by\ sequence similarity they have been shown to belong to the Na⁺ and Cl^-\ -coupled neurotransmitter transporter superfamily. The taurine transporter\ has a predicted length of ~620 amino acids and can also transport -alanine. It has been found to be widely distributed in the body, with\ transcripts being detected in the kidney (high abundance), ileal mucosa,\ liver, heart and in several regions of the brain including: the corpus\ callosum, striatum and anterior commisure. Functional studies have\ revealed that taurine transporter activity is regulated by hypertonicity,\ and this regulation appears to occur at the level of mRNA accumulation [MEDLINE:92390420].

\ \ taurine:sodium symporter activity ; GO:0005369 membrane ; GO:0016020 neurotransmitter transport ; GO:0006836 21070 IPR002433 These enzymes are collectively known as group IV decarboxylases [MEDLINE:94237165].Pyridoxal-dependent decarboxylases acting on ornithine, lysine, arginine and\ related substrates can be classified into two different families on the basis\ of sequence similarities [MEDLINE:89056708], [MEDLINE:94237165].\ Members of this family while most probably evolutionary related, do not share\ extensive regions of sequence similarities. The proteins contain a conserved lysine\ residue which is known, in mouse ODC [MEDLINE:92112641], to be the site of attachment of the\ pyridoxal-phosphate group. The proteins also contain a stretch of three\ consecutive glycine residues and has been proposed to be part of a substrate-\ binding region [MEDLINE:90330576].\

\ The ornithine decarboxylases catalyse the transformation\ of ornithine into putrescine.\ \ \ Phylogenetic analysis of the mRNAs from several mammalian species suggests\ that ODC is encoded by orthologous genes in the different species .\ Analysis of divergence patterns in a number of subregions showed that the\ domains have evolved in a noncoordinate fashion. Evolution of each subregion\ has been episodic, with periods of both rapid and slow divergence, possibly\ indicating the existence of selection pressures that were exerted in a \ time- and domain-specific manner during mammalian speciation.\ The active form of mammalian ODC is a homodimer of 53 kDa subunits (the monomer retains no enzymatic activity). In vitro hybridisation and cross-\ linkage analysis have suggested that the active site of ODC is formed at \ the interface of the two monomers via the interaction of the cysteine-360-\ containing region of one subunit with the lysine-69-containing region of \ the other [MEDLINE:92112641].

\ \ \N \N polyamine biosynthesis ; GO:0006596 21069 IPR002429

Subunit 2 (CO II) transfers the electrons from cytochrome c to the catalytic subunit 1. It contains two adjacent transmembrane regions in its N-terminus and the major part of the protein is exposed to the periplasmic or to the mitochondrial intermembrane space, respectively. CO II provides the substrate-binding site and contains a copper center called Cu(A) (see IPR001505), probably the primary acceptor in cytochrome c oxidase. An exception is the corresponding subunit of the cbb3-type oxidase which lacks the copper A redox-center. Several bacterial CO II have a C-terminal extension that contains a covalently bound heme c.

\ \ copper ion binding activity ; GO:0005507 membrane ; GO:0016020 electron transport ; GO:0006118 21067 IPR002427

The short-chain dehydrogenases/reductases family (SDR) [MEDLINE:95260797] is a very large family of enzymes, most of which are known to be NAD- or NADP-dependent oxidoreductases. As the first member of this family to be characterized was Drosophila alcohol dehydrogenase, this family used to be called [MEDLINE:89210852], [MEDLINE:91364706], [MEDLINE:92155191] 'insect-type', or 'short-chain' alcohol dehydrogenases. Most members of this family are proteins of about 250 to 300 amino acid residues. Most dehydrogenases possess at least two domains [MEDLINE:81247357], the first binding the coenzyme, often NAD, and the second binding the substrate. This latter domain determines the substrate specificity and contains amino acids involved in catalysis. Little sequence similarity has been found in the coenzyme binding domain although there is a large degree of structural similarity, and it has therefore been suggested that the structure of dehydrogenases has arisen through gene fusion of a common ancestral coenzyme nucleotide sequence with various substrate specific domains [MEDLINE:81247357].

Insect ADH is very different from yeast and mammalian ADHs. The enzyme from \ Drosophila lebanonensis has been characterised by protein analysis and was\ found to have a 254-residue protein chain with an acetyl-blocked N-terminal\ Met [MEDLINE:89210852]. Comparisons with the enzyme from other species reveals that they\ have diverged considerably. The structural variation within Drosophila is \ about as large as that for mammalian zinc-containing alcohol dehydrogenase.\ The crystal structure of the apo form of Drosophila ADH has been solved to\ 1.9A resolution. Three structural features \ characterise the active site architecture: (i) a deep cavity, covered by a\ flexible 33-residue loop and an 11-residue C-terminal tail of the \ neighbouring subunit, whose hydrophobic surface is likely to increase the\ specificity of the enzyme for secondary aliphatic alcohols; (ii) the \ Ser-Tyr-Lys residues of the catalytic triad are known to be involved in\ enzymatic catalysis; and (iii) three well-ordered water molecules in hydrogen \ bonding distance of side-chains of the catalytic triad may be significant\ for the proton release steps in the catalysis.

A number of proteins within the SDR family share a strong phylogenetic\ relationship with insect ADH. Amongst these are Drosophila ADH-related\ protein (duplicate of Adh or Adh-dup) [MEDLINE:95260797]; Drosophila fat body protein; and development-specific 25Kd protein from Sarcophaga peregrina.

\ \ oxidoreductase activity ; GO:0016491 \N metabolism ; GO:0008152 21068 IPR002429

\ \ copper ion binding activity ; GO:0005507 membrane ; GO:0016020 electron transport ; GO:0006118 21066 IPR002426

\ Insect ADH is very different from yeast and mammalian ADHs. The enzyme from \ Drosophila lebanonensis has been characterised by protein analysis and was\ found to have a 254-residue protein chain with an acetyl-blocked N-terminal\ Met [MEDLINE:89210852]. Comparisons with the enzyme from other species reveals that they\ have diverged considerably. The structural variation within Drosophila is \ about as large as that for mammalian zinc-containing alcohol dehydrogenase.\ The crystal structure of the apo form of Drosophila ADH has been solved to\ 1.9A resolution. Three structural features \ characterise the active site architecture: (i) a deep cavity, covered by a\ flexible 33-residue loop and an 11-residue C-terminal tail of the \ neighbouring subunit, whose hydrophobic surface is likely to increase the\ specificity of the enzyme for secondary aliphatic alcohols; (ii) the \ Ser-Tyr-Lys residues of the catalytic triad are known to be involved in\ enzymatic catalysis; and (iii) three well-ordered water molecules in hydrogen \ bonding distance of side-chains of the catalytic triad may be significant\ for the proton release steps in the catalysis.

\ \ alcohol dehydrogenase activity ; GO:0004022 \N metabolism ; GO:0008152 21065 IPR002425 The short-chain dehydrogenases/reductases family (SDR) [MEDLINE:95260797] is a very large family of enzymes, most of which are known to be NAD- or NADP-dependent oxidoreductases. As the first member of this family to be characterized was Drosophila alcohol dehydrogenase, this family used to be called [MEDLINE:89210852], [MEDLINE:91364706], [MEDLINE:92155191] 'insect-type', or 'short-chain' alcohol dehydrogenases. Most members of this family are proteins of about 250 to 300 amino acid residues. Most dehydrogenases possess at least two domains [MEDLINE:81247357], the first binding the coenzyme, often NAD, and the second binding the substrate. This latter domain determines the substrate specificity and contains amino acids involved in catalysis. Little sequence similarity has been found in the coenzyme binding domain although there is a large degree of structural similarity, and it has therefore been suggested that the structure of dehydrogenases has arisen through gene fusion of a common ancestral coenzyme nucleotide sequence with various substrate specific domains [MEDLINE:81247357].

\ \ alcohol dehydrogenase activity ; GO:0004022 \N alcohol metabolism ; GO:0006066 21060 IPR002421 The N-terminal and internal 5'3'-exonuclease domains are commonly found together, and are most often associated with 5' to 3' nuclease activities. The XPG protein signatures (PDOC00658).\ \ 5'-3' exonuclease activity ; GO:0008409\ DNA binding activity ; GO:0003677 \N \N 21061 IPR002421 The N-terminal and internal 5'3'-exonuclease domains are commonly found together, and are most often associated with 5' to 3' nuclease activities. The XPG protein signatures (PDOC00658).\ \ 5'-3' exonuclease activity ; GO:0008409\ DNA binding activity ; GO:0003677 \N \N 21062 IPR002422 Amino acid permeases are integral membrane proteins involved in the transportof amino acids into the cell. A number of such proteins have been found to be\ evolutionary related [MEDLINE:89125644], [MEDLINE:90076962], [MEDLINE:93184721].\ These proteins seem to contain up to 12 transmembrane segments. The best conserved region\ in this family is located in the second transmembrane segment. Proteins in this group belong to family II.\ \ amino acid-polyamine transporter activity ; GO:0005279 membrane ; GO:0016020 amino acid transport ; GO:0006865 21063 IPR002423

The assembly of proteins has been thought to be the sole result of properties inherent in the primary sequence of polypeptides themselves. In some cases, however, structural information from other protein molecules is required for correct folding and subsequent assembly into oligomers [MEDLINE:88232881]. These 'helper' molecules are referred to as molecular chaperones, a subfamily of which are the chaperonins [MEDLINE:92256809], which include 10 kDa and 60 kDa proteins. These are found in abundance in prokaryotes, chloroplasts and mitochondria. They are required for normal cell growth (as demonstrated by the fact that no temperature sensitive mutants for the chaperonin genes can be found in the temperature range 20 to 43 degrees centigrade [MEDLINE:88232881]), and are stress-induced, acting to stabilise or protect disassembled polypeptides under heat-shock conditions [MEDLINE:92256809].

The 10 kDa chaperonin (cpn10 - or groES in bacteria) exists as a ring-shaped oligomer of between 6 to 8 identical subunits, whereas the 60 kDa chaperonin (cpn60 - or groEL in bacteria) forms a structure comprising 2 stacked rings, each ring containing 7 identical subunits [MEDLINE:88232881]. These ring structures assemble by self-stimulation in the presence of Mg2+-ATP. The cpn10 and cpn60 oligomers also require Mg2+-ATP in order to interact to form a functional complex, although the mechanism of this interaction is as yet unknown [MEDLINE:92283754]. This chaperonin complex is essential for the correct folding and assembly of polypeptides into oligomeric structures, of which the chaperonins themselves are not a part [MEDLINE:92256809]. The binding of cpn10 to cpn60 inhibits the weak ATPase activity of cpn60.

The 60 kDa form of chaperonin is the immunodominant antigen of patients with Legionnaire's disease [MEDLINE:91169238], and is thought to play a role in the protection of the legionella bacteria from oxygen radicals within macrophages. This hypothesis is based on the finding that the cpn60 gene is upregulated in response to hydrogen peroxide, a source of oxygen radicals. Cpn60 has also been found to display strong antigenicity in many bacterial species [MEDLINE:92182006], and has the potential for inducing immune protection against unrelated bacterial infections. The RuBisCO subunit binding protein (which has been implicated in the assembly of RuBisCO) and cpn60 have been found to be evolutionary homologues, the RuBisCO subunit binding protein having the C-terminal Gly-Gly-Met repeat found in all bacterial cpn60 sequences. Although the precise function of this repeat is unknown, it is thought to be important as it is also found in 70 kDa heat-shock proteins [MEDLINE:91169238]. The crystal structure of E. coli GroEL has been resolved to 2.8A [MEDLINE:95021709]. The TCP-1 family of proteins act as molecular chaperones for tubulin, actin and probably some other proteins. They are weakly, but significantly, related to the cpn60/groEL chaperonin family.

\ \ \N \N \N 21064 IPR002424

\ \ \ alcohol dehydrogenase activity ; GO:0004022 \N metabolism ; GO:0008152 21056 IPR002416 The general (type II) secretion pathway (GSP) within Gram-negative bacteria is a signal sequence-dependent process responsible for protein export. The process has two stages: exoproteins are first translocated\ across the inner membrane by the general signal-dependent export pathway\ (GEP), and then across the outer membrane by a species-specific accessory\ mechanism. \ \

A number of proteins are involved in the GSP; one of these is known as\ protein H (GSPH protein). This protein shares several sequence similarities\ with bacterial fimbrial protein, or pilin, the major structural protein of\ pili (see IPR001120). Fimbrial and GSPG proteins share the following\ characteristics: a methylated, hydrophobic N-terminal residue; a\ hydrophobic leader peptide of five to ten residues, terminating with glycine;\ glutamate as the fifth residue of the mature sequence; and a highly\ hydrophobic N-terminus.

\ \ protein transporter activity ; GO:0008565 type II protein secretion system complex ; GO:0015627 type II protein (Sec) secretion system ; GO:0015628 21057 IPR002417 The glycoproteins of viral haemorrhagic scepticaemia virus [MEDLINE:87198856] and of infectious hematopoietic necrosis virus [MEDLINE:92062736] are similar, and are responsible for forming spikes on\ the surface of the virion. The glycoprotein mediates binding of the virus to susceptible\ host cells and induces uptake of the virus by the cell. The interaction between the\ internal components of the virion and the portion of the glycoprotein exposed on the\ cytoplasmic face of the plasma membrane probably directs envelopment and virus\ budding.\ \ \N \N \N 21058 IPR002418 The class III basic helix-turn-helix (bHLH) transcription factors have proliferative and apoptotic roles and are characterised by the presence of a leucine zipper adjacent to the bHLH domain.The myc oncogene gene was first discovered in small-cell lung cancer cell lines where it is found to \ be deregulated [MEDLINE:88094386]. Although the biochemical function of the gene product is unknown, as a \ nuclear protein with a short half-life it may play a direct or indirect role in controlling gene \ expression [MEDLINE:86317706]. Myc forms a heterodimer with Max, and this complex regulates cell growth through \ direct activation of genes involved in cell replication [MEDLINE:97318600].\

The 'leucine zipper' is a structure that is believed to mediate the\ function of several eukaryotic gene regulatory proteins. The zipper\ consists of a periodic repetition of leucine residues at every seventh\ position, and regions containing them appear to span eight turns of -\ helix. The leucine side chains that extend from one helix interact with\ those from a similar helix, hence facilitating dimerisation in the form\ of a coiled-coil. Leucine zippers are present in many gene regulatory\ proteins, including the CREB proteins, Jun/AP1 transcription factors,\ fos oncogene and fos-related proteins, C-myc, L-myc and N-myc oncogenes,\ and so on.

\ \ transcription factor activity ; GO:0003700 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 21059 IPR002420

Phosphatidylinositol 3-kinase (PI3-kinase) (EC: 2.7.1.137) is an enzyme that phosphorylates phosphoinositides on the 3-hydroxyl group of the inositol\ ring. The usually N-terminal C2 domain interacts mainly with the scaffolding helical domain of the enzyme, and exhibits only minor\ interactions with the catalytic domain [MEDLINE:22147077]. The domain consists of two four-stranded antiparallel -sheets\ that form a -sandwich. Isolated C2 domain binds multilamellar phospholipid\ vesicles which suggests that this domain could play a role in membrane association. Membrane attachment by C2 domains is typically mediated by the loops connecting -strand regions\ that in other C2 domain-containing proteins are calcium-binding region

\ \ \ 1-phosphatidylinositol 3-kinase complex ; GO:0005942\ phosphatidylinositol 3-kinase activity ; GO:0016303 \N \N 21047 IPR002407 Atrial natriuretic peptides (ANPs) are vertebrate hormones that play an important role in the control ofcardiovascular homeostatis, and sodium and water balance in general [MEDLINE:91354028], [MEDLINE:89123413], PUB00005323.\ There are different NPs that vary in length but share a common core. All are processed from a single precursor.\ A disulphide bond resident in the C-terminal section is required for full activity of atriopeptins. The family\ of NPs includes structurally-related peptides that elicit similar pharmacological spectra. Amongst these are\ brain natriuretic peptide (BNP); C-type natriuretic peptide (CNP); ventricular natriuretic peptide (VNP)\ PUB00005323; and green mamba natriuretic peptide (DNP) [MEDLINE:92332489]\

Atrial natriuretic factor (ANF) is a potent vasoactive substance synthesized in mammalian atria and is thought to play a key role in cardiovascular homeostasis. It has a cGMP-stimulating activity.\

\ \ hormone activity ; GO:0005179 extracellular ; GO:0005576 physiological processes ; GO:0007582 21048 IPR002408 Atrial natriuretic peptides (ANPs) are vertebrate hormones that play an important role in the control ofcardiovascular homeostatis, and sodium and water balance in general [MEDLINE:91354028], [MEDLINE:89123413], PUB00005323.\ There are different NPs that vary in length but share a common core. All are processed from a single precursor.\ A disulphide bond resident in the C-terminal section is required for full activity of atriopeptins. The family\ of NPs includes structurally-related peptides that elicit similar pharmacological spectra. Amongst these are\ brain natriuretic peptide (BNP); C-type natriuretic peptide (CNP); ventricular natriuretic peptide (VNP)\ PUB00005323; and green mamba natriuretic peptide (DNP) [MEDLINE:92332489]\ \ hormone activity ; GO:0005179 extracellular ; GO:0005576 \N 21049 IPR002409 Aflatoxins belong to a family of decaketides that are produced as secondary metabolites by Aspergillus flavus and A.parasiticus\ \ \ \ [MEDLINE:94354655]. The aflatoxin\ biosynthetic pathway involves several enzymatic steps that appear to be\ regulated by the aflR genes in A.flavus and A.parasiticus.\ AflR encodes a protein that contains a cysteine-rich motif. Several fungal\ transcriptional activator proteins contain this motif, which binds DNA in\ a zinc-dependent fashion (see IPR001138.\

Aflatoxin biosynthesis regulatory protein is involved in the regulation of aflatoxin biosynthesis and may have a role in nitrate assimilation and sclerotial\ morphogenesis.

\ \ transcription factor activity ; GO:0003700 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 21050 IPR002410 Proline aminopeptidases are serine peptidases that selectively cleave N-terminal proline residues [MEDLINE:95147689], [MEDLINE:95020651].\ Proteolytic enzymes that use serine in their catalytic machinery are \ widespread and numerous, being found in viruses, bacteria and eukaryotes. More than 20 serine\ protease families (denoted S1 - S27) have been identified, which have been\ grouped into 6 clans (SA, SB, SC, SE, SF and SG) on the basis of structural\ and functional similarities . \ \ \ Prolyl aminopeptidase shows sequence \ similarity to the carboxypeptidase C family (S8), and hence this peptiase\ can be grouped into the SC clan [MEDLINE:95147689].\ \ aminopeptidase activity ; GO:0004177 \N proteolysis and peptidolysis ; GO:0006508 21051 IPR002411 Seeds of cereals contain a variety of serine proteases and

-amylase inhibitors. These inhibitors can be grouped into families based on structural\ similarities. Rice seed allergenic protein (RAG) is a trypsin/

-amylase inhibitor. Trypsin/

-amylase inhibitors are specific to trypsin or to

-amylase, and a few are bifunctional. The proteins contain ~10 cysteine residues, all of which are involved in\ disulphide bond formation [MEDLINE:91346619].\ \

The rice seed allergenic proteins (RA) \ are encoded by a multigene family consisting of at\ least four members. A conserved sequence similar to a motif identified in\ rice glutelin promoters was observed in the 5' region of the two genes .\ RA genes are specifically expressed in ripening seeds and their transcripts \ accumulate maximally 15-20 days after flowering [MEDLINE:93144699].

\ \ \N \N \N 21052 IPR002413

The allergens in this family include allergens with the following designations: Dol m 5, Pol d 5, Pol e 5, Pol f 5, Sol i 3, Sol r 3, Ves c 5,Ves f 5, Ves g 5, Ves m 5, Ves p 5, Ves s 5, Ves v 5, Ves vi 5 and Vesp m 5.

Venom allergen 5 (Ves 5) is a major allergen of vespid venom [MEDLINE:93203603]. Regions of conservation have been identified that are\ shared both by a family of proteins from human, mouse and rat testis, and\ by a class of pathogenesis-related proteins from tobacco and tomato leaves. Ves 5 also shares similarity with the Solenopsis invicta 3\ allergen from imported fire ant venom [MEDLINE:94044316].

\ \ \N \N \N 21053 IPR002414

This domain has no known function. It is found in various hypothetical proteins and putative lipoproteins from mycoplasmas.

\ \N \N \N 21054 IPR002414

This domain has no known function. It is found in various hypothetical proteins and putative lipoproteins from mycoplasmas.

\ \N \N \N 21055 IPR002415 The high mobility group (HMG)-like nuclear protein NHP2 from S.cerevisiae has been termed 'HMG-like' in that it shares certain physical/chemical properties with\ HMG proteins from higher eukaryotes\ \ \ \ [MEDLINE:91289691]. It shows no significant\ sequence similarity to such proteins, and thus constitutes a distinct HMG\ protein class. NHP2 does share sequence similarity with two\ ribosomal proteins: the acidic ribosomal protein S6 from H.marismorium\ and mammalian L7a ribosomal protein [MEDLINE:92096469]. \

The biological implications of the observed similarities to S6 and L7a are\ unclear, as biochemical studies have indicated that NHP2 is not a ribosomal\ protein. Nevertheless, deletion experiments have indicated NHP2 to have an\ essential physiological function [MEDLINE:91289691].

\ \ \N \N \N 21043 IPR002403 The cytochrome P450 enzymes usually act as terminal oxidases in multicomponentelectron transfer chains, called P450-containing monooxygenase systems. P450-containing\ monooxygenase systems primarily fall into two major classes: bacterial/mitochondrial\ (type I), and microsomal (type II). All P450 enzymes can be categorised into two\ main groups, the so-called B- and E-classes: P450 proteins of prokaryotic 3-component\ systems and fungal P450nor (CYP55) belong to the B-class; all other known P450 proteins\ from distinct systems are of the E-class.\

E-class P450s may be\ further divided into five subclasses (groups) according to protein sequence\ similarities. The data suggest that divergence of the P450 superfamily \ into B- and E-classes, and further divergence into stable P450 groups \ within the E-class, must be very ancient and had occured before the \ appearance of eukaryotes.

\ There seems to be no particular functional resemblance between cholesterol\ 7--hydroxylase (family CYP7) and lanosterol 14--demethylase \ (CYP51) yet, sequence similarity between these two families is so significant that CYP7 and CYP51 constitute a single group, namely\ group IV PUB00005920. Taking into account the high sequence similarity of CYP7 \ proteins and prostacyclin synthase (CYP8) PUB00005920 the\ CYP8 family alos falls in group IV.

\ \ \ monooxygenase activity ; GO:0004497 \N electron transport ; GO:0006118 21044 IPR002404 Insulin receptor substrate-1 proteins contain both a pleckstrin homology domain IPR001849 and a phosphotyrosine binding (PTB) domain. These domains facilitate \ interaction with the activated tyrosine-phosphorylated insulin receptor.\ The PTB domain is situated towards the N-terminus. Two arginines in this domain are responsible for\ hydrogen bonding phosphotyrosine residues on a Ac-LYASSNPApY-NH2 peptide\ in the juxtamembrane region of the insulin receptor. Further interactions\ via 'bridged' water molecules are coordinated by residues an Asn and a Ser residue\ [MEDLINE:96234229].\

The PTB domain has a compact, 7-stranded -sandwich structure, capped by\ a C-terminal helix. The substrate peptide fits into an L-shaped surface\ cleft formed from the C-terminal helix and strands 5 and 6 [MEDLINE:96185451].

\ \ insulin receptor binding activity ; GO:0005158 \N \N 21045 IPR002405

Inhibins and activins are glycoproteins, secreted by the gonads, that belong to the transforming growth factor family [MEDLINE:86092207]. They participate in differentiation and growth of diverse cell types. Inhibin inhibits secretion of follicle-stimulating hormone by the pituitary [MEDLINE:86287350].

Inhibin has two isoforms, A and B, with the same subunit but different subunits. Inhibin A is a dimer of and A subunits, inhibin B is a dimer of and B subunits.

Activin A is a dimer of A subunits, activin AB is a dimer of A and B chains.

Follistatin is bound to inhibin and activin and indirectly modulates the FSH release. In turn, FSH stimulates inhibin gene expression in the ovarian follicle [MEDLINE:95112839], probably mediated \ by cAMP [MEDLINE:86092207]. The serum levels of inhibin, activin, and follistatin are elevated in pregnant women and decrease after delivery. [MEDLINE:99142964].

Genes coding for mouse activin C and E are closely linked and exhibit a liver-specific expression pattern in adult tissues.

\ \ \N extracellular ; GO:0005576 cell growth and/or maintenance ; GO:0008151 21046 IPR002406 Atrial natriuretic peptides (ANPs) are vertebrate hormones that play an important role in the control ofcardiovascular homeostatis, and sodium and water balance in general [MEDLINE:91354028], [MEDLINE:89123413], PUB00005323.\ There are different NPs that vary in length but share a common core. All are processed from a single precursor.\ \ \ A disulphide bond resident in the C-terminal section is required for full activity of atriopeptins. The family\ of NPs includes structurally-related peptides that elicit similar pharmacological spectra. Amongst these are\ brain natriuretic peptide (BNP); C-type natriuretic peptide (CNP); ventricular natriuretic peptide (VNP)\ PUB00005323; and green mamba natriuretic peptide (DNP) [MEDLINE:92332489]\ \

C-type natriuretic peptide has vasorelaxant and cGMP-stimulating activities.

\ \ hormone activity ; GO:0005179 extracellular ; GO:0005576 \N 21031 IPR002391 The annexins are a family of proteins that bind to phospholipids in a calcium-dependent manner [MEDLINE:91266960]. There are eleven distinct classes of annexin, each\ of which has an amino acid sequence consisting of an N-terminal 'arm' \ followed by either four or eight copies of a conserved domain of 61 residues (only one\ of these residues, an arginine, is conserved between all copies). The\ calcium binding sites are found within the repeated domains PUB00005502. Individual\ repeats (sometimes known as endonexin folds) consist of five

-helices\ wound into a right-handed superhelix. Each annexin class is thought to have\ a specific function, although for some the precise role is unclear. It has\ been suggested that the N-terminal residues confer the functional\ specificity that differentiates each class.\

The type IV class\ has not been identified in all species known to possess annexins, but are\ thought to be required for the budding of clathrin-coated pits.

\ \ \ calcium-dependent phospholipid binding activity ; GO:0005544 \N \N 21032 IPR002392 The annexins are a family of proteins that bind to phospholipids in a calcium-dependent manner [MEDLINE:91266960]. There are eleven distinct classes of annexin, each\ of which has an amino acid sequence consisting of an N-terminal 'arm' \ followed by either four or eight copies of a conserved domain of 61 residues (only one\ of these residues, an arginine, is conserved between all copies). The\ calcium binding sites are found within the repeated domains PUB00005502. Individual\ repeats (sometimes known as endonexin folds) consist of five

Type V\ annexin behaves as an anticoagulant, acting as an indirect inhibitor of the\ thromboplastin-specific complex, which is involved in the blood coagulation\ casacade. It may also act as a form of calcium channel.

\ \ \ anticoagulant activity ; GO:0008435 \N \N 21033 IPR002393 The annexins are a family of proteins that bind to phospholipids in a calcium-dependent manner [MEDLINE:91266960]. There are eleven distinct classes of annexin, each\ of which has an amino acid sequence consisting of an N-terminal 'arm' \ followed by either four or eight copies of a conserved domain of 61 residues (only one\ of these residues, an arginine, is conserved between all copies). The\ calcium binding sites are found within the repeated domains PUB00005502. Individual\ repeats (sometimes known as endonexin folds) consist of five

Type VI annexins\ are found in various secretory cells, e.g. B- and T-cells (where it is\ found in greater concentrations in mature cells), and the lactation ducts of\ non-lactating human breasts. The observation that the protein is absent in\ lactating breasts suggests that it inhibits secretion. The type VI class\ may also play a part in the regulation of some calcium channels, and its\ presence may cause arrest of cell growth, before the DNA-replication stage,\ in cells growing at low serum concentrations. This annexin class is unusual\ in containing eight repeats of the conserved domain rather than the usual four. It\ is thus believed that the protein has arisen from a gene duplication event.

\ \ \ calcium-dependent phospholipid binding activity ; GO:0005544 \N \N 21034 IPR002394

\ \

Nicotinic acetylcholine receptors are ligand-gated ion channels that mediate signal\ transduction at the post-synaptic membrane of cholinergic synapses, such as\ the neuromuscular junction [MEDLINE:92084670]. They belong to a family of neurotransmitter-gated receptors, including glycine, gamma-aminobutyric-acid (GABA),\ serotonin 5HT3 receptors. These are oligomeric transmembrane\ (TM) complexes (pentamers of 2 and 1 , 1 gamma and 1 delta\ subunit) that contain a central channel, which transiently opens upon binding of a specific neurotransmitters. Their sequences are related and share the same topology: each has\ an extracellular, glycosylated N-terminal ligand-binding domain; 3 hydrophobic TM regions, which form the channel; a hydrophilic cytoplasmic\ domain; followed by a fourth putative TM region [MEDLINE:89139580]. The nicotinic receptor ligand binding domain is a specialized pocket of aromatic\ and hydrophobic residues formed at interfaces between protein subunits that changes conformation to convert agonist binding into\ gating of an intrinsic ion channel [MEDLINE:22323407].

\ The expression of acetylcholine receptors is activated during muscle\ differentiation and upon denervation of adult muscle [MEDLINE:90183977]. Receptor function\ is regulated by phosphorylation and dephosphorylation by kinases and\ phosphatases present in the post-synaptic membranes [MEDLINE:92084670]. Most of the\ phosphorylation sites are located in the major intracellular loop between\ the third and fourth TM regions and are closely spaced.

\ \ \ ion channel activity ; GO:0005216 membrane ; GO:0016020 transport ; GO:0006810 21035 IPR002395 High molecular weight kininogen (HK) [MEDLINE:89114719] is synthesised as a single polypeptide chain in the liver and secreted into the plasma, where it complexes with prekallikrein and factor XI. On cleavage by human plasma kallikrein,\ or factor XIIa, HK liberates bradykinin, which mimics inflammatory \ phenomena such as pain induction, vasodilation and increased vascular\ permeability. Kallikrein-\ cleavage yields the nonapeptide bradykinin, together with a cleaved product\ containing an N-terminal heavy chain, bound to a C-terminal light chain by\ a single interchain disulphide bridge.\

Cleavage of HK is required for expression of its procoagulant activity,\ which is contained in the light chain. This activity depends on a number of\ factors, including the binding of cleaved HK to anionic surfaces [MEDLINE:81000161], which\ function is thought to be mediated through a His-Gly-rich region. Evidence has suggested that critical amino acid sequences within the \ His-Gly-rich region of HK serve as a primary structural feature for binding\ to a negatively charged surface [MEDLINE:93284080].

\ \ \N \N \N 21036 IPR002396

Animal lectins display a wide variety of architectures.They are classified according to the carbohydrate-recognition\ domain (CRD) of which there are two main types, S-type and C-type.

C-type lectins IPR001304 display a wide range of specificities.\ They require Ca²⁺ for their activity\ They are found predominantly but not exclusively in vertebrates.

They can be classified into a number of subgroups based on their function and structure:\

Endocytic lectins - \ Membrane-bound receptors that mediate endocytosis \ of glycoproteins

Collectins -\ Represented by the soluble mannose-binding proteins of \ mammalian serum and liver

Selectins - \ Membrane-bound proteins involved in inflammation. There are three main divisions, CD62E, CD62 L and CD62P [MEDLINE:92189729].

\ \

CD62E (also called E-selectin, ELAM-1 or LECAM-2), CD62L (also called L-selectin, LAM-1, LECAM-1, Leu-8, MEL-14 or TQ-1) and CD62P (also called P-selectin, granule membrane protein-140, GMP-140 or platelet activation dependent granule-external membrane protein, PADGEM) belong to this group.\ CD62E mediates leukocyte rolling on activated endothelium at inflammatory sites and may also support tumor cell adhesion during hematogenous metastasis, and play a role in angiogenesis. CD62L mediates lymphocyte homing to high endothelial venules of peripheral lymphoid tissue and leukocyte rolling on activated endothelium at inflammatory sites. Interaction of CD62P with PSGL-1 mediates tethering and rolling of leukocytes on the surface of activated endothelial cells, the first step in leukocyte extravasation and migration towards inflammations. CD62P mediates rolling of platelets on endothelial cells and CD62P-mediated interactions are also involved in platelet-mediated delivery of lymphocytes to high endothelial venules.

\ \

Members of the selectin superfamily have the same domain structure: an N-terminal lectin domain followed by an EGF repeat; a variable \ number (between 2 and 9) of complement regulatory elements; a single trans-\ membrane region; and a short cytoplasmic anchor . Some studies have \ found distinct carbohydrate structures on leukocytes that are adhered to by\ selectins, suggesting that selectins are involved in the selective \ trafficking of blood-borne components of the immune system.

\ \

CD molecules are leucocyte antigens on cell surfaces. CD antigens nomenclature is updated at http://www.ncbi.nlm.nih.gov/PROW/guide/45277084.htm \

\ \ \ cell adhesion molecule activity ; GO:0005194 membrane ; GO:0016020 cell adhesion ; GO:0007155 21042 IPR002402 The cytochrome P450 enzymes usually act as terminal oxidases in multicomponentelectron transfer chains, called P450-containing monooxygenase systems. P450-containing\ monooxygenase systems primarily fall into two major classes: bacterial/mitochondrial\ (type I), and microsomal (type II). All P450 enzymes can be categorised into two\ main groups, the so-called B- and E-classes: P450 proteins of prokaryotic 3-component\ systems and fungal P450nor (CYP55) belong to the B-class; all other known P450 proteins\ from distinct systems are of the E-class.\

\ \ \ monooxygenase activity ; GO:0004497 \N electron transport ; GO:0006118 21041 IPR002401

\ \ The cytochrome P450 enzymes usually act as terminal oxidases in multicomponent\ electron transfer chains, called P450-containing monooxygenase systems. P450-containing\ monooxygenase systems primarily fall into two major classes: bacterial/mitochondrial\ (type I), and microsomal (type II). All P450 enzymes can be categorised into two\ main groups, the so-called B- and E-classes: P450 proteins of prokaryotic 3-component\ systems and fungal P450nor (CYP55) belong to the B-class; all other known P450 proteins\ from distinct systems are of the E-class.\

\ Group I is richest in members, consisting of P450 families CYP1, CYP2,\ CYP17, CYP21 and CYP71 PUB00005920. The members of the first four families are of\ vertebrate origin, while those from CYP71 are derive from plants. CYP1 and CYP2\ enzymes mainly metabolise exogenous substrates, whereas CYP17 and CYP21 are\ involved in metabolism of endogenous physiologically-active compounds.

\ \ \ monooxygenase activity ; GO:0004497 \N electron transport ; GO:0006118 21040 IPR002400 The crystal structures of several proteins have been reported as having unusual folds, involving intramolecular disulphide bridges. In transforming\ growth factor-

2 (TGF-beta2) [MEDLINE:92350287], platelet-derived growth factor (PDGF)\ , nerve growth factor (NGF) [MEDLINE:92065986] and human chorionic gonadotropin (hCG)\ [MEDLINE:94261179], six conserved cysteines (I to VI in sequence order) form three disulphide\ links arranged in a knot-like topology. Cystines [II-V] and [III-VI] form\ a ring of eight amino acids through which the remaining disulphide bond \ (Cys[I-IV]) penetrates.\ \

A similar knotted arrangement of disulphide bonds has been noted in the\ structures of some enzyme inhibitors and neurotoxins that bind to voltage-\ gated Ca2+ channels [MEDLINE:95152384]. In those sequences, however, the cystine topology\ differs. Cys[III-VI] penetrates a macrocyclic ring formed by Cys[I-IV] and\ Cys[II-V]. Thus, cystine knots fall into two structural classes: growth\ factor type and inhibitor-like cystine knots [MEDLINE:96082952].

\ All growth factor cystine knots structures have similar topology, with two\ distorted -hairpin loops "above" the knot and a single loop "below".\ The sizes of the hairpin loop vary significantly.

\ \ \N \N \N 21039 IPR002399 The cytochrome P450 enzymes usually act as terminal oxidases in multicomponentelectron transfer chains, called P450-containing monooxygenase systems. P450-containing\ monooxygenase systems primarily fall into two major classes: bacterial/mitochondrial\ (type I), and microsomal (type II). All P450 enzymes can be categorised into two\ main groups, the so-called B- and E-classes: P450 proteins of prokaryotic 3-component\ systems and fungal P450nor (CYP55) belong to the B-class; all other known P450 proteins\ from distinct systems are of the E-class.\ \ monooxygenase activity ; GO:0004497 \N electron transport ; GO:0006118 21038 IPR002398

Synonym(s): Interleukin 1- converting enzyme (ICE)

Caspase-1 (EC: 3.4.22.36) [MEDLINE:95291179], [MEDLINE:95334823] is responsible for the cleavage of the IL-1 precursor at an Asp-Ala bond to generate the mature biologically active cytokine. ICE a thiol protease composed of two subunits of 10 kDa (p10) and 20 kDa (p20), both derived by the autocleavage of a 45 kDa precursor (p45). ICE belongs to a family of peptidases [MEDLINE:97416345] which is implicated in programmed cell death (apoptosis) and which has been termed 'caspase' for cysteine aspase. ICE is known as Caspase-1 and the other members of this family [MEDLINE:97015072] are:

Caspase-2 (ICH-1, NEDD-2).
Caspase-3 (also known as apopain, CPP32, Yama), a protease which, at the onset of apoptosis, proteolytically cleaves poly(ADP-ribose) polymerase (see IPR001510) at an Asp-Gly bond.
Caspase-4 (ICH-2, TX, ICErel-II).
Caspase-5 (ICH-3, TY, ICErel-III).
Caspase-6 (MCH-2).
Caspase-7 (MCH-3, ICE-LAP3, CMH-1, SCA-2, LICE2).
Caspase-8 (MCH-5, MACH, FLICE).
Caspase-9 (MCH-6, ICE-LAP6).
Caspase-10 (MCH-4, FLICE2).
Caspase-11.
Caspase-12.
Caenorhabditis elegans ced-3 involved in the initiation of apoptosis.
Drosophila Ice.

Note: these proteins belong to family C14 in the classification of peptidases [MEDLINE:93176119].

\ \ caspase activity ; GO:0004199 \N proteolysis and peptidolysis ; GO:0006508 21037 IPR002397 The cytochrome P450 enzymes usually act as terminal oxidases in multicomponentelectron transfer chains, called P450-containing monooxygenase systems. P450-containing\ monooxygenase systems primarily fall into two major classes: bacterial/mitochondrial\ (type I), and microsomal (type II). All P450 enzymes can be categorised into two\ main groups, the so-called B- and E-classes: P450 proteins of prokaryotic 3-component\ systems and fungal P450nor (CYP55) belong to the B-class; all other known P450 proteins\ from distinct systems are of the E-class.\ \ \ monooxygenase activity ; GO:0004497 \N electron transport ; GO:0006118 21023 IPR002381

Prokaryotic ribonuclease PH (EC: 2.7.7.56) (RNase PH) is a phosphorolytic exoribonuclease that removes nucleotide residues following the -CCA terminus\ of tRNA and adds nucleotides to the ends of RNA molecules by using nucleoside\ diphosphates as substrates [MEDLINE:92381029].\ There is a similar protein in C.elegans that belongs to this group.

\ \ tRNA-specific ribonuclease activity ; GO:0004549 \N tRNA processing ; GO:0008033 21024 IPR002383 Coagulation proteins, such as factors VII, IX and X, proteins C and S, and prothrombin, contain gamma-carboxyglutamic acid residues (between 9 and 12 in number) and are produced by post-translational \ modification of Glu residues by a vitamin K-dependent carboxylase. Calcium \ ions bind to the gamma-carboxyglutamic acid residues of the Gla domain and \ support the binding of these vitamin K-dependent proteins to acidic \ phospholipid vesicles, resulting in the production of a soluble fibrin clot.\

The Gla domain is an N-terminal module of about 48 residues that contains\ carboxylated Glu residues responsible for high-affinity calcium binding.\ It terminates with a conserved aromatic residue, and at its centre has a\ conserved Gla-x(3)-Gla-x-Cys motif, which seems to be important for the\ substrate recognition by the carboxylase. The domain is dominated by\ secondary structure comprising three turns of -helix and five short -\ strands arranged into two -structural units. Cys residues 18 and 23 of\ the Gla domain participate in a disulphide bridge to form a small conserved\ loop close to a cluster of conserved aromatic residues [MEDLINE:90057353].

\ \ \N \N \N 21030 IPR002390 The annexins are a family of proteins that bind to phospholipids in a calcium-dependent manner [MEDLINE:91266960]. There are eleven distinct classes of annexin, each\ of which has an amino acid sequence consisting of an N-terminal 'arm' \ followed by either four or eight copies of a conserved domain of 61 residues (only one\ of these residues, an arginine, is conserved between all copies). The\ calcium binding sites are found within the repeated domains PUB00005502. Individual\ repeats (sometimes known as endonexin folds) consist of five

Type III\ annexins inhibit phospholipase A2 activity, and also play a role in\ inositol phosphate metabolism, cleaving the cyclic bond of inositol-1,2-\ cyclic phosphate to yield inositol-1-phosphate.

\ \ \ anticoagulant activity ; GO:0008435 \N \N 21029 IPR002389 The annexins are a family of proteins that bind to phospholipids in a calcium-dependent manner [MEDLINE:91266960]. There are eleven distinct classes of annexin, each\ of which has an amino acid sequence consisting of an N-terminal 'arm' \ followed by either four or eight copies of a conserved domain of 61 residues (only one\ of these residues, an arginine, is conserved between all copies). The\ calcium binding sites are found within the repeated domains PUB00005502. Individual\ repeats (sometimes known as endonexin folds) consist of five

Type II\ annexins bind two calcium ions and inhibit phospholipase A2, following \ dephosphorylation by protein kinases involved in the signal transduction\ pathway. They may also cross-link plasma membrane phospholipids with actin\ and the cytoskeleton, and possibly play a part in exocytosis, since they\ are also involved in granule aggregation and membrane fusion.

\ \ \ anticoagulant activity ; GO:0008435 \N \N 21025 IPR002384 Bone gamma-carboxyglutamic acid protein (BGP) and matrix gamma- carboxyglutamic acid protein (MGP) are the only vitamin K-dependent \ proteins that have been isolated from bone. MGP is a small protein \ found in bone, dentin and cartilage. It contains five gamma-carboxyglutamic \ acid (Gla) residues (formed by post-translational modification of glutamic \ acid by vitamin K-dependent carboxylase) and a single disulphide bond. \ BGP is a 49 residue protein found in bone. It contains three Gla residues and \ a single disulphide bond. There is little similarity between these vitamin \ K-dependent bone proteins and the blood coagulation proteins, though they \ are believed to have diverged from a common ancestor [MEDLINE:88068589].\ \ \N \N \N 21026 IPR002386

Based on their primary sequences and their unique metabolic role, amicyanins are considered as a distinct subclass of cupredoxins,\ although they appear to be closely related to the plant plastocyanins [MEDLINE:94309118].

The structure of amicyanin is a -sandwich, built from nine -strands.\ The copper atom is located between three loops on one end of the molecule.\ Two of these loops contribute the copper ligands. The other three ligands are \ located on the loop between strands 8 and 9. The structure departs from\ the general cupredoxin fold in having a 21-residue N-terminal extension,\ which forms an extra -strand, and it shows significant differences\ between strands 5 and 7 (this forms a helix in azurin and an acidic\ patch in plastocyanin).

\ \ copper ion binding activity ; GO:0005507 \N electron transport ; GO:0006118 21027 IPR002387 Blue or 'type-1' copper proteins are small proteins which bind a singlecopper atom and which are characterized by an intense electronic absorption\ band near 600 nm [MEDLINE:94309118], [MEDLINE:93164266]. The most well known members of this \ class of proteins are the plant chloroplastic plastocyanins, which exchange electrons \ with cytochrome c6, and the distantly related bacterial azurins, which exchange\ electrons with cytochrome c551.\

Plastocyanin participates in electron transfer between P700 and the cytochrome b/f complex in photosystem I.

\ \ copper ion binding activity ; GO:0005507 \N electron transport ; GO:0006118 21028 IPR002388 The annexins are a family of proteins that bind to phospholipids in a calcium-dependent manner [MEDLINE:91266960]. There are eleven distinct classes of annexin, each\ of which has an amino acid sequence consisting of an N-terminal 'arm' \ followed by either four or eight copies of a conserved domain of 61 residues (only one\ of these residues, an arginine, is conserved between all copies). The\ calcium binding sites are found within the repeated domains PUB00005502. Individual\ repeats (sometimes known as endonexin folds) consist of five

Type I\ annexins inhibit phospholipase A2, either in response to inflammation, or\ following dephosphorylation by protein kinases involved in the signal\ transduction pathway. The protein may also associate with the cell\ cytoskeleton by binding to actin fibres.

\ \ \ calcium-dependent phospholipid binding activity ; GO:0005544 \N \N 21018 IPR002374 cGMP-dependent protein kinases are known to play a role in smooth muscle\ relaxation, ion fluxes in kidneys and intestines, and neuronal function.\ The predominant form of cGMP-dependent protein kinase is a dimer of\ identical 75 kDa subunits, although larger subunits of 86 and 130 kDa have\ been found [MEDLINE:89278147]. The enzyme is kept in an inactive form by the interaction\ of the catalytic domain of one subunit with the region on the other subunit\ that precedes the cGMP binding domain. Each subunit contains two cGMP-binding\ regions, found together in the sequence: binding of two molecules of cGMP\ precipitates a conformational change in the active site that allows the\ substrate to bind.\

Although cGMP- and cAMP-dependent protein kinases are similar both in\ structure and sequence around the nucleotide binding site, and in the \ method of activation and inactivation, there are some basic contrasts. The\ major difference is that all of the functional domains of the cGMP-\ dependent enzymes are found on a single polypeptide chain, whereas cAMP-\ dependent protein kinases have separate regulatory (cAMP binding) and\ catalytic chains.

\ \ ATP binding activity ; GO:0005524 \N \N 21019 IPR002375

Phosphoribosyltransferases (PRT) are enzymes that catalyze the synthesis of -n-5'-monophosphates from phosphoribosylpyrophosphate (PRPP) and an enzyme specific amine. A number of PRT's are involved in the biosynthesis of purine,\ pyrimidine, and pyridine nucleotides, or in the salvage of purines and\ pyrimidines. These enzymes include, adenine phosphoribosyltransferase (EC: 2.4.2.7) (APRT) involved in\ purine salvage,\ hypoxanthine-guanine or hypoxanthine phosphoribosyltransferase (EC: 2.4.2.8)\ (HGPRT or HPRT) involved in purine salvage,\ orotate phosphoribosyltransferase (EC: 2.4.2.10) (OPRT) involved\ in pyrimidine biosynthesis,\ amido phosphoribosyltransferase (EC: 2.4.2.14) involved in purine\ biosynthesis and xanthine-guanine phosphoribosyltransferase (EC: 2.4.2.22) (XGPRT)\ involved in purine salvage.

In the sequence of all these enzymes there is a small conserved region which\ may be involved in the enzymatic activity and/or be part of the PRPP binding\ site [MEDLINE:86301884].

\ \ \N \N \N 21020 IPR002376 A number of formyl transferases belong to this group.Methionyl-tRNA formyltransferase transfers a formyl group onto\ the amino terminus of the acyl moiety of the methionyl aminoacyl-tRNA. The formyl group appears to play a dual role in the initiator identity of N-formylmethionyl-tRNA by promoting its recognition by IF2 and by impairing its binding to EFTU-GTP.\ Formyltetrahydrofolate dehydrogenase produces formate from formyl-\ tetrahydrofolate. This is the N-terminal domain of these enzymes and is found upstream of the C-terminal domain (IPR005793).\ \

The trifunctional glycinamide ribonucleotide synthetase-aminoimidazole ribonucleotide synthetase-glycinamide ribonucleotide transformylase catalyses the second, third and fifth steps in de novo purine biosynthesis. The glycinamide ribonucleotide transformylase belongs to this group.

\ \ hydroxymethyl-, formyl- and related transferase activity ; GO:0016742 \N biosynthesis ; GO:0009058 21021 IPR002378 Breast cancer is a common malignancy, affecting 1 in 8 women. A major contributary factor in disease development lies in a positive family\ history, a correlation that is striking for early-onset breast cancer.\ Mutations in BRCA1 are believed to be responsible for 45% of inherited\ breast cancer and more than 80% of inherited breast and ovarian cancer.\

The breast cancer type I susceptibility protein\ contains an N-terminal zinc-finger domain IPR001841, but otherwise appears unrelated\ to currently known protein families. It is hoped that BRCA1 will both\ facilitate early diagnosis of breast and ovarian cancer susceptibility, and \ provide a better understanding of breast cancer biology [MEDLINE:95025896].

\ \ \N \N \N 21022 IPR002379

\ \

\ \ \ \ \ \ \

Synonym(s): ATP synthase, F(1)-ATPase

\ \

The H(+)-transporting two-sector ATPase (EC: 3.6.3.14) produce ATP from ADP in the presence of a proton gradient across the membrane. These ATPases have two components, CF(1) the catalytic core and CF(0) the membrane proton channel. CF(1) has five subunits, (3), (3), gamma (1), delta (1) and epsilon (1). CF(0) seems to have nine subunits, A, B, C, D, E, F, G, F6 and 8 ( or A6L).

The CF(0) C subunit (also called protein 9, proteolipid, or subunit III) [MEDLINE:91355362], [MEDLINE:92235868]\ is a highly hydrophobic protein of about 8 kDa which has been implicated in the\ proton-conducting activity of ATPase. Structurally the C subunit consist of two\ long terminal hydrophobic regions, which probably span the membrane, and a\ central hydrophilic region. N,N'-dicyclohexylcarbodiimide (DCCD) can bind\ covalently to the C subunit thereby abolishing the ATPase activity. DCCD binds to\ a specific glutamate or aspartate residue which is located in the middle of\ the second hydrophobic region near the C-terminal. Proteins in this family include eubacterial, plasma membrane and vacoular ATP synthases.

\ \ hydrogen-transporting two-sector ATPase activity ; GO:0003936 membrane ; GO:0016020 proton transport ; GO:0015992 21015 IPR002371 Within the bacterial flagellum, the basal-body rod, the hook, the hook- associated proteins (HAPs), and the helical filament together constitute an \ axial substructure whose elements share structural features and a common\ export pathway [MEDLINE:90294298]. \

The amino acid sequences of the hook protein and of the \ three hook-associated proteins of Salmonella typhimurium have been deduced from the DNA \ sequences of their structural genes (flgE, flgK, flgL and fliD respectively).\ These sequences have been compared with each other and with those for \ the filament protein (flagellin) and four rod proteins. The hook protein\ was found to be most similar to the distal rod protein (FlgG) and the\ proximal hook-associated protein (HAP1), which are thought to be attached to the proximal and\ distal ends of the hook, the similarities being most pronounced near the N-\ and C-termini.\ It is thought that the axial proteins may adopt amphipathic -helical\ conformations at their N- and C-termini. These regions of the filament and\ hook are believed to be responsible for quaternary interactions between\ subunits. Interaction between N- and C-terminal -helices may be\ important in the formation of the axial structures of the flagellum.\ Although consensus sequences have been noted, no consensus extends to the\ entire set of axial proteins. Thus the basis for recognition of a protein\ for export by the flagellum-specific pathway remains to be identified.

\ \ structural molecule activity ; GO:0005198 flagellar hook (sensu Bacteria) ; GO:0009424 flagella biogenesis ; GO:0009296 21016 IPR002372 Pyrrolo-quinoline quinone (PQQ) is a redox coenzyme, which serves as a cofactor for a number of enzymes (quinoproteins) and particularly for some bacterial\ dehydrogenases [MEDLINE:89372803], [MEDLINE:90020466]. A number of bacterial quinoproteins belong to this family.\ \

Enzymes in this group have repeats of a propeller.

\ \ \N \N electron transport ; GO:0006118 21017 IPR002373

Cyclic AMP (cAMP) is a key intracellular regulator of cell function in both prokaryotes and eukaryotes. One of the ways in which it regulates enzymes\ is by binding to and causing activation of cAMP-dependent protein kinases,\ which in turn activate or deactivate other enzymes by phosphorylating them [MEDLINE:89278147].

In the absence of cAMP, Protein Kinase A (PKA) exists as an equimolar tetramer of regulatory (R) and catalytic (C) subunits [MEDLINE:21592579] ]. In addition to its role as an inhibitor of the C subunit, the R subunit anchors the holoenzyme to specific intracellular locations and prevents the C subunit from entering the nucleus. All R subunits have a conserved domain structure consisting of the N-terminal dimerization domain, inhibitory region, cAMP-binding domain A and cAMP-binding domain B. R subunits interact with C subunits primarily through the inhibitory site. The cAMP-binding domains show extensive sequence similarity and bind cAMP cooperatively.

\ \

Two types of R subunit exist - Type I and Type II - which differ in molecular weight, sequence, autophosphorylation cabaility, cellular location and tissue distribution. Types I and II were further sub-divided into and subtypes, based mainly on sequence similarity. Type I does not undergo such autophosphorylation, but it can be phosphorylated slowly in vitro by cGMP-dependent \ protein kinases [MEDLINE:85023305].

\ cAMP-dependent protein kinases are activated by the binding of two cAMP\ molecules to specific areas at the C-terminus of each regulatory subunit of\ the enzyme. This causes \ in a conformational change in the structure, resulting in dissociation of\ the active catalytic domain from the regulatory domains.

\ \ cAMP-dependent protein kinase, regulator activity ; GO:0008603 cAMP-dependent protein kinase complex ; GO:0005952 protein amino acid phosphorylation ; GO:0006468 21011 IPR002366

Defensins are 2-6 kDa, cationic, microbicidal peptides active against many Gram-negative and Gram-positive bacteria, fungi, and enveloped viruses [MEDLINE:96085805], containing three pairs of intramolecular disulfide bonds [MEDLINE:22068375]. On the basis of their size and pattern of\ disulfide bonding, mammalian defensins are classified into , and theta categories. Alpha-defensins, which have been identified in humans, monkeys and several\ rodent species, are particularly abundant in neutrophils, certain macrophage populations and Paneth cells of the small intestine. Every mammalian species\ explored thus far has -defensins. In cows, as many as 13 -defensins exist in neutrophils. However, in other species, -defensins are more often produced by\ epithelial cells lining various organs (e.g. the epidermis, bronchial tree and genitourinary tract). Theta-defensins are cyclic and have so far only been identified in primate\ phagocytes.

\ \ \N \N \N 21012 IPR002367 Vertebrate endogenous opioid neuropeptides are released by post-translational proteolytic cleavage of precursor proteins. The precursors consist of the following components: a signal sequence that precedes a conserved region of about 50 residues; a variable-length region; and the sequence of the neuropeptide itself. Three types of precursor are known: preproenkephalin A \ (gene PENK), which is processed to produce 6 copies of Met-enkephalin, plus \ Leu-enkephalin; preproenkephalin B (gene PDYN), which is processed to\ produce neoendorphin, dynorphin, leumorphin, rimorphin and Leu-enkephalin; \ and prepronocipeptin (gene PNOC), whose processing produces nociceptin\ (orphanin FQ) and two other potential neuropeptides.\

\ Nociceptin (or orphanin FQ) is a natural agonist of opioid receptor-like\ receptor [MEDLINE:96323281]. The peptide is derived from the prepronociceptin precursor,\ whose gene is predominantly transcribed in the central nervous system \ (brain and spinal cord) and, weakly, in the ovary (the sole peripheral\ organ that expresses the gene) [MEDLINE:96323281]. Studies on rat and mouse nociceptin\ suggest that the protein functions not only as a neuropeptide precursor\ but also as an important component in neuronal differentiation [MEDLINE:96106851].

\ \ \N \N synaptic transmission ; GO:0007268 21013 IPR002368 The ompA outer membrane proteins in this group all contain the ompA-like transmembrane domain at the N terminus and the conserved bacterial outer membrane protein domain at the C terminus.The outer membrane protein A of Escherichia coli (OmpA), is one of the most studied proteins in this group [MEDLINE:20022422]. It has a multifunctional role. OmpA is required for the action of colicins K and L and for the stabilization of mating aggregates in conjugation. It also serves as a receptor for a number of T-even like phages and can act as a porin with low permeability that allows slow penetration of small solutes [MEDLINE:90335311].\ \ structural molecule activity ; GO:0005198 integral to membrane ; GO:0016021 \N 21014 IPR002369

Integrins are the major meazoan receptors for cell adhesion to extracellular matrix proteins and, in vertebrates, also play important roles in certain cell-cell adhesions, make transmembrane connections to the cytoskeleton and activate many intracellular signaling pathways [MEDLINE:22233426]. Integrins are - heterodimers; each subunit crosses the membrane once, with most of the polypeptide in the extracellular space, and has two short cytoplasmic domains. Most integrins recognise relatively short peptide motifs, and in general require an acidic amino acid to be present. Ligand specificity depends on both the and subunits. Many integrins are expressed on cell surfaces in an inactive state in which they do not bind ligands and do not signal. Intergrins frequently intercommunicate and the engagement of one may lead to the activation or inhibition of another.

The structure of unliganded alphaV beta3 showed the molecule to be folded, with the head bent over towards the the C termini of the legs which would normally be inserted into the membrane. The head comprises a propeller domain at the end terminus of the alphaV subunit and an I/A domain inserted into a loop on the top of the hybrid domain in the subunit. The I/A domain consists of a Rossman fold with a core of parallel sheets surrounded by ampipathic helices.

\ Integrins are important therapeutic targets in\ conditions such as atherosclerosis, thrombosis, cancer and asthma [MEDLINE:90337122].\ \

At the N-terminus of the subunit is a cysteine-containing domain\ reminiscent of that found in presenillins and semaphorins, which has hence\ been termed the PSI domain. C-terminal to the PSI domain is an A-domain,\ which has been predicted to adopt a Rossmann fold similar to that of the subunit, but with additional loops between the second and third strands [MEDLINE:97162231]. The murine gene Pactolus shares significant similarity\ with the subunit [MEDLINE:98204856], but lacks either one or both of the inserted \ loops. \ The C-terminal portion of the subunit extracellular domain contains\ an internally disulphide-bonded cysteine-rich region, while the intra-\ cellular tail contains putative sites of interaction with a variety of\ intracellular signalling and cytoskeletal proteins, such as focal adhesion\ kinase and -actinin respectively [MEDLINE:99035556].

\ \ cell adhesion receptor activity ; GO:0004895 integrin complex ; GO:0008305 cell-matrix adhesion ; GO:0007160 21008 IPR002363

\ \ \

Ribosomal protein L10 is one of the proteins from the large ribosomal subunit.\ L10 is a protein of 162 to 185 amino-acid residues. This family only contains eubacterial members. These proteins have a conserved region\ located in the N-terminal region.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 21009 IPR002364 NADP-dependent quinone oxidoreductases (EC: 1.6.5.5) are part of the zinc-containing alcohol dehydrogenase family of enzymes.

The NADP-dependent quinone oxidoreductase (EC: 1.6.5.5) is found in bacteria (gene qor), in yeast and in mammals where, in some\ species such as rodents, it has been recruited as an eye lens protein and is\ known as zeta-crystallin [MEDLINE:93252077]. The sequence of quinone oxidoreductase is\ distantly related to that other zinc-containing alcohol dehydrogenases and it\ lacks the zinc-ligand residues. The torpedo fish and mammalian synaptic vesicle\ membrane protein vat-1 is related to qor.

\ \ zinc ion binding activity ; GO:0008270 \N \N 21010 IPR002365 Several enzymes catalyze mechanistically related reactions which involvethe highly complex cyclic rearrangement of squalene or its 2,3 oxide.\ Lanosterol synthase (EC: 5.4.99.7) (oxidosqualene--lanosterol cyclase) catalyzes the cyclization of (S)-2,3-epoxysqualene to lanosterol, the\ initial precursor of cholesterol, steroid hormones and vitamin D in\ vertebrates and of ergosterol in fungi (gene ERG7).\ Cycloartenol synthase (EC: 5.4.99.8) (2,3-epoxysqualene--cycloartenol\ cyclase), is a plant enzyme that catalyzes the cyclization of (S)-2,3-epoxysqualene to cycloartenol, and hopene synthase (EC: 5.4.99.-) (squalene--hopene cyclase), is a bacterial\ enzyme that catalyzes the cyclization of squalene into hopene, a key step\ in hopanoid (triterpenoid) metabolism.\ These enzymes are evolutionary related [MEDLINE:94089686] proteins of about 70 to 85 kD.\ \ lyase activity ; GO:0016829 \N metabolism ; GO:0008152 21006 IPR002361 The antenna complexes of photosynthetic bacteria function as light-harvesting systems that absorb light and transfer the excitation energyto the reaction centers. The antenna complexes usually comprise 2\ polypeptides (

- and

-chains), 2-3 bacteriochlorophyll molecules\ and some carotenoids [MEDLINE:92249336], [MEDLINE:93094968].\ The

- and

-chains are small proteins of 40-70 residues. Each has \ an N-terminal hydrophilic cytoplasmic domain, a single transmembrane (TM)\ region, and a small C-terminal hydrophilic periplasmic domain. In both\ chains, the TM domain houses a conserved His residue, presumed to be\ involved in binding the magnesium atom of a bacteriochlorophyll group.\ The

-chains are characterised by a further histidine at the C-terminal\ extremity of the cytoplasmic domain, which is also thought to be involved\ in bacteriochlorophyll binding.\ \ lipoate-protein ligase B activity ; GO:0016978 membrane ; GO:0016020 energy pathways ; GO:0006091 21007 IPR002362 The antenna complexes of photosynthetic bacteria function as light-harvesting systems that absorb light and transfer the excitation energyto the reaction centers. The antenna complexes usually comprise 2\ polypeptides (

- and

-chains), 2-3 bacteriochlorophyll molecules\ and some carotenoids [MEDLINE:92249336], [MEDLINE:93094968].\ The

- and

Involucrin [MEDLINE:93061995], [MEDLINE:94104476] is a highly reactive, soluble, transglutaminase substrate protein present in keratinocytes of epidermis and other stratified squamous epithelia. Involucrin first appears in the cell cytosol, but ultimately becomes cross-linked to membrane proteins by transglutaminase\ where it helps in the formation of an insoluble envelope beneath the plasma\ membrane functioning as a glutamyl\ donor during assembly of the cornified envelope.

Structurally involucrin consists of a conserved region of about 75 amino acid\ residues followed by two extremely variable length segments that contain\ glutamine-rich tandem repeats. The glutamine residues in the tandem repeats\ are the substrate for the tranglutaminase in the cross-linking reaction. The\ total size of the protein varies from 285 residues (in dog) to 835 residues\ (in orangutan). The signature pattern for involucrin corresponds to the N-terminal extremity\ of the protein.

\ \ \N \N \N 21004 IPR002359

\ \ \

Ribosomal protein L6 is one of the proteins from the large ribosomal subunit.\ In Escherichia coli, L6 is known to bind directly to the 23S rRNA and is\ located at the aminoacyl-tRNA binding site of the peptidyltransferase center.\ It belongs to a family of ribosomal proteins which, on the basis of sequence\ similarities [MEDLINE:91033042], [MEDLINE:93365023], [MEDLINE:94085364], PUB00005071, groups eubacterial; algal chloroplast; cyanelle; archaebacterial and Marchantia polymorpha mitochondrial L6; yeast mitochondrial YmL6 (gene MRPL6); and mammalian; Drosophila melanogaster; plant and yeast L9. This signature finds the archaebacterial L6 proteins, and L9 proteins, L6 proteins from other organisms are found in IPR002358.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 21003 IPR002358

\ \ \

Ribosomal protein L6 is one of the proteins from the large ribosomal subunit.\ In Escherichia coli, L6 is known to bind directly to the 23S rRNA and is\ located at the aminoacyl-tRNA binding site of the peptidyltransferase center.\ It belongs to a family of ribosomal proteins which, on the basis of sequence\ similarities [MEDLINE:91033042], [MEDLINE:93365023], [MEDLINE:94085364], PUB00005071, groups eubacterial; algal chloroplast; cyanelle; archaebacterial and Marchantia polymorpha mitochondrial L6; yeast mitochondrial YmL6 (gene MRPL6); and mammalian; Drosophila melanogaster; plant and yeast L9. This signature finds the L6 proteins from most organisms, while plant L6 and the L9 proteins are found in IPR002359.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 21001 IPR002354 Cytokines are protein messengers that carry information from cell to cell[MEDLINE:94202209]. Interleukin is one such molecule, and participates in several B-cell \ activation processes: e.g., it enhances production and secretion of IgG1\ and IgE [MEDLINE:86177547]; it induces expression of class II major histocompatability \ complex (MHC) molecules on resting B-cells; and it regulates expression of\ the low affinity Fc receptor for IgE on lymphocytes and monocytes.\ Interleukin-4 (IL4) has a compact, globular fold (similar to other\ cytokines), stabilised by 3 disulphide bonds [MEDLINE:91129220]. One half of the structure\ is dominated by a 4

-helix bundle with a left-handed twist [MEDLINE:93015916]. The\ helices are anti-parallel, with 2 overhand connections, which fall into a\ 2-stranded anti-parallel

-sheet [MEDLINE:93015916].\ \ growth factor activity ; GO:0008083 extracellular ; GO:0005576 immune response ; GO:0006955 21002 IPR002355

Multicopper oxidases [MEDLINE:90126844], [MEDLINE:91138766] are enzymes that possess three spectroscopically different copper centers. These centers are called type 1 (or blue), type 2 (or normal) and type 3 (or coupled binuclear). The enzymes that belong to\ this family include laccase (EC: 1.10.3.2) (urishiol oxidase), an enzyme found in fungi and\ plants, which oxidizes many different types of phenols and diamines; ascorbate oxidase (EC: 1.10.3.3), a higher plant enzyme; ceruloplasmin (EC: 1.16.3.1) (ferroxidase), a protein found in the serum of\ mammals and birds, which oxidizes a great variety of inorganic and organic\ substances. Structurally ceruloplasmin exhibits internal sequence homology,\ and seem to have evolved from the triplication of a copper-binding domain\ similar to that found in laccase and ascorbate oxidase.\ In addition to the above enzymes there are a number of proteins which, on the\ basis of sequence similarities, can be said to belong to this family. These\ proteins include copper resistance protein A (copA) from a plasmid in Pseudomonas syringae; blood coagulation factors V (Fa V) and VIII (Fa VIII);\ yeast FET3 [MEDLINE:94123346], which is required for ferrous iron uptake; and yeast hypothetical protein YFL041w and SpAC1F7.08, the fission yeast\ homolog. Factors V and VIII act as cofactors in blood coagulation and are structurally\ similar [MEDLINE:89024593]. Their sequence consists of a triplicated A domain, a B domain and\ a duplicated C domain; in the following order: A-A-B-A-C-C. The A-type domain\ is related to the multicopper oxidases.

\ \ copper ion binding activity ; GO:0005507 \N \N 21000 IPR002353 Marine teleosts from polar oceans can be protected from freezing in icysea-water by serum antifreeze proteins (AFPs) or glycoproteins (AFGPs) [MEDLINE:95315870].\ These function by binding to, and preventing the growth of, ice crystals\ within the fish. Despite functional similarity, the proteins are\ structurally diverse and include glycosylated and at least 3 non-glycosylated forms: the AFGP of nototheniids and cod are polymers of a\ tripeptide repeat, Ala-Ala-Thr, with a disaccharide attached to the\ threonine residue; type I AFPs are Ala-rich,

-helical peptides\ found in flounder and sculpin; type II AFPs of sea-raven, smelt and\ herring are Cys-rich proteins; and type III AFPs, found in eel pouts,\ are rich in

-structure. Although no direct structural information is available for type II AFPs,\ their sequences are similar to the carbohydrate recognition domain (CRD)\ of Ca²⁺-dependent lectins. This domain is present in a superfamily of\ proteins that bind sugars specifically through contact with a calcium\ ion. The extent of similarity within the superfamily is confined to \ short motifs and single amino acids at intervals throughout the protein.\ \ \N \N \N 20999 IPR002352 Eosinophil granule major basic protein (MBP) is a low molecular weight cationic protein present in the crystalloid core of the eosinophil granule\ [MEDLINE:88315054]. It is a potent toxin for helminths and mammalian cells, and may have\ important roles in allergic and inflammatory reactions, it can release\ histamine from mast cells and damage epithelial cells of bronchial tubes.\ MBP is also involved in antiparasitic defense mechanisms and immune hypersensitivity reactions. The protein is a single arginine-rich polypeptide\ [MEDLINE:90215311], its pro-portion being rich in glutamic and aspartic acids. It has been\ suggested that the protein is translated as a nontoxic precursor that\ protects the eosinophil from damage while it is processed through the endoplasmic reticulum to its sequestered site in the granule core toxic MBP [MEDLINE:89010545].\ The sequence of MBP has been shown to contain a C-type lectin (CTL) domain \ [MEDLINE:92227954]. CTL domains are 110-130 residue motifs that appear to function as \ calcium-dependent carbohydrate-recognition domains [MEDLINE:88315054], [MEDLINE:90215311], [MEDLINE:89010545].\ \ toxin activity ; GO:0015070 \N immune response ; GO:0006955 20998 IPR002351

Nitrophorins are haemoproteins found in saliva of blood-feeding insects [MEDLINE:99193898], [MEDLINE:20513975]. Saliva of the blood-sucking bug Rhodnius prolixus contains four homologous nitrophorins, designated NP1 to NP4 in order of their relative abundance in the glands [MEDLINE:95238361]. As isolated, nitrophorins contain nitric oxide (�NO) ligated to the ferric (FeIII) haem iron. Histamine, which is releasedby the host in response to tissue damage, is another nitrophorin ligand. Nitrophorins transport �NO to the feeding site.\ Dilution, binding of histamine and increase in pH (from pH ~5 in salivary gland to pH ~7.4 in the host tissue) facilitate the release of �NO into the tissue where it induces vasodilatation.

\ \

The salivary nitrophorin from the hemipteran Cimex lectularius has no sequence similarity to Rhodnius prolixus nitrophorins. It is suggested that the two classes of insect nitrophorins have arisen as a product of the convergent\ evolution [MEDLINE:99007203].

\ \

3-D structures of several nitrophorin complexes are known [MEDLINE:20513975]. The nitrophorin structures reveal lipocalin-like\ eight-stranded -barrel, three -helices and two disulphide bonds, with haem inserted into one end of the barrel. Members of the lipocalin family are known to bind a variety of small hydrophobic ligands, including biliverdin, in a similar fashion (see [MEDLINE:96358478] for review). The haem iron is ligated to His59. The position of His59 is restrained through water-mediated\ hydrogen bond to the carboxylate of Asp70. The His59-Fe bond is bent ~15� out of the imidazole plane. Asp70 forms an unusual hydrogen bond with one of the haem propionates, suggesting the residue has an altered pKa. In NP1-histamine\ structure (PDB 1NP1), the planes of His59 and histamine imidazole rings lie in an arrangement almost identical to that found in oxidised cytochrome b5.

\ \ transporter activity ; GO:0005215 \N transport ; GO:0006810 20996 IPR002349

Synonym(s): WWP domain

\ \

The WW domain, a short conserved region found in a number of disparate\ proteins, is characterised by 2 conserved Trp residues and a conserved Pro\ (hence its alternative name, WWP) [MEDLINE:95149368]. Among the proteins known to contain\ WW domains is dystrophin, the product encoded by the gene responsible for\ Duchenne muscular dystrophy. The domain contains around 35-40 residues,\ and may be repeated up to 4 times in some sequences. It appears to bind\ proteins that contain characteristic proline motifs ([AP]-P-P-[AP]-Y),\ and resembles, to an extent, the SH3 domains. It is often associated with\ other domains that typify proteins involved in signal transduction.

\ \ \N \N \N 20997 IPR002350

Kazal inhibitors, which inhibit a number of serine proteases (such astrypsin and elastase), belong to family of proteins that includes\ pancreatic secretory trypsin inhibitor; avian ovomucoid; acrosin inhibitor;\ and elastase inhibitor. These proteins contain between 1 and 7 Kazal-type\ inhibitor repeats [MEDLINE:84138661], [MEDLINE:87157615].

The structure of the Kazal repeat includes a large quantity of extended chain, 2 short -helices and a 3-stranded anti-parallel sheet [MEDLINE:84138661].The inhibitor makes 11 contacts with its enzyme substrate: unusually, 8 of these important residues are hypervariable [MEDLINE:87157615]. Altering the enzyme-contact residues, and especially that of the active site bond, affects the the strength of inhibition and specificity of the inhibitor for particular\ serine proteases [MEDLINE:87157615], [MEDLINE:82231907]. The presence of this Pfam domain is usually indicative of serine protease inhibitors, however, kazal-like domains are also seen in the\ extracellular part of agrins which are not known to be protease inhibitors.

\ \ \N \N \N 20992 IPR002345 The lipocalins are a diverse, interesting, yet poorly understood family of proteins composed, in the main, of extracellular ligand-binding proteins\ displaying high specificity for small hydrophobic molecules [MEDLINE:85168267]. Functions\ of these proteins include transport of nutrients, control of cell regulation, pheromone transport, cryptic colouration, and the enzymatic synthesis\ of prostaglandins.\ The crystal structures of several lipocalins have been solved and show a \ novel 8-stranded anti-parallel

Oxidoreductases, that also bind molybdopterin, have essentially no similarity outside this common domain. They include aldehyde oxidase (EC: 1.2.3.1), that converts an aldehyde and water to an acid and hydrogen peroxide, and xanthine dehydrogenase (EC: 1.1.1.204), that converts xanthine to urate. These enzymes require molybdopterin and FAD as cofactors and have and two 2FE-2S clusters. Another enzyme that contains this domain is the Pseudomonas thermocarboxydovorans carbon monoxide oxygenase.

\ \ oxidoreductase activity ; GO:0016491 \N electron transport ; GO:0006118 20994 IPR002347 Glucose dehydrogenase catalyses the oxidation of D-glucose without priorphosphorylation to D-

-gluconolactone using NAD or NADP as a coenzyme.\ The enzyme is a tetrameric protein, each of the 4 identical subunits\ containing 262 amino acid residues. This family is a subset of a more general family of short-chain dehydrogenases and\ reductases.\ A match to this extension indicates that the protein is not\ an alcohol dehydrogenase, but another type of dehydrogenase\ or reductase.\ \ \ oxidoreductase activity ; GO:0016491 \N metabolism ; GO:0008152 20995 IPR002348 The interleukin-1 (IL1) and heparin-binding growth factor (HBGF) familiesshare low sequence similarity (about 25% [MEDLINE:91195368]) but have very similar\ structures. Coupled with the Kunitz-type soybean trypsin inhibitors (STI),\ they form a structural superfamily. Despite their structural correspondence, however, they show no sequence similarity to the STI family.\ \ The crystal structures of interleukin-1

and HBGF1 have been solved, \ showing both families to have the same 12-stranded

-sheet structure \ [MEDLINE:92148835]; the

-sheets are arranged in 3 similar lobes around a central \ axis, 6 strands forming an anti-parallel

-barrel [MEDLINE:91195367], [MEDLINE:86070224]. The

-sheets \ are generally well preserved and the crystal structures superimpose in\ these areas. The intervening loops are less well conserved - the loop \ between

-strands 6 and 7 is slightly longer in interleukin-1

.\ \ growth factor activity ; GO:0008083 \N \N 20991 IPR002344 The La protein is a 47 kD polypeptide that often acts as an autoantigenin systemic lupus erythematosus and Sjogren's syndrome patients [MEDLINE:90301075]. A\ vital property of the protein is its association with the U-rich termini\ of newly-synthesised RNA polymerase III transcripts. A 32 kD yeast\ protein shows similarity to the N-termini of vertebrate La proteins, \ and also preferentially binds U-rich RNAs [MEDLINE:95097387].\ \ RNA binding activity ; GO:0003723 nucleus ; GO:0005634 \N 20989 IPR002341

The heat shock factor (HSF) type and ETS-type DNA binding domainsare distantly related, as shown by profile-analysis. This similarity\ is supported by the 3D-structures of the HSF-domain [MEDLINE:94112547] and of the ETS\ domain [MEDLINE:96176767], which show that both domains belong to the class of\ winged-helix DNA binding domains. Other members of this structural class\ are the forkhead domain IPR001766 and the catabolite activator protein\ domain.

\ \ DNA binding activity ; GO:0003677 nucleus ; GO:0005634 \N 20990 IPR002343 Many eukaryotic proteins that are either known or thought to bind single-stranded RNA contain one or more copies of a putative RNA-binding domainof about 90 amino acids [MEDLINE:89252819], [MEDLINE:89223025]. This region has been found in, for example,\ heterogeneous nuclear ribonucleoproteins, small nuclear ribonucleoproteins,\ pre-RNA and mRNA associated proteins, Drosophila sex determination and elav\ proteins, human paraneoplastic encephalomyelitis antigen HuD, and many\ others.\ The structure of an RNA-binding domain of Drosophila Sex-lethal (Sxl) \ protein has been determined using multi-dimensional hetero-nuclear NMR [MEDLINE:95034815].\ Sxl contains two RNP consensus-type RNA-binding domains (RBDs) - the\ determined structure represents the second of these (RBD-2) [MEDLINE:95034815]. The\ calculated intermediate-resolution family of structures exhibits the

/beta-

tertiary fold found in other RBD-containing\ proteins [MEDLINE:95034815].\ \ RNA binding activity ; GO:0003723 \N \N 20988 IPR002340 Globins are haem-containing proteins involved in dioxygen binding and/or transport. At present, more than 700 globin sequences are known [MEDLINE:96117669].\ It has been proposed that all globins have evolved from a family of \ ancestral, approximately 17 kD haemoproteins that displayed the globin \ fold and functioned as redox proteins [MEDLINE:96164528]. The globin superfamily includes\ vertebrate haemoglobins (Hb); vertebrate myoglobins (Mb); invertebrate \ globins; plant leghaemoglobins; and bacterial flavohaemoglobins. \ The function of haemoglobins (Hb) is transport of dioxygen in blood plasma.\ Hb binds O(2) in the reduced [Fe(II)] state. The Hb molecule exists as a\ tetramer, typically of two

- and two

-globin chains, which form \ a well-defined quaternary structure. Each monomer binds iron protoporphyrin\ IX (haem). \

The 3D structures of a great number of vertebrate Hbs in various states\ are known. The protein is largely -helical, eight conserved helices \ (A to H) providing the scaffold for a well-defined haem-binding pocket\ (Hb subunits lack helix D [MEDLINE:95322372]). The imidazole ring of the 'proximal'\ His residue provides the fifth haem iron ligand; the other axial haem iron \ position remains essentially free for O(2) coordination. Conserved 'distal'\ His and Val residues block an unhindered access to the sixth coordination \ site so that a controlled binding of small molecules may result only as a \ consequence of side-chain dynamics of the protein. O(2) binding results\ in a transition from high-spin to low-spin iron, with accompanying changes \ in the Fe-N bond lengths and coordination geometry. In Hb, these subtle \ changes lead to the well-known cooperative effect. At the quaternary \ structure level, O(2) binding induces relative reorientation of the \ [-1, -1] and [-2, -2] dimers. \ It has been hypothesised that the embryonic -haemoglobin family\ diverged considerably earlier than the -haemoglobin line [MEDLINE:81006979]. This\ is reflected in a greater variability amongst sequences, such that\ two distinct sub-groups may be distinguished; these have been designated\ zeta and pi. This family contains the zeta haemoglobins.

\ \ \N hemoglobin complex ; GO:0005833 oxygen transport ; GO:0015671 20987 IPR002339 Globins are haem-containing proteins involved in dioxygen binding and/or transport. At present, more than 700 globin sequences are known [MEDLINE:96117669].\ It has been proposed that all globins have evolved from a family of \ ancestral, approximately 17 kD haemoproteins that displayed the globin \ fold and functioned as redox proteins [MEDLINE:96164528]. The globin superfamily includes\ vertebrate haemoglobins (Hb); vertebrate myoglobins (Mb); invertebrate \ globins; plant leghaemoglobins; and bacterial flavohaemoglobins. \ The function of haemoglobins (Hb) is transport of dioxygen in blood plasma.\ Hb binds O(2) in the reduced [Fe(II)] state. The Hb molecule exists as a\ tetramer, typically of two

- and two

-globin chains, which form \ a well-defined quaternary structure. Each monomer binds iron protoporphyrin\ IX (haem). \

\ \ \N hemoglobin complex ; GO:0005833 oxygen transport ; GO:0015671 20986 IPR002338 Globins are haem-containing proteins involved in dioxygen binding and/or transport. At present, more than 700 globin sequences are known [MEDLINE:96117669].\ It has been proposed that all globins have evolved from a family of \ ancestral, approximately 17 kD haemoproteins that displayed the globin \ fold and functioned as redox proteins [MEDLINE:96164528]. The globin superfamily includes\ vertebrate haemoglobins (Hb); vertebrate myoglobins (Mb); invertebrate \ globins; plant leghaemoglobins; and bacterial flavohaemoglobins. \ The function of haemoglobins (Hb) is transport of dioxygen in blood plasma.\ Hb binds O(2) in the reduced [Fe(II)] state. The Hb molecule exists as a\ tetramer, typically of two

- and two

-globin chains, which form \ a well-defined quaternary structure. Each monomer binds iron protoporphyrin\ IX (haem). \

The 3D structures of a great number of vertebrate Hbs in various states\ are known. The protein is largely -helical, eight conserved helices \ (A to H) providing the scaffold for a well-defined haem-binding pocket\ (Hb subunits lack helix D [MEDLINE:95322372]). The imidazole ring of the 'proximal'\ His residue provides the fifth haem iron ligand; the other axial haem iron \ position remains essentially free for O(2) coordination. Conserved 'distal'\ His and Val residues block an unhindered access to the sixth coordination \ site so that a controlled binding of small molecules may result only as a \ consequence of side-chain dynamics of the protein. O(2) binding results\ in a transition from high-spin to low-spin iron, with accompanying changes \ in the Fe-N bond lengths and coordination geometry. In Hb, these subtle \ changes lead to the well-known cooperative effect. At the quaternary \ structure level, O(2) binding induces relative reorientation of the \ [-1, -1] and [-2, -2] dimers. \ Alpha- and -haemoglobins are highly similar; the sequence of -\ differs in length from that of -haemoglobin on average by 5 residues\ (actual lengths 141 and 146 residues respectively). The major structural\ difference between - and -forms is that -haemoglobins contain\ an -helix (the D helix) that is missing in -forms.

\ \ \N hemoglobin complex ; GO:0005833 oxygen transport ; GO:0015671 20985 IPR002337 Globins are haem-containing proteins involved in dioxygen binding and/or transport. At present, more than 700 globin sequences are known [MEDLINE:96117669].\ It has been proposed that all globins have evolved from a family of \ ancestral, approximately 17 kD haemoproteins that displayed the globin \ fold and functioned as redox proteins [MEDLINE:96164528]. The globin superfamily includes\ vertebrate haemoglobins (Hb); vertebrate myoglobins (Mb); invertebrate \ globins; plant leghaemoglobins; and bacterial flavohaemoglobins. \ The function of vertebrate haemoglobins (Hb) is transport of dioxygen in\ blood plasma. Hb binds O(2) in the reduced [Fe(II)] state. The Hb molecule \ exists as a tetramer, typically of two

- and two

-globin chains, \ which form a well-defined quaternary structure. Each monomer binds iron \ protoporphyrin IX (haem). \

The 3D structures of a great number of haemoglobins in various states\ are known. The protein is largely -helical, eight conserved helices \ (A to H) providing the scaffold for a well-defined haem-binding pocket\ (Hb subunits lack helix D [MEDLINE:95322372]). The imidazole ring of the 'proximal'\ His residue provides the fifth haem iron ligand; the other axial haem iron \ position remains essentially free for O(2) coordination. Conserved 'distal'\ His and Val residues block an unhindered access to the sixth coordination \ site so that a controlled binding of small molecules may result only as a \ consequence of side-chain dynamics of the protein. O(2) binding results\ in a transition from high-spin to low-spin iron, with accompanying changes \ in the Fe-N bond lengths and coordination geometry. In Hb, these subtle \ changes lead to the well-known cooperative effect. On the quaternary \ structure level, O(2) binding induces relative reorientation of the \ [-1, -1] and [-2, -2] dimers. \ Alpha- and -haemoglobins are highly similar; the sequence of -\ differs in length from that of -haemoglobin on average by 5 residues\ (actual lengths 146 and 141 residues respectively). The major structural\ difference between - and -forms is that -haemoglobins contain\ an -helix (the D helix) that is missing in -forms.

\ \ \ \N hemoglobin complex ; GO:0005833 oxygen transport ; GO:0015671 20982 IPR002334

The allergens in this family include allergens with the following designations: Dol m 1, Ves m 1 and Ves v 1.

\ \ phospholipase A1 activity ; GO:0008970 \N lipid metabolism ; GO:0006629 20983 IPR002335 Globins are haem-containing proteins involved in dioxygen binding and/or transport PUB00006183, PUB00006183. At present, more than 700 globin sequences are known [MEDLINE:96117669].\ It has been proposed that all globins have evolved from a family of \ ancestral, approximately 17 kD haemoproteins that displayed the globin \ fold and functioned as redox proteins [MEDLINE:96164528]. The globin superfamily includes\ vertebrate haemoglobins (Hb); vertebrate myoglobins (Mb); invertebrate \ globins; plant leghaemoglobins; and bacterial flavohaemoglobins. \ The function of vertebrate myoglobin (Mb) is storage of dioxygen in tissues.\ Mb binds O(2) in the reduced [Fe(II)] state. The Mb molecule exists as a\ monomer that binds iron protoporphyrin IX (haem). \ The 3D structures of a great number of vertebrate Mbs in various states\ are known. The protein is largely

-helical, eight conserved helices \ (A to H) providing the scaffold for a well-defined haem-binding pocket. The\ imidazole ring of the 'proximal' His residue provides the fifth haem iron \ ligand; the other axial haem iron position remains essentially free for \ O(2) coordination. Conserved 'distal' His and Val residues block an \ unhindered access to the sixth coordination site so that a controlled \ binding of small molecules may result only as a consequence of side-chain \ dynamics of the protein PUB00006184. O(2) binding results in a transition from \ high-spin to low-spin iron, with accompanying changes in the Fe-N bond \ lengths and coordination geometry PUB00006184.\ \ \ \N \N oxygen transport ; GO:0015671 20984 IPR002336 Globins are haem-containing proteins involved in dioxygen binding and/or transport PUB00006183, PUB00006183. At present, more than 700 globin sequences are known [MEDLINE:96117669].\ It has been proposed that all globins have evolved from a family of \ ancestral, approximately 17 kDa haemoproteins that displayed the globin \ fold and functioned as redox proteins [MEDLINE:96164528]. The globin superfamily includes\ vertebrate haemoglobins (Hb); vertebrate myoglobins (Mb); invertebrate \ globins; plant leghaemoglobins; and bacterial flavohaemoglobins. \ The function of haemoglobins (Hbs) is transport of dioxygen in blood plasma.\ Erythrocruorins (Ec) are extracellular Hbs found freely dissolved in the \ blood of annelids and arthropods. Ec molecules exist as aggregates of up to\ 200 small globin-like subunits, some of which are disulphide-bonded and not\ all of which contain haem [MEDLINE:86029053]. Nematodes (e.g., Ascaris) possess an octa-\ meric Hb, each subunit containing two globin-like domains. Ascaris Hb binds\ oxygen four orders of magnitude more tightly than does human Hb [MEDLINE:95267047]. The\ brine shrimp Artemia has evolved the longest known concatenation of globin\ domains: each subunit contains 9 globin-like domains, connected by linking\ peptides [MEDLINE:94365847]. Artemia possess three types of dimeric haemoglobins: HbI\ (

+alpha); HbII (

); and HbIII (

+beta). \ The 3D structures of a number of Ecs are known. The protein is largely

-helical, eight conserved helices (A to H) providing the scaffold for \ a well-defined haem-binding pocket. The imidazole ring of the 'proximal' His \ residue provides the fifth haem iron ligand; the other axial haem iron \ position remains essentially free for O(2) coordination. Many Ecs lack\ the 'distal' His and Val residues that are conserved in vertebrate globins.\ \ \N hemoglobin complex ; GO:0005833 oxygen transport ; GO:0015671 20981 IPR002333 Triglyceride lipases (EC: 3.1.1.3) are lipolytic enzymes that hydrolyseester linkages of triglycerides [MEDLINE:89150316]. Lipases are widely distributed in\ animals, plants and prokaryotes. At least three tissue-specific isozymes\ exist in higher vertebrates: pancreatic, hepatic and gastric/lingual. These\ lipases are closely related to each other and to lipoprotein lipase\ (EC: 3.1.1.34), which hydrolyses triglycerides of chylomicrons and very\ low density lipoproteins (VLDL) [MEDLINE:89137092].\ Familial human hepatic lipase deficiency is a rare recessive disorder that\ results from mutation in position 405 of the mature protein. The disease is\ characterised by premature atherosclerosis and abnormal circulating \ lipoproteins [MEDLINE:93250827].\ The structure of the human hepatic triglyceride lipase gene has been\ determined [MEDLINE:90105435]. The hepatic lipase gene spans ~60 kb, and contains 8 introns\ and 9 exons: exon 1 encodes the signal peptide; exon 4, a region that binds\ to the lipoprotein substrate; exon 5, an evolutionarily highly-conserved \ region of potential catalytic function; and exons 6 and 9 encode sequences\ rich in basic amino acids, thought to be important in anchoring the enzyme\ to the endothelial surface by interacting with acidic domains of surface\ glycosaminoglycans [MEDLINE:90105435]. The human lipoprotein lipase gene has an identical\ exon-intron organisation, with analogous structural domains, supporting the\ common evolutionary origin of these two lipolytic enzymes [MEDLINE:87149101].\ \ triacylglycerol lipase activity ; GO:0004806 \N lipid metabolism ; GO:0006629 20980 IPR002332 The P-II protein (gene glnB) is a bacterial protein important for the control of glutamine synthetase [MEDLINE:90089474], [MEDLINE:89201233], [MEDLINE:95171116]. In nitrogen-limiting conditions, when the\ ratio of glutamine to 2-ketoglutarate decreases, P-II is uridylylated on a\ tyrosine residue to form P-II-UMP. P-II-UMP allows the deadenylation of\ glutamine synthetase (GS), thus activating the enzyme. Conversely, in nitrogen\ excess, P-II-UMP is deuridylated and then promotes the adenylation of GS. P-II\ also indirectly controls the transcription of the GS gene (glnA) by preventing\ NR-II (ntrB) to phosphorylate NR-I (ntrC) which is the transcriptional\ activator of glnA. Once P-II is uridylylated, these events are reversed.\ \ P-II is a protein of about 110 amino acid residues extremely well conserved.\ The tyrosine which is urydylated is located in the central part of the\ protein. In cyanobacteria, P-II seems to be phosphorylated on a serine residue rather\ than being urydylated.\ In the red alga, Porphyra purpurea, there is a glnB homolog encoded in the chloroplast genome.\ Other proteins highly similar to glnB include Bacillus subtilis protein nrgB [MEDLINE:94110214]; and E. coli hypothetical protein ybaI [MEDLINE:94124004].\ \ \N \N \N 20979 IPR002331 Triglyceride lipases (EC: 3.1.1.3) are lipolytic enzymes that hydrolyseester linkages of triglycerides [MEDLINE:89150316]. Lipases are widely distributed in\ animals, plants and prokaryotes. At least three tissue-specific isozymes\ exist in higher vertebrates: pancreatic, hepatic and gastric/lingual. These\ lipases are closely related to each other and to lipoprotein lipase\ (EC: 3.1.1.34), which hydrolyses triglycerides of chylomicrons and very\ low density lipoproteins (VLDL) [MEDLINE:89137092].\ Pancreatic lipase (triacylglycerol acylhydrolase, EC: 3.1.1.3) plays a key\ role in dietary fat absorption by hydrolysing dietary long chain triacyl-glycerol to free fatty acids and monoacylglycerols in the intestinal lumen\ [MEDLINE:90062115]. The activity of lipase is stimulated by colipase in the presence of\ bile acids.\

The 3D structure of human pancreatic lipase has been determined by X-ray\ crystallography [MEDLINE:90158821]. The enzyme is a single-chain glycoprotein of 449 amino \ acids. Structural results suggest that Ser 152 is the nucleophilic residue\ essential for catalysis [MEDLINE:90158821]. The residue is located in the N-terminal domain\ at the C-terminal edge of a doubly-wound parallel -sheet, and forms part\ of an Asp-His-Ser triad that is chemically analogous to, but structurally\ different from, that of the serine proteases [MEDLINE:90158821]. The putative hydrolytic\ site is covered by a surface loop, and is thus inaccessible to solvent. \ It is thought that interfacial activation may involve a reorientation of\ this flap, not only in pancreatic lipases but also in the related hepatic\ and lipoprotein lipases [MEDLINE:90158821].

\ \ triacylglycerol lipase activity ; GO:0004806 \N lipid metabolism ; GO:0006629 20978 IPR002330 Lipoprotein lipase (LPL) is a key enzyme of lipid metabolism that hydrolysestriglycerides, providing free fatty acids for cells and affecting the \ maturation of circulating lipoproteins [MEDLINE:87149101]. The enzyme is thought to play\ a role in the development of obesity and atherosclerosis [MEDLINE:87149101]. Human LPL\ contains 448 amino acids; sequence comparison indicates that human LPL,\ hepatic lipase, and pancreatic lipase are members of a gene family [MEDLINE:87149101]. \ Defects in LPL are a cause of familial chylomicronemia syndrome (or type I\ hyperlipoproteinemia) and also of a form of deficiency characterised by\ hypertriglyceridemia. Familial chylomicronemia is a recessive disorder\ usually manifesting in childhood. On a normal diet, patients often present\ with abdominal pain, hepatosplenomegaly, lipemia retinalis, eruptive\ xanthomata, and massive hypertriglyceridemia, sometimes complicated with\ acute pancreatitis.\ LPL and pancreatic lipase share ~30% sequence identity, suggesting a similar\ tertiary fold [MEDLINE:94140900]. Molecular models of LPL have been constructed, based on \ X-ray crystal structures of pancreatic lipase [MEDLINE:93123894]. These models allowed the\ authors to propose hypotheses on the structural determinants of LPL that are\ responsible for heparin binding, dimer formation, and phospholipase activity.\ \ lipoprotein lipase activity ; GO:0004465 \N lipid metabolism ; GO:0006629 20977 IPR002328 Alcohol dehydrogenase (EC: 1.1.1.1) (ADH) catalyzes the reversible oxidation ofethanol to acetaldehyde with the concomitant reduction of NAD:\

\
Ethanol + NAD = Acetaldehyde + NADH\

\ Currently three structurally and catalytically different types of alcohol\ dehydrogenases are known:\

Zinc-containing 'long-chain' alcohol dehydrogenases.
Insect-type, or 'short-chain' alcohol dehydrogenases.
Iron-containing alcohol dehydrogenases.

\ Zinc-containing ADH's [MEDLINE:87304248], [MEDLINE:92277668] are dimeric or tetrameric enzymes that bind two\ atoms of zinc per subunit. One of the zinc atom is essential for catalytic\ activity while the other is not. Both zinc atoms are coordinated by either\ cysteine or histidine residues; the catalytic zinc is coordinated by two\ cysteines and one histidine. Zinc-containing ADH's are found in bacteria,\ mammals, plants, and in fungi. In most species there are more than one isozyme\ (for example, human have at least six isozymes, yeast have three, etc.). \

A\ number of other zinc-dependent dehydrogenases are closely related to zinc\ ADH [MEDLINE:93279386] and are included in this family, including\ xylitol dehydrogenase (EC: 1.1.1.9); sorbitol dehydrogenase (EC: 1.1.1.14);\ aryl-alcohol dehydrogenase (EC: 1.1.1.90); threonine 3-dehydrogenase (EC: 1.1.1.103); cinnamyl-alcohol dehydrogenase (EC: 1.1.1.195) (CAD);\ galactitol-1-phosphate dehydrogenase (EC: 1.1.1.251); and Pseudomonas\ putida 5-exo-alcohol dehydrogenase (EC: 1.1.1.-).

\ \ zinc ion binding activity ; GO:0008270 \N \N 20975 IPR002326 Cytochrome bc1 complex (ubiquinol:ferricytochrome c oxidoreductase) is found in mitochondria, photosynthetic bacteria and other prokaryotes PUB00005919.\ It is minimally composed of three subunits: cytochrome b, carrying a low-\ and a high-potential haem group; cytochrome c1 (cyt c1); and a high-potential Rieske iron-sulphur protein. The general function of the complex \ is electron transfer between two mobile redox carriers, ubiquinol and \ cytochrome c; the electron transfer is coupled with proton translocation \ across the membrane, thus generating proton-motive force in the form of an\ electrochemical potential that can drive ATP synthesis. In its structure and\ functions, the cytochrome bc1 complex bears extensive analogy to the\ cytochrome b6f complex of chloroplasts and cyanobacteria; cyt c1 plays an\ analogous role to cytochrome f, in spite of their different structures PUB00005919.\ \ electron transporter activity ; GO:0005489 mitochondrial electron transport chain ; GO:0005746 electron transport ; GO:0006118 20976 IPR002327 Cytochromes c (cytC) can be defined as electron-transfer proteins having one or several haem c groups, bound to the protein by one or, more \ generally, two thioether bonds involving sulphydryl groups of cysteine \ residues. The fifth haem iron ligand is always provided by a histidine \ residue. CytC possess a wide range of properties and function in a large \ number of different redox processes PUB00006083. \

Ambler PUB00006083 recognised four classes of cytC.

Class I includes the low-spin\ soluble cytC of mitochondria and bacteria, with the haem-attachment site\ towards the N-terminus, and the sixth ligand provided by a methionine\ residue about 40 residues further on towards the C-terminus. On the basis\ of sequence similarity, class I cytC were further subdivided into five\ classes, IA to IE. Class IB includes the eukaryotic mitochondrial cyt C\ and prokaryotic 'short' cyt C2 exemplified by Rhodopseudomonas globiformis\ cyt C2; Class IA includes 'long' cyt C2, such as Rhodospirillum rubrum\ cyt C2 and Aquaspirillum itersonii cyt C-550, which have several extra\ loops by comparison with Class IB cyt C.

The 3D structures of a considerable number of class IA and IB cytC have\ been determined. The proteins consist of 3-6 -helices; the three\ most conserved 'core' helices form a 'basket' around the haem group, with\ one haem edge exposed to the solvent. Most class I cytC have conserved\ aromatic residues clustered around the haem and axial ligands PUB00006084.

\ \ electron transporter activity ; GO:0005489 mitochondrial electron transport chain ; GO:0005746 electron transport ; GO:0006118 20974 IPR002325 The cytochrome b6f integral membrane protein complex transfers electrons between the two reaction center complexes of oxygenic photosynthetic \ membranes, and participates in formation of the transmembrane \ electrochemical proton gradient by also transferring protons from the \ stromal to the internal lumen compartment PUB00001086. The cytochrome b6f complex \ contains four polypeptides: cytochrome f (285 aa); cytochrome b6 (215 aa); \ Rieske iron-sulphur protein (179 aa); and subunit IV (160 aa) PUB00001086. In its \ structure and functions, the cytochrome b6f complex bears extensive analogy\ to the cytochrome bc1 complex of mitochondria and photosynthetic purple \ bacteria; cytochrome f (cyt f) plays a role analogous to that of cytochrome\ c1, in spite of their different structures [MEDLINE:95357908]. \

The 3D structure of turnip cyt f has been determined [MEDLINE:96358127]. The lumen-side \ segment of cyt f includes two structural domains: a small one above a \ larger one that, in turn, is on top of the attachment to the membrane \ domain. The large domain consists of an anti-parallel -sandwich and a \ short haem-binding peptide, which form a three-layer structure. The small \ domain is inserted between -strands F and G of the large domain and is \ an all- domain. The haem nestles between two short helices at the \ N-terminus of cyt f. Within the second helix is the sequence motif for the \ c-type cytochromes, CxxCH (residues 21-25), which is covalently attached to\ the haem through thioether bonds to Cys-21 and Cys-24. His-25 is the fifth \ haem iron ligand. The sixth haem iron ligand is the -amino group of \ Tyr-1 in the first helix [MEDLINE:96358127]. Cyt f has an internal network of water \ molecules that may function as a proton wire [MEDLINE:96358127]. The water chain appears\ to be a conserved feature of cyt f.

\ \ electron transporter activity ; GO:0005489 mitochondrial electron transport chain ; GO:0005746 electron transport ; GO:0006118 20973 IPR002324 Cytochromes c (cytC) can be defined as electron-transfer proteins having one or several haem c groups, bound to the protein by one or, more \ generally, two thioether bonds involving sulphydryl groups of cysteine \ residues. The fifth haem iron ligand is always provided by a histidine \ residue. CytC possess a wide range of properties and function in a large \ number of different redox processes PUB00006083. \

Ambler PUB00006083 recognised four classes of cytC.

Class I includes the low-spin\ soluble cytC of mitochondria and bacteria, with the haem-attachment site\ towards the N-terminus, and the sixth ligand provided by a methionine\ residue about 40 residues further on towards the C-terminus. On the basis\ of sequence similarity, class I cytC were further subdivided into five\ classes, IA to IE.\ Class ID (cyt c8) includes such bacterial proteins as \ Pseudomonas spp. cyt c-551, Hydrogenobacter thermophilus cyt c-552 and \ Rhodospirillum tenue cyt c-553 [MEDLINE:91255245]. Sequence characteristics include several\ Pro residues around the sixth ligand Met, and a conserved Trp residue near\ the C-terminus.

\ \ The 3D structures of cyt C-551 from Pseudomonas aeruginosa and Pseudomonas\ stutzeri have been determined [MEDLINE:78202033]. The proteins consist of 5 -helices;\ three 'core' helices form a 'basket' around the haem group, with one haem \ edge exposed to the solvent.

\ \ electron transporter activity ; GO:0005489 mitochondrial electron transport chain ; GO:0005746 electron transport ; GO:0006118 20970 IPR002321 Cytochromes c (cytC) can be defined as electron-transfer proteins having one or several haem c groups, bound to the protein by one or, more \ generally, two thioether bonds involving sulphydryl groups of cysteine \ residues. The fifth haem iron ligand is always provided by a histidine \ residue. CytC possess a wide range of properties and function in a large \ number of different redox processes PUB00006083. \

Ambler PUB00006083 recognised four classes of cytC.

Class II includes the \ high-spin cytC' and a number of low-spin cytochromes, e.g. cyt c-556. \ The haem-attachment site is close to the C-terminus. The cytC' are capable\ of binding such ligands as CO, NO or CN(-), albeit with rate and equilibrium\ constants 100 to 1,000,000-fold smaller than other high-spin haemoproteins\ [MEDLINE:91255255]; this, coupled with its relatively low redox potential, makes it\ unlikely that cytC' is a terminal oxidase. Thus cytC' probably functions\ as an electron transfer protein [MEDLINE:91255244].

The 3D structures of a number of cytC' have been determined. The molecule \ usually exists as a dimer, each monomer folding as a four--helix bundle\ incorporating a covalently-bound haem group at the core [MEDLINE:91255244]. The Chromatium\ vinosum cytC' exhibits dimer dissociation upon ligand binding [MEDLINE:94047091].

\ \ electron transporter activity ; GO:0005489 mitochondrial electron transport chain ; GO:0005746 electron transport ; GO:0006118 20971 IPR002322 Cytochromes c (cytC) can be defined as electron-transfer proteins having one or several haem c groups, bound to the protein by one or, more \ generally, two thioether bonds involving sulphydryl groups of cysteine \ residues. The fifth haem iron ligand is always provided by a histidine \ residue. CytC possess a wide range of properties and function in a large \ number of different redox processes PUB00006083. \

Ambler PUB00006083 recognised four classes of cytC.

Class III comprises the low \ redox potential multiple haem cytochromes: cyt C7 (trihaem), C3 (tetrahaem),\ and high-molecular-weight cytC, HMC (hexadecahaem), with only 30-40 \ residues per haem group. The haem c groups, all bis-histidinyl coordinated,\ are structurally and functionally nonequivalent and present different redox\ potentials in the range 0 to -400 mV [MEDLINE:95131787]. \ The 3D structures of a number of cyt C3 proteins have been determined. The proteins\ consist of 4-5 -helices and 2 -strands wrapped around a compact\ core of four non-parallel haems, which present a relatively high degree of \ exposure to the solvent. The overall protein architecture, haem plane \ orientations and iron-iron distances are highly conserved [MEDLINE:95131787].

\ \ electron transporter activity ; GO:0005489 mitochondrial electron transport chain ; GO:0005746 electron transport ; GO:0006118 20972 IPR002323 Cytochromes c (cytC) can be defined as electron-transfer proteins having one or several haem c groups, bound to the protein by one or, more \ generally, two thioether bonds involving sulphydryl groups of cysteine \ residues. The fifth haem iron ligand is always provided by a histidine \ residue. CytC possess a wide range of properties and function in a large \ number of different redox processes PUB00006083. \

Ambler PUB00006083 recognised four classes of cytC.

The 3D structure of cyt c5\ from Azotobacter vinelandii has been determined [MEDLINE:85293097]. The protein consists \ of 5 -helices; three 'core' helices form a 'basket' around the haem \ group, with one haem edge exposed to the solvent.

\ \ electron transporter activity ; GO:0005489 mitochondrial electron transport chain ; GO:0005746 electron transport ; GO:0006118 20969 IPR002320

\ \

Class-II tRNA synthetases do not share a high degree of similarity, however at least three conserved regions are present [MEDLINE:94099781], [MEDLINE:91272282], [MEDLINE:91305088].

\ \

Threonyl-tRNA synthetase (EC: 6.1.1.3) exists as a monomer and belongs to class IIa. The enzyme from\ E. coli represses the translation of its own mRNA. The crystal structure of the complex between tRNA(Thr) and ThrRS show structural features that reveal novel strategies for providing specificity in tRNA selection. These include an amino-terminal domain containing a novel protein fold that makes minor groove contacts with the tRNA acceptor stem. The enzyme induces a large deformation of the anticodon loop, resulting in an interaction between two adjacent anticodon bases, which accounts for their prominent role in tRNA identity and translational regulation. A zinc ion found in the active site is implicated in amino acid recognition/discrimination [MEDLINE:99251535]. The zinc ion may act to ensure that only amino acids that possess a hydroxyl group attached to the -position are activated [MEDLINE:20343005].

\ \ ATP binding activity ; GO:0005524 \N threonyl-tRNA aminoacylation ; GO:0006435 20968 IPR002319

\ \

Class-II tRNA synthetases do not share a high degree of similarity, however at least three conserved regions are present [MEDLINE:94099781], [MEDLINE:91272282], [MEDLINE:91305088].

\ \

\ \ ATP binding activity ; GO:0005524 \N phenylalanyl-tRNA aminoacylation ; GO:0006432 20966 IPR002317

\ \

Class-II tRNA synthetases do not share a high degree of similarity, however at least three conserved regions are present [MEDLINE:94099781], [MEDLINE:91272282], [MEDLINE:91305088].

\ \

Seryl-tRNA synthetase (EC: 6.1.1.11) exists as monomer and belongs to class IIa [MEDLINE:95302522].

\ \ ATP binding activity ; GO:0005524 \N seryl-tRNA aminoacylation ; GO:0006434 20967 IPR002318

\ \

Class-II tRNA synthetases do not share a high degree of similarity, however at least three conserved regions are present [MEDLINE:94099781], [MEDLINE:91272282], [MEDLINE:91305088].

\ \

Alanyl-tRNA synthetase (EC: 6.1.1.7) is an alpha4 tetramer that belongs to class IIc.

\ \ ATP binding activity ; GO:0005524 \N alanyl-tRNA aminoacylation ; GO:0006419 20965 IPR002316

\ \

Class-II tRNA synthetases do not share a high degree of similarity, however at least three conserved regions are present [MEDLINE:94099781], [MEDLINE:91272282], [MEDLINE:91305088].

\ \

Prolyl-tRNA synthetase (EC: 6.1.1.15) exists in two forms, which are loosely related. The first form, is present in the majority of eubacteria species. The second one, present in some eubacteria, is essentially present in archaea and eukaryota. \ Prolyl-tRNA synthetase belongs to class IIa. The enzyme from Escherichia coli contains all three of the conserved consensus motifs characteristic of class II aminoacyl-tRNA synthetases [MEDLINE:97215833]. The complex between Thermus thermophilus prolyl-tRNA synthetase (ProRSTT) and its cognate tRNA has been crystallized using two different isoacceptors of tRNA(Pro) [MEDLINE:20133160].

\ \ ATP binding activity ; GO:0005524 \N prolyl-tRNA aminoacylation ; GO:0006433 20964 IPR002315

\ \

Class-II tRNA synthetases do not share a high degree of similarity, however at least three conserved regions are present [MEDLINE:94099781], [MEDLINE:91272282], [MEDLINE:91305088].

\ \

In eubacteria, glycyl-tRNA synthetase (EC: 6.1.1.14) is an alpha2/beta2 tetramer composed of 2 different subunits [MEDLINE:83290996], [MEDLINE:95050870], [MEDLINE:95394831]. In some eubacteria,\ in archaea and eukaryota, glycyl-tRNA synthetase is an alpha2 dimer, this family. It belongs to class IIc and is one of the most complex synthetases. What is most interesting\ is the lack of similarity between the two types: divergence at the sequence\ level is so great that it is impossible to infer descent from common genes. \ The (see IPR002310) also lack significant sequence similarity.\ However, they are translated from a single mRNA [MEDLINE:83290996], and a single chain \ glycyl-tRNA synthetase from Chlamydia trachomatis has been found to have \ significant similarity with both domains, suggesting divergence from a \ single polypeptide chain [MEDLINE:95394831].

The sequence and crystal structure of the homodimeric glycyl-tRNA synthetase from Thermus thermophilus, shows that each monomer consists of an active site strongly resembling that of the aspartyl and seryl enzymes, a C-terminal anticodon recognition domain of 100 residues and a third domain unusually inserted between motifs 1 and 2 almost certainly interacting with the acceptor arm of tRNA(Gly). The C-terminal domain has a novel five-stranded parallel-antiparallel -sheet structure with three surrounding helices. The active site residues most probably responsible for substrate recognition, in particular in the Gly binding pocket, can be identified by inference from aspartyl-tRNA synthetase due to the conserved nature of the class II active site [MEDLINE:96016187], [MEDLINE:99165778].

\ \ ATP binding activity ; GO:0005524 \N glycyl-tRNA aminoacylation ; GO:0006426 20963 IPR002314

\ \

Class-II tRNA synthetases do not share a high degree of similarity, however at least three conserved regions are present [MEDLINE:94099781], [MEDLINE:91272282], [MEDLINE:91305088].

\ \

This family includes the glycine, histidine, proline, threonine and serine tRNA synthetases.

\ \ ATP binding activity ; GO:0005524 \N amino acid activation ; GO:0006418 20962 IPR002313

\ \

Class-II tRNA synthetases do not share a high degree of similarity, however at least three conserved regions are present [MEDLINE:94099781], [MEDLINE:91272282], [MEDLINE:91305088].

\ \

Lysyl-tRNA synthetase (EC: 6.1.1.6) is an 2 homodimer that belong to both class I and class II. In eubacteria and eucaryota lysyl-tRNA synthetases belong to\ class II in the same family as aspartyl tRNA synthetase. The class Ic lysyl-tRNA synthetase family is present in archaea and some eubacteria [MEDLINE:98016282]. Moreover in some eubacteria there is a gene X, which is similar to a part of lysyl-tRNA synthetase from class II. Lysyl-tRNA synthetase is duplicated in some species with, for example in E. coli, as a\ constitutive gene (lysS) and an induced one (lysU). No residues are directly involved in catalysis, but a number of highly conserved amino acids and three metal ions coordinate the substrates and stabilize the pentavalent transition state. Lysine is activated by being attached to the -phosphate of AMP before being transferred to the cognate tRNA. The\ refined crystal structures give "snapshots" of the active site corresponding to key steps in the\ aminoacylation reaction and provide the structural framework for understanding the mechanism\ of lysine activation. The active site of LysU is shaped to position the substrates for the\ nucleophilic attack of the lysine carboxylate on the ATP -phosphate. No residues are\ directly involved in catalysis, but a number of highly conserved amino acids and three metal ions\ coordinate the substrates and stabilize the pentavalent transition state. A loop close to the\ catalytic pocket, disordered in the lysine-bound structure, becomes ordered upon adenine\ binding [MEDLINE:20374515].

\ \ \ ATP binding activity ; GO:0005524 \N lysyl-tRNA aminoacylation ; GO:0006430 20961 IPR002312

\ \

Class-II tRNA synthetases do not share a high degree of similarity, however at least three conserved regions are present [MEDLINE:94099781], [MEDLINE:91272282], [MEDLINE:91305088].

\ \

\ \ ATP binding activity ; GO:0005524 \N aspartyl-tRNA aminoacylation ; GO:0006422 20960 IPR002311

\ \

Class-II tRNA synthetases do not share a high degree of similarity, however at least three conserved regions are present [MEDLINE:94099781], [MEDLINE:91272282], [MEDLINE:91305088].

\ \

The aminoacyl-tRNA synthetases (EC: 6.1.1.-) catalyse the attachment of an amino acid to its cognate transfer RNA molecule in a highly specific two-step reaction. These proteins differ widely in size and oligomeric state, and have limited sequence homology [MEDLINE:90370122]. The 20 aminoacyl-tRNA synthetases are divided into two classes, I and II. Class I aminoacyl-tRNA synthetases contain a characteristic Rossman fold and are mostly monomeric, while class II aminoacyl-tRNA synthetases share an anti-parallel -sheet formation, flanked by -helices [MEDLINE:93372080], and are mostly dimeric or multimeric. In reactions catalysed by the class I aminoacyl-tRNA synthetases,\ the aminoacyl group is coupled to the 2'-hydroxyl of the tRNA, while, in\ class II reactions, the 3'-hydroxyl site is preferred. The synthetases specific for arginine, cysteine , glutamic acid , glutamine, isoleucine, leucine, methionine, tyrosine, tryptophan and valine belong to class I synthetases.\ The synthetases specific for alanine, asparagine, aspartic acid, glycine, histidine, lysine, phenylalanine, proline, serine, and threonine belong to class-II synthetases [Bairoch A. List of aminoacyl-tRNA synthetases http://ca.expasy.org/cgi-bin/lists?aatrnasy.txt].

\ \

Class-II tRNA synthetases do not share a high degree of similarity, however at least three conserved regions are present [MEDLINE:94099781], [MEDLINE:91272282], [MEDLINE:91305088].

In eubacteria, glycyl-tRNA synthetase (EC: 6.1.1.14) is an alpha2/beta2 tetramer composed of 2 different subunits [MEDLINE:83290996], [MEDLINE:95050870], [MEDLINE:95394831]. In some eubacteria,\ in archaea and eukaryota, glycyl-tRNA synthetase is an alpha2 dimer (see IPR002315), this family. It belongs to class IIc and is one of the most complex synthetases. What is most interesting\ is the lack of similarity between the two types: divergence at the sequence\ level is so great that it is impossible to infer descent from common genes. \ The (see IPR002315/>) and subunits also lack significant sequence similarity.\ However, they are translated from a single mRNA [MEDLINE:83290996], and a single chain \ glycyl-tRNA synthetase from Chlamydia trachomatis has been found to have \ significant similarity with both domains, suggesting divergence from a \ single polypeptide chain [MEDLINE:95394831].

\ \ ATP binding activity ; GO:0005524 \N glycyl-tRNA aminoacylation ; GO:0006426 20959 IPR002310

\ \

Class-II tRNA synthetases do not share a high degree of similarity, however at least three conserved regions are present [MEDLINE:94099781], [MEDLINE:91272282], [MEDLINE:91305088].

\ \

In eubacteria, glycyl-tRNA synthetase (EC: 6.1.1.14) is an alpha2/beta2 tetramer composed of 2 different subunits [MEDLINE:83290996], [MEDLINE:95050870], [MEDLINE:95394831]. In some eubacteria,\ in archaea and eukaryota, glycyl-tRNA synthetase is an alpha2 dimer (see IPR002315). It belongs to class IIc and is one of the most complex synthetases. What is most interesting\ is the lack of similarity between the two types: divergence at the sequence\ level is so great that it is impossible to infer descent from common genes. \ The and subunits (see IPR002315/>) also lack significant sequence similarity.\ However, they are translated from a single mRNA [MEDLINE:83290996], and a single chain \ glycyl-tRNA synthetase from Chlamydia trachomatis has been found to have \ significant similarity with both domains, suggesting divergence from a \ single polypeptide chain [MEDLINE:95394831].

\ \ ATP binding activity ; GO:0005524 \N glycyl-tRNA aminoacylation ; GO:0006426 20957 IPR002307

\ \

Tyrosyl-tRNA synthetase (EC: 6.1.1.1) is an alpha2 dimer that belongs to class Ib. \ Studies on tyrosyl-tRNA synthetase provide the first kinetic evidence that the 'KMSKS' motif plays a role in the initial binding of tRNA(Tyr) to tyrosyl-tRNA synthetase [MEDLINE:20098290].

\ \ ATP binding activity ; GO:0005524 \N tyrosyl-tRNA aminoacylation ; GO:0006437 20958 IPR002308

\ \

Cysteinyl-tRNA synthetase (EC: 6.1.1.16) is an monomer and belongs\ to class Ia.

\ \ ATP binding activity ; GO:0005524 \N cysteinyl-tRNA aminoacylation ; GO:0006423 20956 IPR002306

\ \

Tryptophanyl-tRNA synthetase (EC: 6.1.1.2) is an alpha2 dimer that belongs to class Ib. \ The crystal structure of tryptophanyl-tRNA synthetase is known [MEDLINE:20178918].

\ \ ATP binding activity ; GO:0005524 \N tryptophanyl-tRNA aminoacylation ; GO:0006436 20955 IPR002305

\ \

\ \ \ ATP binding activity ; GO:0005524 \N amino acid activation ; GO:0006418 20954 IPR002304

\ \

Methionyl-tRNA synthetase (EC: 6.1.1.10) is an 2 dimer that belongs to class Ia. In some species (archaea, eubacteria and eukaryota) a coding sequence,\ similar to the C-term end of MetRS, is present as an independant gene which is a tRNA binding domain as a dimer. In\ eubacteria, MetRS can also be splitted in two sub-classes corresponding to the presence of one or two CXXC domain\ specific to zinc binding. \ The crystal structures of a number of methionyl-tRNA synthases are known [MEDLINE:20139706], [MEDLINE:91073404], [MEDLINE:20069948].

\ \ ATP binding activity ; GO:0005524 \N methionyl-tRNA aminoacylation ; GO:0006431 20953 IPR002303

\ \

Valyl-tRNA synthetase (EC: 6.1.1.9 ) is an monomer that belongs to class Ia.

\ \ ATP binding activity ; GO:0005524 \N valyl-tRNA aminoacylation ; GO:0006438 20952 IPR002302

\ \

Leucyl tRNA synthetase (EC: 6.1.1.4) is an monomer that belongs to class Ia. There are two different families of leucyl-tRNA synthetases. This family includes the eubacterial and mitochondrial synthetases.\ The crystal structure of leucyl-tRNA synthetase from the hyperthermophile Thermus thermophilus has an overall architecture that is similar to that of isoleucyl-tRNA synthetase, except that the putative editing domain is inserted at a different position in the primary structure. This feature is unique to prokaryote-like leucyl-tRNA synthetases, as is the presence of a novel additional flexibly inserted domain [MEDLINE:20271875].

\ \ ATP binding activity ; GO:0005524 \N leucyl-tRNA aminoacylation ; GO:0006429 20951 IPR002301

\ \

Isoleucyl-tRNA synthetase (EC: 6.1.1.5) is an monomer that belongs to class Ia. The enzyme, isoleucyl-transfer RNA synthetase, activates not only the cognate substrate L-isoleucine but also the minimally distinct L-valine in the first, aminoacylation step. Then, in a second, "editing" step, the synthetase itself rapidly\ hydrolyzes only the valylated products [MEDLINE:98221234], [MEDLINE:99377249] as shown from the crystal structures.

\ \ ATP binding activity ; GO:0005524 \N isoleucyl-tRNA aminoacylation ; GO:0006428 20950 IPR002300

\ \

\ \ \ ATP binding activity ; GO:0005524 \N amino acid activation ; GO:0006418 20949 IPR002299

Porins are found in the outer membranes of Gram-negative bacteria,mitochondria and chloroplasts, where they form ion-selective channels for\ small hydrophilic molecules (up to ~600 D) [MEDLINE:91134313], [MEDLINE:92219987]. X-ray structure\ analyses of several bacterial porins [MEDLINE:91192174], [MEDLINE:92222788], [MEDLINE:95055730] have revealed a large 16-stranded\ anti-parallel -barrel structure enclosing the transmembrane pore, by\ contrast with all other integral membrane proteins described to date,\ which are -helical. Three subunits form a trimer; the 3-fold axis is\ approximately parallel to the barrel axes and is assumed to be\ perpendicular to the membrane plane PUB00001081.

From the range of porins now known, similarities have been observed between\ porins from different species, and between porins of different specificity\ within the same species. But most porins cannot be related to each other on\ the basis of sequence alone, and this is reflected in the lengths of the\ known porin sequences, which range from 282-483 residues/monomer.

\ \ transporter activity ; GO:0005215 membrane ; GO:0016020 transport ; GO:0006810 20948 IPR002298 DNA carries the biological information that instructs cells how to existin an ordered fashion. Accurate replication is thus one of the most\ important events in the cell life cycle. This function is mediated by\ DNA-directed DNA polymerases, which add nucleotide triphosphate (dNTP)\ residues to the 5'-end of the growing DNA chain, using a complementary \ DNA as template. Small RNA molecules are generally used as primers for\ chain elongation, although terminal proteins may also be used.\ DNA-dependent DNA polymerases have been grouped into families, denoted A, B\ and X, on the basis of sequence similarities [MEDLINE:88068579], [MEDLINE:90319059]. Members of family A, \ which includes bacterial and bacteriophage polymerases, share significant\ similarity to E.coli polymerase I; hence family A is also known as the pol I\ family. The bacterial polymerases also contain an exonuclease activity,\ which is coded for in the N-terminal portion. \ Three motifs, A, B and C, as defined by Delarue et al. [MEDLINE:90319059], are seen to be \ conserved across all DNA polymerases, with motifs A and C also seen in RNA \ polymerases. They are centered on invariant residues, and their structural \ significance was implied from the Klenow (E.coli) structure. Motif A \ contains a strictly-conserved aspartate at the junction of a

-strand \ and an

-helix; motif B contains an

-helix with positive charges; \ and motif C has a doublet of negative charges, located in a

-turn-

secondary structure [MEDLINE:90319059].\ \ DNA-directed DNA polymerase activity ; GO:0003887 \N DNA replication ; GO:0006260 20946 IPR002296

In prokaryotes, the major role of DNA methylation is to protect host DNA against degradation by restriction enzymes. There are 2 major classes of DNA methyltransferase that differ in the nature of the modifications they effect. The members of one class (C-MTases) methylate a ring carbon and form C5-methylcytosine (see IPR001525). Members of the second class (N-MTases) methylate exocyclic nitrogens and form either N4-methylcytosine(N4-MTases) or N6-methyladenine (N6-MTases). Both classes of MTase utilise the cofactor S-adenosyl-L-methionine (SAM) as the methyl donor and are active as monomeric enzymes [MEDLINE:95392155].

N-6 adenine-specific DNA methylases (EC: 2.1.1.72) (A-Mtase) are enzymes that specifically methylate the amino group at the C-6 position of adenines in DNA.\ Such enzymes are found in the three existing types of bacterial \ restriction-modification systems (in type I system the A-Mtase is the product of the hsdM\ gene, and in type III it is the product of the mod gene). All of these enzymes\ recognize a specific sequence in DNA and methylate an adenine in that\ sequence. It has been shown [MEDLINE:88118919], [MEDLINE:89252878], [MEDLINE:89236400], [MEDLINE:95331587] that A-Mtases contain a conserved motif Asp/Asn-Pro-Pro-Tyr/Phe in their N-terminal section, this conserved region could be\ involved in substrate binding or in the catalytic activity. The structure of N6-MTase TaqI (M.TaqI) has been resolved to 2.4 A [MEDLINE:95062184]. The molecule folds into\ 2 domains, an N-terminal catalytic domain, which contains the catalytic and cofactor binding sites, and comprises a central 9-stranded -sheet, surrounded by 5 helices; and a C-terminal DNA recognition domain, which is formed by 4 small -sheets and 8 -helices. The N- and C-terminal domains form a cleft that accommodates the DNA substrate. A classification of N-MTases has been proposed, based on conserved motif (CM) arrangements [MEDLINE:95331587]. According to this classification, N6-MTases that\ have an NPPY motif (CM II) occuring after the FxGxG motif (CM I) are\ designated N12 class N6-adenine MTases.

\ \ N-methyltransferase activity ; GO:0008170 \N DNA methylation ; GO:0006306 20947 IPR002297 DNA carries the biological informatio'n that instructs cells how to existin an ordered fashion. Accurate replication is thus one of the most\ important events in the cell life cycle. This function is mediated by\ DNA-directed DNA-polymerases, which add nucleotide triphosphate (dNTP)\ residues to the 5'-end of the growing DNA chain, using a complementary \ DNA as template. Small RNA molecules are generally used as primers for\ chain elongation, although terminal proteins may also be used.\ DNA-dependent DNA-polymerases have been grouped into families, denoted A, B\ and X, on the basis of sequence similarities [MEDLINE:88068579], [MEDLINE:90319059]. Members of family A, \ which includes bacterial and bacteriophage polymerases, share significant\ similarity to E.coli polymerase I; hence family A is also known as the pol I\ family. The bacterial polymerases also contain an exonuclease activity,\ which is coded for in the N-terminal portion. The yeast gamma polymerases\ show some similarity to the prokaryotic nuclear polymerases of family A,\ but their function is restricted to mitochondrial DNA replication and \ repair [MEDLINE:86250881].\ Three motifs, A, B and C, as defined by Delarue et al. [MEDLINE:90319059], are seen to be \ conserved across all DNA-polymerases, with motifs A and C also seen in RNA- \ polymerases. They are centered on invariant residues, and their structural \ significance was implied from the Klenow (E.coli) structure. Motif A \ contains a strictly-conserved aspartate at the junction of a

-strand \ and an

-helix; motif B contains an

-helix with positive charges; \ and motif C has a doublet of negative charges, located in a

-turn-

secondary structure [MEDLINE:90319059].\ \ gamma DNA-directed DNA polymerase activity ; GO:0003895 gamma DNA polymerase complex ; GO:0005760 DNA replication ; GO:0006260 20945 IPR002295

N-6 adenine-specific DNA methylases (EC: 2.1.1.72) (A-Mtase) are enzymes that specifically methylate the amino group at the C-6 position of adenines in DNA.\ Such enzymes are found in the three existing types of bacterial \ restriction-modification systems (in type I system the A-Mtase is the product of the hsdM\ gene, and in type III it is the product of the mod gene). All of these enzymes\ recognize a specific sequence in DNA and methylate an adenine in that\ sequence. It has been shown [MEDLINE:88118919], [MEDLINE:89252878], [MEDLINE:89236400], [MEDLINE:95331587] that A-Mtases contain a conserved motif Asp/Asn-Pro-Pro-Tyr/Phe in their N-terminal section, this conserved region could be\ involved in substrate binding or in the catalytic activity. The structure of N6-MTase TaqI (M.TaqI) has been resolved to 2.4 A [MEDLINE:95062184]. The molecule folds into\ 2 domains, an N-terminal catalytic domain, which contains the catalytic and cofactor binding sites, and comprises a central 9-stranded -sheet, surrounded by 5 helices; and a C-terminal DNA recognition domain, which is formed by 4 small -sheets and 8 -helices. The N- and C-terminal domains form a cleft that accommodates the DNA substrate. A classification of N-MTases has been proposed, based on conserved motif (CM) arrangements [MEDLINE:95331587]. According to this classification, N6-MTases that\ have a DPPY motif (CM II) occuring before the FxGxG motif (CM I) are\ designated D21 class N6-adenine MTases.

\ \ N-methyltransferase activity ; GO:0008170 \N DNA methylation ; GO:0006306 20943 IPR002293 Amino acid permeases are integral membrane proteins involved in the transportof amino acids into the cell. A number of such proteins have been found to be\ evolutionary related [MEDLINE:89125644], [MEDLINE:90076962], [MEDLINE:93184721]. These proteins include several yeast specific and general amino acid permeases; Emericella nidulans proline transport protein (gene prnB);\ Trichoderma harzianum amino acid permease INDA1; Salmonella typhimurium L-asparagine permease (gene ansP); and several E. coli and other bacterial permeases and transport proteins. These proteins seem to contain up to 12 transmembrane segments. This entry is for family I.\ \ amino acid-polyamine transporter activity ; GO:0005279 membrane ; GO:0016020 amino acid transport ; GO:0006865 20942 IPR002292 The ornithine carbamoyltransferases are a family of enzymes that catalyse the production of citrulline from carbamoyl-phosphate and ornithine [MEDLINE:91033057]. \ This reaction is part of the arginine biosynthetic pathway, and in some \ organisms the reaction is also part of the arginine deaminase pathway [MEDLINE:87246664]. \ In most prokaryotes, and some lower eukaryotes, the enzyme is found in the \ cytoplasm, but in higher eukaryotes, such as mammals, the enzyme is found\ in the mitochondrial matrix and functions as part of the urea cycle. In\ most organisms analysed to date, the enzyme has been shown to consist of a \ trimer of identical or nonidentical subunits [MEDLINE:87275920]. Extensive similarity has \ been found within the ornithine carbamoyltransferase family, some of the\ conserved areas being important in catalysis [MEDLINE:87014107]. \

The C-terminal region of these enzymes shows a degree of similarity to the \ aspartate carbamoyltransferases, which are also known to bind carbamoyl-\ phosphate [MEDLINE:91109740]. This region contains a highly conserved Cys residue (in a\ His-Cys-Lys-Pro motif) implicated in ornithine binding [MEDLINE:87275920].

\ \ \ ornithine carbamoyltransferase activity ; GO:0004585 ornithine carbamoyltransferase complex ; GO:0009348 amino acid metabolism ; GO:0006520 20944 IPR002294

N-6 adenine-specific DNA methylases (EC: 2.1.1.72) (A-Mtase) are enzymes that specifically methylate the amino group at the C-6 position of adenines in DNA.\ Such enzymes are found in the three existing types of bacterial \ restriction-modification systems (in type I system the A-Mtase is the product of the hsdM\ gene, and in type III it is the product of the mod gene). All of these enzymes\ recognize a specific sequence in DNA and methylate an adenine in that\ sequence. It has been shown [MEDLINE:88118919], [MEDLINE:89252878], [MEDLINE:89236400], [MEDLINE:95331587] that A-Mtases contain a conserved motif Asp/Asn-Pro-Pro-Tyr/Phe in their N-terminal section, this conserved region could be\ involved in substrate binding or in the catalytic activity. The structure of N6-MTase TaqI (M.TaqI) has been resolved to 2.4 A [MEDLINE:95062184]. The molecule folds into\ 2 domains, an N-terminal catalytic domain, which contains the catalytic and cofactor binding sites, and comprises a central 9-stranded -sheet, surrounded by 5 helices; and a C-terminal DNA recognition domain, which is formed by 4 small -sheets and 8 -helices. The N- and C-terminal domains form a cleft that accommodates the DNA substrate. A classification of N-MTases has been proposed, based on conserved motif (CM) arrangements [MEDLINE:95331587]. According to this classification, N6-MTases that\ have a DPPY motif (CM II) occuring after the FxGxG motif (CM I) are\ designated D12 class N6-adenine MTases.

\ \ N-methyltransferase activity ; GO:0008170 \N DNA methylation ; GO:0006306 20940 IPR002290

Eukaryotic protein kinases PUB00001071, PUB00001071, [MEDLINE:92065854], [MEDLINE:92065863], [MEDLINE:88264399] are enzymesthat belong to a very extensive family of proteins which share a conserved catalytic core common with\ both serine/threonine and tyrosine protein kinases. There are a number of conserved regions in the\ catalytic domain of protein kinases. In the N-terminal extremity of the catalytic domain there is a\ glycine-rich stretch of residues in the vicinity of a lysine residue, which has been shown to be involved\ in ATP binding. In the central part of the catalytic domain there is a conserved aspartic acid residue\ which is important for the catalytic activity of the enzyme [MEDLINE:91320112].

CAUTION: Despite SMART having created two different HMMs for Serine/Threonine protein kinase and for Tyrosine protein kinase, large number of proteins matches both signatures, as SMART considers it to be natural for these two closely related families.

\ \ ATP binding activity ; GO:0005524 \N protein amino acid phosphorylation ; GO:0006468 20941 IPR002291 Phosphorylase B kinase (EC: 2.7.1.38) belongs to a family of proteins involved in glycogen biosynthesis [MEDLINE:95160664]. The protein has a subunit composition\ of (

, gamma, delta)4, where the

and

subunits are \ regulatory, delta is calmodulin, and the gamma subunit is catalytic. The \ enzyme is believed to have a dual role, the first is connected with glycogen\ degradation via phosphorylation of glycogen phosphorylase; the second \ controls glycogen biosynthesis on the sarcoplasmic reticular membrane more\ directly by phosphorylation, and thus inhibition, of glycogen synthase [MEDLINE:95246834].\

The gamma catalytic chain contains three domains; one protein kinase and two\ calmodulin-binding domains. Calcium and magnesium ions, together with cyclic\ AMP, positively affect the efficiency of the enzyme, which is believed to \ be associated with its auto-kinase activity [MEDLINE:95160664], [MEDLINE:96138604].

The full extent of the effects of deficiencies in this enzyme in humans is \ unknown; but case studies have been documented [MEDLINE:97099674], [MEDLINE:98214569], [MEDLINE:96006280] that detail symptoms as\ mild as 'exercise intolerance' [MEDLINE:97099674], to infant mortality arising from floppy\ infant syndrome [MEDLINE:98214569].

\ \ phosphorylase kinase, catalyst activity ; GO:0008606 phosphorylase kinase complex ; GO:0005964 protein amino acid phosphorylation ; GO:0006468 20939 IPR002289

\ \

A cDNA encoding the human GABAA receptor 2 subunit has been cloned and\ sequenced [MEDLINE:94088484]. Expression of recombinant human GABAA receptors containing\ different subunits ( 1, 2 or 3) in both transfected\ cells and Xenopus laevis oocytes, has revealed the influence of the subunit on\ the pharmacology of the receptor. For a number of benzodiazepine binding\ site compounds, a barbiturate, and several neurosteroids, neither the\ affinity nor the efficacy of the compounds is influenced by the type of subunit present in the receptor molecule [MEDLINE:94088484]. These observations\ suggest that the subunit does not significantly influence the\ benzodiazepine, barbiturate, or steroid site pharmacologies of human GABAA\ receptor subtypes [MEDLINE:94088484].

\ \ ion channel activity ; GO:0005216 membrane ; GO:0016020 ion transport ; GO:0006811 20937 IPR002286

The P2Y receptor is found in smooth muscle (e.g., taeni caeci) and in\ vascular tissue, where it induces vasodilation through endothelium-dependent\ release of nitric oxide. The receptor activates phosphoinositide metabolism\ through a pertussis-toxin-insensitive G-protein, probably belonging to\ the Gi/Go class PUB00005868.

\ \ purinergic nucleotide receptor activity, G-protein coupled ; GO:0045028 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20938 IPR002288

Topoisomerases catalyse the interconversion of topological isomers of DNA and play a key role in DNA metabolism. Topoisomerase I catalyses an ATP-independent reaction, \ while topoisomerase II catalyses an ATP-dependent reaction, resulting in the formation \ of DNA supercoils [MEDLINE:91339166], [MEDLINE:91270367], [MEDLINE:89017161]. Eukaryotic enzymes can form \ both positive and negative supercoils, while prokaryotic enzymes form only negative \ supercoils.

\ \

Eukaryotic topoisomerase II exists as a homodimer; in bacteriophage T4 it \ consists of three heterologous subunits; in prokaryotes it exists as a tetramer\ of two subunits (two each of gyrA and gyrB); and in E.coli, a second type II\ topoisomerase, involved in chromosome segregation (topoisomerase IV),\ consists of two subunits (parC and parE). GyrB, parE, and the product of \ bacteriophage T4 gene 39, are all similar to the eukaryotic proteins.

Structural studies of E.coli topoisomerase II have shown that the enzyme\ binds to DNA, forming a complex in which a DNA strand of approximately 120\ base pairs is wound around a protein core. At low resolution, this\ complex resembles a flattened sphere, and may be heart-shaped, with the DNA\ embedded in the protein. There is evidence for channels or cavities in\ the complex, which may have a role in the DNA translocation process [MEDLINE:91270367].

The gyrB protein possesses 2 uniquely-folded domains. The N-terminal domain\ (domain 1) possesses ATP-binding and hydrolysis functions, and forms an\ 8-stranded anti-parallel -sheet with unusual strand connectivities - the\ structure, which is stabilised by a hydrophobic core, can be subdivided\ into 6- and 2-stranded anti-parallel sheets, connected by a parallel sheet. The C-terminal domain (domain 2) contains a 4-stranded mixed parallel\ and anti-parallel -sheet. Four helices are also present, 2 of which are\ rich in arginine residues. The gyrB dimer is punctured by a 20A hole, which\ may provide a gateway through which DNA is passed during supercoiling.\ Every arginine of domain 2 protrudes into this hole, possibly creating a \ DNA-binding surface [MEDLINE:91270367].

From this structural information and results of various biochemical studies,\ a possible mechanism has been proposed: DNA is first bound by the gyrB\ dimer, then cleaved by gyrA. A large conformational change allows passage\ of another DNA strand through the double-stranded break and into the protein\ complex. This may involve ATP binding, exploiting the energy of association\ of ATP to the complex to stabilise an unfavourable protein conformation.\ The DNA break is then repaired by ligation, and the whole DNA molecule\ released - this possibly involves hydrolysis of ATP to ADP and organic\ phosphorous, which can dissociate from the protein, allowing the protein\ complex to return to its favoured conformation, and releasing the DNA [MEDLINE:91270367].

\ \ ATP binding activity ; GO:0005524 \N DNA topological change ; GO:0006265 20936 IPR002285

Vasoactive intestinal polypeptide (VIP) has a wide physiological profile.\ In the periphery, it induces relaxation in smooth muscle; inhibits\ secretion in certain tissues, but stimulates secretion in others; and\ modulates activity of cells in the immune system. In the CNS, it has a\ range of both excitatory and inhibitory actions. VIP receptors are\ distributed widely in the periphery, and occur throughout the gastrointestinal tract and genitourinary system, other smooth muscles and\ secretory glands. In the CNS, they are found abundantly in, e.g. the cortex,\ hippocampus and thalamus PUB00005907. All VIP receptors activate adenylyl cyclase.

There are two structurally distinct receptors that recognise pituitary\ adenylate cyclase activating polypeptide (PACAP) and VIP peptides with\ similar affinities (PACAP/VIPR-1, PACAP/VIPR-2), as well as a specific\ receptor for the PACAP peptide (PACAP-1) PUB00005907. PACAP type I receptors are\ present in the hypothalamus and anterior pituitary, where they regulate the\ release of adrenocorticotropin, luteinising hormone, growth hormone and\ prolactin, and in the adrenal medulla, where they regulate the release of\ epinephrine [MEDLINE:93317678]. The receptors are also found in high concentrations in\ testicular germ cells, where they may regulate spermatogenesis, and in some\ transformed cell lines, such as the rat pancreatic acinar carcinoma cell\ AR4-2J [MEDLINE:93317678].

\ \ vasoactive intestinal polypeptide receptor activity ; GO:0004999 membrane ; GO:0016020 G-protein coupled receptor protein signaling pathway ; GO:0007186 20935 IPR002284

There are two structurally distinct receptors that recognise VIP peptides\ and pituitary adenylate cyclase activating polypeptide (PACAP) with similar\ affinities (PACAP/VIPR-1, PACAP/VIPR-2), as well as a specific receptor for\ the PACAP peptide (PACAP-1). RNA transcripts for all three receptor types\ are found in human heart, brain and adipose tissue PUB00005907. By contrast with\ VIPR-1, which is constitutively expressed, the expression of VIPR-2 is\ induced only following stimulation through the TCR-associated CD3 complex [MEDLINE:96378694].\ VIP induces the expression of the VIPR-2 gene in the absence of additional\ stimuli. Differential expression and regulation of the two VIP receptors in\ T lymphocytes suggests different physiological roles in mediating the\ immunomodulatory activities of VIP and related neuropeptides [MEDLINE:96378694].

\ \ vasoactive intestinal polypeptide receptor activity ; GO:0004999 membrane ; GO:0016020 G-protein coupled receptor protein signaling pathway ; GO:0007186 20934 IPR002283 Isopenicillin N synthase (IPNS) is a nonheme-Fe²⁺-dependent enzyme thatbelongs to a class of nonheme Fe²⁺-containing enzymes, which includes\ 2-oxoglutarate-dependent dioxygenases, 2-oxoglutarate-dependent hydroxy-\ lases, and enzymes involved in ethylene formation and anthocyaninidin\ biosynthesis. IPNS catalyses the stereospecific formation of the

-lactam \ and thiazolidine rings of IPN via a 4-electron oxidation of the tripeptide\ ACV. The enzyme uses, as the sole electron acceptor, one molecule of\ dioxygen, which is completely reduced to two molecules of water. The oxygen \ stoichiometry shown by IPNS is the same as that for cytochrome C oxidase,\ but is unusual for nonheme-iron-containing enzymes, which typically catalyse\ the transfer of one or both atoms of dioxygen into their substrates. IPNS\ thus provides an interesting contrast to dioxygenase enzymes.\

All IPNS proteins reported to date have a molecular mass of 30-40 kD and\ are highly conserved. The degree of identity in the predicted amino acid\ sequence ranges from 54-75%. Two cysteines are invariant in all known IPNS\ sequences; these residues are believed to be functionally important for\ iron binding. Histidine and aspartic acid residues in the sequence\ constitute the endogenous ligands of the ferrous active site.

\ \ isopenicillin N synthetase activity ; GO:0016216 \N antibiotic biosynthesis ; GO:0017000 20933 IPR002282

Platelet-activating factor (PAF), a unique phospholipid mediator, possesses\ potent proinflammatory, smooth-muscle contractile and hypotensive activities,\ and appears to be crucial in the pathogenesis of bronchial asthma and in the\ lethality of endotoxin and anaphylactic shock [MEDLINE:91101726], [MEDLINE:92347886]. However, little is\ known of the molecular properties of the PAF receptor and related signal\ transduction systems [MEDLINE:91101726]. The gene for the human PAF receptor (PAFR) has\ been isolated, and encodes a protein that is highly similar to the guinea\ pig PAF receptor. Analysis of somatic cell hybrids suggests that PAFR is\ encoded by a single gene on human chromosome 1 [MEDLINE:91101726].

\ \ platelet activating factor receptor activity ; GO:0004992 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20932 IPR002281

Several 7TM receptors have been cloned but their endogenous ligands are\ unknown; these have been termed orphan receptors. A GPCR similar to the\ receptor for the blood clotting enzyme thrombin has been cloned [MEDLINE:95197620]. Like\ the thrombin receptor, this receptor is activated by N-terminal proteolytic\ cleavage. Thus, because the physiological agonist at the receptor is\ unknown, it has been provisionally named proteinase-activated receptor 2\ (PAR-2) [MEDLINE:95197620]. Human PAR-2 (hPAR-2) resides both on the plasma membrane and\ in the Golgi apparatus [MEDLINE:96177879]. hPAR-2 mRNA is highly expressed in human\ pancreas, kidney, colon, liver and small intestine, and by A549 lung and\ SW480 colon adenocarcinoma cells [MEDLINE:96177879]. Hybridisation in situ reveals high\ expression in intestinal epithelial cells throughout the gut [MEDLINE:96177879], where it\ is thought that PAR-2 may serve as a trypsin sensor [MEDLINE:96177879]. Its expression\ by cells and tissues not normally exposed to pancreatic trypsin suggests\ that other proteases could serve as physiological activators [MEDLINE:96177879].

\ \ thrombin receptor activity ; GO:0015057 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20930 IPR002279

Melatonin is secreted by the pineal gland during darkness. It regulates\ a variety of neuroendocrine functions and is thought to play an essential\ role in circadian rhythms. Drugs that modify the action of melatonin,\ and hence influence circadian cycles, are of clinical interest (for example,\ in the treatment of jet-lag). Melatonin receptors are found in the\ retina, in the pars tuberalis of the pituitary, and in discrete areas of\ the brain. The receptor inhibits adenylyl cyclase via a pertussis-toxin-sensitive G-protein, probably of the Gi/Go class PUB00005892.

Three sub-types have been cloned, designated Mel1a, Mel1b and Mel1c,\ together with a closely-related orphan receptor, termed Mel1x. Chick brain\ and Xenopus Mel1c receptors are 80% identical and are distinct from the\ Mel1a and Mel1b subtypes. Similar ligand binding and functional\ characteristics are observed in expressed Mel1a and Mel1c receptors.\ The widespread distribution of Mel1a and Mel1c mRNA in brain provides a\ molecular substrate for the profound actions of melatonin in birds\ \ \ \ PUB00005892.

\ \ melatonin receptor activity ; GO:0008502 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20931 IPR002280

Three sub-types have been cloned, designated Mel1a, Mel1b and Mel1c,\ together with a closely-related orphan receptor, termed Mel1x. Mel1x from\ human pituitary is a protein of 613 amino acids that is 45% identical to\ human Mel1a and Mel1b receptors. Although closely related to the\ melatonin receptor family, the sequence is unusual in lacking N-linked\ glycosylation sites and in bearing a >300 residue C-terminal tail. The\ receptor does not bind [¹²⁵I]-melatonin or [³H]-melatonin. Its mRNA is\ expressed in hypothalamus and pituitary, suggesting that the receptor and\ its natural ligand are involved in neuroendocrine function PUB00005892.

\ \ melatonin receptor activity ; GO:0008502 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20929 IPR002278

Three sub-types have been cloned, designated Mel1a, Mel1b and Mel1c,\ together with a closely-related orphan receptor, termed Mel1x. The Mel1a\ receptor appears to mediate the circadian and reproductive effects of the\ hormone. In situ hybridisation indicates that Mel1a receptor messenger\ RNA is expressed in the hypothalamic suprachiasmatic nuclei and hypophyseal\ pars tuberalis, presumed sites of the circadian and some of reproductive\ actions of melatonin, respectively PUB00005892.

\ \ melatonin receptor activity ; GO:0008502 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20928 IPR002277

EDG-2 was originally identified as a gene involved in neuron production from\ embryonic cerebral cortex [MEDLINE:21164675]. EDG-2 is widely distributed, with highest levels in the brain (in which expression correlates with development of\ oligodendrocytes and Schwann cells) [MEDLINE:21164675]. In the periphery, EDG-2 is found in many tissues, including the heart, kidney, testis, spleen and muscle in both humans and mouse [MEDLINE:20545693]. The receptor is also expressed in a number of cancers [MEDLINE:21164675]. Upon binding of LPA, EDG-2 couples to G proteins of the Gi, Gq and G12/13 classes, to mediate a range of effects including: inhibition of adenylyl cyclase; activation of phospholipase C, serum response element and MAP kinases; and actomyosin stimulation. These processes lead to cell rounding and proliferation [MEDLINE:20545693].

\ \ lysosphingolipid and lysophosphatidic acid receptor activity ; GO:0001619 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20926 IPR002275

Several 7TM receptors have been cloned but their endogenous ligands are\ unknown; these have been termed orphan receptors. Several novel human genes\ encoding GPCRs that most closely resemble peptide binding receptors have\ been isolated and characterised [MEDLINE:95154831]. Gene GPR1, which is intronless in the\ coding region, encodes a receptor that shares identity in the TM regions\ with the opioid receptors. GPR1 transcripts are expressed in the human\ hippocampus [MEDLINE:95154831]. By contrast, the rat GPR1 gene is not expressed in\ hippocampus, demonstrating a functional variation for this receptor in\ these two species [MEDLINE:95110347].

\ \ \ G-protein coupled receptor activity, unknown ligand ; GO:0016526 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20927 IPR002276

Several 7TM receptors have been cloned but their endogenous ligands are unknown; these have been termed orphan receptors. A novel GPCR (GPR4) from the critical myotonic dystrophy (DM) region on chromosome 19q13.3 has been sequenced [MEDLINE:96129306], [MEDLINE:95134353]. The gene is intronless and contain an open reading frame encoding a protein of 362\ amino acids. Two isoforms of GPR4 are expressed in humans, differing in their 3'\ untranslated region as a result of the use of alternate polyadenylation signals. GPR4 is\ widely expressed, with higher levels in kidney, heart, and especially lung [MEDLINE:96129306]. Sequence\ analysis suggests that GPR4 is a peptide receptor; it shares strongest similarity with\ purinergic receptors and receptors for angiotensin II, platelet activating factor, thrombin\ and bradykinin [MEDLINE:96129306], [MEDLINE:95134353].

\ \ G-protein coupled receptor activity, unknown ligand ; GO:0016526 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20923 IPR002272

The gonadotrophins (luteinising hormone, choriogonadotrophin, follicle-stimulating hormone) and thyroid-stimulating hormone are heterotrimeric\ glycoproteins composed of a common -subunit and distinct -subunits\ PUB00005886. The carbohydrate moiety of the glycoproteins has an essential role in\ receptor recognition. The receptors share close sequence similarity, and\ are characterised by large extracellular domains believed to be involved\ in hormone binding via leucine-rich repeats (LRR) PUB00005886. Modelling of this\ portion of the receptors suggests that they contain three-dimensional\ structures similar to that of porcine ribonuclease inhibitor [MEDLINE:96363672].

FSH is released from the anterior pituitary under the influence of\ gonadotrophin-releasing hormone and oestrogens, and from the placenta during\ pregnancy. In females, it acts on the ovaries, promoting development\ of follicles and is the principal hormone regulating secretion of\ oestrogens. In males, it is responsible for the integrity of the\ seminiferous tubules and acts on Sertoli cells to support gametogenesis.\ FSH is used clinically to treat infertility in females and for some types\ of spermatogenesis in males. The receptor is found in ovary and testis,\ its predominant effector pathway being via activation of adenylyl cyclase\ through Gs PUB00005886.

\ \ follicle stimulating hormone receptor activity ; GO:0004963 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20924 IPR002273

The subunits of LH (also known as lupotrophin) and hCG are closely\ related in sequence and elicit their biological actions via the same\ receptor. LH is released from the anterior pituitary under the\ influence of gonadotrophin-releasing hormone and progesterones. CG is\ released by the placenta during pregnancy. In females, LH stimulates\ ovulation and is the major hormone involved in the regulation of\ progesterone secretion by the corpus luteum. In males, it stimulates\ Leydig cells to secrete androgens, particularly testosterone. The receptor\ is found in organs involved in reproductive physiology, including testicular\ Leydig cells, ovarian theca, granulosa, luteal and interstitial cells.\ The receptor activates adenylyl cyclase through Gs and stimulates the\ phosphoinositide pathway through a pertussis-toxin-insensitive G-protein PUB00005886.

Familial male precocious puberty (FMPP) is a gonadotropin-independent\ disorder that is inherited in an autosomal dominant, male-limited pattern\ PUB00005886. Affected males generally exhibit signs of puberty by age 4 [MEDLINE:94019815].\ Testosterone production and Leydig cell hyperplasia occur in the context of\ prepubertal levels of luteinising hormone (LH). FMPP was thought to be due\ to a mutant receptor activated in the presence of little or no agonist. A\ single A-G base change that results in substitution of glycine for aspartate\ at position 578 in LH receptor TM domain 6 was found in affected individuals\ from eight different families [MEDLINE:94019815]. Linkage of the mutation to FMPP was\ supported by restriction-digest analysis [MEDLINE:94019815]. Further results suggest that\ autonomous Leydig cell activity in FMPP is caused by a constitutively\ activated LH receptor [MEDLINE:94019815].

\ \ lutropin-choriogonadotropic hormone receptor activity ; GO:0004964 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20925 IPR002274

TSHR (also known as thyrotrophin) is synthesised in the thyrotroph cells of\ the anterior pituitary under the influence of TRH and thyroid hormones.\ It acts on the thyroid gland, stimulating iodine uptake, synthesis and\ release of thyroid hormones, hypertrophy and hyperplasia. Graves disease\ is caused by stimulatory anti-TSH receptor antibodies. The receptor is\ found in thyroid follicular cells and related cell lines, its predominant\ effector pathway being via activation of adenylyl cyclase through Gs PUB00005886.

Activating somatic mutations in the TSH receptor have been identified as a\ cause of hyperfunctioning thyroid adenomas, and germline mutations have been\ found in familial non-autoimmune hyperthyroidism and sporadic congenital\ hyperthyroidism PUB00005886. To date, all reported mutations have been located in\ the TM domain. Now, an example of an activating mutation in the extracellular, TSH-binding domain, has been found in a male infant with\ congenital hyperthyroidism due to a toxic adenoma [MEDLINE:97439786]. The results indicate\ that activating mutations can also occur in the extracellular domain of the\ TSH receptor, and support a model in which this domain serves to restrain\ receptor function in the absence of TSH or antibody-induced conformational\ changes [MEDLINE:97439786].

\ \ protein-hormone receptor activity ; GO:0016500 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20922 IPR002271

The connexins are a family of integral membrane proteins that oligomerise to form intercellular channels that are clustered at gap junctions. These channels are specialised sites of cell-cell contact that allow the passage of ions, intracellular metabolites and messenger molecules (with molecular weight less than 1-2 kD) from the cytoplasm of one cell to its opposing neighbours. They are found in almost all vertebrate cell types, and somewhat similar proteins have been cloned from plant species. Invertebrates utilise a different family of molecules, innexins, that share a similar predicted secondary structure to the vertebrate connexins, but have no sequence identity to them [MEDLINE:98441865].

Vertebrate gap junction channels are thought to participate in diverse biological functions. For instance, in the heart they permit the rapid cell-cell transfer of action potentials, ensuring coordinated contraction of the cardiomyocytes. They are also responsible for neurotransmission at specialised 'electrical' synapses. In non-excitable tissues, such as the liver, they may allow metabolic cooperation between cells. In the brain, glial cells are extensively-coupled by gap junctions; this allows waves of intracellular Ca²⁺ to propagate through nervous tissue, and may contribute to their ability to spatially-buffer local changes in extracellular K⁺ concentration [MEDLINE:93296897].

\ \

The connexin protein family is encoded by at least 13 genes in rodents, with many homologues cloned from other species. They show overlapping tissue expression patterns, most tissues expressing more than one connexin type. Their conductances, permeability to different molecules, phosphorylation and voltage-dependence of their gating, have been found to vary. Possible communication diversity is increased further by the fact that gap junctions may be formed by the association of different connexin isoforms from apposing cells. However, in vitro studies have shown that not all possible combinations of connexins produce active channels [MEDLINE:96407100], [MEDLINE:96190804].

\ \

Hydropathy analysis predicts that all cloned connexins share a common transmembrane (TM) topology. Each connexin is thought to contain 4 TM\ domains, with two extracellular and three cytoplasmic regions. This model\ has been validated for several of the family members by in vitro biochemical\ analysis. Both N- and C-termini are thought to face the cytoplasm, and the\ third TM domain has an amphipathic character, suggesting that it contributes\ to the lining of the formed-channel. Amino acid sequence identity between\ the isoforms is ~50-80%, with the TM domains being well conserved. Both\ extracellular loops contain characteristically conserved cysteine residues,\ which likely form intramolecular disulphide bonds. By contrast, the single\ putative intracellular loop (between TM domains 2 and 3) and the cytoplasmic\ C-terminus are highly variable among the family members.\ Six connexins are\ thought to associate to form a hemi-channel, or connexon. Two connexons then\ interact (likely via the extracellular loops of their connexins) to form the\ complete gap junction channel.

\ \

\ NH2-*** *** *************-COOH\ ** ** ** **\ ** ** ** ** Cytoplasmic\ ---**----**-----**----**----------------\ ** ** ** ** Membrane\ ** ** ** **\ ---**----**-----**----**----------------\ ** ** ** ** Extracellular\ ** ** ** **\ ** **\

\ \

Two sets of nomenclature have been used to identify the connexins. The\ first, and most commonly used, classifies the connexin molecules according\ to molecular weight, such as connexin43 (abbreviated to Cx43), indicating\ a connexin of molecular weight close to 43 kD. However, studies have\ revealed cases where clear functional homologues exist across species\ that have quite different molecular masses; therefore, an alternative\ nomenclature was proposed based on evolutionary considerations, which\ divides the family into two major subclasses, and , each with a\ number of members [MEDLINE:92322997]. Due to their ubiquity and overlapping tissue distributions, it has proved difficult to elucidate the functions of individual connexin isoforms. To circumvent this problem, particular connexin-encoding genes have been subjected to targeted-disruption in mice, and the phenotype of the resulting animals investigated. Around half the connexin isoforms have been investigated in this manner [MEDLINE:99078662]. Further insight into the functional roles of connexins has come from the discovery that a number of human diseases are caused by mutations in connexin genes. For instance, mutations in Cx32 give rise to a form of inherited peripheral neuropathy called X-linked dominant Charcot-Marie-Tooth disease [MEDLINE:96031414]. Similarly, mutations in Cx26 are responsible for both autosomal recessive and dominant forms of nonsyndromic deafness, a disorder characterised by hearing loss, with no apparent effects on other organ systems.

\ \

Gap junction -5 protein (also called connexin30.3, or Cx30.3) is a\ connexin of 266 amino acid residues that shares ~70% amino acid identity\ with both Cx31 and Cx31.1. It is most closely related to the latter;\ together these molecules share a rather restricted expression pattern,\ being preferentially expressed in the skin, and undetectable in most other\ tissues. Additionally, the genes encoding them have been found to be\ rather closely-linked on mouse chromosome 4 [MEDLINE:92381038].

\ \ connexon channel activity ; GO:0015285 connexon complex ; GO:0005922 cell communication ; GO:0007154 20921 IPR002270

\ \

Gap junction -4 protein (also called connexin31.1, or Cx31.1) is a\ connexin of 271 amino acid residues. It is most closely related to Cx30.3,\ being ~70% identical. Together, these connexin molecules show a very\ restricted expression pattern, being preferentially expressed in the skin,\ with minor levels of Cx31.1 also being detected in the testis [MEDLINE:92381038].\ Additionally, Cx31.1 shares ~65% identity with Cx31. That Cx31.1 is able to\ form gap junction channels remains to be proven, attempts at heterologous\ expression having so far failed to generate functional channels.

\ \ \ connexon channel activity ; GO:0015285 connexon complex ; GO:0005922 cell communication ; GO:0007154 20920 IPR002269

\ \

Gap junction -3 protein (also called connexin31, or Cx31) is a connexin\ of 270 amino acid residues, and belongs to a family that also includes Cx26,\ Cx31.1 and Cx32. At the mRNA level, it has been found to be expressed in the\ skin, ear, placenta and eye. Mutations in Cx31 have been found to be\ responsible for two quite different inherited human diseases: erythro-keratomdermia variablis and autosomal dominant hearing impairment. The\ former is a hereditary skin disease characterised by transient figurate red\ patches of skin and hyperkeratosis. In the Cx31 molecule of these patients,\ either a conserved glycine has been substituted by a charged residue, or a\ cysteine has been changed to a to serine residue [MEDLINE:90368755]. In the latter,\ mutations in Cx31 result in high-frequency hearing impairment, making it\ the second connexin molecule (together with Cx26) in which mutations have\ been found to be responsible for an inherited hearing disorder.

\ \ connexon channel activity ; GO:0015285 connexon complex ; GO:0005922 cell communication ; GO:0007154 20919 IPR002268

\ \

Gap junction -2 protein (also called connexin26, or Cx26) is a connexin\ of 226 amino acid residues that is often found together with Cx32 in\ epithelial tissues. In rodents, it seems essential for normal embryonic\ development; mice lacking Cx26 die in utero at about embryonic day 11.\ Absence of Cx26 impairs transplacental movement of glucose, thus impairing\ embryonic development. In humans, spontaneously-occurring mutations in the\ gene encoding Cx26 have been found to be associated with a quite different\ disorder, non-syndromic neurosensory autosomal recessive deafness, the most\ common form of inherited hearing loss. Consistent with a role in auditory\ transduction, Cx26 is the predominant connexin isoform expressed in the\ organ of Corti of the cochlea. Here, it may be involved in maintaining the\ ionic balance of the endolymph, by providing a pathway for ions necessary\ to maintain this potassium-rich fluid.

\ \ connexon channel activity ; GO:0015285 connexon complex ; GO:0005922 cell communication ; GO:0007154 20918 IPR002267

\ \

Gap junction -1 protein (also called connexin32, or Cx32) is a connexin\ of 283 amino acid residues (human isoform) that is widely expressed in many\ tissues, including the liver, exocrine pancreas, central nervous system and\ epithelium of the gastrointestinal tract. The amphibian isoform from the\ African clawed frog, Xenopus laevis, is slightly shorter, containing 264\ amino acid residues. In the adult frog, the protein is present in the lungs,\ alimentary tract and ovaries [MEDLINE:88331091].\ In humans, Cx32 appears to be critical to the functioning of Schwann cells,\ which are responsible for the myelination of nerves in the peripheral\ nervous system. Mutations in the gene encoding Cx32 give rise to a form of\ inherited neuropathy called X-linked Charcot-Marie-Tooth disease, which\ affects nervous conduction in both motor and sensory axons. To date, >40\ different mutations have been identified, and these are spread throughout\ most of the Cx32 molecule. The effects of some of these mutations have been\ determined, and several of them lead to a complete loss of gap junction\ function. Targeted-gene disruption of Cx32 in mice has confirmed its role\ in Schwann cell function; such Cx32-null mice also develop a form of\ peripheral neuropathy similar to Charcot-Marie-Tooth disease.

\ \ connexon channel activity ; GO:0015285 connexon complex ; GO:0005922 cell communication ; GO:0007154 20917 IPR002266

\ \

Gap junction -8 protein (also called connexin50, Cx50, or lens fibre\ protein MP70) is a connexin of ~431 amino acid residues. The chicken isoform\ is shorter (399 residues) and is hence known as Cx45.6. Cx50 and Cx46 are\ the two gap junction proteins normally found in lens fibre cells of the eye.\ Evidence from both genetically-engineered mice, and from the identification\ of mutations in the human Cx50-encoding gene, highlight the importance of\ this connexin in maintaining lens transparency. Deletion of mice Cx50\ produces a viable phenotype, but these animals start to develop cataracts\ (of the zonular pulverant type) at about one week old. They also have\ abnormally small eyes and lenses. Similarly, mutations in the human gene\ encoding Cx50 have been associated with the occurrence of congenital\ cataracts. Affected individuals develop cataracts (with zonular pulverent\ opacities), and analysis shows they have a single point mutation in the Cx50\ coding region, resulting in a non-conservative substitution in the second\ putative TM domain of a serine residue for a proline.

\ \ connexon channel activity ; GO:0015285 connexon complex ; GO:0005922 cell communication ; GO:0007154 20916 IPR002265

\ \

Gap junction -6 protein (also called connexin45, or Cx45) is a connexin\ of 396 amino acid residues. It is one of four isoforms expressed in the\ heart (together with Cx43, Cx40 and Cx37). All four isoforms show differing\ distribution patterns within the human heart: Cx45 tends to be detectable\ only at rather low levels, with a trend toward higher levels in the atria\ than the ventricles. Cx45 is also thought to be involved in the formation of\ gap junctions between the bone-forming cells, osteoblasts; the extent of\ their cell-cell coupling may act to modulate their gene expression.

\ \ connexon channel activity ; GO:0015285 connexon complex ; GO:0005922 cell communication ; GO:0007154 20915 IPR002264

\ \

Gap junction -5 protein (also called connexin40, or Cx40) is a connexin\ of ~357 amino acid residues. The chicken isoform is about ten residues\ longer, and is hence known as connexin42 (Cx42), as it has a molecular mass\ of ~42 kD. Targeted disruption of the gene encoding Cx40 in mice suggests\ that Cx40-containing gap junctions are involved in the rapid conduction of\ impulses in the His-Purkinje system of the heart, which is responsible for\ the coordinated spread of excitation from the atrioventricular (A-V) node\ to the ventricular myocardium. Mice lacking Cx40 are viable and fertile;\ however, they have subtle electrocardio-graphic abnormalities, such as\ partial A-V block. Studies of the distribution of Cx40 support these\ findings, since Cx40 has been reported to be prominently expressed in the\ Purkinje fibres of the heart.

\ \ connexon channel activity ; GO:0015285 connexon complex ; GO:0005922 cell communication ; GO:0007154 20913 IPR002262

\ \

Gap junction -3 protein (also called connexin46, or Cx46) is a connexin\ of ~415 amino acid residues. The bovine form is slightly shorter (401\ residues) and is hence known as Cx44, having a molecular mass of ~44 kD.\ Cx46 (together with Cx50) is a connexin isoform expressed in the lens fibres\ of the eye. Here, gap junctions join the cells into a functional syncytium,\ and also couple the fibres to the epithelial cells on the anterior surface\ of the lens. The lens fibres depend on this epithelium for their metabolic\ support, since they lose their intra-cellular organelles, and accumulate\ high concentrations of crystallins, in order to produce their optical\ transparency. Genetically-engineered mice deficient in Cx46 demonstrate the\ importance of Cx46 in forming lens fibre gap junctions; these mice develop\ normal lenses, but subsequently develop early onset senile-type cataracts\ that resemble human nuclear cataracts. Aberrant proteolysis of crystallin\ proteins has been observed in the lenses of Cx46-null mice.

\ \ connexon channel activity ; GO:0015285 connexon complex ; GO:0005922 cell communication ; GO:0007154 20914 IPR002263

\ \

Gap junction -4 protein (also called connexin37, or Cx37) is a connexin\ of 333 amino acids (human isoform) with a predicted molecular mass of ~37\ kD. It is expressed in many organs and tissues, including: brain, heart,\ uterus, ovary, and endothelial cells of blood vessels. When heterologously\ expressed, Cx37 forms intercellular channels that are more sensitive to\ voltage and show faster voltage-gating kinetics than most other previously-characterised gap junction channels. The recent generation of mice lacking\ the gene encoding Cx37 (GJA4 or CXN-37) has shed some light on its function\ in vivo. Female mice lacking Cx37 are viable and apparently in good health,\ but are rendered infertile, as a result of a failure to ovulate. It appears\ that in the ovarian follicle, functional gap junctions (formed by Cx37) are\ critical for communication between the oocyte and the surrounding granulosa\ cells. Without Cx37, follicular development is arrested, and subsequently\ ovulation does not occur.

\ \ connexon channel activity ; GO:0015285 connexon complex ; GO:0005922 cell communication ; GO:0007154 20912 IPR002261

\ \

\ \ connexon channel activity ; GO:0015285 connexon complex ; GO:0005922 cell communication ; GO:0007154 20911 IPR002260

\ \

Connexin36 (Cx36), which was recently cloned from mammalian brain, encodes\ a protein containing 321 amino acid residues and predicted molecular mass\ of ~36 kD [MEDLINE:98424111]. The rat and mouse forms of Cx36 are near-identical,\ differing by only a single residue. Studies of its distribution (by mRNA\ analysis), have found that is is highly expressed in the adult retina of\ these species, and also (less-abundantly) in the brain. Within the latter,\ the highest expression levels are found in several discrete regions,\ including: the inferior olive, olfactory bulb, the CA3/CA4 sub-fields of\ the hippocampus, and several of the brainstem nuclei.

\ \ connexon channel activity ; GO:0015285 connexon complex ; GO:0005922 cell communication ; GO:0007154 20909 IPR002258

Several 7TM receptors have been cloned but their endogenous ligands are\ unknown; these have been termed orphan receptors. A novel GPCR has been\ isolated from a cDNA derived from the cell line NH15-CA2 and a cDNA library\ from adult mouse brain [MEDLINE:97289630]. The amino acid sequence of the receptor, DEZ,\ shows closest resemblance to neuropeptide and chemoattractant receptors,\ with highest similarity to the orphan receptor GPR-1. In situ hybridisation\ experiments indicate that dez is differentially regulated during development,\ with prominent expression in developing osseous and cartilaginous tissue [MEDLINE:97289630].\ It is also detectable in adult parathyroid glands, suggesting a possible\ function in bone metabolism.

\ \ \ G-protein coupled receptor activity, unknown ligand ; GO:0016526 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20910 IPR002259

Delayed-early response (DER) gene products include growth progressionfactors and several unknown products of novel cDNAs. Murine and human cDNAs\ from one novel DER gene (DER12) have been characterised to identify its\ product and to examine its role in the growth response [MEDLINE:95367016]. Both sequences\ encode a hydrophobic 36kD protein that is predicted to contain 8\ transmembrane (TM) domains. The protein has been localised to the nucleolus,\ where its concentration increases following mitogen stimulation [MEDLINE:95367016].

Although the function of the protein is unknown, its identification as a\ nucleolar gene transcriptionally activated by growth factors implicates it\ as participating in the proliferative response [MEDLINE:95367016]. Sequence analysis\ reveals the protein to share a high degree of similarity with the C-terminal\ portion of equilibrative nucleoside transporters. These proteins are integral membrane proteins which enable the movement of hydrophilic nucleosides\ and nucleoside analogs down their concentration gradients across cell membranes. ENT family members have been identified in humans, mice, fish, tunicates, slime molds, and bacteria [MEDLINE:22337202].

\ \ nucleoside transporter activity ; GO:0005337 membrane ; GO:0016020 transport ; GO:0006810 20907 IPR002256 Flavin-containing monooxygenases (FMOs) constitute a family of xenobiotic-metabolising enzymes [MEDLINE:94145088]. Using an NADPH cofactor and FAD prosthetic group,\ these microsomal proteins catalyse the oxygenation of nucleophilic nitrogen,\ sulphur, phosphorous and selenium atoms in a range of structurally diverse\ compounds. Five mammalian forms of FMO are now known and have been designated\ FMO1-FMO5 [MEDLINE:91286259], [MEDLINE:90202836], [MEDLINE:92179247], [MEDLINE:93038564], [MEDLINE:93252844].\

FMO4 mRNA is present in low abundance in several foetal and adult tissues\ and the corresponding gene thus appears to be expressed constitutively [MEDLINE:96184548].\ Sequence analysis reveals that FMO4 is 56% identical to FMO3; each is\ encoded by a single gene [MEDLINE:94245761]. The deduced amino acid sequence of human FM04 \ includes the putative FAD- (GxGxxG) and NADP⁺ pyrophosphate-binding (GxGxxA)\ sites characteristic of mammalian FMOs, a 'FATGY' motif that has also been\ observed in a range of siderphore biosynthetic enzymes [MEDLINE:98199514], and a C-terminal\ hydrophobic segment that is believed to anchor the monooxygenase to the\ microsomal membrane [MEDLINE:90285148].

\ \ dimethylaniline monooxygenase (N-oxide forming) activity ; GO:0004499 microsome ; GO:0005792 electron transport ; GO:0006118 20908 IPR002257 Flavin-containing monooxygenases (FMOs) constitute a family of xenobiotic-metabolising enzymes [MEDLINE:94145088]. Using an NADPH cofactor and FAD prosthetic group,\ these microsomal proteins catalyse the oxygenation of nucleophilic nitrogen,\ sulphur, phosphorous and selenium atoms in a range of structurally diverse\ compounds. Five mammalian forms of FMO are now known and have been designated\ FMO1-FMO5 [MEDLINE:91286259], [MEDLINE:90202836], [MEDLINE:92179247], [MEDLINE:93038564], [MEDLINE:93252844].\

The deduced amino acid sequence of human FM05 includes the putative FAD- \ (GxGxxG) and NADP⁺ pyrophosphate-binding (GxGxxA) sites characteristic of \ mammalian FMOs [MEDLINE:98241973], a 'FATGY' motif that has also been observed in a range\ of siderphore biosynthetic enzymes [MEDLINE:98199514], and a C-terminal hydrophobic segment\ that is believed to anchor the monooxygenase to the microsomal membrane [MEDLINE:90285148].\ Human and guinea pig FMO5, like other FMOs, are encoded by multiple\ transcripts. FMO5 has been identified in livers of adult humans, rabbits\ and guinea pigs, and foetal livers of humans\ \ \ \ [MEDLINE:95177663]. Neither the human nor \ guinea pig enzyme effectively catalyse the metabolism of methimazole, a\ general FMO substrate; however, both are active with n-octylamine [MEDLINE:95177663]. The\ responses to detergent, ions and elevated temperature are all similar to \ those observed in rabbit FMO5, suggesting that these properties are species-\ independent and that this form of FMO is not readily classified as a drug-\ metabolising enzyme [MEDLINE:95177663].

\ \ dimethylaniline monooxygenase (N-oxide forming) activity ; GO:0004499 microsome ; GO:0005792 electron transport ; GO:0006118 20906 IPR002255

Flavin-containing monooxygenases (FMOs) constitute a family of xenobiotic-metabolising enzymes [MEDLINE:94145088]. Using an NADPH cofactor and FAD prosthetic group,\ these microsomal proteins catalyse the oxygenation of nucleophilic nitrogen,\ sulphur, phosphorous and selenium atoms in a range of structurally diverse\ compounds. Five mammalian forms of FMO are now known and have been designated\ FMO1-FMO5 [MEDLINE:91286259], [MEDLINE:90202836], [MEDLINE:92179247], [MEDLINE:93038564], [MEDLINE:93252844].

The mRNA encoding FMO3 is abundant in adult liver and is also present, in\ low abundance, in some foetal tissues. Thus, like FMO1, FMO3 is subject\ to developmental and tissue-specific regulation, with a developmental switch\ in the expression of the genes taking place in the liver [MEDLINE:96184548]. \ The deduced amino acid sequence of human FM03 includes the putative FAD-\ (GxGxxG) and NADP⁺ pyrophosphate-binding (GxGxxA) sites characteristic of\ mammalian FMOs [MEDLINE:98008021], a 'FATGY' motif that has also been observed in a range\ of siderphore biosynthetic enzymes [MEDLINE:98199514], and a C-terminal hydrophobic \ segment that is believed to anchor the monooxygenase to the microsomal \ membrane [MEDLINE:90285148].\ Mutations in human FMO3 impair N-oxygenation of xenobiotics and are \ responsible for the trimethylaminuria phenotype [MEDLINE:98204808]. Three disease-causing\ mutations have been identified. Nonsense and missense mutations are \ associated with a severe phenotype and are also implicated in impaired\ metabolism of other nitrogen- and sulphur-containing substrates, including\ biogenic amines, both clinically and when mutated proteins expressed from\ cDNA are studied in vitro [MEDLINE:98204808]. Human FMO3 thus plays a critical role in the\ metabolism of xenobiotic substrates and endogenous amines.

\ \ dimethylaniline monooxygenase (N-oxide forming) activity ; GO:0004499 microsome ; GO:0005792 electron transport ; GO:0006118 20905 IPR002254

Guinea pig and rabbit both express two variants of 'lung' FMO, observed as\ three distinct phenotypes based on mobility differences in SDS-PAGE [MEDLINE:93306345].\ The coding regions of the guinea pig variants differ at only two positions,\ both of which result in amino acid substitutions [MEDLINE:93306345]. Similarly, the\ nucleotide and amino acid sequences of the rabbit variants differ at only\ two positions. The amino sequence contains putative FAD- (GxGxxG) and NADP⁺-\ binding (GxGxxA) sites, a 'FATGY' motif that has also been observed in a \ range of siderphore biosynthetic enzymes [MEDLINE:98199514], and a C-terminal hydrophobic\ segment that is believed to anchor the monooxygenase to the microsomal\ membrane [MEDLINE:90285148].\ The activities of the enzymes are characteristic of the lung FMO, and the\ mobilities of the expressed enzymes are the same as those observed for the\ variants present in guinea pig pulmonary microsomal preparations [MEDLINE:93306345]. Both\ rabbit and guinea pig lung FMO are associated with a single gene. Rabbit \ lung FMO exists in tight association with the calcium-binding protein, \ calreticulin [MEDLINE:92002038]. It is thought that complexation of calreticulin with \ rabbit lung FMO could account for some of the unusual physical properties\ of this FMO enzyme form.

\ \ dimethylaniline monooxygenase (N-oxide forming) activity ; GO:0004499 microsome ; GO:0005792 electron transport ; GO:0006118 20904 IPR002253 Flavin-containing monooxygenases (FMOs) constitute a family of xenobiotic-metabolising enzymes [MEDLINE:94145088]. Using an NADPH cofactor and FAD prosthetic group,\ these microsomal proteins catalyse the oxygenation of nucleophilic nitrogen,\ sulphur, phosphorous and selenium atoms in a range of structurally diverse\ compounds. FMOs have been implicated in the metabolism of a number of\ pharmaceuticals, pesticides and toxicants. In man, lack of hepatic FMO-\ catalysed trimethylamine metabolism results in trimethylaminuria (fish \ odour syndrome).\ Five mammalian forms of FMO are now known and have been designated\ FMO1-FMO5 [MEDLINE:91286259], [MEDLINE:90202836], [MEDLINE:92179247], [MEDLINE:93038564], [MEDLINE:93252844]. \

Human FMO1 mRNA is more abundant in foetal than in adult liver, indicating \ that the enzyme is subject to developmental regulation in man\ \ \ \ [MEDLINE:91286259]. The deduced amino sequence \ contains putative FAD- (GxGxxG) and NADP⁺-binding (GxGxxA) sites, a 'FATGY'\ motif that has also been observed in a range of siderphore biosynthetic\ enzymes [MEDLINE:98199514], and a C-terminal hydrophobic segment that is believed to anchor\ the monooxygenase to the microsomal membrane [MEDLINE:90285148]. The human sequence shares \ 88 and 86% identity, respectively, with pig and rabbit 'hepatic' forms of\ FMO, but is only 58% similar to the rabbit 'pulmonary' FMO [MEDLINE:91286259].

\ \ dimethylaniline monooxygenase (N-oxide forming) activity ; GO:0004499 microsome ; GO:0005792 electron transport ; GO:0006118 20903 IPR002252

Glycoside hydrolase family 36 CAZY:GH_36).

\ \

Alpha-galactosidase (melibiase) catalyses the hydrolysis of melibiose into\ galactose and glucose [MEDLINE:95242831]. In man, deficiency in the enzyme results in\ Fabry's disease (X-linked sphingolipidosis). An E.coli plasmid-encoded -galactosidase (rafA) [MEDLINE:90078124] contains a region of about 50 amino acids\ that is similar to a domain of the eukaryotic -galactosidases.

\ \ alpha-galactosidase activity ; GO:0004557 \N carbohydrate metabolism ; GO:0005975 20902 IPR002251

Chloride channels (CLCs) constitute an evolutionarily well-conserved family of voltage-gated channels that are structurally unrelated to the other known voltage-gated channels. They are found in organisms ranging from bacteria to yeasts and plants, and also to animals. Their functions in higher animals likely include the regulation of cell volume, control of electrical excitability and trans-epithelial transport [MEDLINE:97198187].

The first member of the family (CLC-0) was expression-cloned from the electric organ of Torpedo marmorata [MEDLINE:91061906], and subsequently nine CLC-like proteins have been cloned from mammals. They are thought to function as multimers of two or more identical or homologous subunits, and they have varying tissue distributions and functional properties. To date, CLC-0, CLC-1, CLC-2, CLC-4 and CLC-5 have been demonstrated to form functional Cl- channels; whether the remaining isoforms do so is either contested or unproven. One possible explanation for the difficulty in expressing activatable Cl- channels is that some of the isoforms may function as Cl- channels of intracellular compartments, rather than of the plasma membrane. However, they are all thought to have a similar transmembrane (TM) topology, initial hydropathy analysis suggesting 13 hydrophobic stretches long enough to form putative TM domains [MEDLINE:91061906]. Recently, the postulated TM topology has been revised, and it now seems likely that the CLCs have 10 (or possibly 12) TM domains, with both N- and C-termini residing in the cytoplasm [MEDLINE:97352851].

\ \

A number of human disease-causing mutations have been identified in the genes encoding CLCs. Mutations in CLCN1, the gene encoding CLC-1, the major skeletal muscle Cl- channel, lead to both recessively and dominantly-inherited forms of muscle stiffness or myotonia [MEDLINE:96090261]. Similarly, mutations in CLCN5, which encodes CLC-5, a renal Cl- channel, lead to several forms of inherited kidney stone disease [MEDLINE:96158876]. These mutations have been demonstrated to reduce or abolish CLC function.

\ \ \

In plants, chloride channels contribute to a number of plant-specific\ functions, such as regulation of turgor, stomatal movement, nutrient\ transport and metal tolerance. By contrast with Cl^- channels in animal cells, they are also responsible for the generation of action potentials.\ The best documented examples are the chloride channels of guard cells,\ which control opening and closing of stomata. Recently, four homologous\ proteins that belong to the CLC family have been cloned from Arabidopsis\ thaliana (mouse ear-cress)\ \ \ \ [MEDLINE:97126010]. Hydropathy analysis suggests that they have\ a similar membrane topology to other CLC proteins, with up to 12 TM domains.\ Expression in Xenopus oocytes failed to generate measurable Cl^- currents,\ although protein analysis suggested they had been synthesised and inserted\ into cell membranes. However, similar CLC proteins have since been cloned\ from other plants, and one, CIC-Nt1 (from tobacco), has been demonstrated to\ form funtional Cl^- channels, suggesting that at least some of these proteins\ do function as Cl^- channels in plants [MEDLINE:96206817].

\ \ voltage-gated chloride channel activity ; GO:0005247 membrane ; GO:0016020 chloride transport ; GO:0006821 20901 IPR002250

\ \

\ \ \

Two highly similar members of the CLC family have been cloned that appear\ to be kidney-specific isoforms. These are known as CLC-Ka and CLC-Kb in\ humans and are ~90% identical (at the amino acid level); in other species,\ they are named CLC-K1 and CLC-K2 [MEDLINE:94316614], [MEDLINE:94292532]. Within species, the two isoforms\ show differing distribution patterns in the kidney, possibly suggesting\ diferent roles in renal function. To date, attempts at functional expression\ of CLC-K isoforms have not yielded measurable Cl^- currents; however, that\ they play a key role in normal kidney function had been made clear by the\ fact that naturally occurring mutations in the human gene CLCNKB (encoding\ CLC-Kb) lead to a form of Bartter's syndrome, an inherited kidney disease\ characterised by hypokalaemic alkalosis [MEDLINE:97467727]. Similarly, transgenic mice,\ whose CLC-K1 channel has been rendered dysfunctional by targeted gene\ disruption, develop overt diabetes, suggesting that these channels are\ important for urinary concentration [MEDLINE:99113836].

\ \ voltage-gated chloride channel activity ; GO:0005247 membrane ; GO:0016020 chloride transport ; GO:0006821 20900 IPR002249

\ \

\ \ \

CLC-7 is a CLC that, together with CLC-6, forms a distinct branch of the\ CLC gene family. CLC-7 consists of 789 amino acid residues (human isoform)\ and is ~45% identical to CLC-6 (at the amino acid level). CLC-7 is broadly\ expressed, but, to date, functional studies have not generated measurable\ Cl^- currents; its identification as a functional Cl^- channel therefore\ remains putative. Interestingly, CLC-7 is the only known eukaryotic CLC\ protein to lack a highly conserved glycosylation site between hydrophobic\ domains D8 and D9 [MEDLINE:96130311].

\ \ voltage-gated chloride channel activity ; GO:0005247 membrane ; GO:0016020 chloride transport ; GO:0006821 20899 IPR002248

\ \

\ \ \

CLC-6 is a CLC that, together with CLC-7, forms a distinct branch of the\ CLC gene family. CLC-6 consists of 869 amino acids residues (human isoform)\ and is ~45% identical to CLC-7 (at the amino acid level). CLC-6 is broadly\ expressed, but, to date, functional studies have not generated measurable\ Cl^- currents; its identification as a functional Cl^- channel therefore\ remains putative [MEDLINE:96130311]. Analysis of human CLC-6 mRNAs reveals that transcripts\ of the encoding gene (CLCN6) are alternatively-spliced, resulting in the\ expression of four different CLC-6 isoforms (CLC-6a to CLC-6d). These show\ different levels of abundance and tissue distribution patterns, with one,\ CLC-6c, apparently being a kidney-specific isoform [MEDLINE:97344267].

\ \ voltage-gated chloride channel activity ; GO:0005247 membrane ; GO:0016020 chloride transport ; GO:0006821 20898 IPR002247

\ \

\ \ \

CLC-5, with 746 amino acid residues, is a member of the CLC family that\ shows most similarity to the CLC-3 and CLC-4 channels, to which it is ~80%\ identical at the amino acid level. It is predominantly expressed in the\ kidney, but can be found in the brain and liver [MEDLINE:96125100]. As mentioned above,\ mutations in the CLCN5 gene cause certain hereditary kidney stone diseases,\ including Dent's disease, an X-chromosome linked syndrome characterised by\ proteinuria, hypercalciuria, and kidney stones (nephrolithiasis), leading to\ progressive renal failure. When the native protein is expressed, it gives\ rises to strongly outwardly-rectifying Cl^- currents; however, the mutated\ channel forms show loss-of-function [MEDLINE:96125100], [MEDLINE:99091628]. Recent studies have suggested\ that CLC-5 may play an important role in endocytosis in renal proximal\ tubule cells (probably by providing a shunt for the potential generated by\ the H⁺-ATPase), and that disruption of this function may impair endocytosis,\ accounting for the proteinuria observed in Dent's disease [MEDLINE:98318613].

\ \ \ voltage-gated chloride channel activity ; GO:0005247 membrane ; GO:0016020 chloride transport ; GO:0006821 20897 IPR002246

\ \

\ \ \

CLC-4 was initially identified as a putative member of the CLC family\ following mapping of the human Xp22.3 chromosome region [MEDLINE:94348498]. Together with\ CLC-5 and CLC-3, it forms a distinct branch of the CLC gene family. Initial\ expression studies of CLC-4 did not yield measurable Cl^- currents; however,\ recent studies of human CLC-4 have revealed that it gives rise to Cl^-\ currents that rapidly activate at positive voltages, and are sensitive to\ extracellular pH, with currents decreasing when pH falls below 6.5 [MEDLINE:99091628].

\ \ voltage-gated chloride channel activity ; GO:0005247 membrane ; GO:0016020 chloride transport ; GO:0006821 20896 IPR002245

\ \

\ \ \

CLC-3 is a member of the CLC family initially cloned from rat kidney [MEDLINE:95394449]\ and localised to chromosome 4 in humans [MEDLINE:99091628]; the human isoform contains 762\ amino acid residues. Together with CLC-4 and CLC-5, it forms a distinct\ branch of the CLC gene family, the three members showing ~80% residue\ identity. Expression of CLC-3 produces outwardly-rectifying Cl^- currents\ that are inhibited by protein kinase C activation [MEDLINE:95394449],[MEDLINE:98049352].\ More recently, it has been suggested that CLC-3 may be a ubiquitous swelling\ -activated Cl^- channel that has very similar characteristics to those of\ native volume-regulated Cl^- currents [MEDLINE:98049352].

\ \ voltage-gated chloride channel activity ; GO:0005247 membrane ; GO:0016020 chloride transport ; GO:0006821 20895 IPR002244

\ \

\ \ \

CLC-2 is a member of the CLC family that is ubiquitously expressed in\ mammalian tissues. It is 898 amino acid residues in length (human isoform)\ and shows ~50% amino acid identity to CLC-1, to which it is most closely\ related [MEDLINE:97198187]. The channel is normally closed at physiological membrane\ potentials, but can be activated by rather strong hyperpolarisation.\ However, it is activated by cell swelling, suggesting a role for it in cell\ volume regulation. It is also activated by acidic extracellular pH; the\ region of the molecule (near the N-terminus) that imparts sensitivity to\ both cell swelling and extracellular pH has been elucidated [MEDLINE:93101216].

\ \ voltage-gated chloride channel activity ; GO:0005247 membrane ; GO:0016020 chloride transport ; GO:0006821 20894 IPR002243

\ \

\ \ \

CLC-1 was the first member of the CLC family cloned from mammalian species\ [MEDLINE:92065954], and has 998 amino acid residues (human isoform). It is principally\ expressed in skeletal muscle, but low transcript levels can be detected in\ kidney, heart and smooth muscle. In skeletal muscle, it gives rise to the\ majority of the muscle membrane Cl^- conductance (which accounts for ~70-80%\ of the total resting conductance). These channels are partially open under\ resting conditions, and it is likely that following a prolonged series of\ muscle action potentials, they act to reduce excitability, limiting tetanic\ activation. As mentioned above, mutations in CLC-1 can cause recessive\ (Becker) as well as dominant (Thomsen) myotonia. Such mutations reduce\ channel function, rendering skeletal muscle hyperexcitable. This leads to\ defective muscle relaxation after voluntary contraction.

\ \ voltage-gated chloride channel activity ; GO:0005247 membrane ; GO:0016020 chloride transport ; GO:0006821 20892 IPR002241

Glycoside hydrolase family 27 CAZY:GH_27).

Alpha-galactosidase (melibiase) catalyses the hydrolysis of melibiose into\ galactose and glucose [MEDLINE:95242831]. In man, deficiency in the enzyme results in\ Fabry's disease (X-linked sphingolipidosis). Alpha-N-acetylgalactosaminidase\ catalyses the hydrolysis of terminal non-reducing N-acetyl-D-galactosamine\ residues in N-acetyl--D-galactosaminides [MEDLINE:91072392]. Two conserved Asp residues may be involved in the catalytic mechanism in these enzymes. Deficiency in this enzyme \ results in Schindler and Kanzaki diseases.

\ \ hydrolase activity, hydrolyzing O-glycosyl compounds ; GO:0004553 \N carbohydrate metabolism ; GO:0005975 20893 IPR002242

\ \

\ \ \

CLC-0 is the principal Cl^- channel of the electric organ of the Torpedo\ species. These marine electric rays generate high voltage pulses (to stun\ their prey) by the concerted action of Cl^- channels and nicotinic acetylcholine receptors, in specialised cells known as electrocytes. The\ properties of the CLC-0 channel (consisting of 805-809 amino acids) have\ been extensively studied after reconstitution into lipid bilayers. It has\ a peculiar double-barrelled structure, appearing to have two identical ion\ pores that close and open independently, but which can be also closed\ together by another common gate. Further evidence also suggests it may\ function as a homodimer [MEDLINE:96404355], [MEDLINE:96404356].

\ \ voltage-gated chloride channel activity ; GO:0005247 membrane ; GO:0016020 chloride transport ; GO:0006821 20891 IPR002240

Chemokines are proteins that have important physiological and pathophysiological roles in a wide range of acute and chronic inflammatory\ processes. Their sequences are similar and are characterised by a\ 4-cysteine motif: the family can be divided according to whether the\ first 2 Cys residues are adjacent (the C-C family), or separated by an\ intervening residue (the C-x-C family). C-C chemokines are chemoattractant\ for monocytes but not for neutrophils. The C-C family includes human\ monocyte chemotactic protein-1 (MCP-1), regulated on activation, normal\ T cell expressed and secreted (RANTES) and macrophage inflammatory proteins\ (MIP-1a and MIP-1b) PUB00005876.

C-C chemokine receptors are found in monocytes, lymphocytes, basophils and\ eosinophils; mRNA is also found in some cell lines. MCP-1 and MIP-1a\ induce activation in low nanomolar concentrations and are highly selective\ relative to C-x-C receptors. Calcium mobilisation has been demonstrated in\ monocytes and in cells expressing the recombinant C-C receptor via an\ uncharacterised G-protein; pertussis toxin inhibits some of its actions PUB00005876.\ A novel chemokine receptor, encoded 18 kilobase pairs downstream of the\ MCP-1 receptor (CCR2) gene on human chromosome 3p21, has been identified\ [MEDLINE:96291862]. The deduced amino acid sequence of the receptor, designated CCR5, is\ most similar to CCR2B, sharing 71% identical residues [MEDLINE:96291862]. Transfected cells\ expressing the receptor bind RANTES, MIP-1beta and MIP-1alpha with high\ affinity, and generate inositol phosphates in response to these chemokines.\ The same combination of chemokines has been shown potently to inhibit human\ immunodeficiency virus replication in human peripheral blood leukocytes [MEDLINE:96291862].

CCR5 is expressed in lymphoid organs, such as thymus and spleen, as well as\ in peripheral blood leukocytes, including macrophages and T cells [MEDLINE:96291862].

\ \ \ C-C chemokine receptor activity ; GO:0016493 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20889 IPR002238

Chemokines are proteins that have important physiological and pathophysiological roles in a wide range of acute and chronic inflammatory\ processes. Their sequences are similar and are characterised by a\ 4-cysteine motif: the family can be divided according to whether the\ first 2 Cys residues are adjacent (the C-C family), or separated by an\ intervening residue (the C-x-C family). C-C chemokines are chemoattractant\ for monocytes but not for neutrophils. The C-C family includes human\ monocyte chemotactic protein-1 (MCP-1), regulated on activation, normal\ T cell expressed and secreted (RANTES) and macrophage inflammatory proteins\ (MIP-1a and MIP-1b) PUB00005876.

C-C chemokine receptors are found in monocytes, lymphocytes, basophils and\ eosinophils; mRNA is also found in some cell lines. MCP-1 and MIP-1a\ induce activation in low nanomolar concentrations and are highly selective\ relative to C-x-C receptors. Calcium mobilisation has been demonstrated in\ monocytes and in cells expressing the recombinant C-C receptor via an\ uncharacterised G-protein; pertussis toxin inhibits some of its actions PUB00005876.\ A human cDNA encoding an eosinophil-selective chemokine receptor (designated\ CC chemokine receptor 3 (CC CKR3)) has been isolated [MEDLINE:95348056]. When [Ca²⁺]i changes were monitored in stably transfected human embryonic kidney 293\ cells, MIP-1 and RANTES were both potent agonists for CC CKR3 and\ CC CKR1 [MEDLINE:95348056]. However, MIP-1 was also an agonist for CC CKR3 but not CC\ CKR1; MCP-3 was an agonist for CC CKR1 but not CC CKR3 [MEDLINE:95348056]. CC CKR3 may be\ one of the host factors responsible for selective recruitment of eosinophils\ to sites of inflammation [MEDLINE:95348056].

\ \ \ C-C chemokine receptor activity ; GO:0016493 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20890 IPR002239

Chemokines are proteins that have important physiological and pathophysiological roles in a wide range of acute and chronic inflammatory\ processes. Their sequences are similar and are characterised by a\ 4-cysteine motif: the family can be divided according to whether the\ first 2 Cys residues are adjacent (the C-C family), or separated by an\ intervening residue (the C-x-C family). C-C chemokines are chemoattractant\ for monocytes but not for neutrophils. The C-C family includes human\ monocyte chemotactic protein-1 (MCP-1), regulated on activation, normal\ T cell expressed and secreted (RANTES) and macrophage inflammatory proteins\ (MIP-1a and MIP-1b) PUB00005876.

C-C chemokine receptors are found in monocytes, lymphocytes, basophils and\ eosinophils; mRNA is also found in some cell lines. MCP-1 and MIP-1a\ induce activation in low nanomolar concentrations and are highly selective\ relative to C-x-C receptors. Calcium mobilisation has been demonstrated in\ monocytes and in cells expressing the recombinant C-C receptor via an\ uncharacterised G-protein; pertussis toxin inhibits some of its actions PUB00005876.\ The murine homologue of human CC chemokine receptor-4 (CC CKR-4) has been\ cloned [MEDLINE:96136324]. The gene product is 85% identical to human CC CKR-4, to which\ it shows similar binding characteristics and tissue distribution [MEDLINE:96136324]. Murine\ CC CKR-4 was detected in the thymus and T-cell lines by Northern blot\ analysis [MEDLINE:96136324].

\ \ \ C-C chemokine receptor activity ; GO:0016493 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20888 IPR002237

Chemokines are proteins that have important physiological and pathophysiological roles in a wide range of acute and chronic inflammatory\ processes. Their sequences are similar and are characterised by a\ 4-cysteine motif: the family can be divided according to whether the\ first 2 Cys residues are adjacent (the C-C family), or separated by an\ intervening residue (the C-x-C family). C-C chemokines are chemoattractant\ for monocytes but not for neutrophils. The C-C family includes human\ monocyte chemotactic protein-1 (MCP-1), regulated on activation, normal\ T cell expressed and secreted (RANTES) and macrophage inflammatory proteins\ (MIP-1a and MIP-1b) PUB00005876.

C-C chemokine receptors are found in monocytes, lymphocytes, basophils and\ eosinophils; mRNA is also found in some cell lines. MCP-1 and MIP-1a\ induce activation in low nanomolar concentrations and are highly selective\ relative to C-x-C receptors. Calcium mobilisation has been demonstrated in\ monocytes and in cells expressing the recombinant C-C receptor via an\ uncharacterised G-protein; pertussis toxin inhibits some of its actions PUB00005876.\ A novel murine C-C chemokine receptor, designated mCCR2, has been cloned\ from the mouse monocyte cell line WEHI265.1 [MEDLINE:96216064]. When stably expressed in\ human embryonic kidney 293 cells, mCCR2 specifically binds 125I-JE with high\ affinity [MEDLINE:96216064]. FIC is less potent than JE in competing 125I-JE binding to\ mCCR2-expressing cells, while three other mouse chemokines, MIP-1alpha, C10\ and N51/KC, do not compete. mccr2 mRNA is detected in elicited peritoneal\ macrophages as well as in several mouse organs [MEDLINE:96216064].

\ \ \ C-C chemokine receptor activity ; GO:0016493 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20887 IPR002236

Chemokines are proteins that have important physiological and pathophysiological roles in a wide range of acute and chronic inflammatory\ processes. Their sequences are similar and are characterised by a\ 4-cysteine motif: the family can be divided according to whether the\ first 2 Cys residues are adjacent (the C-C family), or separated by an\ intervening residue (the C-x-C family). C-C chemokines are chemoattractant\ for monocytes but not for neutrophils. The C-C family includes human\ monocyte chemotactic protein-1 (MCP-1), regulated on activation, normal\ T cell expressed and secreted (RANTES) and macrophage inflammatory proteins\ (MIP-1a and MIP-1b) PUB00005876.

C-C chemokine receptors are found in monocytes, lymphocytes, basophils and\ eosinophils; mRNA is also found in some cell lines. MCP-1 and MIP-1a\ induce activation in low nanomolar concentrations and are highly selective\ relative to C-x-C receptors. Calcium mobilisation has been demonstrated in\ monocytes and in cells expressing the recombinant C-C receptor via an\ uncharacterised G-protein; pertussis toxin inhibits some of its actions PUB00005876.\ Human and murine MIP-1 , human MCP-1 and RANTES all bind to the C-C\ CKR-1 with varying affinities [MEDLINE:93161416]. Chemokine binding affinity does not\ predict how well the ligand will transmit a signal through the receptor:\ RANTES and human MIP-1 induce a similar intracellular calcium flux\ but bind with disparate affinities, while MCP-1 and human MIP-1 induce\ calcium mobilisation only at high concentrations [MEDLINE:93161416]. C-C chemokines have\ been shown to bind a C-C CKR-1-related gene product encoded by cytomegalovirus, suggesting a role for C-C chemokines in viral immunity [MEDLINE:93161416].

\ \ \ C-C chemokine receptor activity ; GO:0016493 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20885 IPR002234

The accumulation of phagocytic cells at the site of injury or infection is\ regulated by substances that stimulate chemotaxis, granule secretion,\ superoxide generation and upregulation of cell surface adhesion molecules\ in cells of the immune system. The chemoattractant substances include\ C5a, N-formylmethionyl-containing peptides, interleukin 8, leukotriene B4\ and platelet activating factor, many of which participate in anaphylactoid\ and septic shock PUB00005873. The C5a receptor is found on cells of the immune\ system (e.g., neutrophils, macrophages, mast cells and related cell lines),\ and is also present in smooth muscle. The amino acid sequence of the\ receptor contains several N-terminal acidic residues, which may be\ involved in binding the basic C5a peptide.

An orphan GPCR with 37% nucleotide identity to the C5a receptor PUB00005873 has\ been identified [MEDLINE:96355342]. By contrast with C5aR and other GPCRs, a novel feature\ of the gene product is the presence of an unusually large predicted extracellular loop, containing in excess of 160 amino acid residues, between\ TM domains 4 and 5 [MEDLINE:96355342]. In human tissues, expression of mRNA for this\ receptor is similar to, but distinct from C5aR expression [MEDLINE:96355342]. Although\ there are some differences, transcripts for both receptors are detected\ in tissues throughout the body and the central nervous system [MEDLINE:96355342]. This\ novel gene has been shown to encode the human anaphylatoxin C3a receptor\ [MEDLINE:96355342]. The C3aR appears to be widely expressed in different lymphoid tissues,\ providing evidence for a central role of the C3a anaphylatoxin in\ inflammatory processes [MEDLINE:96350520].

\ \ \ anaphylatoxin receptor activity ; GO:0004942 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20886 IPR002235

Chemokines are proteins that have important physiological and patho- physiological roles in a wide range of acute and chronic inflammatory processes PUB00005876. Their sequences are similar and are characterised by a 4-cysteine motif: the family can be divided according to whether the first 2\ Cys residues are adjacent (the C-C family), or separated by an intervening\ residue (the C-x-C family).

A novel chemokine, CXCL16, has been identified that is a member of the C-X-C\ family PUB00005876, [MEDLINE:21186241]. Despite possessing the CXC motif, however, it is distantly related to the other family members and has greatest sequence similarity to members of the C-C family [MEDLINE:21186241]. CXCL16 also differs in structure from the other family members (all of which are secreted proteins) and contains a TM domain linked to the chemokine domain by a heavily glycosylated mucin stalk. This structure is similar to that of the CX3C chemokine fractalkine, the only other known chemokine with a TM domain. CXCL16 has been found to be expressed in the spleen, lymph nodes, Peyer's patches and thymus. In non-lymphoid tissues, CXCL16 is found in the lung, small intestine, kidney, heart and liver [MEDLINE:21177382]. The chemokine appears to be expressed as a membrane-bound cell surface ligand on antigen presenting cells (APCs), such as B cells and macrophages [MEDLINE:21186241]. CXCL16 can also be shed from the cell surface in an active, soluble form [MEDLINE:21177382], [MEDLINE:21186241]. These two forms may have different functions. Expression of CXCL16 is upregulated by exposure to inflammatory stimuli.

The receptor for CXCL16 has been identified as an orphan receptor, Bonzo,\ which has now been renamed CXCR6 [MEDLINE:21177382]. CXCL16 does not activate any other known chemokine receptor, making this pairing highly specific [MEDLINE:21186241]. CXCR6 is expressed in lymphoid tissues and activated T cells and is induced in peripheral blood leukocytes [MEDLINE:97311099]. It has also been found on natural killer cells [MEDLINE:21177382]. Binding of CXCL16 to CXCR6 causes chemotactic migration in activated T cells. This chemotactic response is sensitive to pertussis toxin and CXCL16 also results in calcium mobilisation, suggesting coupling to a Gi/o protein [MEDLINE:21177382]. A number of roles have been suggested for CXCR6. Subset-specific immune responses may be regulated by cell-cell contacts between activated subsets of T cells (expressing CXCR6) and APCs (expressing CXCL16). CXCR6 may also be involved in cell-cell contacts during chronic inflammation [MEDLINE:21186241]. Additional roles for the receptor include T cell migration in the splenic red pulp, thymocyte development and effector T cell trafficking. CXCR6 also acts as a coreceptor for T cell line-tropic and macrophage-tropic HIV-1 strains, and may play a role in the establishment and progression of HIV infection [MEDLINE:97311099].

\ \ C-X-C chemokine receptor activity ; GO:0016494 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20884 IPR002233

In the periphery, the adrenergic system plays an important role in regulating the cardiovascular system PUB00005869. Increased sympathetic discharge to the heart increases the rate and force of contraction mediated through -1 receptors. Circulating adrenaline also acts on cardiac tissue, and, in addition, acts both on -1 adrenoceptors in arterial smooth muscle, stimulating vasoconstriction, and on -2 adrenoceptors in vascular beds of skeletal muscle, stimulating vasodilation. In the CNS, noradrenaline is thought to be involved in the regulation of mood, and various psychoactive drugs alter noradrenergic function. Numerous drugs exert their actions via adrenoceptors: e.g., -2 selective agonists such as salbutamol are used in the acute treatment of asthma, while agonists prolong the action of local anaesthetics, and act as nasal decongestants PUB00005869.

Adrenoceptors can be divided into three main classes based on sequence similarity, receptor pharmacology and signalling mechanisms. Further subdivisions exist within each class. A large number of agonists and antagonists distinguish between the different classes of adrenoceptor; by contrast, relatively small differences in agonist and antagonist affinities are demonstrated, especially within the -1 and -2 adrenoceptor subtypes PUB00005869.

\ \ adrenoceptor activity ; GO:0004935 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20883 IPR002232

Numerous receptor subtypes have been classified according to their antagonist susceptibilities and their affinities for 5HT. Five 5HT1 subtypes and at least three 5HT2 subtypes have now been identified, in addition to subtypes 5HT3-7 PUB00005889. All share a high degree of sequence similarity, and have overlapping pharmacological specificities.

The 5HT5 receptor has a similar pharmacology to the 5HT1D receptor. In\ the CNS, its mRNA is found in the cerebral cortex, hippocampus, habenula,\ olfactory bulb and granular layer of the cerebellum. There are no\ selective agonists, and the receptor does not appear to be linked to the\ adenylyl cyclase or phosphoinositide pathways PUB00005889.

\ \ \N integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20882 IPR002231

\ \ \N integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20880 IPR002229

Proteins in this group are responsible for the molecular basis of the blood group antigens, surface markers on the outside of the red blood cell membrane. Most of these markers are proteins, but some are carbohydrates attached to lipids or proteins [Reid M.E., Lomas-Francis C. The Blood Group Antigen FactsBook Academic Press, London / San Diego, (1997)]. The RH(CE) polypeptide (Rhesus C/E antigens) and RH(D) polypeptide (Rhesus D antigen) belong to the Rh blood group system and are associated with antigens that include C/c, E/e, D, f, C(e), C(w), C(x), V, E(w), G, Tar, VS, D(w), cE, and others.

The Rh (Rhesus) blood group system is important in clinical medicine by\ virtue of being involved in haemolytic disease of the newborn, transfusion\ reactions, autoimmune haemolytic anaemias, and haemolytic reactions of \ nonimmune origin [MEDLINE:93066356]. The RH locus from RH(D)-positive donors contains 2\ homologous structural genes, one of which encodes the D protein that\ carries the major antigen of the Rh system. Hydropathy analysis of the \ RhD gene product reveals 13 hydrophobic domains, all of which have been \ assumed to be transmembrane (TM) [MEDLINE:93066356].

\ \ \N membrane ; GO:0016020 \N 20881 IPR002230

The ability of marijuana to activate the cannabinoid receptor provides a\ molecular explanation for its psychoactive effects and other CNS actions\ (which include hallucinations, memory deficits, altered time and space\ perception, CNS depression and appetite stimulation). The endogenous\ ligand at the cannabinoid receptor is unknown, although it may be a\ derivative of arachidonic acid. The cannabinoid receptor is widespread\ throughout the CNS, high levels occurring in the dendate gyrus, hippocampus\ and cerebral cortex, with more moderate levels in the hypothalamus and\ amygdala. It is also present in various cell lines, and in the periphery\ it is found in the testis and vas deferens PUB00005670.

\ \ \ cannabinoid receptor activity ; GO:0004949 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20876 IPR002225 The enzyme 3

-hydroxysteroid dehydrogenase/5-ene-4-ene isomerase (3

-HSD) catalyses the oxidation and isomerisation \ of 5-ene-3

-hydroxypregnene and 5-ene-hydroxyandrostene \ steroid precursors into the corresponding 4-ene-ketosteroids necessary\ for the formation of all classes of steroid hormones.\ \ \ 3-beta-hydroxy-delta(5)-steroid dehydrogenase activity ; GO:0003854\ \N \N steroid biosynthesis ; GO:0006694 20877 IPR002226 Catalase is a constitutive peroxisomal enzyme [MEDLINE:91378551] that catalyses the conversion of hydrogen peroxide to water and molecular oxygen in a \ 'catalatic' reaction, which protects the cell from the toxic effects of \ hydrogen peroxide [MEDLINE:82122604]. It can also oxidise a number of other compounds in \ the presence of hydrogen peroxide in a 'peroxidatic' reaction [MEDLINE:82122604], which\ is responsible for ethanol oxidation in liver, if the concentration of \ hydrogen peroxide is high enough. Different catalase isoforms can be \ identified within a particular species, the number of isoforms ranging\ from 1 in lentil cotyledons to 12 in mustard cotyledons [MEDLINE:91378551]. Most catalases\ exist as tetramers of 65 kD subunits, each subunit containing a protohaem\ IX group [MEDLINE:91100337] buried deep within the structure, but which is accessible \ through hydrophobic channels [MEDLINE:82122604].\ \ catalase activity ; GO:0004096 \N response to oxidative stress ; GO:0006979 20878 IPR002227 Tyrosinase (EC: 1.14.18.1) [MEDLINE:88218028] is a copper monooxygenases that catalyzes thehydroxylation of monophenols and the oxidation of o-diphenols to o-quinols.\ This enzyme, found in prokaryotes as well as in eukaryotes, is involved in the\ formation of pigments such as melanins and other polyphenolic compounds.\ Tyrosinase binds two copper ions (CuA and CuB). Each of the two copper ions has\ been shown [MEDLINE:91190082] to be bound by three conserved histidines residues. The regions\ around these copper-binding ligands are well conserved and also shared by some\ hemocyanins, which are copper-containing oxygen carriers from the hemolymph of\ many molluscs and arthropods\ \ \ \ [MEDLINE:89314165], [MEDLINE:91095437].\ At least two proteins related to tyrosinase are known to exist in mammals, and include TRP-1 (TYRP1) [MEDLINE:95112790], which is responsible for the conversion of 5,6-dihydro-xyindole-2-carboxylic acid (DHICA) to indole-5,6-quinone-2-carboxylic acid; and TRP-2 (TYRP2) [MEDLINE:92164640], which is the melanogenic enzyme DOPAchrome tautomerase\ (EC: 5.3.3.12) that catalyzes the conversion of DOPAchrome to DHICA. TRP-2\ differs from tyrosinases and TRP-1 in that it binds two zinc ions instead\ of copper [MEDLINE:95071460].\ Other proteins that belong to this family are plant polyphenol oxidases (PPO) (EC: 1.10.3.1), which catalyze the oxidation\ of mono- and o-diphenols to o-diquinones [MEDLINE:93004477]; and \ Caenorhabditis elegans hypothetical protein C02C2.1.\ \ oxidoreductase activity ; GO:0016491 \N metabolism ; GO:0008152 20879 IPR002228

The muscarinic acetylcholine receptors, present in the central nervous\ system, spinal cord motoneurons and autonomic preganglia, modulate a\ variety of physiological functions: these include airway, eye and intestinal\ smooth muscle contractions; heart rate; and glandular secretions. The\ receptors mediate adenylate cyclase attenuation, calcium and potassium\ channel activation, and phosphatidyl inositol turnover [MEDLINE:88217874]. This diversity\ may result from the occurrence of multiple receptor subtypes, which have\ been classified based on observed differences in ligand binding to\ receptors in membranes from several tissues.

The M1 receptor is found in high levels in neuronal cells of the CNS; it\ is particularly abundant in the cerebral cortex and hippocampus. Its\ distribution largely overlaps with that of M3 and M4 subtypes. In the\ periphery, M1 receptors are found in autonomic ganglia and certain\ secretory glands, and they are also found in cell lines. No truly\ selective agonist has been described PUB00005867.

\ \ muscarinic acetylcholine receptor activity ; GO:0004981 membrane ; GO:0016020 G-protein coupled receptor protein signaling pathway ; GO:0007186 20875 IPR002223 The Kunitz family of serine protease inhibitors are short (~50 residue)

proteins with few secondary structures. The fold is constrainedby 3 disulphide bonds.\ The prototype for this family is bovine pancreatic trypsin inhibitor [MEDLINE:91332906] (or \ basic protease inhibitor), but the family includes numerous other members\ [MEDLINE:91118234], [MEDLINE:92277669], [MEDLINE:94211862], [MEDLINE:93284121], such as snake venom basic protease; mammalian inter-

-trypsin\ inhibitors; trypstatin, a rat mast cell inhibitor of trypsin; a domain\ found in an alternatively-spliced form of Alzheimer's amyloid

-protein;\ domains at the C-termini of the

(1) and

(3) chains of type VII\ and type VI collagens; and tissue factor pathway inhibitor precursor.\ \ serine protease inhibitor activity ; GO:0004867 \N \N 20872 IPR002219 Diacylglycerol (DAG) is an important second messenger. Phorbol esters (PE) are analogues of DAG and potent tumor promoters that cause a variety of physiological changes when administered to both cells and tissues. DAG activates a family of serine/threonine protein kinases, collectively known as protein kinase C (PKC) [MEDLINE:93011080]. Phorbol esters can directly stimulate PKC. The N-terminal region of PKC, known as C1, has been shown [MEDLINE:89296905] to bind PE and DAG in a phospholipid and zinc-dependent fashion. The C1 region contains one or two copies (depending on the isozyme of PKC) of a cysteine-rich domain about 50 amino-acid residues long and essential for DAG/PE-binding. The DAG/PE-binding domain binds two zinc ions; the ligands of these metal ions are probably the six cysteines and two histidines that are conserved in this domain.\ \N \N intracellular signaling cascade ; GO:0007242 20873 IPR002220 Dihydropicolinate synthase (DHDPS) is the key enzyme in lysine biosynthesisvia the diaminopimelate pathway of prokaryotes, some phycomycetes and\ higher plants. The enzyme catalyses the condensation of L-aspartate-

-\ semialdehyde and pyruvate to dihydropicolinic acid via a ping-pong\ mechanism in which pyruvate binds to the enzyme by forming a Schiff-base\ with a lysine residue [MEDLINE:95156485]. Three other proteins are structurally related to DHDPS and probably also act\ via a similar catalytic mechanism. These are E. coli N-acetylneuraminate lyase (EC: 4.1.3.3) (gene nanA), which\ catalyzes the condensation of N-acetyl-D-mannosamine and pyruvate to form\ N-acetylneuraminate; Rhizobium meliloti protein mosA [MEDLINE:93352426], which is involved in the biosynthesis\ of the rhizopine 3-o-methyl-scyllo-inosamine; and E. coli hypothetical protein yjhH.\ The sequences of DHDPS from different sources are well-conserved. The\ structure takes the form of a homotetramer, in which 2 monomers are\ related by an approximate 2-fold symmetry [MEDLINE:95156485]. Each monomer comprises\ 2 domains: an 8-fold

-barrel, and a C-terminal

-helical\ domain. The fold resembles that of N-acetylneuraminate lyase. The active\ site lysine is located in the barrel domain, and has access via 2 channels\ on the C-terminal side of the barrel.\ \ \N \N \N 20874 IPR002222

\ \ \

The small subunit ribosomal proteins can\ be categorised as: primary binding proteins, which bind directly and\ independently to 16S rRNA; secondary binding proteins, which display no\ specific affinity for 16S rRNA, but its assembly is contingent upon the\ presence of one or more primary binding proteins; and tertiary binding\ proteins, which require the presence of one or more secondary binding\ proteins and sometimes other tertiary binding proteins.\ The small ribosomal subunit protein S19 contains 88-144 amino acid residues.\ In Escherichia coli, S19 is known to form a complex with S13 that binds \ strongly to 16S ribosomal RNA. Experimental evidence [MEDLINE:98058740] has revealed that \ S19 is moderately exposed on the ribosomal surface, and is designated \ a secondary rRNA binding protein. S19 belongs to a family of ribosomal \ proteins [MEDLINE:98058740], [MEDLINE:91257304] that includes: eubacterial S19; algal and plant chloroplast \ S19; cyanelle S19; archaebacterial S19; plant mitochondrial S19; and \ eukaryotic S15 ('rig' protein).

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 20871 IPR002218 Bacterial glucose inhibited division protein A (gene gidA) is a protein of 70 Kd whose function is not yet known and whose sequence is highly conserved. It is evolutionary related to yeast hypothetical protein YGL236C, Caenorhabditis elegans hypothetical protein F52H3.2 and a Bacillus subtilis protein called gid (and which is different from B.subtilis gidA).\ \N \N \N 20870 IPR002217

A major antigen has been recognised in Helicobacter pylori, a protein with an apparent molecular weight of 20,000 and mass 18,283 kDa [MEDLINE:95014026]. DNA sequence analysis revealed a 525 bp gene, encoding a 175-amino acid residue product with a typical 21-residue lipoprotein signal peptide and consensus prolipoprotein processing site [MEDLINE:95014026]. Results of experimental work with Lpp20 are consistent with it being a nonessential lipoprotein [MEDLINE:95014026].

Prokaryotic membrane lipoproteins are synthesised with precursor signal peptides that are cleaved by specific peptidases (signal peptidase II). The enzyme recognises a conserved sequence, cutting upstream of a cysteine residue to which a glyceride-fatty acid lipid is attached [MEDLINE:90361710].

\ \ defense/immunity protein activity ; GO:0003793 external outer membrane (sensu Gram-negative Bacteria) ; GO:0009279 \N 20869 IPR002214

Hantaviruses are ssRNA negative-strand viruses. The nucleocapsid protein is an internal protein of the virus particle [MEDLINE:97352173], [MEDLINE:96118169].

\ \ \N viral nucleocapsid ; GO:0019013 \N 20868 IPR002213

UDP glycosyltransferases (UGT) are a superfamily of enzymes that catalyzes the addition of the glycosyl group from a UTP-sugar to a small hydrophobic molecule. This family currently consist of:

Mammalian UDP-glucoronosyl transferases (EC: 2.4.1.17) (UDPGT) [MEDLINE:91369477], PUB00006590. A large family of membrane-bound microsomal enzymes which catalyze the transfer of glucuronic acid to a wide variety of exogenous and endogenous lipophilic substrates. These enzymes are of major importance in the detoxification and subsequent elimination of xenobiotics such as drugs and carcinogens.
A large number of putative UDPGT from Caenorhabditis elegans.
Mammalian 2-hydroxyacylsphingosine 1--galactosyltransferase PUB00006590 (EC: 2.4.1.45) (also known as UDP-galactose-ceramide galactosyltransferase). This enzyme catalyzes the transfer of galactose to ceramide, a key enzymatic step in the biosynthesis of galactocerebrosides, which are abundant sphingolipids of the myelin membrane of the central nervous system and peripheral nervous system.
Plants flavonol O(3)-glucosyltransferase (EC: 2.4.1.91). An enzyme PUB00004530 that catalyzes the transfer of glucose from UDP-glucose to a flavanol. This reaction is essential and one of the last steps in anthocyanin pigment biosynthesis.
Baculoviruses ecdysteroid UDP-glucosyltransferase (EC: 2.4.1.-) PUB00004530 (egt). This enzyme catalyzes the transfer of glucose from UDP-glucose to ectysteroids which are insect molting hormones. The expression of egt in the insect host interferes with the normal insect development by blocking the molting process.
Prokaryotic zeaxanthin glucosyl transferase (EC: 2.4.1.-) (gene crtX), an enzyme involved in carotenoid biosynthesis and that catalyses the glycosylation reaction which converts zeaxanthin to zeaxanthin--diglucoside.
Streptomyces macrolide glycosyltransferases (EC: 2.4.1.-) [MEDLINE:94063510]. These enzymes specifically inactivates macrolide anitibiotics via 2'-O-glycosylation using UDP-glucose.

These enzymes share a conserved domain of about 50 amino acid residues located in their C-terminal section.

\ \ transferase activity, transferring hexosyl groups ; GO:0016758 \N metabolism ; GO:0008152 20867 IPR002212

Transforming growth factor (TGF-)-binding protein-like (TB) domain comes from human fibrillin-1[MEDLINE:93372860]. This domain is found in fibrillins and latent TGF--binding proteins (LTBPs) which are localized to\ fibrillar structures in the extracellular matrix.[MEDLINE:98031893].

\ \ \N \N \N 20865 IPR002210 Papillomaviruses are members of the papovavirus superfamily. More than 70 different types of papillomavirus have been discovered in humans, some of which have been shown to cause genital carcinomas and cutaneous warts. The viruses contain a circular dsDNA genome surrounded by an icosahedral capsid. Two proteins are involved in capsid formation: a major (L1) and a minor (L2) protein, in the approximate proportion 95:5%. Experiments have indicated that intermolecular disulphide bonding is responsible for cohesion of the L1 capsid proteins [MEDLINE:96005069].\ structural molecule activity ; GO:0005198 viral capsid ; GO:0019028 \N 20866 IPR002211

Human and mouse LSP1 proteins consist of two domains: an N-terminal acidic domain and a C-terminal basic domain [MEDLINE:90111116], [MEDLINE:89035543]. The C-terminal domains are highly conserved and include several putative Ser/Thr phosphorylation sites [MEDLINE:90111116]. Immunoprecipitation of LSP1 from 32P-orthophosphate-loaded cells indicates that LSP1 is a phosphoprotein [MEDLINE:90111116]. The N-terminal domain of mouse LSP1 contains two putative Ca2(+)-binding sites, but these are not conserved in human LSP1; nevertheless, a different Ca2(+)-binding site may exist in the human protein, indicating functional rather than strict sequence conservation of the two proteins [MEDLINE:90111116], [MEDLINE:89035543].

Although the precise function of LSP is unclear, it is an F-actin binding protein thought to be involved in transmembrane signal transduction via its postulated calcium-binding function [MEDLINE:95021322] (although evidence for the existence of the calcium-binding sites is weak). The expression pattern of LSP1 is highly restricted. Non-lymphoid cell lines or normal mouse tissues such as brain, lung, liver, skeletal muscle, kidney or testis do not express the protein, and it appears that its expression in the hematopoietic system is restricted to the lymphocyte, macrophage and neutrophil lineages [MEDLINE:95021322].

\ \ signal transducer activity ; GO:0004871 \N signal transduction ; GO:0007165 20864 IPR002209

Heparin-binding growth factors I and II (HBGF) [MEDLINE:89372809], [MEDLINE:89223029] (also known as acidic and basic fibroblast growth factors (FGF) are structurally related mitogens which stimulate growth or differentiation of a wide variety of cells of mesodermal or neuroectodermal origin. These two proteins belong to a family of growth factors and oncogenes which is a member of a superfamily that also contains the interleukin-1 proteins, Kunitz-type soybean trypsin inhibitors (STI) (see IPR002160), they show none at all to the STIs.

HBGFs are involved in many different processes related to cell differentiation and growth control [MEDLINE:89372809]. HBGF1 and HBGF2 have similar effects: they induce mesoderm formation in embryogenesis, and mediate wound repair, angiogenesis and neural outgrowth; they also induce proliferation and migration of fibroblasts, endothelial cells and astroglial cells. HBGF3 (int-2) and HBGF4 (hst/ks) are known oncogenes, from stomach tumours and Kaposi sarcoma respectively. HBGF5 and HBGF6 are also oncogene products. HBGF7, keratinocyte growth factor, is possibly the major paracrine effector of normal epithelial cell proliferation.

These growth factors cause dimerisation of their tyrosine kinase receptors leading to intracellular signaling. There are currently four known tyrosine kinase receptors for fibroblast growth factors. These receptors can each bind several different members of this family [MEDLINE:96059371].

The crystal structures of HBGF1 and HBGF2 [MEDLINE:91195367] have been solved, showing them to have the same 12-stranded -sheet structure as both interleukin-1 and the Kunitz-type soybean trypsin inhibitors [MEDLINE:92148835]; HBGF1 and interleukin-1 had been found to be similar, and they were predicted to have similar structures [MEDLINE:86070224]. The -sheets are arranged in 3 similar lobes around a central axis, 6 strands forming an anti-parallel -barrel. Several regions of HBGF1 have been implicated in receptor binding, notably -strands 1-3, and the loop between strands 8 and 9. The loop between strands 10 and 11 is hought to be involved in binding heparin.

\ \ \N \N \N 20863 IPR002208

The translocase itself comprises 7 proteins, including a chaperone protein (SecB), an ATPase (SecA), an integral\ membrane complex (SecCY, SecE and SecG), and two additional membrane proteins that promote the release of\ the mature peptide into the periplasm (SecD and SecF) [MEDLINE:90361702]. The chaperone protein SecB [MEDLINE:21235707] is a highly acidic homotetrameric protein that exists as a "dimer of dimers" in the bacterial cytoplasm.\ SecB maintains preproteins in an unfolded state after translation, and targets these to the peripheral membrane\ protein ATPase SecA for secretion [MEDLINE:99346703]. The structure of the Escherichia coli SecYEG assembly revealed a sandwich of two membranes\ interacting through the extensive cytoplasmic domains [MEDLINE:22157987] ]. Each membrane is composed of dimers of SecYEG. The\ monomeric complex contains 15 transmembrane helices.

The eubacterial secY protein [MEDLINE:93023870] interacts with the signal sequences of secretory proteins as well as with two other components of the protein translocation system: secA and secE. SecY is an integral plasma membrane protein of 419 to 492 amino acid residues that apparently contains 10 transmembrane (TM), 6 cytoplasmic and 5 periplasmic regions.

Cytoplasmic regions 2 and 3, and TM domains 1, 2, 4, 5, 7 and 10 are well conserved: the conserved cytoplasmic regions are believed to interact with cytoplasmic secretion factors, while the TM domains may participate in protein export [MEDLINE:90251170]. Homologs of secY are found in archaebacteria [MEDLINE:92110434]. SecY is also encoded in the chloroplast genome of some algae [MEDLINE:92183838] where it could be involved in a prokaryotic-like protein export system across the two membranes of the chloroplast endoplasmic reticulum (CER) which is present in chromophyte and cryptophyte algae.

\ \ protein translocase activity ; GO:0015450 membrane ; GO:0016020 protein secretion ; GO:0009306 20860 IPR002205

Topoisomerases are ubiquitous enzymes that catalyze cleavage and religation of DNA molecules allowing for the interconversion of topological isomers of DNA and play a key role in DNA metabolism. Topoisomerases of type I and type II cleave one and two DNA\ strands, respectively. Topoisomerase I catalyses an ATP-independent reaction, \ while topoisomerase II catalyses an ATP-dependent reaction, resulting in the formation \ of DNA supercoils [MEDLINE:91339166], [MEDLINE:91270367], [MEDLINE:89017161]. Eukaryotic enzymes can form \ both positive and negative supercoils, while prokaryotic enzymes form only negative \ supercoils.

\ \

Eukaryotic topoisomerase II exists as a homodimer; in bacteriophage T4 it \ consists of three heterologous subunits; most bacteria have\ two homologous type II enzymes: DNA gyrase (topoisomerase II, Gyr) and topoisomerase IV (Par). Each enzyme is composed of\ two subunits. GyrA is involved in breakage and reunion of DNA and GyrB functions as an ATPase. GyrB, parE, and the product of \ bacteriophage T4 gene 39, are all similar to the eukaryotic proteins.

This family includes subunit A, encoded by DNA gyrase A (gyrA) and parC. GyrA is composed of two fragments. The structure of the 59 kDa N-terminal fragment of the E. coli enzyme has been\ determined and the position of the catalytic tyrosine has been localized. The C-terminal 38kDa fragment of GyrA still remains the\ largest piece of the topoisomerase sequence without structural information. It lacks catalytic activity, but can complement the N-terminal fragment increasing its\ supercoiling activity. The C-terminal fragment acts as a non-specific DNA-binding protein and is probably involved in\ stabilization of the DNA-topoisomerase complex [MEDLINE:21946018].

\ \ ATP binding activity ; GO:0005524 \N DNA topological change ; GO:0006265 20862 IPR002207

Peroxidases are haem-containing enzymes that use hydrogen peroxide as the electron acceptor to catalyse a number of oxidative reactions. They are found in bacteria, fungi, plants and animals. On the basis of sequence similarity, fungal, plant and bacterial peroxidases can be viewed as members of a superfamily consisting of 3 major classes PUB00001075. Class I, the intracellular peroxidases, includes yeast cytochrome c peroxidase (CCP), ascorbate peroxidase (AP) and bacterial catalase-peroxidases.

In chloroplasts of higher plants, oxygen consumption in the absence of electron acceptors is accompanied by production of H2O2 and activated forms of oxygen. Chloroplasts contain several protective systems (such as superoxide dismutase (SOD), -tocopherol and carotenoids), which are effective against various forms of activated oxygen. However, they lack catalase, and the disposal of H2O2 is accomplished by other means PUB00001075.

Ascorbic acid is a strong antioxidant that is effective in scavenging superoxide (O2-'), hydroxyl (OH') radicals and singlet oxygen. It can also remove H2O2 in the following reaction:

       Ascorbate + H2O2  --> dehydroascorbate + 2 H2O

Ascorbate peroxidase (AP) is the main enzyme responsible for hydrogen peroxide removal in the chloroplasts and cytosol of higher plants\ \ \ PUB00005930.

The 3D structure of pea cytosolic ascorbate peroxidase has an overall fold virtually identical to that of CCP PUB00005930. The protein consists of 2 all- domains, between which is embedded the haem group. The most pronounced difference between the AP and CCP structures is the absence of an antiparallel -hairpin between the G and H helices in the AP molecule.

\ \ \ peroxidase activity ; GO:0004601 \N peroxidase reaction ; GO:0006804 20861 IPR002206

Recently, a non-visual opsin (designated P-opsin or pinopsin) has beenisolated from chick pineal gland [MEDLINE:95059405], [MEDLINE:95184012]. Environmental light signals reset\ the phase of the endogenous circadian pacemaker that controls the rhythmic\ production of melatonin via this protein [MEDLINE:95184012]. Sharing ~45% identity with\ retinal opsins, pinopsin is thought to have diverged early in opsin\ evolution [MEDLINE:95184012]. The protein is maximally sensitive to light of wavelength\ ~500nm and produces a slow, prolonged photo-transduction response consistent\ with the non-visual function of pineal photo-reception.

\ \ \ rhodopsin-like receptor activity ; GO:0001584 integral to membrane ; GO:0016021 phototransduction ; GO:0007602 20859 IPR002204

3-hydroxyisobutyrate dehydrogenase (EC: 1.1.1.31) catalyzes the NAD-dependent, reversible oxidation of 3-hydroxbutyrate to methylmalonate [MEDLINE:89174651]. In eukaryotes, it is a homodimeric mitochondrial protein involved in valine catabolism. In Pseudomonas aeruginosa\ \ \ [MEDLINE:92317087] (gene mmsB), it is involved in the distal valine metabolic pathway.

The sequence of 3-hydroxyisobutyrate dehydrogenase from eukaryotic and prokaryotic sources show that this enzyme has been well conserved throughout evolution. A number of hypothetical proteins are evolutionary related to 3-hydroxyisobutyrate dehydrogenase:

Escherichia coli hypothetical protein ybbQ.
Escherichia coli hypothetical protein ygbJ.
Escherichia coli hypothetical protein yhaE.
Escherichia coli hypothetical protein yihU.
Bacillus subtilis hypothetical protein yfjR.
Bacillus subtilis hypothetical protein ykwC.
Mycobacterium tuberculosis hypothetical protein Rv0770.
Synechocystis strain PCC 6803 hypothetical protein slr0229.

A highly conserved glycine-rich region located at the proteins' N-terminus is probably involved in binding NAD.

\ \ \ 3-hydroxyisobutyrate dehydrogenase activity ; GO:0008442\ \N \N valine metabolism ; GO:0006573 20858 IPR002202

Hydroxymethylglutaryl-coenzyme A reductase (EC: 1.1.1.34) (HMG-CoA reductase) [MEDLINE:91370847], [MEDLINE:89127221] catalyzes the NADP-dependent synthesis of mevalonate from 3-hydroxy-3-methylglutaryl-CoA. In vertebrates, HMG-CoA reductase is the rate-limiting enzyme in cholesterol biosynthesis. In plants, mevalonate is the precursor of all isoprenoid compounds. The reduction of HMG-CoA to mevalonate is regulated by feedback inhibition by sterols and non-sterol metabolites derived from mevalonate [MEDLINE:85261451], including cholesterol.

\ \ hydroxymethylglutaryl-CoA reductase (NADPH) activity ; GO:0004420 \N biosynthesis ; GO:0009058 20856 IPR002200

Elicitins are a family of small, highly-conserved proteins secreted by phytopathogenic fungi belonging to the phytophthora species [MEDLINE:95273323], PUB00001484. They are toxic proteins reponsible for inducing a necrotic and systemic hypersensitive response in plants from the solanaceae and cruciferae families. Leaf necrosis provides immediate control of fungal invasion and induces systemic acquired resistance; both responses mediate basic protection against subsequent pathogen inoculation.

Members of this family share a high level of sequence similarity, but they differ in net charge, dividing them into two classes: and PUB00001484, PUB00004516. Alpha-elicitins are highly acidic, with a valine residue at position 13, whereas -elicitins are basic, with a lysine at the same position. Residue 13 is known to be involved in the control of necrosis and, being exposed, is thought to be involved in ligand/receptor binding PUB00004516, [MEDLINE:98046740]. Phenotypically, the two classes can be distinguished by their necrotic properties: -elicitins are 100-fold more toxic and provide better subsequent protection [MEDLINE:95273323], PUB00001484.

\ \ defense/immunity protein activity ; GO:0003793 extracellular ; GO:0005576 pathogenesis ; GO:0009405 20857 IPR002201

Glycosyltransferase family 9 CAZY:GT_9), heptosyltransferase (EC: 2.4.-.-"/).

\ \

Heptosyltransferase I is thought to add L-glycero-D-manno-heptose to the inner\ 3-deoxy-D-manno-octulosonic acid (Kdo) residue of the lipopolysaccharide core PUB00007032.\ Heptosyltransferase II is a glycosyltransferase involved in the synthesis of the inner core region of lipopolysaccharide [MEDLINE:20507564]. Lipopolysaccharide is a major component of the outer leaflet of the outer membrane in Gram-negative bacteria. It is composed of three domains; lipid A, Core oligosaccharide and the O-antigen. These enzymes transfer heptose to the lipopolysaccharide core [MEDLINE:98112827].

\ \ \N \N \N 20853 IPR002196

Glycoside hydrolase family 24 CAZY:GH_24).

\ This family includes lambda phage lysozyme and Escherichia coli endolysin [MEDLINE:87226186]. Lysozyme helps to release mature phage particles from the cell wall by breaking down the peptidoglycan. The enzyme hydrolyses the 1,4-

linkages between N-acetyl-D-glucosamine and N-acetylmuramic acid in peptidoglycan heteropolymers of prokaryotic cell walls. E. coli endolysin also functions in bacterial cell lysis and acts as a transglycosylase.\ \ The T4 lysozyme structure contains 2 domains, the interface between which forms the active-site cleft. The N-terminus of the 2 domains undergoes a 'hinge-bending' motion about an axis passing through the molecular waist [MEDLINE:87226186], [MEDLINE:91043097]. This mobility is thought to be important in allowing access of substrates to the enzyme active site.\ \ lysozyme activity ; GO:0003796 \N cell wall catabolism ; GO:0016998 20854 IPR002197

The Factor for Inversion Stimulation (FIS) protein is a regulator of bacterial functions, and binds specifically to weakly related DNA sequences \ [MEDLINE:95238273],[MEDLINE:20572089]. It activates ribosomal RNA transcription, and is involved in upstream\ activation of rRNA promoters. Found in gamma proteobacterial microbes, the\ protein has been shown to play a role in the regulation of virulence factors\ in both Salmonella typhimurium and Esherichia coli [MEDLINE:21424668]. Some of its\ functions include inhibition of the initiation of DNA replication from the\ OriC site, and promotion of Hin-mediated DNA inversion.

\ \

\ The 3-dimensional structure of the E. coli FIS DNA-binding protein has been\ determined by means of X-ray diffraction to 2.0A resolution [MEDLINE:92318262],[MEDLINE:20500109]. FIS is\ composed of four -helices tightly intertwined to form a globular dimer\ with two protruding HTH motifs. The 24 N-terminal amino acids are poorly \ defined, indicating that they might act as 'feelers' suitable for DNA or\ protein (invertase) recognition [MEDLINE:92318262]. Other proteins belonging to this subfamily include:

E.coli: atoC, hydG, ntrC, fhlA, tyrR,
Rhizobium: ntrC, nifA, dctD

\ \ transcription factor activity ; GO:0003700 \N regulation of transcription, DNA-dependent ; GO:0006355 20855 IPR002198 The short-chain dehydrogenases/reductases family (SDR) [MEDLINE:95260797] is a very large family of enzymes, most of which are known to be NAD- or NADP-dependent oxidoreductases. As the first member of this family to be characterized was Drosophila alcohol dehydrogenase, this family used to be called [MEDLINE:89210852], [MEDLINE:91364706], [MEDLINE:92155191] 'insect-type', or 'short-chain' alcohol dehydrogenases. Most member of this family are proteins of about 250 to 300 amino acid residues. Most dehydrogenases possess at least 2 domains [MEDLINE:81247357], the first binding the coenzyme, often NAD, and the second binding the substrate. This latter domain determines the substrate specificity and contains amino acids involved in catalysis. Little sequence similarity has been found in the coenzyme binding domain although there is a large degree of structural similarity, and it has therefore been suggested that the structure of dehydrogenases has arisen through gene fusion of a common ancestral coenzyme nucleotide sequence with various substrate specific domains [MEDLINE:81247357].\ oxidoreductase activity ; GO:0016491 \N metabolism ; GO:0008152 20852 IPR002195

In bacteria, DHOase is a dimer of identical chains of about 400 amino-acid residues (gene pyrC). In higher eukaryotes, DHOase is part of a large multi-functional protein known as 'rudimentary' in Drosophila' and CAD in mammals and which catalyzes the first three steps of pyrimidine biosynthesis [MEDLINE:93256915]. The DHOase domain is located in the central part of this polyprotein. In yeasts, DHOase is encoded by a monofunctional protein (gene URA4). However, a defective DHOase domain [MEDLINE:89378778] is found in a multifunctional protein (gene URA2) that catalyzes the first two steps of pyrimidine biosynthesis.

The comparison of DHOase sequences from various sources shows [MEDLINE:88232423] that there are two highly conserved regions. The first located in the N-terminal extremity contains two histidine residues suggested [MEDLINE:89378778] to be involved in binding the zinc ion. The second is found in the C-terminal part. Members of this family of proteins are predicted to adopt a TIM barrel fold [MEDLINE:97290007].

Allantoinase (EC: 3.5.2.5) is the enzyme that hydrolyzes allantoin into allantoate. In yeast (gene DAL1) [MEDLINE:92206070], it is the first enzyme in the allantoin degradation pathway; in amphibians\ \ \ \ [MEDLINE:94216348] and fishs it catalyzes the second step in the degradation of uric acid. The sequence of allantoinase is evolutionary related to that of DHOases.

\ \ hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in cyclic amides ; GO:0016812 \N \N 20850 IPR002192 This enzyme catalyses the reversible conversion of ATP to AMP, pyrophosphate and phosphoenolpyruvate (PEP) [MEDLINE:96181461]. Residues at the N-terminus correspond to the transit peptide which is indispensable for the transport of the precursor protein into chloroplasts in plants\ \ \ [MEDLINE:88298745]. This domain is present at the N-terminus of some PEP-utilizing enzymes IPR000121.\ \ kinase activity ; GO:0016301 \N phosphorylation ; GO:0016310 20848 IPR002190

The first mammalian members of the MAGE (melanoma-associated antigen) genefamily were originally described as completely silent in normal adult tissues,\ with the exception of male germ cells and, for some of them, placenta. By\ contrast, these genes were expressed in various kinds of tumors. However, other\ members of the family were recently found to be expressed in normal cells,\ indicating that the family is larger and more disparate than initially\ expected. MAGE-like genes have also been identified in non-mammalian species,\ like the zebrafish or Drosophila melanogaster. Although no MAGE homologous\ sequences have been identified in Caenorhabditis elegans, Saccharomyces\ cerevisiae or Schizosaccharomyces pombe, MAGE sequences have been found in\ several vegetal species, including Arabidopsis thaliana [MEDLINE:21347234].

\ The only region of homology shared by all of the members of the family is a\ stretch of about 200 amino acids which has been named the MAGE conserved\ domain. The MAGE conserved domain is usually located close to the C-terminal,\ although it can also be found in a more central position in some proteins. The\ MAGE conserved domain is generally present as a single copy but it is\ duplicated in some proteins. It has been proposed that the MAGE conserved\ domain of MAGE-D proteins might interact with p75 neurotrophin or related\ receptors [MEDLINE:21347234].

\ \ \N \N \N 20849 IPR002191

The fliL operon of Escherichia coli contains seven genes (including fliO, fliP, fliQ and fliR) involved in the biosynthesis and functioning of the flagellar organelle [MEDLINE:94110225]. The fliO, fliP, fliQ and fliR genes encode highly hydrophobic polypeptides. The fliQ gene product, a small integral membrane protein that contains two putative transmembrane (TM) regions, is required for the assembly of the rivet at the earliest stage of flagellar biosynthesis.

Proteins sharing an evolutionary relationship with FliQ have been found in a range of bacteria: these include Yop translocation protein S from Yersinia sp.\ \ \ \ [MEDLINE:94131934]; surface antigen-presentation protein SpaQ from Salmonella typhimurium and Shigella flexneri\ \ \ \ [MEDLINE:94008985]; and probable translocation protein Y4YM from Rhizobium sp.\ \ \ \ [MEDLINE:97305956]. All of these members export proteins, that do not possess signal peptides, through the membrane. Although the proteins that these exporters move may be different, the exporters are thought to function in similar ways [MEDLINE:95113771].

\ \ \N membrane ; GO:0016020 protein secretion ; GO:0009306 20851 IPR002194

The TCP-1 protein [MEDLINE:92334422], PUB00001019 (Tailless Complex Polypeptide 1) was first identified in mice where it is especially abundant in testis but present in all cell types. It has since been found and characterized in many other animal species, as well as in yeast, plants and protists. TCP-1 is a highly conserved protein of about 60 kDa (556 to 560 residues) which participates in a hetero-oligomeric 900 kDA double-torus shaped particle PUB00001019 with 6 to 8 other different subunits. These subunits, the chaperonin containing TCP-1 (CCT) subunit , gamma, delta, epsilon, zeta and eta are evolutionary related to TCP-1 itself [MEDLINE:95041331], [MEDLINE:95149373]. The CCT is known to act as a molecular chaperone for tubulin, actin and probably some other proteins.

The CCT subunits are highly related to archaebacterial counterparts:

TF55 and TF56 [MEDLINE:92086050], a molecular chaperone from Sulfolobus shibatae. TF55 has ATPase activity, is known to bind unfolded polypeptides and forms a oligomeric complex of two stacked nine-membered rings.
Thermosome [MEDLINE:95314774], from Thermoplasma acidophilum. The thermosome is composed of two subunits ( and ) and also seems to be a chaperone with ATPase activity. It forms an oligomeric complex of eight-membered rings.

The TCP-1 family of proteins are weakly, but significantly [MEDLINE:92310542], related to the cpn60/groEL chaperonin family (see IPR001844).

\ \ \N \N \N 20847 IPR002189

The actin filament system, a prominent part of the cytoskeleton in eukaryotic cells, is both a static structure and a dynamic network that can undergo rearrangements: it is thought to be involved in processes such as cell movement and phagocytosis [MEDLINE:90256797], as well as muscle contraction.

The F-actin capping protein binds in a calcium-independent manner to the fast growing ends of actin filaments (barbed end) thereby blocking the exchange of subunits at these ends. Unlike gelsolin and severin this protein does not sever actin filaments. The F-actin capping protein is a heterodimer composed of two unrelated subunits: and (see IPR001698.

The subunit is a protein of about 268 to 286 amino acid residues whose sequence is well conserved in eukaryotic species [MEDLINE:91284215].

\ \ F-actin capping activity ; GO:0003782 actin capping protein complex ; GO:0008290 actin cytoskeleton organization and biogenesis ; GO:0030036 20846 IPR002188

In addition to their role in energy metabolism, purines (especially\ adenosine and adenine nucleotides) produce a wide range of pharmacological\ effects mediated by activation of cell surface receptors. ATP is a\ co-transmitter in sympathetic nerves in the autonomic nervous system,\ where it exerts an important physiological role in the regulation of\ smooth muscle activity, stimulating relaxation of intestinal smooth muscle\ and contraction of the bladder. Receptors for adenine nucleotides are\ involved in a number of other physiological pathways, including stimulation\ of platelet activation by ADP, which is released from the vascular\ endothelium following injury. ATP has excitatory effects in the CNS.\ Distinct receptors exist for adenosine. The main effects of adenosine in\ the periphery include vasodilation, bronchoconstriction, immunosuppression,\ inhibition of platelet aggregation, cardiac depression, stimulation of\ nociceptive afferents, inhibition of neurotransmitter release, and\ inhibition of the release of hormones. In the CNS, adenosine exerts a\ pre- and post-synaptic depressant action, reducing motor activity,\ depressing respiration, inducing sleep and relieving anxiety. The\ physiological role of adenosine is believed to be to adjust energy demands\ in line with oxygen supply PUB00005868.

Purinoceptors have been classified as P1 or P2, depending on their\ preference for adenosine or adenine nucleotides respectively. Adenosine\ receptors (P1 purinoceptors) are characterised by their affinity for\ adenosine and by the ability of methylxanthines to act as antagonists.\ Adenosine has very low affinity for P2 purinoceptors.

A novel gene has been cloned that codes for a member of the GPCR superfamily\ [MEDLINE:93329058]. The 308 amino acid transcript has seven hydrophobic, presumably TM,\ domains and a consensus site for interaction with G proteins [MEDLINE:93329058]. Tissue\ distribution studies suggest that gene expression is restricted to activated\ T cells [MEDLINE:93329058]. The message appears 1 hour after activation and is maintained\ for at least 45 hours. Transcription of the gene is induced by a number of\ T cell stimuli and is inhibited by cyclosporin A, but not by cycloheximide\ [MEDLINE:93329058]. This is the first description of a member of this superfamily expressed\ specifically in activated T cells, the gene product possibly providing a\ link between T cell growth factors and G-protein activation [MEDLINE:93329058].

\ \ purinergic nucleotide receptor activity, G-protein coupled ; GO:0045028 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20843 IPR002185

Dopamine neurons in the vertebrate central nervous system are involved in\ the initiation and execution of movement, the maintenance of emotional\ stability, and the regulation of pituitary function [MEDLINE:90099344]. Various human\ neurological diseases (e.g., Parkinson disease and schizophrenia), are\ believed to be manifestations of dopamine and dopamine receptor imbalance.\ The receptors have been divided into several different subtypes,\ distinguished by their G-protein coupling, ligand specificity, anatomical\ distribution and physiological effects.

D4 receptors have a similar pharmacological profile to D2 receptors. They\ are expressed in the brain, predominantly in the medulla, amgdala, midbrain\ and frontal cortex; lower levels are found in the striatum and olfactory\ tubercle. D4 receptor mRNA has also been detected in peripheral tissues,\ and the protein appears to be expressed preferentially in the cardiovascular\ system in the rat. They inhibit adenylyl cyclase through a pertussis-toxin-sensitive G-protein, probably belonging to the Gi/Go class PUB00005878.

\ \ dopamine receptor activity ; GO:0004952 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20842 IPR002184

Animals recognise a wide variety of chemicals using their senses of taste and smell. The nematode Caenorhabditis elegans has only 14 types of chemosensory neuron, yet is able to respond to dozens of chemicals because each neuron detects several stimuli. More than 40 highly divergent transmembrane proteins that could contribute to this functional diversity have been described [MEDLINE:96028095]. Most of the candidate receptor genes are in clusters of similar genes; 11 of these appear to be expressed in small subsets of chemosensory neurons. A single type of neuron can potentially express at least 4 different receptor genes [MEDLINE:96028095]. Some of these might encode receptors for water-soluble attractants, repellents and pheromones, which may be divergent members of the G-protein-coupled receptor family [MEDLINE:96028095].

Sequences of the srb family of C.elegans receptor-like proteins contain 6-8 hydrophobic, putative transmembrane, regions. These can be distinguished from other 7TM proteins (especially those known to couple G-proteins, see IPR000276) by their own characteristic TM signatures.

\ \ transmembrane receptor activity ; GO:0004888 membrane ; GO:0016020 \N 20844 IPR002186

Neocarzinostatin is a potent enediyne antitumor antibiotic complex in which a labile chromophore is tightly and noncovalently bound to a carrier protein. The protein regulates availability of the drug by proper release of the biologically active chromophore. The chromophore, with an unusual bicyclic dienediyne structure, abstracts hydrogens from the sugar moiety of DNA, following cycloaromatization to a reactive radical intermediate. It causes single- and double-strand breaks in DNA when activation occurs after it has become interchelated into the nucleic acid molecule [MEDLINE:94053744]. The chromophore becomes inactivated soon after release by the apo-protein.

\ \

The protein has 2 disulphide bridges and is kidney-shaped with 2 defined domains that hold a binding cavity. The larger domain forms a 7-stranded antiparallel -barrel and the smaller domain consists of 2 anti-parallel strands of sheet that are perpendicular to each other.

\ \ defense/immunity protein activity ; GO:0003793 \N \N 20845 IPR002187

In Gram-negative bacteria, the activity and concentration of glutamine synthetase (GS) is regulated in response to nitrogen source availability. PII, a tetrameric protein encoded by the glnB gene, is a component of the adenylation cascade involved in the regulation of GS activity [MEDLINE:91094780]. In nitrogen-limiting conditions, when the ratio of glutamine to 2-ketoglutarate decreases, P-II is uridylylated on a tyrosine residue to form P-II-UMP. P-II-UMP allows the deadenylation of GS, thus activating the enzyme. Conversely, in nitrogen excess, P-II-UMP is deuridylated and then promotes the adenylation of GS. P-II also indirectly controls the transcription of the GS gene (glnA) by preventing NR-II (ntrB) to phosphorylate NR-I (ntrC) which is the transcriptional activator of glnA. Once P-II is uridylylated, these events are reversed.

P-II is a protein of about 110 amino acid residues extremely well conserved. The tyrosine which is urydylated is located in the central part of the protein. In cyanobacteria, P-II seems to be phosphorylated on a serine residue rather than being urydylated. In methanogenic archaebacteria, the nitrogenase iron protein gene (nifH) is followed by two open reading frames highly similar to the eubacterial P-II protein [MEDLINE:91297201]. These proteins could be involved in the regulation of nitrogen fixation. In the red alga, Porphyra purpurea, there is a glnB homolog encoded in the chloroplast genome.

Other proteins highly similar to glnB are:

Bacillus subtilis protein nrgB [MEDLINE:94110214].
Escherichia coli hypothetical protein ybaI [MEDLINE:94124004].

\ \ enzyme regulator activity ; GO:0030234 \N regulation of nitrogen utilization ; GO:0006808 20840 IPR002182

This is the NB-ARC domain, a novel signalling motif found in bacteria and eukaryotes, shared by plant resistance gene products and regulators of cell death in animals [MEDLINE:98212083].

\ ATP binding activity ; GO:0005524 \N apoptosis ; GO:0006915 20841 IPR002183

Interleukin-3 (IL3) is a cytokine that regulates blood-cell production by controlling the production, differentiation and function of granulocytes and macrophages [MEDLINE:87305582], [MEDLINE:86014349]. The protein, which exists in vivo as a monomer, is produced in activated T-cells and mast cells [MEDLINE:87305582], [MEDLINE:86014349], and is activated by the cleavage of an N-terminal signal sequence [MEDLINE:86014349].

IL3 is produced by T-lymphocytes and T-lymphomas only after stimulation with antigens, mitogens, or chemical activators such as phorbol esters. However, IL3 is constitutively expressed in the myelomonocytic leukaemia cell line WEHI-3B [MEDLINE:86014349]. It is thought that the genetic change of the cell line to constitutive production of IL3 is the key event in development of this leukaemia [MEDLINE:86014349].

\ \ growth factor activity ; GO:0008083 extracellular ; GO:0005576 immune response ; GO:0006955 20838 IPR002180 This family includes the

chain of 6,7-dimethyl-8-ribityllumazine synthase EC: 2.5.1.9, an enzyme involved in riboflavin biosynthesis. The family also includes a subfamily of distant archaebacterial proteins that may also have the same function for example O28856.\ riboflavin synthase activity ; GO:0004746 riboflavin synthase complex ; GO:0009349 vitamin B2 biosynthesis ; GO:0009231 20839 IPR002181

Fibrinogen [MEDLINE:84305751], the principal protein of vertebrate blood clotting is an hexamer containing two sets of three different chains (, , and gamma), linked to each other by disulfide bonds. The N-terminal sections of these three chains are evolutionary related and contain the cysteines that participate in the cross-linking of the chains. However, there is no similarity between the C-terminal part of the chain and that of the and gamma chains. The C-terminal part of the and gamma chains forms a domain of about 270 amino-acid residues. As shown in the schematic representation this domain contains four conserved cysteines involved in two disulfide bonds.

\ xxxxCxxxxxxxxxxxxCxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxCxxxxxCxxxxxxxxxxx\ | | | |\ +------------+ +-----+\ \ 'C': conserved cysteine involved in a disulfide bond.\

Such a domain has been recently found [MEDLINE:90192754] in other proteins which are listed below.

Two sea cucumber fibrinogen-like proteins (FReP-A and FReP-B). These are proteins, of about 260 amino acids, which have a fibrinogen /gamma C-terminal domain.
In the C-terminus of Drosophila protein scabrous (gene sca). Scabrous is involved in the regulation of neurogenesis in Drosophila and may encode a lateral inhibitor of R8 cells differentiation.
In the C-terminus of a mammalian T-cell specific protein of unknown function.
In the C-terminus of a human protein of unknown function which is encoded on the opposite strand of the steroid 21-hydroxylase/complement component C4 gene locus.

The function of this domain is not yet known, but it has been suggested [MEDLINE:90192754] that it could be involved in protein-protein interactions.

\ \ \N \N \N 20836 IPR002178

The phosphoenolpyruvate-dependent sugar phosphotransferase system (PTS) [MEDLINE:94066914], [MEDLINE:90328751] is a major carbohydrate transport system in bacteria. The PTS catalyzes the phosphorylation of incoming sugar substrates concomitant with their translocation across the cell membrane. The general mechanism of the PTS is the following: a phosphoryl group from phosphoenolpyruvate (PEP) is transferred to enzyme-I (EI) of PTS which in turn transfers it to a phosphoryl carrier protein (HPr). Phospho-HPr then transfers the phosphoryl group to a sugar-specific permease which consists of at least three structurally distinct domains (IIA, IIB, and IIC) [MEDLINE:92165716] which can either be fused together in a single polypeptide chain or exist as two or three interactive chains, formerly called enzymes II (EII) and III (EIII).

The first domain (IIA), carries the first permease-specific phosphorylation site, an histidine which is phosphorylated by phospho-HPr. The second domain (IIB) is phosphorylated by phospho-IIA on a cysteinyl or histidyl residue, depending on the permease. Finally, the phosphoryl group is transferred from the IIB domain to the sugar substrate in a process catalyzed by the IIC domain; this process is coupled to the transmembrane transport of the sugar.

\ \ sugar porter activity ; GO:0005351 \N phosphoenolpyruvate-dependent sugar phosphotransferase system ; GO:0009401 20837 IPR002179

Proteoglycans [MEDLINE:86294337] are complex glycoconjugates containing a core protein to which a variable number of glycosaminoglycan chains (such as heparin sulfate, chondroitin sulfate, etc.) are covalently attached. The glycosaminoglycans are attached to the core proteins through a xyloside residue which is in turn linked to a serine residue of the protein. A consensus sequence for the attachment site seems to exist [MEDLINE:87204104]. However, it must be noted that this consensus is only based on the sequence of three proteoglycan core proteins.

Note: No protein matches are shown due to the low specificity of this rule.

\ \ \N \N \N 20835 IPR002177

Escherichia coli protein dps [MEDLINE:94040726] is a DNA-binding protein, synthesized during prolonged starvation, that seems to protect DNA from oxidative damage. Dps binds DNA without any apparent sequence specificity. It is a protein of about 19 kDa that associates into a complex of 12 subunits forming two stacked hexameric rings.

Proteins similar to Dps have been found in other bacteria:

Bacillus subtilis protein mrgA.
Antigen TpF1/TyF1 from Treponema pallidum and pertenue.
Haemophilus ducreyi fine tangled pili major subunit (gene ftpA).
Helicobacter pylori neutrophil-activating protein A (gene napA).
Listeria innocua non-heme iron-containing ferritin.
Synechococcus PCC 7942 nutrient-stress induced DNA binding protein (gene dpsA).
A low-temperature induced protein from Anabaena variabilis.
Haemophilus influenzae hypothetical protein HI1349.
Synechocystis strain PCC 6803 hypothetical protein slr1894.
A hypothetical protein encoded in the 5' region of a gene coding for a bromoperoxidase, in plasmid pOP2621 of Streptomyces aureofaciens.

All these proteins share a conserved region of about 50 residues in their central region.

Note: there seems [MEDLINE:97166164] to be a structural similarity between this family and that of eukaryotic ferritins (see IPR001519).

\ \ \N \N response to stress ; GO:0006950 20833 IPR002175

Endothelins play an important role in the regulation of the cardiovascular\ system PUB00005879. They are the most potent vasoconstrictors identified, stimulate\ cardiac constraction, regulate release of vasoactive substances, and\ stimulate mitogenesis in blood vessels in primary culture. They also\ stimulate contraction in almost all other smooth muscles (e.g., uterus,\ bronchus, vas deferens, stomach) and stimulate secretion in several tissues\ (e.g., kidney, liver and adrenals). Endothelin receptors have also been\ found in the brain, e.g. cerebral cortex, cerebellum and glial cells.\ Endothelins have been implicated in a variety of pathophysiological\ conditions associated with stress.

The ETA receptor is the predominant type of endothelin receptor. It\ mediates contraction in blood vessels, bronchus, uterus and heart; it also\ inhibits aldosterone secretion. The receptors have been identified in glial\ cells in the CNS. They activate the phosphoinositide pathway through a\ pertussis-toxin-insensitive G-protein, probably of the Gq/G11 class PUB00005879.

\ \ endothelin receptor activity ; GO:0004962 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20834 IPR002176

The Escherichia coli ruvC gene is involved in DNA repair and in the late step of RecE and RecF pathway recombination [MEDLINE:92097558]. RuvC protein (EC: 3.1.22.4) cleaves cruciform junctions, which are formed by the extrusion of inverted repeat sequences from a super-coiled plasmid and which are structurally analogous to Holliday junctions, by introducing nicks into strands with the same polarity. The nicks leave a 5'terminal phosphate and a 3'terminal hydroxyl group which are ligated by E.coli or T4 DNA ligases. Analysis of the cleavage sites suggests that DNA topology rather than a particular sequence determines the cleavage site. RuvC protein also cleaves Holliday junctions that are formed between gapped circular and linear duplex DNA by the function of RecA protein. The active form of RuvC protein is a dimer. This is mechanistically suited for an endonuclease involved in swapping DNA strands at the crossover junctions. It is inferred that RuvC protein is an endonuclease that resolves Holliday structures in vivo [MEDLINE:92097558].

RucC is a small protein of about 20 kD. It requires and binds a magnesium ion. The structure of E.coli ruvC is a 3-layer - sandwich containing a 5-stranded -sheet sandwiched between 5 -helices [MEDLINE:94334989].

\ \ lipoate-protein ligase B activity ; GO:0016978 \N DNA recombination ; GO:0006310 20832 IPR002173

It has been shown [MEDLINE:91216983], [MEDLINE:91164390], [MEDLINE:91071601] that the following carbohydrate and purine kinases are evolutionary related and can be grouped into a single family, which is known [MEDLINE:91216983] as the 'pfkB family':

Fructokinase (EC: 2.7.1.4) (gene scrK).
6-phosphofructokinase isozyme 2 (EC: 2.7.1.11) (phosphofructokinase-2) (gene pfkB). pfkB is a minor phosphofructokinase isozyme in Escherichia coli and is not evolutionary related to the major isozyme (gene pfkA). Plants 6-phosphofructokinase also belong to this family.
Ribokinase (EC: 2.7.1.15) (gene rbsK).
Adenosine kinase (EC: 2.7.1.20) (gene ADK).
2-dehydro-3-deoxygluconokinase (EC: 2.7.1.45) (gene: kdgK).
1-phosphofructokinase (EC: 2.7.1.56) (fructose 1-phosphate kinase) (gene fruK).
Inosine-guanosine kinase (EC: 2.7.1.73) (gene gsk).
Tagatose-6-phosphate kinase (EC: 2.7.1.144) (phosphotagatokinase) (gene lacC).
Escherichia coli hypothetical protein yeiC.
Escherichia coli hypothetical protein yeiI.
Escherichia coli hypothetical protein yhfQ.
Escherichia coli hypothetical protein yihV.
Yeast hypothetical protein YJR105w.

All the above kinases are proteins of from 280 to 430 amino acid residues that share a few region of sequence similarity.

Note: some bacterial fructokinases belong to the ROK family (see IPR000600).

\ \ \N \N \N 20830 IPR002171

\ \ \

Ribosomal protein L2 is one of the proteins from the large ribosomal subunit. In Escherichia coli, L2 is known to bind to the 23S rRNA and to have peptidyltransferase activity. It belongs to a family of ribosomal proteins which, on the basis of sequence similarities [MEDLINE:92253345], PUB00005071, groups:

Eubacterial L2.
Algal and plant chloroplast L2.
Cyanelle L2.
Archaebacterial L2.
Plant L2.
Slime mold L2.
Marchantia polymorpha mitochondrial L2.
Paramecium tetraurelia mitochondrial L2.
Fission yeast K5, K37 and KD4.
Yeast YL6.
Vertebrate L8.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 20831 IPR002172

Low density lipoprotein (LDL) is the major cholesterol-carrying lipoprotein of plasma. The receptor protein binds LDL and transports it into cells by endocytosis. In order to be internalised, the receptor-ligand complex must first cluster into clathrin-coated pits. Seven successive cysteine-rich repeats of about 40 amino acids are present in the N-terminal of this multidomain membrane protein [MEDLINE:85024898].

The LDL-receptor class A domain contains 6 disulfide-bound cysteines [MEDLINE:96006161] and a highly conserved cluster of negatively charged amino acids, of which many are clustered on one face of the module [MEDLINE:95327641]. A schematic representation of this domain is shown here:

\ +---------------------+ +--------------------------------+\ | | | |\ -CxxxxxxxxxxxxCxxxxxxxxCxxxxxxxxCxxxxxxxxxxCxxxxxxxxxxxxxxxxxxxxxC-\ | |\ +----------------------------+\ \ 'C': conserved cysteine involved in a disulfide bond.\ 'x': any residue.\

In LDL-receptors the class A domains form the binding site for LDL [MEDLINE:85024898] and calcium [MEDLINE:88087025]. The acidic residues between the fourth and sixth cysteines are important for high-affinity binding of positively charged sequences in LDLR's ligands [MEDLINE:88204890]. The repeat has been shown [MEDLINE:95327641] to consist of a -hairpin structure followed by a series of turns. In the absence of calcium, LDL-A domains are unstructured; the bound calcium ion imparts structural integrity.

\ \

Following these repeats is a 350 residue domain that resembles part of the epidermal growth factor (EGF) precursor [MEDLINE:84205692], [MEDLINE:85024898].

Similar domains have been found (see references in [MEDLINE:95327641]) in several extracellular and membrane proteins (see examples).

\ \

\ Numerous familial hypercholestorolemia mutations of the LDL receptor alter the calcium coordinating residue of LDL-A domains or other crucial scaffolding residues.\

\ \ \N \N \N 20829 IPR002171

\ \ \

Eubacterial L2.
Algal and plant chloroplast L2.
Cyanelle L2.
Archaebacterial L2.
Plant L2.
Slime mold L2.
Marchantia polymorpha mitochondrial L2.
Paramecium tetraurelia mitochondrial L2.
Fission yeast K5, K37 and KD4.
Yeast YL6.
Vertebrate L8.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 20828 IPR002170

Parathyroid hormone (PTH) is involved in calcium homeostasis within the body in combination with calcitonin and vitamin D. PTH is released in response to hypocalcaemia and stimulates a rise in blood calcium; the converse is true for calcitonin. The principle targets for PTH are bone and kidney. Antagonists at the PTH receptor are of potential clinical use in the treatment of hyperparathyroidism and short-term hypercalcaemic states. In addition to its presence in bone and kidney, the receptor is found in lower levels in blood vessels, where it mediates vasodilation. The principle second messenger pathway is activation of adenylyl cyclase through Gs. In addition, PTH stimulates phosphoinositide metabolism on the expressed receptor.

\ \ parathyroid hormone receptor activity ; GO:0004991 membrane ; GO:0016020 \N 20827 IPR002169

Metalloproteases can be split into five clans, and futher sub-divided into families, on the basis of their metal binding residues.

Microbial collagenases have been identified from bacteria of both the\ Vibrio and Clostridium genuses. They are zinc-containing metallopeptidases\ that belong to the M25 protease family, which form part of the MA clan\ [MEDLINE:95405261]. Collagenase is used during bacterial attack to degrade the collagen\ barrier of the host during invasion. Vibrio bacteria are non-pathogenic, and\ are sometimes used in hospitals to remove dead tissue from burns and ulcers. Clostridium histolyticum is a pathogen that causes gas gangrene;\ nevertheless, the isolated collagenase has been used to treat bed sores.\ Collagen cleavage occurs at an Xaa+Gly in Vibrio bacteria and at Yaa+Gly\ bonds in Clostridium collagenases PUB00005935.

\ \

Analysis of the primary structure of the gene product from Clostridium\ perfringens has revealed that the enzyme is produced with a stretch of 86\ residues that contain a putative signal sequence PUB00005935. Within this stretch\ is found PLGP, an amino acid sequence typical of collagenase substrates.\ This sequence may thus be implicated in self-processing of the\ collagenase [MEDLINE:94110220].

\ \ collagenase activity ; GO:0008133 extracellular ; GO:0005576 proteolysis and peptidolysis ; GO:0006508 20822 IPR002164

It is thought that NAPs act as histone chaperones, shuttling both core and linker histones from their site of synthesis in the cytoplasm to the nucleus. The proteins may be involved in regulating gene expression and therefore cellular differentiation [MEDLINE:97468138], [MEDLINE:97081766].

The centrosomal protein c-Nap1, also known as Cep250, has been implicated in the\ cell-cycle-regulated cohesion of microtubule-organizing centers. This 281 kDa\ protein consists mainly of domains predicted to form coiled coil structures. The C-terminal\ region defines a novel histone-binding domain that is responsible for targeting CNAP1, and possibly condensin, to mitotic\ chromosomes [MEDLINE:22133591]. During interphase, C-Nap1 localizes to the proximal\ ends of both parental centrioles, but it dissociates from these structures at the onset of mitosis. Re-association with centrioles\ then occurs in late telophase or at the very beginning of G1 phase, when daughter cells are still connected by post-mitotic\ bridges. Electron microscopic studies performed on isolated centrosomes suggest that a proteinaceous linker connects parental centrioles and C-Nap1 may be part of a linker structure that assures the cohesion of duplicated centrosomes during interphase, but that is dismantled upon centrosome separation at the onset of mitosis [MEDLINE:22135747].

\ \ DNA binding activity ; GO:0003677 nucleus ; GO:0005634 nucleosome assembly ; GO:0006334 20823 IPR002165 A cysteine rich repeat found in several different extracellular receptors. The function of the repeat is unknown. Three copies of the repeat are found Plexin (P70206) contains four copies of the repeat. The Met receptor contains a single copy of the repeat.\ receptor activity ; GO:0004872 membrane ; GO:0016020 \N 20824 IPR002166 The RNA dependent RNA polymerase is also known as non-structural protein NS5B. NS5B is a 65 kDa protein that resembles other viral RNA polymerases. HCV replication is thought to occur in membrane bound replication complexes. These complexes transcribe the positive strand and the resulting minus strand is used as a template for the synthesis of genomic RNA. There are two viral proteins involved in the reaction, NS3 and NS5B [MEDLINE:98001363], [MEDLINE:96176756], [MEDLINE:98183394].\ ATP binding activity ; GO:0005524 \N viral genome replication ; GO:0019079 20825 IPR002167

A variety of substrate carrier proteins that are involved in energy transferare found in the inner mitochondrial membrane [MEDLINE:90223523], [MEDLINE:93314266], [MEDLINE:94188573], [MEDLINE:93253777]. Such proteins include:\ ADP,ATP carrier protein (ADP/ATP translocase); 2-oxoglutarate/malate carrier\ protein; phosphate carrier protein; tricarboxylate transport protein (or\ citrate transport protein); Graves disease carrier protein; yeast\ mitochondrial proteins MRS3 and MRS4; yeast mitochondrial FAD carrier protein;\ and many others.

Graves disease carrier protein (GDC) is a protein of as yet uncharacterised\ function that belongs to the mitochondrial metabolite carrier family\ (which includes the ADP/ATP translocator, the phosphate carrier and the\ hydrogen ion uncoupling protein) [MEDLINE:93314266], [MEDLINE:90114217]. The protein is recognised by IgG\ from patients with active Graves disease.

GDC is an integral membrane protein thought to reside in the inner\ mitochondrial membrane. The predicted amino acid sequence of 348 residues\ comprises three similar domains.

\ \ binding activity ; GO:0005488 mitochondrial inner membrane ; GO:0005743 transport ; GO:0006810 20826 IPR002168

These enzymes contain a Ser-centered consensus sequence and a conserved His-Gly dipeptide found in most lipase amino-terminal domains. These sequences are involved in the lipase active site conformation since\ substitution of the conserved Ser or His residues by Ala and Gln, respectively, results in the\ loss of both lipase and esterase activities.

\ \ hydrolase activity ; GO:0016787 \N metabolism ; GO:0008152 20820 IPR002161

Members of this family are involved in the pyridoxine biosynthetic pathway [MEDLINE:97113448], [MEDLINE:99009008]. The regulation of cellular growth and proliferation in response to environmental cues is critical for development and the maintenance of viability in all organisms. In unicellular\ organisms, such as the budding yeast Saccharomyces cerevisiae, growth and proliferation\ are regulated by nutrient availability.

\ \ \N \N \N 20821 IPR002163

The calcitonin (CT) gene is alternatively expressed in a tissue-specific manner, producing either the calcium regulatory hormone CT in the thyroid, or the neuropeptide calcitonin gene related peptide (CGRP) in the brain [MEDLINE:85180007]. In medullary carcinoma of the thyroid, both peptides are produced [MEDLINE:85180007].

CGRP is a 37-residue peptide produced by alternative splicing of the CT gene. CGRP induces vasodilation in various vessels, including those of the coronary, cerebral and systemic vasculature. A neurotransmitter or neuro-modulator role is suggested by its abundance in the CNS [MEDLINE:85180007]. The structure of human CGRP has been determined by 1H NMR [MEDLINE:91105142]. The main conformational feature of the hormone is an N-terminal disulphide-bonded loop (residues 2-7), leading into a well-defined -helix between residues 8 and 18; thereafter, the structure is predominantly disordered, although there are indications of a preference for a turn-type conformation between residues 19 and 21 [MEDLINE:91105142].

\ \ hormone activity ; GO:0005179 extracellular ; GO:0005576 \N 20818 IPR002159

CD36 is a transmembrane, highly glycosylated, 88kDa glycoprotein expressed by monocytes, macrophages, platelets, microvascular endothelial cells and adipose tissues. Platelet glycoprotein IV (GP IV) (GPIIIb) (CD36 antigen) is also called GPIV, OKM5-antigen or PASIV. CD36 recognizes oxidized low density lipoprotein, long chain fatty acids, anionic phospholipids, collagen types I, IV and V, thrombospondin (TSP) and Plasmodium falciparum infected erythrocytes. The recognition of apoptotic neutrophils is in co-operation with TSP and avb3.\ Other ligands may still be unknown.

\ \

CD36 is a scavenger receptor for oxidized LDL and shed photoreceptor outer segments and in recognition and phagocytosis of apoptotic cells and is the cell adhesion molecule in platelet adhesion and aggregation, platelet-monocyte and platelet-tumor cell\ interaction [MEDLINE:98148020].

\ \

CD molecules are leucocyte antigens on cell surfaces. CD antigens nomenclature is updated at http://www.ncbi.nlm.nih.gov/PROW/guide/45277084.htm \

\ \ \ \N membrane ; GO:0016020 cell adhesion ; GO:0007155 20819 IPR002160

The soybean trypsin inhibitor (Kunitz) family (STI) [MEDLINE:80264016] is one of the numerous families of proteinase inhibitors. It comprise plant proteins which have inhibitory activity against serine proteinases from the trypsin and subtilisin families, thiol proteinases and aspartic proteinases as well as some proteins that are probably involved in seed storage. The STIs belong to a superfamily that also contains the interleukin-1 proteins, heparin binding growth factors (HBGF) and histactophilin, all of which have very similar structures, but share no sequence similarity with the STI family.

Inhibitors from cereals are active against subtilisin and endogenous -amylases, while some also inhibit tissue plasminogen activator. The inhibitors are usually specific for either trypsin or chymotrypsin, and some are effective against both. They are thought to protect the seeds against consumption by animal predators, while at the same time existing as seed storage proteins themselves - all the actively inhibitory members contain 2 disulphide bridges. The existence of a member with no inhibitory activity, winged bean albumin 1, suggests that the inhibitors may have evolved from seed storage proteins.

Proteins from the Kunitz family contain from 170 to 200 amino acid residues and one or two intrachain disulfide bonds. The best conserved region is found in their N-terminal section. The crystal structures of soybean trypsin inhibitor (STI), trypsin inhibitor DE-3 from Erythrina caffra (ETI) [MEDLINE:91108811] and the bifunctional proteinase K/-amylase inhibitor from wheat (PK13) have been solved, showing them to share the same 12-stranded -sheet structure as those of interleukin-1 and heparin-binding growth factors [MEDLINE:92148835]. The -sheets are arranged in 3 similar lobes around a central axis, 6 strands forming an anti-parallel -barrel. Despite the structural similarity, STI shows no interleukin-1 bioactivity, presumably as a result of their primary sequence disparities. The active inhibitory site containing the scissile bond is located in the loop between -strands 4 and 5 in STI and ETI.

\ \ endopeptidase inhibitor activity ; GO:0004866 \N \N 20816 IPR002157

In eukaryotes, a number of proteins are involved in the binding and transport of cobalamin (vitamin B12) [MEDLINE:84024175]. Some of them have been sequenced and have been shown [MEDLINE:91210312], [MEDLINE:93176815] to be evolutionary related and are listed below:

Intrinsic factor (IF). The function of IF is to promote the absorption of cobalamin in the ileum by specific receptor-mediated endocytosis.
Transcobalamin I (TC1) (also called R-binder protein). TC1 transports cobalamin from blood to cells.
Transcobalamin II (TC2). TC2 transports cobalamin from blood to cells.
Haptocorrin (cobalophilin). Haptocorrin binds to cobalamin and to cobalamin derivatives such as cobinamide. It may play a role in preventing the absorption of cobalamin analogues produced by bacteria.

\ \

These glycoproteins are polypeptides of about 400 amino acids that share many regions of similarity.

\ \ binding activity ; GO:0005488 \N transport ; GO:0006810 20817 IPR002158

A structure, referred to as the 'leucine zipper' [MEDLINE:88248716], [MEDLINE:90246531], has been proposed to explain how some eukaryotic gene regulatory proteins work. The leucine zipper consist of a periodic repetition of leucine residues at every seventh position over a distance covering eight helical turns. The segments containing these periodic arrays of leucine residues seem to exist in an -helical conformation. The leucine side chains extending from one -helix interact with those from a similar helix of a second polypeptide, facilitating dimerization; the structure formed by cooperation of these two regions forms a coiled coil [MEDLINE:89100305]. The leucine zipper pattern is present in many gene regulatory proteins, such as:

The CCATT-box and enhancer binding protein (C/EBP).
The cAMP response element (CRE) binding proteins (CREB, CRE-BP1,
The Jun/AP1 family of transcription factors.
The yeast general control protein GCN4.
The fos oncogene, and the fos-related proteins fra-1 and fos B.
The C-myc, L-myc and N-myc oncogenes.
The octamer-binding transcription factor 2 (Oct-2/OTF-2).

Note: No protein matches are shown due to the low specificity of this rule.

\ \ DNA binding activity ; GO:0003677 \N regulation of transcription, DNA-dependent ; GO:0006355 20815 IPR002156

The RNase H domain is responsible for hydrolysis of the RNA portion of RNA x DNA hybrids, and this activity requires the presence of divalent cations (Mg2+ or Mn2+) that bind its active site. This domain is a part of a large family of homologous RNase H enzymes of which the RNase HI protein from Escherichia coli is the best characterized [MEDLINE:98412882]. Secondary structure predictions for the enzymes from E. coli, yeast, human liver and diverse retroviruses (HIV, Rous sarcoma virus, foamy viruses) supported, in every case, the five -strands (1 to 5) and four or five -helices (A, B/C, D, E) that have been identified by crystallography in the RNase H domain of HIV-1 reverse transcriptase and in E. coli RNase H [MEDLINE:20068746]. Reverse transcriptase (RT) is a modular enzyme carrying polymerase and ribonuclease H (RNase H) activities in separable domains. Reverse transcriptase (RT) converts the single-stranded RNA genome of a retrovirus into a double-stranded DNA copy for integration into the host genome. This process requires ribonuclease H as well as RNA- and DNA-directed DNA polymerase activities.

Retroviral RNase H is synthesised as part of the POL polyprotein that contains; an aspartyl protease, a reverse transcriptase, RNase H and integrase. POL polyprotein undergoes specific enzymatic cleavage to yield the mature proteins. Bacterial RNase H (EC: 3.1.26.4) catalyses endonucleolytic cleavage to 5'-phosphomonoester acting on RNA-DNA hybrids.

\ \ ribonuclease H activity ; GO:0004523 \N \N 20814 IPR002155

Two different types of thiolase [MEDLINE:92096120], [MEDLINE:90285166], [MEDLINE:92365084] are found both in eukaryotes and in prokaryotes: acetoacetyl-CoA thiolase (EC: 2.3.1.9) and 3-ketoacyl-CoA thiolase (EC: 2.3.1.16). 3-ketoacyl-CoA thiolase (also called thiolase I) has a broad chain-length specificity for its substrates and is involved in degradative pathways such as fatty acid -oxidation. Acetoacetyl-CoA thiolase (also called thiolase II) is specific for the thiolysis of acetoacetyl-CoA and involved in biosynthetic pathways such as poly -hydroxybutyrate synthesis or steroid biogenesis.

In eukaryotes, there are two forms of 3-ketoacyl-CoA thiolase: one located in the mitochondrion and the other in peroxisomes.

\ \

There are two conserved cysteine residues important for thiolase activity. The first located in the N-terminal section of the enzymes is involved in the formation of an acyl-enzyme intermediate; the second located at the C-terminal extremity is the active site base involved in deprotonation in the condensation reaction.

\ \

Mammalian nonspecific lipid-transfer protein (nsL-TP) (also known as sterol carrier protein 2) is a protein which seems to exist in two different forms: a 14 Kd protein (SCP-2) and a larger 58 Kd protein (SCP-x). The former is found in the cytoplasm or the mitochondria and is involved in lipid transport; the latter is found in peroxisomes. The C-terminal part of SCP-x is identical to SCP-2 while the N-terminal portion is evolutionary related to thiolases [MEDLINE:92096120].

\ \ \N \N \N 20811 IPR002153

Transient receptor potential (Trp) and related proteins are thought to beCa²⁺ ion channel subunits that mediate capacitative Ca²⁺ entry in response\ to a range of external and internal cell stimuli. Such Ca²⁺ entry is thought\ to be an essential component of cellular responses to many hormones and\ growth factors, and acts to replenish intracellular Ca²⁺ stores that have\ been emptied through the action of inositol triphosphate (IP3) and other\ agents. In non-excitable cells, i.e. those that lack voltage-gated Ca²⁺\ channels, such as hepatocytes, this mode of Ca²⁺ entry is thought to be an\ important step in generating the oscillations of intracellular Ca²⁺\ concentration that characterise their response to stimulatory agents [MEDLINE:96234226].\ Studies on the visual transduction system in Drosophila led to the molecular\ cloning of Trp and the cDNA of a related protein, Trp-like, which show\ similarity to voltage gated Ca²⁺ channels in the regions known as S3 through\ S6, including the S5-S6 linker that forms the ion-selective channel pore [MEDLINE:98037793].\ This provided evidence that Trp and/or related proteins might form mammalian\ capacitative Ca²⁺ entry channels. They have varying lengths (usually 800-1000\ amino acid residues), and hydropathy analyses suggest that they have six or\ more transmebrane (TM) regions, flanked by cytosolic N- and C-termini.

\ \ calcium channel activity ; GO:0005262 membrane ; GO:0016020 calcium ion transport ; GO:0006816 20812 IPR002154

Neuregulins are a sub-family of EGF-like molecules that have been shown to play multiple essential roles in vertebrate embryogenesis including: cardiac development, Schwann cell and oligodendrocyte differentiation, some aspects of neuronal development, as well as the formation of neuromuscular synapses [MEDLINE:99110959], [MEDLINE:97352457]. Included in the family are heregulin; neu differentiation factor; acetylcholine receptor synthesis stimulator; glial growth factor; and sensory and motor-neuron derived factor [MEDLINE:99023998]. Multiple family members are generated by alternate splicing or by use of several cell type-specific transcription initiation sites. In general, they bind to and activate the erbB family of receptor tyrosine kinases (erbB2 (HER2), erbB3 (HER3), and erbB4 (HER4)), functioning both as heterodimers and homodimers.

The transmembrane forms of neuregulin 1(NRG1) are present within synaptic vesicles, including those containing glutamate [MEDLINE:22233215]. After\ exocytosis, NRG1 is in the presynaptic membrane, where the ectodomain of NRG1 may be cleaved off. The ectodomain\ then migrates across the synaptic cleft and binds to and activates a member of the EGF-receptor family on the postsynaptic\ membrane. This has been shown to increase the expression of certain glutamate-receptor subunits. NRG1 appears to signal for glutamate-receptor subunit\ expression, localization, and /or phosphorylation facilitating subsequent glutamate transmission.

The NRG1 gene has been identified as a potential gene determining susceptibility to schizophrenia by a combination of genetic linkage and association approaches [MEDLINE:22233215].

\ \ receptor binding activity ; GO:0005102 \N embryonic development ; GO:0009790 20813 IPR002155

In eukaryotes, there are two forms of 3-ketoacyl-CoA thiolase: one located in the mitochondrion and the other in peroxisomes.

\ \

\ \ \N \N \N 20809 IPR002151 Kinesin [MEDLINE:96124206] is a microtubule-associated force-producing protein that may play a role in organelle transport. Kinesin is an oligomeric complex composed of two heavy chains and two light chains. The light chain has been proposed to function in the coupling of cargo to the heavy chain or in the modulation of its ATPase activity [MEDLINE:93293894]. It is a well conserved protein which is composed of a core that consist of a coiled-coil domain followed by four imperfect tandem repeats of a 42 residue domain. The N- and C-termini are more variable and alternative splicing is responsible for the production of isoforms that differ in those two regions.\ microtubule motor activity ; GO:0003777 kinesin complex ; GO:0005871 \N 20810 IPR002152

Goose-type lysozyme (lysozyme G) hydrolyses 1,4--linkages between\ N-acetyl-D-glucosamine and N-acetylmuramic acid in peptidoglycan hetero-polymers of prokaryote cell walls. Lysozyme G shows preference for\ N-acetylmuramic acid residues that are substituted with a peptide moiety;\ it acts only as a glycanohydrolase.

The structure of goose egg-white lysozyme (GEWL) with a bound trisaccharide\ has been refined to 1.6A resolution [MEDLINE:95123646]. The trisaccharide occupies\ analogous sites to the B, C and D subsites of chicken (HEWL) and phage T4\ (T4L) lysozymes. All of these enzymes display the same characteristic\ hydrogen bonding pattern between protein and substrate [MEDLINE:95123646]. Glu73 of GEWL corresponds closely to Glu35 of HEWL (Glu11 of T4L), supporting the view\ that this group is critical to the catalytic mechanism. However, lysozyme G\ has no obvious counterpart to Asp52 of chicken lysozyme (Asp20 in T4L),\ suggesting that a second acidic residue is not essential for its catalytic\ activity, and may not be required for the activity of other lysozymes.\ The structure of GEWL belongs to the mainly class, its sequence\ showing no discernible similarity to other lysozymes. The enzyme has\ been classified as belonging to family 23 of glycosyl hydrolases [MEDLINE:96257770], PUB00005672 (CAZY:GH_23).

\ \ lysozyme activity ; GO:0003796 \N cell wall catabolism ; GO:0016998 20806 IPR002148 This protein is also known as NSP1. NS53 is encoded by gene 5. It is made in low levels in the infected cells and is a component of early replication. The protein is known to accumulate on the cytoskeleton of the infected cell. NS53 is an RNA binding protein that contains a characteristic cysteine rich region [MEDLINE:93362432], [MEDLINE:97167412].\ RNA binding activity ; GO:0003723 \N \N 20807 IPR002149 The A-latrotoxin receptor interaction domain is found in rabphilin-3A, which is involved in protein transport; and synaptotagmins, which may play a regulatory role in membrane interactions during trafficking of synaptic vesicles at the active zone of the synapse. synaptotagmins bind acidic phospholipids with a specificity that requires the presence of both an acidic head group and a diacyl backbone.\ transporter activity ; GO:0005215 membrane ; GO:0016020 transport ; GO:0006810 20808 IPR002150

\ \ \

Ribosomal protein L31 is one of the proteins from the large ribosomal subunit. L31 is a protein of 66 to 97 amino-acid residues which has only been found so far in eubacteria and in some algal chloroplasts.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 20803 IPR002145

CopG, also known as RepA, is responsible for the regulation of plasmid copy number. It binds to the repAB promoter and controls synthesis of the plasmid replication initiator protein RepB. Many bacterial transcription regulation proteins bind DNA through a 'helix-turn-helix' motif, nevertheless CopG displays a fully defined HTH-motif structure that is involved not in DNA-binding, but in the maintenance of the intrinsic dimeric functional structure and cooperativity [MEDLINE:98377966], [MEDLINE:99077807].

\ DNA binding activity ; GO:0003677 \N regulation of transcription, DNA-dependent ; GO:0006355 20804 IPR002146

\ \

\ \ \ \ \ \ \

The CF(0) B/B' subunits are thought to interact with the stalk of the CF(1) subunits.

\ \ hydrogen-transporting two-sector ATPase activity ; GO:0003936 \N proton transport ; GO:0015992 20802 IPR002144

Secretin stimulates secretion of enzymes and ions in the pancreas and\ intestine, and is present in small amounts in the brain (e.g., in the\ hypothalamus, brainstem and cerebral cortex). Secretin receptors are\ found in high levels in the pancreas, stomach and heart PUB00005907. They activate\ adenylyl cyclase through stimulation of Gs.

\ \ G-protein coupled receptor activity ; GO:0004930 membrane ; GO:0016020 \N 20805 IPR002147

5HT1-like receptors were originally classified according to their nanomolar affinity for 5HT, susceptibility to antagonism by methiothepin and/or\ methysegide, resistance to antagonism by 5HT2 and 5HT3 antagonists, and\ high affinity for the agonist 5-carboxamidotryptamine. Five subtypes\ of 5HT1-like receptors have now been identified - these do not fit all the\ above criteria, and 5HT1C has been reclassified 5HT2C PUB00005889. All are linked\ to the inhibition of adenylyl cyclase, share a high degree of sequence\ similarity, and have overlapping pharmacological specificities.

The 5HT1B receptor was first identified in rats, where it has a distinct\ pharmacological profile. In humans, however, it shares an almost\ identical pharmacology with the 5HT1D receptor. In the CNS, the receptor\ is found in the striatum, medulla, hippocampus, frontal cortex and\ amygdala. In the periphery, it is found in vascular smooth muscle.\ The 5HT1B/5HT1D receptor may be the therapeutic substrate of the anti-migraine drug, sumatriptan; these sites are also implicated in feeding\ behaviour, anxiety, depression, cardiac function and movement PUB00005889.

\ \ \N integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20797 IPR002139

Ribokinases participate in the first step of ribose metabolism, and are members of the superfamily of carbohydrate kinases. Ribokinases phosphorylate ribose to ribose-5-phosphate in the presence of ATP and magnesium [MEDLINE:98046763]:

\
ATP + D-Ribose = ADP + D-Ribose-5-Phosphate\

The phosphorylated sugar may then enter the pentose phosphate pathway [MEDLINE:96165550].

There are indications that the phosphorylated sugar may also be used in the synthesis of amino acids (histidine and tryptophan). Further, links to mammalian adenosine kinase have been identified, through sequence similarity, suggesting possible homology [MEDLINE:96165550], [MEDLINE:97075030].

\ \ ribokinase activity ; GO:0004747 \N ribose metabolism ; GO:0006014 20798 IPR002140

A number of uncharacterized hydrophilic proteins of about 30 kDa share regions of similarity. These include,

Mouse protein 22A3.
Yeast chromosome XII hypothetical protein YLR022c.
Caenorhabditis elegans hypothetical protein W06E11.4.
Methanococcus jannaschii hypothetical protein MJ0592.

\ \ molecular_function unknown ; GO:0005554 \N \N 20799 IPR002141 Influenza virus nucleoprotein is a structural protein which encapsidates the negative strand viral RNA. NP is one of the main determinants of species specificity. The question of how far the NP gene can cross the species barrier by reassortment and become adapted by mutation to the new host has been discussed [MEDLINE:85274879].\ structural molecule activity ; GO:0005198 \N \N 20800 IPR002142 Peptidases are proteolytic enzymes that exploit serine in their catalytic activity. This family belongs to family U7 of the peptidase classification, and includes the potential protease SohB, a suppressor of the HTRA phenotype; and protease IV, an endopeptidase required to maintain proper secretion of mature proteins across the membrane.\ serine-type endopeptidase activity ; GO:0004252 \N proteolysis and peptidolysis ; GO:0006508 20801 IPR002143

\ \ \

Ribosomal protein L1 is the largest protein from the large ribosomal subunit. In Escherichia coli, L1 is known to bind to the 23S rRNA. It belongs to a family of ribosomal proteins which, on the basis of sequence similarities [MEDLINE:96205873], [MEDLINE:96183058], groups:

Eubacterial L1.
Algal and plant chloroplast L1.
Cyanelle L1.
Archaebacterial L1.
Vertebrate L10A.
Yeast SSM1.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 20796 IPR002138

Synonym(s): Interleukin 1- converting enzyme (ICE)

Caspase-2 (ICH-1, NEDD-2).
Caspase-3 (also known as apopain, CPP32, Yama), a protease which, at the onset of apoptosis, proteolytically cleaves poly(ADP-ribose) polymerase (see IPR001309/>) at an Asp-Gly bond.
Caspase-4 (ICH-2, TX, ICErel-II).
Caspase-5 (ICH-3, TY, ICErel-III).
Caspase-6 (MCH-2).
Caspase-7 (MCH-3, ICE-LAP3, CMH-1, SCA-2, LICE2).
Caspase-8 (MCH-5, MACH, FLICE).
Caspase-9 (MCH-6, ICE-LAP6).
Caspase-10 (MCH-4, FLICE2).
Caspase-11.
Caspase-12.
Caenorhabditis elegans ced-3 involved in the initiation of apoptosis.
Drosophila Ice.

Note: these proteins belong to family C14 in the classification of peptidases [MEDLINE:93176119].

\ \ caspase activity ; GO:0004199 \N proteolysis and peptidolysis ; GO:0006508 20795 IPR002137 Beta-lactamases (EC: 3.5.2.6) [MEDLINE:81101305], [MEDLINE:91186832] are enzymes which catalyze the hydrolysis of an amide bond in the

-lactam ring of antibiotics belonging to the penicillin/cephalosporin family. Four kinds of

-lactamase have been identified [MEDLINE:89271760]. Class-B enzymes are zinc containing proteins whilst class -A, C and D enzymes are serine hydrolases. The three classes of serine

-lactamases are evolutionary related and belong to a superfamily [MEDLINE:88183346] that also includes DD-peptidases and a variety of other penicillin-binding proteins (PBP's). All these proteins contain a Ser-x-x-Lys motif, where the serine is the active site residue. Although clearly homologous, the sequences of the three classes of serine

-lactamases exhibit a large degree of variability and only a small number of residues are conserved in addition to the catalytic serine.\ beta-lactamase activity ; GO:0008800 \N antibiotic catabolism ; GO:0017001 20794 IPR002136

\ \ \

This family includes ribosomal L4/L1 from eukaryotes and plants and L4 from eubacteria. L4 from yeast has been shown to bind rRNA [MEDLINE:99057590]. These proteins have 246 (plant) to 427 (human) amino acids.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 20793 IPR002134 The histidine-rich calcium-binding protein (HCP) of sarcoplasmic reticulum [MEDLINE:90036884] may play a role in the regulation of calcium sequestration or release in the SR of skeletal and cardiac muscle. This protein is very acidic (31% of Asp and Glu) and rich in histidine (13%). The sequence of HCP contains 10 tandem repeats of a 26 to 29 amino acid residues domain. This domain starts with an invariant hexapeptide (HRHRGH), followed by a stretch of acidic residues. The end of the domain consist of an almost invariant nonapeptide (STESDRHQA). The highly acidic central cores of each repeat are likely to constitute the calcium-binding sites of HCP.\ calcium ion binding activity ; GO:0005509 \N \N 20789 IPR002132

\ \ \

Ribosomal protein L5 is one of the proteins from the large ribosomal subunit. In Escherichia coli, L5 is known to be involved in binding 5S RNA to the large ribosomal subunit. It belongs to a family of ribosomal proteins which, on the basis of sequence similarities [MEDLINE:90335268], [MEDLINE:91200661], [MEDLINE:92110433], PUB00005071, groups:

Eubacterial L5.
Algal chloroplast L5.
Cyanelle L5.
Archaebacterial L5.
Mammalian L11.
Tetrahymena thermophila L21.
Dictyostelium discoideum L5
Saccharomyces cerevisiae L16 (39A).
Plant mitochondrial L5.

L5 is a protein of about 180 amino-acid residues.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 20790 IPR002133

S-adenosylmethionine synthetase (MAT, EC: 2.5.1.6) is the enzyme that catalyzes the formation of S-adenosylmethionine (AdoMet) from methionine and ATP [MEDLINE:90337979]. AdoMet is an important methyl donor for transmethylation and is also the propylamino donor in polyamine biosynthesis.

In bacteria there is a single isoform of AdoMet synthetase (gene metK), there are two in budding yeast (genes SAM1 and SAM2) and in mammals while in plants there is generally a multigene family.

The sequence of AdoMet synthetase is highly conserved throughout isozymes and species. The active sites of both the Escherichia coli and rat liver MAT reside between two subunits, with contributions from side chains of residues from both subunits,\ resulting in a dimer as the minimal catalytic entity. The side chains that contribute to the ligand binding sites are conserved between the two proteins. In the\ structures of complexes with the E. coli enzyme, the phosphate groups have the same positions in the (PPi plus Pi) complex and the (ADP plus Pi) complex,\ and are located at the bottom of a deep cavity with the adenosyl group nearer the entrance [MEDLINE:76119102].

\ \ ATP binding activity ; GO:0005524 \N one-carbon compound metabolism ; GO:0006730 20787 IPR002131

\ \ protein-hormone receptor activity ; GO:0016500 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20788 IPR002132

\ \ \

Eubacterial L5.
Algal chloroplast L5.
Cyanelle L5.
Archaebacterial L5.
Mammalian L11.
Tetrahymena thermophila L21.
Dictyostelium discoideum L5
Saccharomyces cerevisiae L16 (39A).
Plant mitochondrial L5.

L5 is a protein of about 180 amino-acid residues.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 20791 IPR002133

In bacteria there is a single isoform of AdoMet synthetase (gene metK), there are two in budding yeast (genes SAM1 and SAM2) and in mammals while in plants there is generally a multigene family.

\ \ ATP binding activity ; GO:0005524 \N one-carbon compound metabolism ; GO:0006730 20792 IPR002133

In bacteria there is a single isoform of AdoMet synthetase (gene metK), there are two in budding yeast (genes SAM1 and SAM2) and in mammals while in plants there is generally a multigene family.

\ \ ATP binding activity ; GO:0005524 \N one-carbon compound metabolism ; GO:0006730 20786 IPR002130

Cyclophilin PUB00005503 is the major high-affinity binding protein in vertebrates for the immunosuppressive drug cyclosporin A (CSA), but is also found in other organisms. It exhibits a peptidyl-prolyl cis-trans isomerase activity (EC: 5.2.1.8) (PPIase or rotamase). PPIase is an enzyme that accelerates protein folding by catalyzing the cis-trans isomerization of proline imidic peptide bonds in oligopeptides PUB00005503. It is probable that CSA mediates some of its effects via an forming a tight complex with cyclophilin that inhibits thephosphatase activity of calcineurin [MEDLINE:94245744], [MEDLINE:94162250]\ . Cyclophilin A is a cytosolic and highly abundant protein. The protein belongs to a family of isozymes, including cyclophilins B and C, and natural killer cell cyclophilin-related protein [MEDLINE:93099949], [MEDLINE:94009030], [MEDLINE:95058188]. Major isoforms have been found throughout the cell, including the ER, and some are even secreted. The sequences of the different forms of cyclophilin-type PPIases are well conserved.

Note: FKBP's, a family of proteins that bind the immunosuppressive drug FK506, are also PPIases, but their sequence is not at all related to that of cyclophilin (see IPR001179).

\ \ \N \N protein folding ; GO:0006457 20784 IPR002128 This domain represents a C-terminal extension of NADH-Ubiquinone/plastoquinone (complex I) chains (see IPR001750.\ NADH dehydrogenase (ubiquinone) activity ; GO:0008137 chloroplast ; GO:0009507 oxidative phosphorylation, NADH to ubiquinone ; GO:0006120 20785 IPR002129 A number of pyridoxal-dependent decarboxylases share regions of sequence similarity, particularly in the vicinity of a conserved lysine residue, which provides the attachment site for the pyridoxal-phosphate (PLP) group [MEDLINE:94237165], [MEDLINE:91080170]. Among these enzymes are aromatic-L-amino-acid decarboxylase (L-dopa decarboxylase or tryptophan decarboxylase), which catalyses the decarboxylation of tryptophan to tryptamine [MEDLINE:97044752]; tyrosine decarboxylase, which converts tyrosine into tyramine; and histidine decarboxylase, which catalyses the decarboxylation of histidine to histamine [MEDLINE:90138901]. These enzymes belong to the group II decarboxylases [MEDLINE:94237165], [MEDLINE:97044752].\ carboxy-lyase activity ; GO:0016831 \N amino acid metabolism ; GO:0006520 20779 IPR002123 This family contains acyltransferases involved in phospholipid biosynthesis and other proteins of unknown function [MEDLINE:97411131]. This family also includes tafazzin subfamily (Q16635.\ acyltransferase activity ; GO:0008415 \N metabolism ; GO:0008152 20780 IPR002124

In eukaryotes, in addition to the \ three large subunits, I, II and III, that form the catalytic center of the enzyme complex, there are \ a variable number of small polypeptidic subunits. One of these subunits is known as Vb in mammals, V in slime mold and IV in yeast, binds a zinc atom. The sequence of subunit Vb is well conserved and includes three conserved cysteines that coordinate the zinc ion [MEDLINE:92096446], [MEDLINE:96216288]. Two of these cysteines are clustered in the C-terminal section of the subunit.

\ \ cytochrome c oxidase activity ; GO:0004129 mitochondrial membrane ; GO:0005740 electron transport ; GO:0006118 20781 IPR002125

Cytidine deaminase (EC: 3.5.4.5) (cytidine aminohydrolase) catalyzes the hydrolysis of cytidine into uridine and ammonia while deoxycytidylate deaminase (EC: 3.5.4.12) (dCMP deaminase) hydrolyzes dCMP into dUMP. Both enzymes are known to bind zinc and to require it for their catalytic activity [MEDLINE:92232718], [MEDLINE:93155023]. These two enzymes do not share any sequence similarity with the exception of a region that contains three conserved histidine and cysteine residues which are thought to be involved in the binding of the catalytic zinc ion.

Such a region is also found in other proteins [MEDLINE:94339846], [MEDLINE:94262159]:

Yeast cytosine deaminase (EC: 3.5.4.1) (gene FCY1) which transforms cytosine into uracil.
Mammalian apolipoprotein B mRNA editing protein, responsible for the postranscriptional editing of a CAA codon into a UAA (stop) codon in the APOB mRNA.
Riboflavin biosynthesis protein ribG, which converts 2,5-diamino-6-(ribosylamino)-4(3H)-pyrimidinone 5'-phosphate into 5-amino-6-(ribosylamino)-2,4(1H,3H)-pyrimidinedione 5'-phosphate.
Bacillus cereus blasticidin-S deaminase (EC: 3.5.4.23), which catalyzes the deamination of the cytosine moiety of the antibiotics blasticidin S, cytomycin and acetylblasticidin S.
Bacillus subtilis protein comEB. This protein is required for the binding and uptake of transforming DNA.
B. subtilis hypothetical protein yaaJ.
Escherichia coli hypothetical protein yfhC.
Yeast hypothetical protein YJL035c.

\ \ hydrolase activity ; GO:0016787 \N \N 20778 IPR002122

Adrenocorticotrophin (ACTH), melanocyte-stimulating hormones (MSH) and -endorphin are peptide products of pituitary pro-opiomelanocortin.\ ACTH regulates synthesis and release of glucocorticoids and aldosterone\ in the adrenal cortex; it also has a trophic action on these cells.\ ACTH and -endorphin are synthesised and released in response to\ corticotrophin-releasing factor at times of stress (heat, cold, infections,\ etc.) - their release leads to increased metabolism and analgesia res..\ MSH has a trophic action on melanocytes, and regulates pigment production\ in fish and amphibia. The ACTH receptor is found in high levels in\ the adrenal cortex - binding sites are present in lower levels in the\ CNS. The MSH receptor is expressed in high levels in melanocytes,\ melanomas and their derived cell lines PUB00005891. Receptors are found in low\ levels in the CNS. MSH regulates temperature control in the septal region\ of the brain and releases prolactin from the pituitary.

A further gene, which encodes a melanocortin receptor that is functionally\ distinct from the ACTH and MSH receptors, has also been characterised PUB00005891, [MEDLINE:94226597], [MEDLINE:94022273].\ The protein contains ~323 amino acids, with calculated molecular mass of\ 35,800 Da, and potential N-linked glycosylation and phosphorylation sites\ [MEDLINE:94226597]. The melanocortin 3 receptor (MC3-R) is found in neurons of the arcuate\ nucleus known to express proopiomelanocortin and in a subset of the nuclei\ to which these neurons send projections [MEDLINE:94022273]. The MC3-R is 43% identical to\ the MSH receptor present in melanocytes and is strongly coupled to adenylyl\ cyclase [MEDLINE:94022273].

\ \ melanocortin receptor activity ; GO:0004977 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20783 IPR002127

Tetracycline binds to the prokaryotic ribosomal 30S subunit and inhibits binding of aminoacyl-tRNAs. The tetracycline resistance (Tcr) proteins tetM/tetO from bacteria such as Campylobacter jejuni, Enterococcus faecalis, Streptococcus mutans and Ureaplasma urealyticum, abolish the inhibitory effect of tetracycline on protein synthesis [MEDLINE:88226013], [MEDLINE:88298672], [MEDLINE:94058212], [MEDLINE:92378171]. Comparison of the amino acid sequences of TetO and TetM reveals 76% similarity, and hydropathy analyses show almost identical profiles, suggesting that TcR determinants in Gram-positive bacteria and in C.jejuni may have a common ancestry [MEDLINE:88226013].

The ribosome protection type of tetracycline resistance has been found in a variety of bacterial species. It first appeared that this type of resistance emerged recently in evolution and spread among different species of bacteria by horizontal transmission.

The Tcr gene product from Bacteroides, a genus of Gram-negative, obligately anaerobic bacteria that is phylogenetically distant from the diverse species in which tetM and tetO have been found, has been shown to be 40% identical to TetM and TetO. The Bacteroides Tcr gene thus defines a new class of ribosome protection resistance genes, designated tetQ [MEDLINE:92378171]. Like tetM and tetO, tetQ appears to have spread by horizontal transmission, but only within the Bacteroides group [MEDLINE:92378171]. Many human colonic Bacteroides strains carry large (greater than 70kbp) self-transmissible chromosomal Tcr elements [MEDLINE:92378171].

The TetM/TetO group of Tcr proteins shows significant similarity to translational elongation factors of prokaryotes and eukaryotes.

\ \ GTP binding activity ; GO:0005525 \N protein biosynthesis ; GO:0006412 20782 IPR002126

Cadherins are a family of adhesion molecules that mediate Ca2+-dependent cell-cell adhesion in all solid tissues of the organism which modulate a wide variety of processes including cell polarization and migration [MEDLINE:90328741], PUB00005514. Cadherin-mediated cell-cell junctions are formed as a result of interaction between extracellular domains of identical cadherins, which are located on the membranes of the neighboring cells. The stability of these adhesive junctions is ensured by binding of the intracellular cadherin\ domain with the actin cytoskeleton. There are a number of different isoforms distributed in a tissue-specific manner in a wide variety of organisms. Cells containing different cadherins tend to segregate in vitro, while those that contain the same cadherins tend to preferentially aggregate together. This observation is linked to the finding that cadherin expression causes morphological changes involving the positional segregation of cells into layers, suggesting they may play an important role in the sorting of different cell types during morphogenesis, histogenesis and regeneration. They may also be involved in the regulation of tight and gap junctions, and in the control of intercellular spacing. Cadherins are evolutionary related to the desmogleins which are component of intercellular desmosome junctions involved in the interaction of plaque proteins.

Structurally, cadherins comprise a number of domains: classically, these include a signal sequence; a propeptide of around 130 residues; a single transmembrane domain and five tandemly repeated extracellular cadherin domains, 4 of which are repeats of about 110 residues, and the fifth contains 4 conserved cysteines and a N-terminal cytoplasmic domain PUB00005514. Crystal structures have revealed that multiple cadherin domains form Ca2+-dependent rod-like structures with a conserved Ca2+-binding pocket at the\ domain-domain interface. Cadherins depend on calcium for their\ function: removal of calcium abolishes adhesive activity, renders cadherins vulnerable to proteases.

\ \ calcium ion binding activity ; GO:0005509 membrane ; GO:0016020 homophilic cell adhesion ; GO:0007156 20775 IPR002119 Histone H2A is a small, highly conserved nuclear protein that, together with 2 molecules each of histones H2B, H3 and H4, forms the eukaryotic nucleosome core [MEDLINE:94167243]; the nucleosome octamer winds ~146 DNA base-pairs.\ DNA binding activity ; GO:0003677 nucleus ; GO:0005634 chromosome organization and biogenesis (sensu Eukarya) ; GO:0007001 20776 IPR002120

Thyrotrophin-releasing hormone (thyroliberin) (TRH) stimulates synthesis\ and release of thyroid-stimulating hormone in the anterior pituitary.\ It also stimulates synthesis and release of prolactin. In the CNS, TRH\ stimulates a number of behavioural and pharmacological actions, including\ increased turnover of catecholamines in the nucleus accumbens. TRH\ receptors are found in high levels in the anterior pituitary, and are also\ found in the retina and in certain areas of the brain. The receptors\ activate phosphoinositide metabolism through a pertussis-toxin-insensitive\ G-protein, probably of the Gq/G11 class PUB00005906.

\ \ thyrotropin-releasing hormone receptor activity ; GO:0004997 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20772 IPR002115

Low molecular weight (LMW) phosphotyrosine protein phosphatase (or acid phosphatase) acts on tyrosine phosphorylated proteins, low-MW aryl phosphates and natural and synthetic acyl phosphates [MEDLINE:92268143], [MEDLINE:93284125]. It is a cytoplasmic enzyme that catalyses the reaction:

protein tyrosine phosphate + H(2)O = protein tyrosine + orthophosphate.

The structure of the protein has been solved by NMR [MEDLINE:95244419]. It belongs to the / class, with 6 -helices and 4 -strands forming a 3-layer -- sandwich architecture.

\ \ non-membrane spanning protein tyrosine phosphatase activity ; GO:0004726 \N protein amino acid dephosphorylation ; GO:0006470 20773 IPR002116

The allergens in this family include allergens with the following designations: Api m 3.

\ \

Melittin is the principal protein component of the venom of the honeybee, Apis mellifera. It inhibits protein kinase C, Ca²⁺/calmodulin-dependent protein kinase II, myosin light chain kinase and Na⁺/K⁺-ATPase (synaptosomal membrane) and is a cell membrane lytic factor. Melittin is a small peptide with no disulfide bridge; the N-terminal part of the molecule is predominantly hydrophobic and the C-terminal part is hydrophilic and strongly basic.

The molecular mechanisms underlying the various effects of melittin on membranes have not been completely defined and much of the evidence indicates that different molecular mechanisms may underlie different actions of the peptide [MEDLINE:90254148].

Extensive work with melittin has shown that the venom has multiple effects, probably, as a result of its interaction with negatively changed phospholipids. It inhibits well known transport pumps such as the Na⁺-K⁺-ATPase and the H⁺-K⁺-ATPase. Melittin increases the permeability of cell membranes to ions, particularly Na⁺ and indirectly Ca²⁺, because of the Na⁺-Ca²⁺-exchange. This effect results in marked morphological and functional changes, particularly in excitable tissues such as cardiac myocytes. In some other tissues, e.g., cornea, not only Na⁺ but Cl- permeability is also increased by melittin. Similar effects to melittin on H⁺-K⁺-ATPase have been found with the synthetic amphipathic polypeptide Trp-3 [MEDLINE:99172423].

The study of melittin in model membranes has been useful for the development of methodology for determination of membrane protein structures. A molecular dynamics simulation of melittin in a hydrated dipalmitoylphosphatidylcholine (DPPC) bilayer was carried out. The effect of melittin on the surrounding membrane was localized to its immediate vicinity, and its asymmetry with respect to the two layers may be a result of the fact that it is not fully transmembranal. Melittin's hydrophilic C-terminus anchors it at the extracellular interface, leaving the N-terminus "loose" in the lower layer of\ the membrane [MEDLINE:20158709].

\ \ toxin activity ; GO:0015070 \N \N 20777 IPR002121 The HRDC (Helicase and RNase D C-terminal) domain has a putative role in nucleic acid binding. Mutations in the HRDC domain associated with the human BLM gene result in Bloom Syndrome (BS), an autosomal recessive disorder characterized by proportionate pre- and postnatal growth deficiency; sun-sensitive, telangiectatic, hypo- and hyperpigmented skin; predisposition to malignancy; and chromosomal instability [MEDLINE:98060076].\ nucleic acid binding activity ; GO:0003676 intracellular ; GO:0005622 \N 20774 IPR002117

The p53 tumor antigen [MEDLINE:91260846], [MEDLINE:90304157], [MEDLINE:90326417], [MEDLINE:90169509], [MEDLINE:92348363] is a protein found in increased amounts in a wide variety of transformed cells. It is also detectable in many proliferating nontransformed cells, but it is undetectable or present at low levels in resting cells. It is frequently mutated or inactivated in many types of cancer. p53 seems to act as a tumor suppressor in some, but probably not all, tumor types. p53 has been implicated in cell cycle regulation, particularly in the monitoring of genomic DNA integrity prior to replication; for this reason it has been dubbed 'guardian of the genome'. P53 is a sequence-specific DNA-binding protein and transcription factor; downstream targets include the gene for p21, whose product inhibits cyclin-dependent kinase-4, thereby blocking cell division.

p53 is an about 390 amino acids phosphoprotein whose sequence is well conserved in vertebrate species; attempts to identify p53 in other eukaryotic philum has so far been unsuccessful. The structure of P53 comprises 4 domains: an N-terminal transactivation domain; a central DNA-binding domain; an oligomerisation domain; and a C-terminal, basic, regulatory domain [MEDLINE:95316682], [MEDLINE:94294808]. The structure of the oligomerisation domain consists of a dimer of dimers, each dimer consisting of 2 anti-parallel -helices and an anti-parallel -sheet. The sheets lie on opposite sides of the tetramer and the helices form an unusual 4-helix bundle [MEDLINE:95316682], [MEDLINE:94294808]. While the majority of P53 mutations found in human cancers are located in the DNA-binding domain, some are also found in the oligomerisation domain.

\ \ transcription factor activity ; GO:0003700 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 20771 IPR002114 HPr is a small cytoplasmic protein IPR000032.In some bacteria HPr is a domain in a larger protein that includes a EIII(Fru)\ (IIA) domain and in some cases also a EI domain IPR000032/>. HPr is a\ component of the phosphoenolpyruvate-dependent sugar phosphotransferase\ system (PTS) major carbohydrate transport system in bacteria [MEDLINE:94066914], [MEDLINE:90328751].\

There is a conserved histidine in the N-terminus of HPr IPR001020, which serves as an acceptor for\ the phosphoryl group of EI. In the central part of HPr there is a conserved serine\ which, in Gram-positive bacteria only, is phosphorylated by an\ ATP-dependent protein kinase; a process which probably play a regulatory role in sugar\ transport.

\ \ sugar porter activity ; GO:0005351 \N phosphoenolpyruvate-dependent sugar phosphotransferase system ; GO:0009401 20770 IPR002113

Sequence analysis of selected members of the carrier protein family has\ suggested the presence of six transmembrane (TM) domains, with varying\ degrees of sequence conservation and hydrophilicity [MEDLINE:93314266]. The TM regions,\ and adjacent hydrophilic loops, are more highly conserved than other\ regions of the proteins [MEDLINE:93314266]. All members of the family appear to consist\ of a tripartite structure, each of the repeated segments being ~100 residues\ in length [MEDLINE:93314266]. Each repeat contains two TM domains, the first being more\ hydrophobic, with conserved glycyl and prolyl residues. Five of the six TM\ domains are followed by the conserved sequence (D/E)-Hy(K/R){where - denotes\ any residue, and Hy is a hydrophobic position} [MEDLINE:93314266].

\ \

Mitochondrial ADP/ATP translocase, an abundant component of the inner\ membrane, carries ATP from the matrix into the inter-membrane space and\ transports ADP back [MEDLINE:89236396]. The protein is an integral membrane protein that\ functions as a homodimer.

\ \ transporter activity ; GO:0005215 mitochondrial inner membrane ; GO:0005743 transport ; GO:0006810 20767 IPR002110

The ankyrin repeat is one of the most common protein-protein interaction motifs in nature. Ankyrin repeats are tandemly repeated modules of about 33 amino acids. They occur in a large number of functionally diverse proteins mainly from eukaryotes. The few known examples from prokaryotes and viruses may be the result of horizontal gene transfers [MEDLINE:94151289]. The repeat has been found in proteins of diverse function such as transcriptional initiators, cell-cycle regulators, cytoskeletal, ion transporters and signal transducers. The ankyrin fold appears to be defined by its structure rather than its function since there is no specific sequence or structure which is universally recognised by it.

The conserved fold of the ankyrin repeat unit is known from several crystal and solution structures [MEDLINE:97035414], [MEDLINE:98013176], [MEDLINE:98128030], [MEDLINE:99081291]. Each repeat folds into a helix-loop-helix structure with a -hairpin/loop region projecting out from the helices at a 90^o angle. The repeats stack together to form an L-shaped structure [MEDLINE:97035414], PUB00009776.

\ \ \ \ \N \N \N 20768 IPR002111 Cation channels are transport proteins responsible for the movement of cations through the membrane. These proteins contain 6 transmembrane helices in which the last two helices flank a loop which determines ion selectivity. In some sub-families (e.g. Na channels) the domain is repeated four times, whereas in others (e.g. K channels) the protein forms as a tetramer in the membrane. This profile finds the TM region of most cation channels, except K⁺.\ cation channel activity ; GO:0005261 membrane ; GO:0016020 cation transport ; GO:0006812 20769 IPR002112

AP-1 (activator protein 1), also known as c-jun, is the cellular homologue of the avian sarcoma virus oncogene v-jun, and as such can be referred to as a proto-oncogene. Implicit in the growth regulatory functions of all proto-oncogenes is the potential to induce abnormal cell growth and cancer as a result of alterations in gene expression [MEDLINE:88070595]. This may be a qualitative or quantitative alteration, the viral oncogenes activating this potential by transducing a truncated or mutated form of the protein product, or by increasing transcription of the proto-oncogene by the integration of a viral promoter and enhancer sequence in its vicinity.

The jun gene encodes a protein that is structurally and funtionally identical to the transcription factor AP-1, which is itself identical to yeast transcriptional activator GCN4 [MEDLINE:89057892]. Such similarities imply that the jun product acts in the nucleus as a transcription factor, the high structural identity with GCN4 suggesting that the 2 proteins may recognise similar DNA sequences (GCN4 binds to the 5'-TGA(C/G)TCA-3' consensus sequence). It has been proposed that the highly basic region in the C-terminus of the protein may be the DNA-binding domain [MEDLINE:88144462]. The gene products of jun and fos can come together as a dimer to bind DNA via a leucine zipper, which occurs just after the DNA-binding site.

The 'leucine zipper' is a structure that is believed to mediate the function of several eukaryotic gene regulatory proteins (see IPR004827). The zipper consists of a periodic repetition of leucine residues at every seventh position, and regions containing them appear to span 8 turns of -helix. The leucine side chains that extend from one helix interact with those from a similar helix, hence facilitating dimerisation in the form of a coiled-coil. Leucine zippers are present in many gene regulatory proteins, including the CREB proteins, Jun/AP1 transcription factors, fos oncogene and fos-related proteins, C-myc, L-myc and N-myc oncogenes, and so on.

\ \ transcription factor activity ; GO:0003700 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 20764 IPR002107 This protein has been called NSP4, NSP5, NS28, and NCVP5. The final steps in the assembly of rotavirus occur in the lumen of the endoplasmic reticulum (ER). Targeting of the immature inner capsid particle (ICP) to this compartment is mediated by the cytoplasmic tail of NSP4, located in the ER membrane [MEDLINE:89356642], [MEDLINE:97042338].\ \N \N \N 20765 IPR002108

The ADF/cofilins are a family of actin-binding proteins expressed in all eukaryotic cells so far examined. Members of this family remodel the actin cytoskeleton, for example during cytokinesis, when the actin-rich contractile ring shrinks as it contracts\ through the interaction of ADF/cofilins with both monomeric and filamentous actin. ADF/cofilins sever actin filaments (F-actin) and/or bind to actin monomers, or G-actin, thus preventing actin-polymerization by sequestering the monomers. The ADF/cofilins are formed by a single folded domain, the ADF homology domain, which is also found in other actin-binding\ protein families and is the most conserved region of these proteins consisting of a twenty amino-acid segment that ends some 30 residues from their C-terminal extremity [MEDLINE:92218370]. The main actin-binding structure being a long -helix.

Plants and animals have multiple ADF/cofilin genes, belonging\ in vertebrates to two types, ADF and cofilins. Other eukaryotes (such as yeast, Acanthamoeba and slime moulds) have a single\ ADF/cofilin gene. The following proteins are evolutionary related and belong to a family of low molecular weight (137 to 166 residues) actin-depolymerizing proteins [MEDLINE:94002009], [MEDLINE:93178959], [MEDLINE:93363583], [MEDLINE:94150469]:

\ \

Cofilin from vertebrates, slime mold and yeast. Cofilin binds to F-actin and acts as a pH-dependent actin-depolymerizing protein.
Destrin from vertebrates. Destrin binds to G-actin in a pH-independent manner and prevents polymerization.
Caenorhabditis elegans unc-60.
Acanthamoeba castellanii actophorin.
Plants actin depolymerizing factor (ADF).

\ \ \ actin binding activity ; GO:0003779 intracellular ; GO:0005622 \N 20766 IPR002109

Glutaredoxin [MEDLINE:90198521], [MEDLINE:88225730], [MEDLINE:89340492], also known as thioltransferase, is a small protein of approximately one hundred amino-acid residues. It functions as an electron carrier in the glutathione-dependent synthesis of deoxyribonucleotides by the enzyme ribonucleotide reductase. Like thioredoxin, which functions in a similar way, glutaredoxin possesses an active center disulfide bond. It exists in either a reduced or an oxidized form where the two cysteine residues are linked in an intramolecular disulfide bond.

Glutaredoxin has been sequenced in a variety of species. On the basis of extensive sequence similarity, it has been proposed [MEDLINE:91135007] that vaccinia protein O2L is most probably a glutaredoxin. Finally, it must be noted that phage T4 thioredoxin seems also to be evolutionary related.

\ \

Note: in position 5 of the pattern, all glutaredoxin sequences have Pro while T4 thioredoxin has Val.

\ \ electron transporter activity ; GO:0005489 \N electron transport ; GO:0006118 20761 IPR002103

Luminous bacteria are abundant and widely distributed Gram-negative motile rods. The enzyme responsible for bioluminescence, bacterial luciferase [MEDLINE:91232440], [MEDLINE:93380586], [MEDLINE:92219988] (EC: 1.14.14.3), talyzes the oxidation of reduced riboflavin phosphate (FMNH2) and a long chain fatty aldehyde with the emission of blue green light (490 nm). Luciferase is a heterodimeric enzyme composed of an subunit (gene luxA) and a subunit (gene luxB). The two subunits appear to have arisen by gene duplication.

The bioluminescence operon of some species of Photobacterium encodes a protein known as the non-fluorescent flavoprotein (NFP) (gene luxF). NFP, whose function is not yet known, contains an unusual non-covalently bound flavin. It is evolutionary related to the luxA/luxB subunits.

\ \ \N \N \N 20762 IPR002104

Members of this family cleave DNA substrates by a series of staggered cuts, during which the protein becomes covalently linked to the DNA through a catalytic tyrosine residue at the carboxy end of the alignment [MEDLINE:97238925], [MEDLINE:97433323].

The catalytic site residues in CRE recombinase (P06956) are Arg-173, His-289, Arg-292 and Tyr-324.

\ \ DNA binding activity ; GO:0003677 \N DNA integration ; GO:0015074 20763 IPR002105

Gram-positive, thermophilic anaerobes such as Clostridium thermocellum or Clostridium cellulolyticum secretes a highly active and thermostable cellulase complex (cellulosome) responsible for the degradation of crystalline cellulose [MEDLINE:91069220], [MEDLINE:93122570]. The cellulosome contains at least 30 polypeptides, the majority of the enzymes are endoglucanases (EC: 3.2.1.4), but there are also some xylanases (EC: 3.2.1.8), -glucosidases (EC: 3.2.1.21) and endo--1,3-1,4-glucanases (EC: 3.2.1.73).

Complete sequence data for many of these enzymes has been obtained. A majority of these proteins contain a highly conserved region of about 65 to 70 residues which is generally (but not always) located in the C terminus. This region contains a duplicated segment of 24 amino acids, the dockerin domain, which is the binding partner of the cohesin domain (see IPR002102.

\ \ \N \N polysaccharide catabolism ; GO:0000272 20759 IPR002101

Myristoylated alanine-rich C-kinase substrate (MARCKS) is a predominent cellular substrate for protein kinase C (PKC) that has been implicated in the regulation of brain development, \ macrophage activation, neuro-secretion and growth factor-dependent\ mitogenesis [MEDLINE:93131879], [MEDLINE:21818447]. The N-terminal glycine is the site of myristoylation, \ which allows effective binding of the protein to the plasma membrane, where\ it co-localises with PKC [MEDLINE:91238951]. MARCKS binds calmodulin in a calcium-dependent\ manner; the region responsible for calcium-binding is highly basic, a domain\ of about 25 amino acids known as the PSD or effector domain, which also contains the PKC\ phosphorylation sites and has been shown to contribute to membrane binding. When not phosphorylated, the effector domain can bind\ to filamentous actin [MEDLINE:92220195]. It is believed that MARCKS may be a regulated \ crossbridge between actin and the plasma membrane; modulation of the actin\ cross-linking activity by calmodulin and phosphorylation, represent a\ potential convergence of the calcium-calmodulin and PKC signal transduction\ pathways in regulation of the actin cytoskeleton. MARCKS also contains an MH2 domain of unknown function.

MARCKS-related protein (MRP) is similar to MARCKS in terms of properties\ such as its myristoylation, phosphorylation and calmodulin-binding, and\ shares a high degree of sequence similarity. The two regions that show the highest\ similarity are the kinase C phosphorylation site domain and the N-terminal\ region containing the myristoylation site [MEDLINE:91323504]. MARCKS and MRP amino acid \ compositions are similar, but the alanine content of the latter is lower. MARCKS proteins appear to adopt a native unfolded conformation i.e. as randomly folded chains arranged in non-classical extended conformations, in common with other substrates of PKC.

\ \ calmodulin binding activity ; GO:0005516 \N \N 20760 IPR002102

Cohesin domains interact with a complementary domain, termed the dockerin domain (see IPR002105.

\ \

The scaffoldin component of the cellulolytic bacterium Clostridium thermocellum is a non-hydrolytic protein which\ organizes the hydrolytic enzymes in a large complex, called the cellulosome. Scaffoldin comprises a series of functional domains,\ amongst which is a single cellulose-binding domain and nine cohesin domains which are responsible for integrating the individual\ enzymatic subunits into the complex.

\ \ \N cell wall (sensu Bacteria) ; GO:0009274 polysaccharide catabolism ; GO:0000272 20756 IPR002098 Seminal vesicle protein I (SVP-1) is one of the four major secretory proteins secreted by guinea-pig seminal vesicle epithelium. It is a clotting\ protein that serves as the substrate in the formation of the copulatory plug.\ Covalent clotting of this protein is catalyzed by a transglutaminase and\ involves the formation of gamma-glutamyl-epsilon-lysine crosslinks. SVP-1\ sequence contains eight repeats of a twenty four amino acid residue domain.\ There are seven invariant residues in these repeats, three of them (two\ lysines and one glutamine) probably participate in the cross-links [MEDLINE:88016161]. \ \

These repeats are also present twice in the N-terminal region of the\ precursor of human skin elafin, an inhibitor of elastase as well as in the\ precursor of pig sodium/potassium atpase inhibitor SPAI-2.

\ \ \N extracellular ; GO:0005576 copulation ; GO:0007620 20757 IPR002099 Mismatch repair contributes to the overall fidelity of DNA replication. It involves the correction of mismatched base pairs that have been missed by the\ proofreading element of the DNA polymerase complex [MEDLINE:87297443]. The sequence of some\ proteins involved in mismatch repair in different organisms have been found to\ be evolutionary related.\ \ \N \N mismatch repair ; GO:0006298 20758 IPR002100 Human serum response factor (SRF) is a ubiquitous nuclear protein important for cell proliferation and differentiation. SRF function is essential\ for transcriptional regulation of numerous growth-factor-inducible genes,\ such as c-fos oncogene and muscle-specific actin genes. \ A core domain of around 90 amino acids is sufficient for the activities\ of DNA-binding, dimerisation and interaction with accessory factors. Within\ the core is a DNA-binding region, designated the MADS box [MEDLINE:95364921], that is\ highly similar to many eukaryotic regulatory proteins: among these are\ MCM1, the regulator of cell type-specific genes in fission yeast; DSRF,\ a Drosophila trachea development factor; the MEF2 family of myocyte-specific enhancer factors; and the Agamous and Deficiens families of\ plant homeotic proteins. \

Proteins belonging to the MADS family function as dimers, the primary\ DNA-binding element of which is an anti-parallel coiled coil of two\ amphipathic -helices, one from each subunit. The DNA wraps around\ the coiled coil allowing the basic N-termini of the helices to fit into\ the DNA major groove. The chain extending from the helix N-termini reaches\ over the DNA backbone and penetrates into the minor groove. A 4-stranded,\ anti-parallel -sheet packs against the coiled-coil face opposite the\ DNA and is the central element of the dimerisation interface.\ The MADS-box domain is commonly found associated with K-box region see IPR002487

\ \ transcription factor activity ; GO:0003700 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 20752 IPR002092 Many forms of RNA polymerase (EC: 2.7.7.6) are known. Most RNA polymerases are multimeric enzymes. This is a family of single chain polymerases, which\ are evolutionary related, and which originate from bacteriophages or from\ mitochondria [MEDLINE:95058168].\ \ DNA-directed RNA polymerase activity ; GO:0003899 \N transcription ; GO:0006350 20753 IPR002093

The breast cancer type 2 susceptibility protein has a number of 39 amino acid repeats [MEDLINE:96241568] that are critical for binding to RAD51 (a key protein in DNA recombinational repair) and resistance to methyl methanesulfonate treatment [MEDLINE:98070349], [MEDLINE:98226807], [MEDLINE:99030662]. BRCA2 is a breast tumor suppressor with a potential function in the cellular response to DNA damage. At the cellular level, expression\ is regulated in a cell-cycle dependent manner and peak expression of BRCA2 mRNA is found in S phase, suggesting BRCA2 may participate in regulating cell proliferation. There are eight repeats in BRCA2 designated as BRC1\ to BRC8. BRC1, BRC2, BRC3, BRC4, BRC7, and BRC8 are highly conserved and bind to Rad51, whereas BRC5 and BRC6 are less\ well conserved and do not bind to Rad51 [MEDLINE:20020267].

\ \ \N \N \N 20754 IPR002095

Monellin is an intensely sweet-tasting protein derived from African berries. The protein has a very high specificity for the sweet receptors, making it\ ~100,000 times sweeter than sugar on a molar basis and several thousand \ times sweeter on a weight basis [MEDLINE:91136778]. Like the sweet-tasting protein\ thaumatin, it neither contains carbohydrates nor modified amino acids.\ Although there is no sequence similarity between the proteins, antibodies\ for thaumatin compete for monellin (and other sweet compounds, but not for \ chemically modified non-sweet monellin) and vice versa. It is thought\ that native conformations are important for the sweet taste.

Monellin is a heterodimer, comprising an A chain of 44 amino acid residues, \ and a B chain of 50 residues [MEDLINE:76161292]. The individual subunits are not sweet, \ nor do they block the sweet sensation of sucrose or monellin. However, \ blocking the single SH of monellin abolishes its sweetness, as does reaction \ of its methionyl residue with CNBr. The cysteinyl and methionyl residues\ are adjacent and it has been suggested that this part of the \ molecule is essential for its sweetness [MEDLINE:87287292].\

\ \ \N \N \N 20755 IPR002097 Profilin is a small eukaryotic protein that binds to monomeric actin (G-actin) in a 1:1 ratio thus preventing the polymerization of actin into\ filaments (F-actin). It can also in certain circumstance promote actin\ polymerization. Profilin also binds to polyphosphoinositides such as PIP2.\ Overall sequence similarity among profilin from organisms which belong to\ different phyla (ranging from fungi to mammals) is low, but the N-terminal\ region is relatively well conserved. That region is thought to be involved in\ the binding to actin. \

A protein structurally similar to profilin is present in the genome of variola\ and vaccinia viruses (gene A42R).

\ \

The allergens in this family include allergens with the following designations: Ara t 8, Bet v 2, Cyn d 12, Hel a 2, Mer a 1 and Phl p 11.

\ \ actin binding activity ; GO:0003779 actin cytoskeleton ; GO:0015629 cytoskeleton organization and biogenesis ; GO:0007010 20751 IPR002091 Amino acid permeases are integral membrane proteins involved in the transportof amino acids into the cell. A number of such proteins have been found to be\ evolutionary related [MEDLINE:89125644], [MEDLINE:90076962], [MEDLINE:93184721]. \

Aromatic amino acids are concentrated in the cytoplasm of E.coli by 4 \ distinct transport systems: a general aromatic amino acid permease, and a\ specific permease for each of the 3 types (Phe, Tyr and Trp) [MEDLINE:91100270]. It has been shown [MEDLINE:91216998] that some permeases in Escherichia coli and related bacteria are evolutionary related.\ These permeases are proteins of about 400 to 420 amino acids and are located in the cytoplasmic membrane and, like bacterial sugar/cation transporters, are thought to contain 12 transmembrane (TM)\ regions [MEDLINE:91100270] - hydropathy analysis, however, is inconclusive, suggesting the\ possibility of 10 to 12 membrane-spanning domains [MEDLINE:91216998]. The best conserved domain is a stretch of 20 residues which seems to be located in a cytoplasmic loop between the\ first and second transmembrane region.

\ \ amino acid-polyamine transporter activity ; GO:0005279 membrane ; GO:0016020 amino acid transport ; GO:0006865 20745 IPR002085 Alcohol dehydrogenase (EC: 1.1.1.1) (ADH) catalyzes the reversible oxidation ofethanol to acetaldehyde with the concomitant reduction of NAD:\

\
Ethanol + NAD = Acetaldehyde + NADH\

\ Currently three structurally and catalytically different types of alcohol\ dehydrogenases are known:\

Zinc-containing 'long-chain' alcohol dehydrogenases.
Insect-type, or 'short-chain' alcohol dehydrogenases.
Iron-containing alcohol dehydrogenases.

In addition, this family includes NADP-dependent quinone oxidoreductase (EC: 1.6.5.5),\ an enzyme found in bacteria (gene qor), in yeast and in mammals where, in some\ species such as rodents, it has been recruited as an eye lens protein and is\ known as zeta-crystallin [MEDLINE:93252077]. The sequence of quinone oxidoreductase is\ distantly related to that other zinc-containing alcohol dehydrogenases and it\ lacks the zinc-ligand residues. The torpedo fish and mammalian synaptic vesicle\ membrane protein vat-1 is related to qor.

\ \ zinc ion binding activity ; GO:0008270 \N \N 20748 IPR002088 Protein prenyltransferases catalyze the transfer of an isoprenyl moiety to a cysteine four residues from the C-terminus of several proteins. They are heterodimeric enzymes\ consisting of

and

subunits. The

subunit is thought to participate in \ a stable complex with the isoprenyl substrate; the

subunit binds the peptide \ substrate. Both the

and

subunit show repetitive sequence motifs [MEDLINE:92322645]. These repeats have distinct structural and functional \ implications and are unrelated to each other. Known protein prenyltransferase

subunits are the mammalian protein farnesyltransferase

subunit, yeast protein RAM2, \ a protein farnesyltransferase

subunit and yeast protein BET4, a protein \ geranylgeranyltransferase

subunit.\ \ protein prenyltransferase activity ; GO:0008318 \N protein amino acid prenylation ; GO:0018346 20749 IPR002089 This protein spans the viral membrane with an extracellularamino-terminus external and a cytoplasmic carboxy-terminus. Influenza virus M2 acts as an ion channel protein [MEDLINE:98024731]. The channel pore is formed by the transmembrane domain of the M2 protein and the wild-type M2 channel was found to be regulated by pH and may have a pivotal role in the biology of\ influenza virus infection [MEDLINE:92257592].\ \ \N \N \N 20750 IPR002090

\ \ \

NHE6 is a putative human mitochondrial Na⁺/H⁺ exchanger that is similar to\ NHa2, an S.cerevisiae mitochondrial Na⁺/H⁺ exchanger [MEDLINE:98175963]. NHE6 (although\ ubquitously expressed) is particularly abundant in mitochondrion-rich\ tissues such as brain, skeletal muscle and heart.

\ \ ion channel activity ; GO:0005216 membrane ; GO:0016020 sodium ion transport ; GO:0006814 20743 IPR002083 Secreted forms of the

The MATH domain is hugely expanded in the nematode\ Caenorhabditis elegans\ \ \ \ [MEDLINE:99069615].

A number of other proteins are found. These include the \ ubiquitin C-terminal hydrolases.\

\ \ \N \N \N 20744 IPR002084 Binding of a specific DNA fragment and S-adenosyl methionine (SAM) co-repressor molecules to the E. coli methionine repressor (MetJ) leads to a significant reduction in dynamic flexibility of the ternary complex, with considerable entropy-enthalpy compensation, not necessarily involving any overall conformational change [MEDLINE:94298951]. MetJ is a regulatory protein which when combined with\ S-adenosylmethionine (SAM) represses the expression of the methionine\ regulon and of enzymes involved in SAM synthesis. It is also autoregulated.\

The crystal structure of the met repressor-operator complex shows two dimeric\ repressor molecules bound to adjacent sites 8 base pairs apart on an 18-base-pair\ DNA fragment. Sequence specificity is achieved by insertion of double-stranded\ antiparallel protein -ribbons into the major groove of B-form DNA, with direct\ hydrogen-bonding between amino-acid side chains and the base pairs. The\ repressor also recognizes sequence-dependent distortion or flexibility of the operator\ phosphate backbone, conferring specificity even for inaccessible base pairs [MEDLINE:93024895].

\ \ transcription factor activity ; GO:0003700 \N methionine metabolism ; GO:0006555 20747 IPR002087 A family of anti-proliferative proteins has been shown to include mammalian and avian protein BTG1 (which appears to be involved in negative regulation of cell proliferation) and rat/mouse NGF-inducible protein PC3/TIS21 (BTG2) [MEDLINE:92224907], [MEDLINE:93314978], [MEDLINE:91195349].\ These proteins have from 158 to 363 amino acid residues, that are highly similar and include 3 conserved cysteine residues . BTG2 seems to have a\ signal sequence; while the other proteins may lack such a domain. The sequence\ of the N-terminal half of these proteins is well conserved.\ \ \N \N \N 20746 IPR002086 Aldehyde dehydrogenases (EC: 1.2.1.3 and EC: 1.2.1.5) are enzymes which oxidizea wide variety of aliphatic and aromatic aldehydes using NADP as a cofactor. In mammals at least four\ different forms of the enzyme are known [MEDLINE:89229122]: class-1 (or Ald C) a tetrameric\ cytosolic enzyme, class-2 (or Ald M) a tetrameric mitochondrial enzyme, class-\ 3 (or Ald D) a dimeric cytosolic enzyme, and class IV a microsomal enzyme.\ Aldehyde dehydrogenases have also been sequenced from fungal and bacterial\ species. A number of enzymes are known to be evolutionary related to aldehyde\ dehydrogenases.\ A glutamic acid and a cysteine residue have been implicated in the catalytic\ activity of mammalian aldehyde dehydrogenase. These residues are conserved in\ all the enzymes of this family.\ \

The allergens in this family include allergens with the following designations: Alt a 10 and Cla h 3.

\ \ oxidoreductase activity ; GO:0016491 \N metabolism ; GO:0008152 20738 IPR002078 Some bacterial regulatory proteins activate the expression of genes frompromoters recognized by core RNA polymerase associated with the alternative\ sigma-54 factor. These have a conserved domain of about 230 residues involved\ in the ATP-dependent [MEDLINE:94012464], [MEDLINE:91252264] interaction with sigma-54. \ About half of the proteins in which this domain is found (algB, dcdT, flbD, hoxA, hupR1, hydG, ntrC, pgtA and pilR) belong to signal transduction two-component systems [MEDLINE:90146217] and possess a domain that can be phosphorylated by a sensor-kinase protein in their N-terminal section.\ Almost all of these proteins possess a helix-turn-helix DNA-binding domain in their C-terminal section.\ The domain which interacts with the sigma-54 factor has an ATPase activity.\ This may be required to promote a conformational change necessary for the\ interaction [MEDLINE:92289687]. The domain contains an atypical ATP-binding motif A (P-loop) as well as a form of motif B. The two ATP-binding motifs are located in the N-terminal section of the domain.\ \ DNA binding activity ; GO:0003677 \N regulation of transcription, DNA-dependent ; GO:0006355 20739 IPR002079 The retroviral p12 protein is a proline rich virion structural protein found in the inner coat. The function carried out byp12 in assembly and replication is unknown.\ p12 is associated with pathogenicity of the virus [MEDLINE:93381801].\ \ \N viral capsid ; GO:0019028 \N 20740 IPR002080 Seminal vesicle protein II (SVP-II) [MEDLINE:90277684] is one of the six major secretoryproteins secreted by rat seminal vesicle. It is a clotting protein that serves\ as the substrate in the formation of the copulatory plug. Covalent clotting\ of this protein is catalyzed by a transglutaminase and involves the formation\ of gamma-glutamyl-epsilon-lysine crosslinks. SVS-II sequence contains thirteen\ repeats of a thirteen amino acid residue domain which is probably involved in\ the cross-linking. There are a number of invariant residues in this domain,\ four of them (two lysines and two glutamines) probably participate in the\ cross-links.\ \ \N \N \N 20741 IPR002081 Deoxyribodipyrimidine photolyase (EC: 4.1.99.3) (DNA photolyase) PUB00005325, PUB00005325 is a DNArepair enzyme. It binds to UV-damaged DNA containing pyrimidine dimers and,\ upon absorbing a near-UV photon (300 to 500 nm), breaks the cyclobutane ring\ joining the two pyrimidines of the dimer. DNA photolyase is an enzyme that\ requires two choromophore-cofactors for its activity: a reduced FADH2 and\ either 5,10-methenyltetrahydrofolate (5,10-MTFH) or an oxidized 8-hydroxy-5-\ deazaflavin (8-HDF) derivative (F420). The folate or deazaflavin chromophore\ appears to function as an antenna, while the FADH2 chromophore is thought to\ be responsible for electron transfer. On the basis of sequence similarities\ \ [MEDLINE:95112825] DNA photolyases can be grouped into two classes. \

The first class contains\ enzymes from Gram-negative and Gram-positive bacteria, the halophilic\ archaebacteria Halobacterium halobium, fungi and plants. Class 1 enzymes bind\ either 5,10-MTHF (Escherichia coli, fungi, etc.) or 8-HDF (Streptomyces griseus, H.halobium). There are a number of conserved sequence regions in all known class 1 DNA\ photolyases, especially in the C-terminal part.

\ \

This family also includes Arabidopsis thaliana cryptochromes 1 (CRY1) and 2 (CRY2),\ which are blue light photoreceptors that mediate blue light-induced gene\ expression.

\ \ DNA photolyase activity ; GO:0003913 \N \N 20742 IPR002082

Aspartate carbamoyltransferase (ATCase) catalyses the formation of carbamoyl-aspartate in the pyrimidine biosynthesis pathway, by the \ association of aspartate and carbamoyl-phosphate. This is the commitment \ step in the Escherichia coli pathway and is regulated by feedback inhibition by CTP, \ the final product of the pathway.

The structural organisation of the ATCase protein varies considerably \ between different organisms. In bacteria such as E.coli, Salmonella typhimurium and\ Serratia marcescens, the ATCase is a dodecamer of 2 catalytic (c) trimers\ and 3 regulatory (r) dimers. The catalytic domains are coded for by the\ pyrB gene, and the regulatory domains by pyrI. In Gram-positive bacteria\ such as Bacillus subtilis, ATCase exists as a trimer of catalytic subunits, but\ unlike in E.coli, it neither contains nor binds to regulatory subunits. In\ eukaryotes, ATCase is found as a single domain in a multifunctional enzyme\ that contains activity for glutamine amidotransferase, carbamoylphosphate\ synthetase, dihydroorotase, and aspartate carbamoyltransferase.

\ \ \ \N aspartate carbamoyltransferase complex ; GO:0009347 'de novo' pyrimidine base biosynthesis ; GO:0006207 20735 IPR002075

Ran (IPR002041) is an evolutionary conserved member of the Ras superfamily of small GTPases that regulates all receptor-mediated transport between the nucleus and the cytoplasm. Import\ receptors bind their cargos in the cytoplasm where the concentration of RanGTP is low and release their cargos in the\ nucleus where the concentration of RanGTP is high [MEDLINE:22014335]. Export receptors respond to Ran GTP in the opposite\ manner.

Nuclear transport factor 2 (NTF2) is a homodimer of approximately 14kDa subunits which stimulates efficient nuclear import\ of a cargo protein. NTF2 binds to both RanGDP and FxFG repeat-containing nucleoporins. NTF2 binds to RanGDP\ sufficiently strongly for the complex to remain intact during transport through NPCs,\ but the interaction between NTF2 and FxFG nucleoporins is much more transient,\ which would enable NTF2 to move through the NPC by hopping from one repeat to\ another [MEDLINE:21011915], [MEDLINE:20389379].

NTF2 folds into a cone with a deep hydrophobic cavity, the opening of which is surrounded by several negatively charged residues. RanGDP binds to NTF2 by inserting a conserved phenylalanine residue into the hydrophobic pocket of NTF2 and making electrostatic interactions with the conserved negatively charged residues that surround the cavity.

A structurally similar domain appears in other nuclear import proteins.

\ \ protein transporter activity ; GO:0008565 nucleus ; GO:0005634 protein-nucleus import ; GO:0006606 20736 IPR002076 This group of eukaryotic integral membrane proteins are evolutionary related, but exactfunction has not yet clearly been established.\ The proteins have from 290 to 435 amino acid residues. Structurally, they seem\ to be formed of three sections: a N-terminal region with two transmembrane\ domains, a central hydrophilic loop and a C-terminal region that contains from\ one to three transmembrane domains. As a signature pattern we selected a\ conserved region that contains three histidines. This region is located in the\ hydrophilic loop.\ \ \N integral to membrane ; GO:0016021 \N 20737 IPR002077

Cation channels are transport proteins responsible for the movement of cations through the membrane. These proteins contain 6 transmembrane helices in which the last two helices flank a loop which determines ion selectivity. In some sub-families (e.g. Na channels) the domain is repeated four times, whereas in others (e.g. K channels) the protein forms as a tetramer in the membrane.

Calcium channel proteins are involved in the control of neurotransmitter\ release from neurons [MEDLINE:92335886], and play an important role in the regulation of\ a variety of cellular functions, including membrane excitability, muscle\ contraction and synaptic transmission [MEDLINE:91187110]. The channel proteins are\ composed of 4 tightly-coupled subunits (-1, -2, and gamma),\ the -1 subunit from each creating the pore for the import of\ extracellular calcium ions. The -1 subunit shares sequence\ characteristics with all voltage-dependent cation channels, and exploits\ the same 6-helix bundle structural motif - in both sodium and calcium\ channels, this motif is repeated 4 times within the sequence to give a\ 24-helix bundle. There are several tissue-specific pharmacologically and\ electrophysiologically distinct isoforms of calcium channels, coded for\ by separate genes in a multi-gene family. In skeletal muscle, each\ tightly-bound assembly of , and gamma subunits associates with\ 4 others to form a pentameric macromolecule [MEDLINE:91009241].

\ \ \ voltage-gated calcium channel activity ; GO:0005245 voltage-gated calcium channel complex ; GO:0005891 calcium ion transport ; GO:0006816 20731 IPR002071 Staphylococcus aureus secretes a thermostable nuclease (EC: 3.1.31.1), known asthermonuclease (TNase), which is a calcium-dependent enzyme that catalyzes the\ hydrolysis of both DNA and RNA at the 5' position of the phosphodiester bond\ yielding 3'-mononucleotides and dinucleotides [MEDLINE:91376042]. Three residues, two\ arginines and a glutamate, have been implicated in the catalytic mechanism.\ The sequence of the TNase of S.aureus is evolutionary related [MEDLINE:94320785] to other TNase's of other Staphylococcus spp as well as to several other proteins.\ \ nuclease activity ; GO:0004518 \N \N 20732 IPR002072 During the development of the vertebrate nervous system, many neuronsbecome redundant (because they have died, failed to connect to target\ cells, etc.) and are eliminated. At the same time, developing neurons send\ out axon outgrowths that contact their target cells [MEDLINE:90316101]. Such cells control\ their degree of innervation (the number of axon connections) by the\ secretion of various specific neurotrophic factors that are essential for\ neuron survival. One of these is nerve growth factor (NGF or

-NGF), a vertebrate protein that stimulates\ division and differentiation of sympathetic and embryonic sensory neurons [MEDLINE:87234351],\ [MEDLINE:93255617]. NGF is mostly found outside the central\ nervous system (CNS), but slight traces have been detected in adult CNS\ tissues, although a physiological role for this is unknown [MEDLINE:90316101]; it has also\ been found in several snake venoms [MEDLINE:93120151], [MEDLINE:91138755].\

NGF is a protein of about 120 residues that is cleaved from a larger\ precursor molecule. It contains six cysteines all involved in intrachain\ disulfide bonds. A schematic representation of the structure of NGF is shown\ below:\

\ +------------------------+\ | |\ | |\ xxxxxxCxxxxxxxxxxxxxxxxxxxxxCxxxxCxxxxxCxxxxxxxxxxxxxCxCxxxx\ | | | |\ +--------------------------|-----+ |\ +---------------------+\ \ \ 'C': conserved cysteine involved in a disulfide bond.\

\ \ \N \N \N 20733 IPR002073 Retinal 3',5'-cGMP phosphodiesterase (EC: 3.1.4.17) (PDE) is located in photoreceptorouter segments PUB00005667: it is light activated, playing a pivotal role in\ signal transduction. In rod cells, PDE is oligomeric, comprising an

-, a

- and 2 gamma-subunits, while in cones, PDE is a homodimer\ of

chains, which are associated with several smaller subunits.\ Both rod and cone PDEs catalyse the hydrolysis of cAMP or cGMP to the\ corresponding nucleoside 5' monophosphates, both enzymes also binding\ cGMP with high affinity. The cGMP-binding sites are located in the\ N-terminal half of the protein sequence, while the catalytic core \ resides in the C-terminal portion.\ \ \ 3',5'-cyclic-nucleotide phosphodiesterase activity ; GO:0004114\ \N \N signal transduction ; GO:0007165 20734 IPR002074

Somatostatin is a neurotransmitter/hormone with a wide range of biologial\ functions PUB00005902. It has an important role in the neuroendocrine system and\ inhibits secretion of growth hormone and prolactin in the anterior\ pituitary. It also inhibits secretion in the intestine (including gastric\ acid in the stomach), pancreatic acinar cells and pancreatic -cells,\ stimulates absorption in the intestine and modulates smooth muscle\ contractility. In the CNS, it is a neurotransmitter activating a hyperpolarising K⁺ current and inhibiting Ca²⁺ influx, and is believed to\ play important roles in regulating locomotor activity and cognitive\ function. Receptor subtypes were originally proposed on the basis of\ functional and radio-ligand binding studies, and cloning has now confirmed\ the presence of at least 4 subtypes.

High levels of mRNA for human SS2 receptors have been found in the brain,\ kidney and pituitary, with lower levels in the jejunum, pancreas, colon and\ liver. The receptor is coupled to Go and Gi3 and is linked to inhibition\ of adenylyl cyclase PUB00005902.

\ \ somatostatin receptor activity ; GO:0004994 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20729 IPR002069 Interferon gamma (IFN-gamma) is produced by lymphocytes activated by specific antigens or mitogens. IFN-gamma shows antiviral activity and has important immunoregulatory functions. It is a potent activator of microphages and had antiproliferative effects on transformed cells. It can potentiate the antiviral and antitumor effects of the type I interferons.\ interferon-gamma receptor ligand activity ; GO:0005133 extracellular ; GO:0005576 immune response ; GO:0006955 20730 IPR002070

The T-box gene family is an ancient group of putative transcription factors that appear to play a critical role in the development of all animal species.

These genes were uncovered on the basis of similarity to the DNA binding domain [MEDLINE:98164794] of murine Brachyury (T) gene product, which similarity is the defining feature of the family. The Brachyury gene is named for its phenotype, which was identified 70 years ago as a mutant mouse strain with a short blunted tail. The gene, and its paralogues, have become a well-studied model for the family, and hence much of what is known about the T-box family is derived from the murine Brachyury gene.

Consistent with its nuclear location, Brachyury protein has a sequence-specific DNA-binding activity and can act as a transcriptional regulator [MEDLINE:98163742]. Homozygous mutants for the gene undergo extensive developmental anomalies, thus rendering the mutation lethal [MEDLINE:98055660]. The postulated role of Brachyury is as a transcription factor, regulating the specification and differentiation of posterior mesoderm during gastrulation in a dose-dependent manner [MEDLINE:98164794].

Common features shared by T-box family members are, DNA-binding and transcriptional regulatory activity, a role in development and conserved expression patterns, most of the known genes in all species being expressed in mesoderm of mesoderm precursors [MEDLINE:97339734]. Members of the T-box family contain a domain of about 170 to 190 amino acids known as the T-box domain [MEDLINE:95004605], [MEDLINE:97032942], [MEDLINE:97339734] and which probably binds DNA.

\ \ transcription factor activity ; GO:0003700 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 20728 IPR002068

Prokaryotic and eukaryotic organisms respond to heat shock or otherenvironmental stress by inducing the synthesis of proteins collectively known\ as heat-shock proteins (hsp) [MEDLINE:89192244]. Amongst them is a family of proteins with an\ average molecular weight of 20 Kd, known as the hsp20 proteins [MEDLINE:95010094]. These\ seem to act as chaperones that can protect other proteins against heat-induced\ denaturation and aggregation. Hsp20 proteins seem to form large\ heterooligomeric aggregates. Structurally, this family is characterized by the presence of a conserved C-terminal domain of about 100 residues.

\ \ \N \N \N 20726 IPR002065

Escherichia coli protein Tpx [MEDLINE:96081923] is an antioxidant protein with a thiolperoxidase activity. It is a small protein of 18 kDa whose sequence is well\ conserved in other bacterial species.

\ \ thiol peroxidase activity ; GO:0009031 \N peroxidase reaction ; GO:0006804 20727 IPR002067

A variety of substrate carrier proteins that are involved in energy transferare found in the inner mitochondrial membrane [MEDLINE:90223523], [MEDLINE:93314266], [MEDLINE:94188573], [MEDLINE:93253777]. Such proteins include:\ ADP/ATP carrier protein (ADP/ATP translocase); 2-oxoglutarate/malate carrier\ protein; phosphate carrier protein; tricarboxylate transport protein (or \ citrate transport protein); Graves disease carrier protein; yeast mitochondrial proteins MRS3 and MRS4; yeast mitochondrial FAD carrier protein;\ and many others.

Sequence analysis of selected members of the carrier protein family has\ suggested the presence of six transmembrane (TM) domains, with varying \ degrees of sequence conservation and hydrophilicity [MEDLINE:93314266]. The TM regions,\ and adjacent hydrophilic loops, are more highly conserved than other\ regions of the proteins [MEDLINE:93314266]. All members of the family appear to consist\ of a tripartite structure, each of the repeated segments being about 100 residues\ in length [MEDLINE:93314266]. Each repeat contains two TM domains, the first being more\ hydrophobic, with conserved glycyl and prolyl residues. Five of the six TM\ domains are followed by the conserved sequence (D/E)-Hy(K/R) {where - denotes\ any residue, and Hy is a hydrophobic position} [MEDLINE:93314266].

\ \ \ binding activity ; GO:0005488 mitochondrial inner membrane ; GO:0005743 transport ; GO:0006810 20722 IPR002060 Squalene synthase (EC: 2.5.1.21) (farnesyl-diphosphate farnesyltransferase) (SQS) and Phytoene synthase (EC 2.5.1.-) (PSY) share a number of functional similarities. These similarities are also reflected at the level of their primary structure [MEDLINE:94123996], [MEDLINE:93233634], [MEDLINE:94071905]. In particular three well conserved regions are shared bySQS and PSY; they could be involved in substrate binding and/or the catalytic\ mechanism. \

SQS catalyzes the conversion of two molecules of farnesyl diphosphate (FPP) into squalene. It is the first committed step in the cholesterol biosynthetic pathway. The reaction carried out by SQS is catalyzed in two separate steps: the first is a head-to-head condensation of the two molecules of FPP to form presqualene diphosphate; this intermediate is then rearranged in a NADP-dependent reduction, to form squalene:\

\
2 FPP -> presqualene  diphosphate + NADP  -> squalene\

\ SQS is found in eukaryotes. In yeast it is encoded by the ERG9 \ gene, in mammals by the FDFT1 gene. SQS seems to be membrane-bound.

PSY catalyzes the conversion of two molecules of geranylgeranyl diphosphate (GGPP) into phytoene. It is the second step in the biosynthesis of carotenoids from isopentenyl diphosphate. The reaction carried out by PSY is catalyzed in two separate steps: the first is a head-to-head condensation of the two molecules of GGPP to form prephytoene diphosphate; this intermediate is then rearranged to form phytoene.\

\
2 GGPP ->  prephytoene diphosphate -> phytoene\

\ PSY is found in all organisms that synthesize carotenoids: plants and \ photosynthetic bacteria as well as some non- photosynthetic bacteria and \ fungi. In bacteria PSY is encoded by the gene crtB. In plants PSY is localized in the chloroplast.

\ \ transferase activity ; GO:0016740 \N biosynthesis ; GO:0009058 20723 IPR002061 Scorpion toxins, which may be mammal or insect specific, bind to sodiumchannels, inhibiting the inactivation of activated channels and blocking\ neuronal transmission. The complete covalent structure of the toxins has\ been deduced: it comprises around 66 amino acid residues and is cross-\ linked by 4 disulphide bridges [MEDLINE:90184494], [MEDLINE:83198579]. An anti-epilepsy peptide isolated\ from scorpion venom [MEDLINE:89193444] shows similarity to both scorpion neurotoxins \ and anti-insect toxins.\ \ toxin activity ; GO:0015070 extracellular ; GO:0005576 pathogenesis ; GO:0009405 20724 IPR002062

Vasopressin and oxytocin are members of the neurohypophyseal hormone family\ found in all mammalian species. They are present in high levels in the\ posterior pituitary. Oxytocin stimulates contraction of uterine smooth\ muscle, and stimulates milk secretion in response to suckling by inducing\ contraction of myoepithelial cells in the mammary gland PUB00005908. Clinically, it\ is used to induce labour and promote lactation.

Oxytocin receptors are found in uterine smooth muscle, myoepithelial\ cells in the mammary gland, and in the pituitary. Activation of\ phosphoinositide metabolism is effected via a pertussis-toxin-insensitive\ G-protein, probably of the Gq/G11 class PUB00005908.

\ \ oxytocin receptor activity ; GO:0004990 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20725 IPR002063 Marine invertebrates such as annelids or sipunculans possess two completelydifferent types of oxygen binding proteins: porphyrin-containing pigments, such as haemoglobin; and hemerythrin,\ found in the vascular system and coelemic fluid, or in muscles (myohem-\ erythrin) [MEDLINE:91293305]. The active centre of both proteins is a binuclear iron\ complex, bound directly to the protein via 7 amino acid side chains [MEDLINE:85140167], \ 5 His, 1 Glu and 1 Asp [MEDLINE:91293305].\

Hemerythrins and myohemerythrins [MEDLINE:88062755], [MEDLINE:90301732]\ are small proteins of about 110 to 129 amino acid residues that bind two iron\ atoms. Hemerythrins comprise left-twisted 4--\ helical bundles, which provide a hydrophobic pocket where dioxygen binds\ as a peroxo species, interacting with adjacent aliphatic side chains via\ van der Waals forces [MEDLINE:85140167].

\ Ovohemerythrin [MEDLINE:93049299], a yolk protein from the leech Theromyzon tessulatum seems\ to belong to this family of proteins, it may play a role in the detoxification\ of free iron after a blood meal [MEDLINE:93049299].\ \ iron ion binding activity ; GO:0005506 \N transport ; GO:0006810 20720 IPR002058

These PAP/25A associated domains are found in uncharacterised eukaryotic proteins, a number of which are described as 'topoisomerase 1-related' though they appear to have little or no homology to topoisomerase 1. The signatures that define this group of sequences often occur towards the C-terminus after the PAP/25A core domain IPR001201.

\ \N \N \N 20721 IPR002059 When Escherichia coli is exposed to a temperature drop from 37 to 10 degreescentigrade, a 4-5 hour lag phase occurs, after which growth is resumed at\ a reduced rate [MEDLINE:92003709]. During the lag phase, the expression of around 13\ proteins, which contain specific DNA-binding regions [MEDLINE:91062413], is increased\ 2-10 fold. These so-called 'cold shock' proteins are thought to help the\ cell to survive in temperatures lower than optimum growth temperature, by\ contrast with heat shock proteins, which help the cell to survive in\ temperatures greater than the optimum, possibly by condensation of the\ chromosome and organization of the prokaryotic nucleoid [MEDLINE:92003709].\ A conserved domain of about 70 amino acids has been found in prokaryotic and\ eukaryotic DNA-binding proteins [MEDLINE:92322642], [MEDLINE:90231432], [MEDLINE:94293754]. This domain is known as the\ 'cold-shock domain' (CSD), part of which is highly similar [MEDLINE:92310987] to the RNP-1 RNA-binding motif.\ \ DNA binding activity ; GO:0003677 \N regulation of transcription, DNA-dependent ; GO:0006355 20718 IPR002056 Virtually all mitochondrial precursors are imported via the same mechanism [MEDLINE:95224769]: precursors first bind to receptors on the mitochondrial\ surface, then insert into the translocation channel in the outer membrane.\ Many outer-membrane proteins participate in the early stages of import,\ four of which (MAS20, MAS22, MAS37 and MAS70) are components of the receptor.\ MAS20, which forms a subcomplex with MAS22, seems to interact with most or\ all mitochondrial precursors, suggesting that the protein binds directly\ to mitochondrial targeting sequences. The MAS37 and MAS70 components also\ form a subcomplex, the two subcomplexes possibly binding via their trans-\ membrane (TM) regions - the TM region of MAS70 promotes oligomerisation\ of attatched protein domains and shares sequence similarity with the\ TM region of MAS20 [MEDLINE:94216342].\ \ \N mitochondrial outer membrane translocase complex ; GO:0005742 intracellular protein transport ; GO:0006886 20719 IPR002057 Isopenicillin N synthase (IPNS) is a nonheme-Fe²⁺-dependent enzyme thatbelongs to a class of nonheme Fe²⁺-containing enzymes, which includes\ 2-oxoglutarate-dependent dioxygenases, 2-oxoglutarate-dependent hydroxy-\ lases, and enzymes involved in ethylene formation and anthocyaninidin\ biosynthesis. IPNS catalyses the stereospecific formation of the

Two cysteines are conserved in fungal\ and bacterial IPNS sequences; these may be involved in iron-binding and/or\ substrate-binding.

\ Cephalosporium acremonium DAOCS/DACS PUB00000767 is a bifunctional enzyme involved in\ cephalosporin biosynthesis. The DAOCS domain, which is structurally related to\ IPNS, catalyzes the step from penicillin N to deacetoxy-cephalosporin C - used\ as a substrate by DACS to form deacetylcephalosporin C. Streptomyces\ clavuligerus possesses a monofunctional DAOCS enzyme (gene cefE) PUB00000767 also\ related to IPNS.

\ \ oxidoreductase activity ; GO:0016491 \N biosynthesis ; GO:0009058 20716 IPR002053

Glycoside hydrolase family 25 CAZY:GH_25).

It has been shown [MEDLINE:92009192], [MEDLINE:92082464] that a number of cell-wall lytic enzymes are evolutionary related and can be classified into a single family.\ Two residues, an aspartate and a glutamate, have been shown [MEDLINE:79005662] to be\ important for the catalytic activity of the Charalopsis enzyme. These residues\ as well as some others in their vicinity are conserved in all proteins from\ this family.

\ \ lysozyme activity ; GO:0003796 \N cell wall catabolism ; GO:0016998 20717 IPR002054

DNA\ carries the biological information that instructs cells how to existin an ordered fashion: accurate replication is thus one of the most\ important events in the cell life cycle. This function is mediated by\ DNA-directed DNA-polymerases, which add nucleotide triphosphate (dNTP)\ residues to the 5'-end of the growing DNA chain, using a complementary \ DNA as template. Small RNA molecules are generally used as primers for\ chain elongation, although terminal proteins may also be used. Three motifs, A, B and C, as defined by Delarue et al. [MEDLINE:90319059], are seen to be conserved across all DNA-polymerases, with motifs A and C also seen in RNA- polymerases. They are centered on invariant residues, and their structural significance was implied from the Klenow (E.coli) structure: motif A contains a strictly-conserved aspartate at the junction of a -strand and an -helix; motif B contains an -helix with positive charges; and motif C has a doublet of negative charges, located in a -turn- secondary structure [MEDLINE:90319059].

DNA polymerases (EC: 2.7.7.7) can be classified, on the basis of sequence\ similarity [MEDLINE:88068579], [MEDLINE:90319059], into at least four different groups: A, B, C and X. Members of family X are small (about 40 Kd) compared with other polymerases and encompass two distinct polymerase enzymes that have similar functionality: vertebrate polymerase (yeast pol 4), and terminal deoxynucleotidyl-transferase (TdT) (EC: 2.7.7.31). The former functions in DNA repair, while\ the latter terminally adds single nucleotides to polydeoxynucleotide chains.\ Both enzymes catalyse addition of nucleotides in a distributive manner, i.e. they\ dissociate from the template-primer after addition of each nucleotide.\ DNA-polymerases show a degree of structural similarity with RNA-polymerases.

\ \ DNA-directed DNA polymerase activity ; GO:0003887 \N DNA replication ; GO:0006260 20715 IPR002052

In prokaryotes, the major role of DNA methylation is to protect host DNA against degradation by restriction enzymes. There are 2 major classes of DNA methyltransferase that differ in the nature of the modifications they effect. The members of one class (C-MTases) methylate a ring carbon and form C5-methylcytosine (see PRINTS signature C5METTRFRASE). Members of the second class (N-MTases) methylate exocyclic nitrogens and form either N4-methylcytosine(N4-MTases) or N6-methyladenine (N6-MTases). Both classes of MTase utilise the cofactor S-adenosyl-L-methionine (SAM) as the methyl donor and are active as monomeric enzymes [MEDLINE:95392155].

The structure of N6-MTase TaqI (M.TaqI) has been resolved to 2.4 A [MEDLINE:95062184]. The molecule folds into\ 2 domains, an N-terminal catalytic domain, which contains the catalytic and cofactor binding sites, and comprises a central 9-stranded -sheet, surrounded by 5 helices; and a C-terminal DNA recognition domain, which is formed by 4 small -sheets and 8 -helices. The N- and C-terminal domains form a cleft that accommodates the DNA substrate. A classification of N-MTases has been proposed, based on conserved motif (CM) arrangements [MEDLINE:95331587]. Three such classes include the D12, D21 and N12 classes.

\ \ N-methyltransferase activity ; GO:0008170 \N DNA methylation ; GO:0006306 20712 IPR002049 Laminins [MEDLINE:90127898] are the major noncollagenous components of basement membranesthat mediate cell adhesion, growth migration, and differentiation. They are\ composed of distinct but related

and gamma chains. The three\ chains form a cross-shaped molecule that consist of a long arm and three short\ globular arms. The long arm consist of a coiled coil structure contributed by\ all three chains and cross-linked by interchain disulfide bonds.\ Beside different types of globular domains each subunit contains, in its first\ half, consecutive repeats of about 60 amino acids in length that include eight\ conserved cysteines [MEDLINE:89325648]. The tertiary structure [MEDLINE:96196434], [MEDLINE:96196435] of this domain is\ remotely similar in its N-terminal to that of the EGF-like module (see PDOC00021). It is known as a 'LE' or 'laminin-type EGF-like' domain. The\ number of copies of the LE domain in the different forms of laminins is highly\ variable; from 3 up to 22 copies have been found.\ A schematic representation of the topology of the four disulfide bonds in\ the LE domain is shown below.\ \

\
         +-------------------+\
       +-|-----------+       |  +--------+  +-----------------+\
       | |           |       |  |        |  |                 |\
     xxCxCxxxxxxxxxxxCxxxxxxxCxxCxxxxxGxxCxxCxxgaagxxxxxxxxxxxCxx\
       sssssssssssssssssssssssssssssssssss\
\
'C': conserved cysteine involved in a disulfide bond\
'a': conserved aromatic residue\
'G': conserved glycine (lower case = less conserved)\
's': region similar to the EGF-like domain\

\ In mouse laminin gamma-1 chain, the seventh LE domain has been shown to be the\ only one that binds with a high affinity to nidogen [MEDLINE:95300958]. The binding-sites are\ located on the surface within the loops C1-C3 and C5-C6 [MEDLINE:96196434], [MEDLINE:96196435]. Long\ consecutive arrays of LE domains in laminins form rod-like elements of limited\ flexibility [MEDLINE:90127898], which determine the spacing in the formation of laminin\ networks of basement membranes [MEDLINE:93352514].\ \ structural molecule activity ; GO:0005198 \N \N 20713 IPR002050 Enveloped viruses such as Human immunodeficiency virus 1, influenza virus, and Ebola virus express a surface glycoprotein that mediates both cell attachment and fusion of viral and cellular membranes.The ENV polyprotein (coat polyprotein) usually contains two coat proteins which differ depending on the source.\ \ structural molecule activity ; GO:0005198 viral capsid ; GO:0019028 \N 20714 IPR002051 Heme oxygenase (EC: 1.14.99.3) (HO) [MEDLINE:88255650] is the microsomal enzyme that, inanimals, carries out the oxidation of heme, it cleaves the heme ring at the

methene bridge to form biliverdin and carbon monoxide [MEDLINE:87194929]. Biliverdin is\ subsequently converted to bilirubin by biliverdin reductase.\ In mammals there are three isozymes of heme oxygenase: HO-1 to HO-3. The first\ two isozymes differ in their tissue expression and their inducibility: HO-1 is\ highly inducible by its substrate heme and by various non-heme substances,\ while HO-2 is non-inducible. It has been suggested [MEDLINE:93126835] that HO-2 could be\ implicated in the production of carbon monoxide in the brain where it is said\ to act as a neurotransmitter.\ In the genome of the chloroplast of red algae as well as in cyanobacteria,\ there is a heme oxygenase (gene pbsA) that is the key enzyme in the synthesis\ of the chromophoric part of the photosynthetic antennae [MEDLINE:97471037]. An heme oxygenase\ is also present in the bacteria Corynebacterium diphtheriae (gene hmuO), where\ it is involved in the acquisition of iron from the host heme [MEDLINE:97158681].\ There is, in the central section of these enzymes, a well conserved region\ centered on a histidine residue.\ \ heme oxygenase (decyclizing) activity ; GO:0004392 \N heme oxidation ; GO:0006788 20709 IPR002045

\ \

Crustacean MTs belong to family 3. They are small proteins, with 18 totally conserved cysteines. The members of this family are recognised by the sequence pattern P-[GD]-P-C-C-x(3,4)-C-x-C located at the Nterm. The taxonomic range of the members extends to crustaceans. Known characteristics of this family are: 58 to 60 AAs; variants exist with and without the N-terminal Met. Protein sequence is divided into two structural domains, containing each 9 Cys binding 3 bivalent metal ions. Family 3 includes subfamilies : c1, c2, c. All sequences are very similar. c1 and c2 are forming two distinct monophyletic groups in the AA phylogenetic tree. c are crustacean MTs different from c1 and c2 based on phylogenetic analyses.

\ \ heavy metal binding activity ; GO:0005505 \N \N 20710 IPR002047 Adipokinetic hormones (AKH) [MEDLINE:90351346], [MEDLINE:89145002] are small active peptides produced by someinsect species. They bring on the release of diglycerides from the fat body\ and then stimulate the flight muscles to use them as an energy source. There are other\ types of active peptides structurally related to AKH.\ These peptides are eight to ten amino acid residues long.\ \ hormone activity ; GO:0005179 extracellular ; GO:0005576 \N 20711 IPR002048 Many calcium-binding proteins belong to the same evolutionary family and share a type of calcium-binding domain known as the EF-hand. This type of\ domain consists of a twelve residue loop flanked on both side by a twelve\ residue

-helical domain. In an EF-hand loop the calcium ion is\ coordinated in a pentagonal bipyramidal configuration. The six residues\ involved in the binding are in positions 1, 3, 5, 7, 9 and 12; these residues\ are denoted by X, Y, Z, -Y, -X and -Z. The invariant Glu or Asp at position 12\ provides two oxygens for liganding Ca (bidentate ligand).\ \ calcium ion binding activity ; GO:0005509 \N \N 20703 IPR002038 The major event of endochondrial ossification is the proteolyticdegradation of calcified cartilage and the extracellular matrix, and their\ substitution with bone-specific extracellular matrix produced and organised\ by osteoblasts [MEDLINE:91236779]. One of the most abundant products of osteoblasts is\ osteopontin, a glycosylated phosphoprotein with a high acidic amino acid\ content and one copy of the cell attachment sequence RGD [MEDLINE:91236779]. It is thought\ that osteopontin may act as a bridge between osteoblasts and the apatite\ mineral of the bone [MEDLINE:91236779]. Osteopontin-K is a kidney protein, similar to\ osteopontin and probably also involved in cell adhesion [MEDLINE:93034432]\ \ \N \N cell adhesion ; GO:0007155 20704 IPR002040 Tachykinins [MEDLINE:88208276], [MEDLINE:90201634], [MEDLINE:92375028] are a group of biologically active peptides which exciteneurons, evoke behavioral responses, are potent vasodilatators and contract\ (directly or indirectly) many smooth muscles. This family includes many other peptides.\ Tachykinins, like most other active peptides, are synthesized as larger\ protein precursors that are enzymatically converted to their mature forms.\ Tachykinins are from ten to twelve residues long.\ \ \N \N synaptic transmission ; GO:0007268 20705 IPR002041

Ran (or TC4), is an evolutionary conserved member of the Ras superfamily of small GTPases that regulates all receptor-mediated transport between the nucleus and the cytoplasm. Ran has been implicated in a large number of processes including nucleocytoplasmic transport, RNA synthesis, processing and export and cell cycle checkpoint control [MEDLINE:95191689], [MEDLINE:97003732]. Ran plays a crucial role in both import/export pathways and determines the directionality of nuclear transport. Import receptors bind their cargos in the cytoplasm where the concentration of RanGTP is low and release their cargos in the nucleus where the concentration of RanGTP is high [MEDLINE:22014335]. Export receptors respond to Ran GTP in the opposite manner. Furthermore, it has been shown that nuclear\ transport factor 2 (NTF2,IPR002075.

Ran is generally included in the RAS 'superfamily' of small GTP-binding\ proteins [MEDLINE:91230096], but it is only slightly related to the other RAS proteins. It\ also differs from RAS proteins in that it lacks cysteine residues at its C-\ terminal and is therefore not subject to prenylation. Instead Ran has an\ acidic C-terminus. It is, however similar to RAS family members in requiring a\ specific guanine nucleotide exchange factor (GEF) and a specific GTPase\ activating protein (GAP) as stimulators of overall GTPase activity.

Ran consists of a core domain that is structurally similar to the GTP-binding domains of other small GTPases but, in addition, Ran has a\ C-terminal extension consisting of an unstructured linker and a 16 residue -helix that is located opposite the "Switch I" region\ in the RanGDP structure [MEDLINE:22047866]. Three regions of Ran change conformation depending on the nucleotide bound, the Switch I and II regions, which interact with\ the bound nucleotide, as well as the C-terminal extension. In RanGDP, the C-terminal extension contacts the core of the protein, while in RanGTP,\ the extension is extending away from the core, most likely due to a steric clash between the switch I region and the linker part of the C-terminal extension. This suggests that the C-terminal extension in RanGDP is crucial for shielding residues in the core domain and preventing the switch regions from\ adopting a GTP-like form. This prevents binding of transport factors to RanGDP that would otherwise lead to uncoordinated interaction between importin -like\ proteins and cellular factors.

\ \ GTP binding activity ; GO:0005525 \N intracellular protein transport ; GO:0006886 20706 IPR002042 Uricase (EC: 1.7.3.3) (urate oxidase) [MEDLINE:89034153] is the peroxisomal enzyme responsiblefor the degradation of urate into allantoin:\

\
Urate + O₂ + H₂O = 5-hydroxyisourate + H₂O₂\

\ Some species, like primates and\ birds, have lost the gene for uricase and are therefore unable to degrade\ urate [MEDLINE:90083277]. Uricase is a protein of 300 to 400 amino acids, its sequence is well conserved.\ It is mainly localised in the liver,\ where it forms a large electron-dense paracrystalline core in many\ peroxisomes [MEDLINE:90249502].\ The enzyme exists as a tetramer of identical subunits, \ each containing a possible type 2 copper-binding site [MEDLINE:90083277]. In legumes, 2\ forms of uricase are found: in the roots, the tetrameric form; and, in \ the uninfected cells of root nodules, a monomeric form, which plays an\ important role in nitrogen-fixation PUB00004611.\ \ urate oxidase activity ; GO:0004846 \N purine base metabolism ; GO:0006144 20707 IPR002043 Uracil-DNA glycosylase EC: 3.2.2.- (UNG) [MEDLINE:89024574] is a DNA repair enzyme thatexcises uracil residues from DNA by cleaving the N-glycosylic bond. Uracil in\ DNA can arise as a result of misincorportation of dUMP residues by DNA\ polymerase or deamination of cytosine.\ The sequence of uracil-DNA glycosylase is extremely well conserved [MEDLINE:90059899] in\ bacteria and eukaryotes as well as in herpes viruses. More distantly related\ uracil-DNA glycosylases are also found in poxviruses\ \ \ \ [MEDLINE:93281610].\ In eukaryotic cells, UNG activity is found in both the nucleus and the\ mitochondria. Human UNG1 protein is transported to both the mitochondria and\ the nucleus [MEDLINE:93324318]. The N-terminal 77 amino acids of UNG1 seem to be required for\ mitochondrial localization [MEDLINE:93324318], but the presence of a mitochondrial transit\ peptide has not been directly demonstrated.\ The most N-terminal conserved region contains an aspartic acid residue which has been\ proposed, based on X-ray structures [MEDLINE:95147968], [MEDLINE:95211838] to act as a general base in the\ catalytic mechanism.\ \ uracil DNA N-glycosylase activity ; GO:0004844 \N DNA repair ; GO:0006281 20708 IPR002044

This domain binds to starch, and is found often at the C-terminus of a variety of glycosyl hydrolases acting on polysaccharides more rapidly than on oligosaccharides. Reations include: the hydrolysis of terminal 1,4-linked -D-glucose residues successively from non-reducing ends of the chains with release of -D-glucose, the degradation of starch to cyclodextrins by formation of a 1,4--D-glucosidic bond, and hydrolysis of 1,4--glucosidic linkages in polysaccharides to remove successive maltose units from the non-reducing ends of the chains.

\ \ enzyme activity ; GO:0003824 \N carbohydrate metabolism ; GO:0005975 20697 IPR002032 The consensus features of a tyrosine sulfation site have been described intwo reviews PUB00005327, PUB00005327:\

The presence of an acidic (Glu or Asp) amino acid within two residues of the tyrosine (typically at -1).
The presence of at least three acidic residues from -5 to +5.
No more than one basic residue and three hydrophobic residues from -5 to +5.
Presence of turn-inducing amino acids: at least one Pro or Gly (the amino acids with the strongest turn potential) from -7 to -2 and from +1 to +7, or at least two or three Asp, Ser or Asn from -7 to +7.
Absence of disulfide-bonded cysteine residues from -7 to +7.
Absence of N-linked glycans near the tyrosine.

\ It must be noted that tyrosine sulfation is physiologically relevant only to\ proteins or domains passing through or located in the Golgi lumen. \

Note: No protein matches are shown due to the low specificity of this rule.

\ \ \N \N \N 20698 IPR002033

In E.coli the mttABC operon contains three genes mttA, mttB and mttC.These three genes are transcribed polycistronically. It has\ been suggested that mttA is involved in Sec-independent\ translocation of proteins [MEDLINE:98206471]. The target proteins of this\ pathway contain a twin arginine leader motif (S/TRRXFLK).\ It has been suggested that members of this family form a\ translocation complex with mttA and mttC [MEDLINE:98206471].

\ \ \N \N \N 20699 IPR002034 A number of enzymes have been shown to be functionally as well asevolutionary related [MEDLINE:91216974]. The nifV and leuA genes encode homocitrate synthase and

-isopropylmalate synthase, respectively\ The N-terminal parts of NifV and LeuA from bacteria are highly similar to each other [MEDLINE:97284496]. Homocitrate synthase (EC 4.1.3.21) (gene nifV) is involved in the biosynthesis of the iron-molybdenum cofactor of nitrogenase and catalyzes the condensation of acetyl-CoA and

-ketoglutarate into homocitrate. Alpha-isopropylmalate synthase (EC 4.1.3.12) catalyses the first step in the biosynthesis of leucine, the condensation ofacetyl-CoA and

- ketoisovalerate to form 2-isopropylmalate synthase.\ \ lyase activity ; GO:0016829 \N metabolism ; GO:0008152 20700 IPR002035 The von Willebrand factor is a large multimeric glycoprotein found in bloodplasma. Mutant forms are involved in the aetiology of bleeding disorders \ [MEDLINE:93178773]. In von Willebrand factor, the type A domain (vWF) is the prototype for\ a protein superfamily. The vWF domain is found in various plasma proteins:\ complement factors B, C2, CR3 and CR4; the integrins (I-domains); collagen \ types VI, VII, XII and XIV; and other extracellular proteins [MEDLINE:94018965], [MEDLINE:94194513], [MEDLINE:91323531]. Although the majority of VWA-containing proteins are extracellular, the most ancient ones present in all eukaryotes are all intracellular proteins involved in functions such as transcription, DNA repair, ribosomal and membrane transport and the proteasome. A common feature appears to be involvement in multiprotein complexes. Proteins\ that incorporate vWF domains participate in numerous biological events\ (e.g. cell adhesion, migration, homing, pattern formation, and signal\ transduction), involving interaction with a large array of ligands [MEDLINE:94018965]. A number of human diseases arise from mutations in VWA domains. Secondary structure prediction from 75 aligned vWF sequences has revealed a largely alternating sequence of

-helices and

-strands [MEDLINE:94194513]. Fold\ recognition algorithms were used to score sequence compatibility with a\ library of known structures: the vWF domain fold was predicted to be a\ doubly-wound, open, twisted

-sheet flanked by

-helices [MEDLINE:95145726]. \ 3D structures have been determined for the I-domains of integrins CD11b\ (with bound magnesium) [MEDLINE:95171458] and CD11a (with bound manganese) [MEDLINE:96036067]. The domain \ adopts a classic

Rossmann fold and contains an unusual metal \ ion coordination site at its surface. It has been suggested that this site\ represents a general metal ion-dependent adhesion site (MIDAS) for binding \ protein ligands [MEDLINE:95171458]. The residues constituting the MIDAS motif in the CD11b\ and CD11a I-domains are completely conserved, but the manner in which the \ metal ion is coordinated differs slightly [MEDLINE:96036067].\ \ \N \N \N 20696 IPR002031

Presenilins are polytopic transmembrane (TM) proteins, mutations in which are associated with the occurrence of early-onset familial Alzheimer's \ disease, a rare form of the disease that results from a single-gene\ mutation [MEDLINE:99007742], [MEDLINE:98180715]. While the aetiology of Alzheimer's disease is unresolved,\ all forms are typified by a global cognitive decline and the occurrence of \ characteristic neuropathological changes. Invariably, post-mortem brains\ from Alzheimer's patients contain abundant neurofibrillary tangles, together\ with depositions of -amyloid protein as senile plaques.\ The physiological functions of presenilins are unknown, but they may be \ related to developmental signalling, apoptotic signal transduction, or\ processing of selected proteins, such as the -amyloid precursor protein\ (-APP). That presenilin homologues have been identified in species that\ do not have an Alzhemier's disease correlate suggests that they may have \ functions unrelated to the disease, homologues having been identified in\ mouse, Drosophila and C.elegans. In the latter, the sel-12 protein (a worm\ homologue of the mammalian presenilins) has been demonstrated to facilitate\ the function of the Notch receptor, which plays a role in cell-cell\ signalling during cell differentiation in development. Intriguingly,\ presenilin 1 is able to restore function in a C.elegans mutant lacking\ sel-12, suggesting presenilin may also be involved in cell-cell signalling\ in higher species.

In humans, there are two presenilin genes (PS1 and PS2), encoding proteins\ of 467 and 448 amino acids respectively. They share 67% amino acid identity,\ the greatest divergence between the two falling in the N-terminus and in the\ large hydrophilic loop towards the C-terminal part of each molecule. Six to\ nine TM domains are predicted for each, and biochemical analysis has\ demonstrated that their C-termini are cytoplasmic; but the orientation of\ their N-termini and large hydrophilic loops remains to be resolved. They\ are expressed in almost all tissues, including the brain and, at a cellular\ level, they have been localised to the nuclear envelope, endoplasmic\ reticulum and Golgi apparatus. \ Presenilin 1 has been shown to be phosphorylated by protein kinase C, and is\ endogenously cleaved into 28kD N-terminal and 19kD C-terminal fragments.\ Consequently, little of the uncleaved peptide is detectable in vivo. PS1\ gene mutations are thought to account for the majority of early-onset\ familial Alzheimer's disease cases. To date, 45 different mutations have\ been identified in PS1, all but one of which result in a single amino change\ in the presenilin 1 molecule. Affected residues always occur in regions of\ the sequence that are conserved between presenilins 1 and 2, and the C.elegans\ homologue, sel-12 [MEDLINE:99007744]. The mutations are thought to be responsible for ~50%\ of cases of early-onset familial Alzheimer's disease, in contrast, less than\ 1% resulting from mutations in PS2. How the mutations trigger disease is \ unknown, but one biochemical effect consistently associated with them is an\ alteration in the proteolytic cleavage of -APP such that there is\ overproduction of long-tailed -amyloid peptide derivatives.

\ \ \N membrane ; GO:0016020 intracellular signaling cascade ; GO:0007242 20701 IPR002036 These, as yet, uncharacterised proteins are of 17 to 21 kDa. They contain a conserved region with three histidines at the C-terminal.\ molecular_function unknown ; GO:0005554 \N \N 20702 IPR002037

Glycoside hydrolase family 8 CAZY:GH_8.

\ \ hydrolase activity, hydrolyzing O-glycosyl compounds ; GO:0004553 \N carbohydrate metabolism ; GO:0005975 20692 IPR002024 Bacterioferritin (BFR; also known as cytochrome b1 or cytochrome b557) [MEDLINE:91114915], [MEDLINE:91265528] of Escherichia coli is an iron-storage protein consisting of 24 identical\ subunits that pack together to form a highly symmetrical, nearly spherical \ shell surrounding a central cavity of about 8 nm diameter [MEDLINE:96332624], [MEDLINE:96103172]. X-ray \ crystallographic studies have revealed a close structural similarity \ between BFR and the ferritins, a family of iron-storage proteins found in \ both eukaryota and prokaryota\ \ \ \ [MEDLINE:96332624]. Common to both ferritins and BFRs is a \ capacity to store large quantities of iron within their hollow interior, in\ the form of a hydrated ferric oxide mineral containing variable amounts of\ phosphate anion. However, a major difference between them is that BFR \ contains up 12 b-type haem groups, while ferritins, as isolated, do not \ contain haem. \ The building block for the BFR shell is a protein dimer (subunits A and B) \ binding the single haem group. Each subunit consists of four nearly \ parallel

-helices. The haem is bound symmetrically to subunits A and B\ by Met(A)-52 and Met(B)-52 residues [MEDLINE:95393179]. Each subunit includes a binuclear \ metal-binding site linking together the four major helices of the subunit, \ which has been identified as the ferroxidase centre of BFR [MEDLINE:96103172]:\ \

\ Glu-127\ |\ O C O\ | / \\ |\ Glu-18--C--O O O O--C--Glu-94\ 'M1' 'M2'\ His-54--+--N' 'O O' 'N--+--His-130\ | \\ \\ / / |\ | / C \\ |\ +--N | N--+\ Glu-51\

\ (M1 and M2 are the metal centres 1 and 2). BFR mutants with Met-52 replaced\ are haem-free, but appear to be correctly assembled and are capable of \ accumulating iron [MEDLINE:96007460].\ \ ferric iron binding activity ; GO:0008199 \N iron ion homeostasis ; GO:0006879 20693 IPR002026

Urease EC: 3.5.1.5 is a nickel-binding enzyme that catalyzes the hydrolysis of urea to carbon dioxideand ammonia [MEDLINE:88296463]:\

\
Urea + H₂O = CO₂ + 2 NH₃ \

\ Historically, it was the first enzyme to be crystallized (in 1926). It is mainly\ found in plantseeds and microorganisms. In plants, urease is a hexamer of identical chains. In bacteria\ [MEDLINE:89218765], it consists of either two or three different subunits (

IPR005847 and gamma, described in this entry). The structure of the\ urease complex is known [MEDLINE:95273988].

\ \ This subunit does not appear to take part in the catalytic mechanism.\ \ nickel ion binding activity ; GO:0016151 \N nitrogen metabolism ; GO:0006807 20694 IPR002028

Tryptophan synthase (EC: 4.2.1.20) catalyzes the last step in the biosynthesisof tryptophan [MEDLINE:90024964], [MEDLINE:90329239]:\

\
L-serine + 1-(indol-3-yl)glycerol 3-phosphate = L-tryptophan + glyceraldehyde 3-phosphate + H₂O\

\ It has two functional domains, each found in bacteria and plants on a\ separate subunit:

chain is for the aldol cleavage of indoleglycerol phosphate to indole and\ glyceraldehyde 3-phosphate and

chain IPR006653 is for the synthesis of tryptophan from\ indole and serine. In fungi the two domains are fused together on a single multifunctional protein [MEDLINE:89282819].

\ \

Two acidic residues are believed to serve as proton donors/acceptors in the enzyme's\ catalytic mechanism.

\ \ tryptophan synthase activity ; GO:0004834 \N tryptophan metabolism ; GO:0006568 20691 IPR002023 Respiratory-chain NADH dehydrogenase (ubiquinone) (EC: 1.6.5.3) PUB00001096, PUB00001096 (also known as complexI or NADH-ubiquinone oxidoreductase) is an oligomeric enzymatic complex\ located in the inner mitochondrial membrane which also seems to exist in\ the chloroplast and in cyanobacteria (as a NADH-plastoquinone oxidoreductase).\ Among the 25 to 30 polypeptide subunits of this bioenergetic enzyme complex\ there is one with a molecular weight of 24 kDa (in mammals), which is a\ component of the iron-sulfur (IP) fragment of the enzyme. It seems to bind a\ 2Fe-2S iron-sulfur cluster. The 24 kDa subunit is nuclear encoded, as a\ precursor form with a transit peptide in mammals, and in Neurospora crassa.\ There is a highly conserved region, located in the\ central section of this subunit that contains two conserved cysteines\ that are probably involved in the binding of the 2Fe-2S center.\ \ NADH dehydrogenase (ubiquinone) activity ; GO:0008137 \N oxidative phosphorylation, NADH to ubiquinone ; GO:0006120 20695 IPR002030 A variety of substrate carrier proteins that are involved in energy transfer are found in the inner mitochondrial membrane [MEDLINE:90223523], PUB00001076, PUB00001076, [MEDLINE:93253777], [MEDLINE:94265916], [MEDLINE:94120553]. Such proteins include:\ ADP,ATP carrier protein (ADP/ATP translocase); 2-oxoglutarate/malate carrier\ protein; phosphate carrier protein; tricarboxylate transport protein (or \ citrate transport protein); Graves disease carrier protein; yeast mito-\ chondrial proteins MRS3 and MRS4; yeast mitochondrial FAD carrier protein;\ and many others.\

The brown fat uncoupling protein (UCP) dissipates oxidative energy into heat\ by transporting protons from the cytosol into the mitochondrial matrix [MEDLINE:90338166].\ UCP functions as a dimer, forming a proton channel that leads to uncoupling\ of oxidative phosphorylation by dissipation of the electrochemical potential\ across the inner membrane.

The protein has a tripartite structure, with 3 similar ~100 residue domains.\ The domains exhibit striking conservation of several residues, especially\ of glycine and proline, which may constitute structurally strategic\ positions [MEDLINE:86081749]. The protein is thought to contain 6 transmembrane helices\ [MEDLINE:88315014]. These characteristics are shared by the ADP/ATP carrier protein, which\ is a member of the mitochondrial carrier family.

\ \ \ binding activity ; GO:0005488 membrane ; GO:0016020 mitochondrial transport ; GO:0006839 20685 IPR002017 Spectrin repeats [MEDLINE:94090340] are found in several proteins involved incytoskeletal structure. These include spectrin,

-actinin\ and dystrophin. \ The spectrin repeat forms a\ three helix bundle. The second helix is interrupted by proline\ in some sequences. The repeats are defined by a characteristic\ tryptophan (W) residue at position 17 in helix A and a leucine\ (L) at 2 residues from the carboxyl end of helix C.\ \ \N \N \N 20686 IPR002018 Higher eukaryotes have many distinct esterases. Among the different types arethose which act on carboxylic esters (EC: 3.1.1.-). Carboxyl-esterases have\ been classified into three categories (A, B and C) on the basis of\ differential patterns of inhibition by organophosphates. The sequence of a\ number of type-B carboxylesterases indicates [MEDLINE:88216148], [MEDLINE:91319741], [MEDLINE:93200914] that the majority are evolutionary related. As is the case for lipases and serine proteases, the catalytic apparatus of\ esterases involves three residues (catalytic triad): a serine, a glutamate or\ aspartate and a histidine.\ \ carboxylic ester hydrolase activity ; GO:0016789 \N \N 20687 IPR002019

Urease EC: 3.5.1.5 is a nickel-binding enzyme that catalyzes the hydrolysis of urea to carbon dioxideand ammonia [MEDLINE:88296463]:\

\
Urea + H₂O = CO₂ + 2 NH₃ \

IPR005847). The structure of the\ urease complex is known [MEDLINE:95273988].

\ This subunit does not appear to take part in the catalytic mechanism. \ This subunit is known (confusingly) as

in Helicobacter.\ \ nickel ion binding activity ; GO:0016151 \N nitrogen metabolism ; GO:0006807 20688 IPR002020 Citrate synthase EC: 4.1.3.7 is a member of a small family of enzymes that can directlyform a carbon-carbon bond without the presence of metal ion cofactors [MEDLINE:90248434].\ It catalyses the first reaction in the Krebs' cycle [MEDLINE:90248434]:\

\
Citrate + CoA = acetyl-CoA + H₂O + oxaloacetate\

\ This reaction is an an important function in both energy generation and carbon assimilation [MEDLINE:83210236].\ The reaction proceeds via a non-covalently bound intermediate citryl-\ coenzyme A intermediate, and is thus thought to be a 2-step process [MEDLINE:90248434]. \ The enzyme exists as a globular homodimer (a hexamer in prokaryotes), which \ is almost completely helical (20 helices per monomer), which is unusual for\ such a large enzyme [MEDLINE:83010291]. In\ eukaryotes, there are two isozymes of citrate synthase: one is found in the\ mitochondrial matrix, the second is cytoplasmic. Both seem to be dimers of\ identical chains. Each monomer is divided into a large and a small \ domain, the cleft between these domains forming the active site where both \ citrate and acetyl-coenzyme A have been shown to bind [MEDLINE:83010291]. The enzyme\ undergoes a conformational change upon binding of the oxaloacetate, whereby\ the active site cleft closes over [MEDLINE:83010291].\ There are a number of regions of sequence similarity between prokaryotic and\ eukaryotic citrate synthases. One of the best conserved contains a histidine\ which is one of three residues shown [MEDLINE:90248434] to be involved in the catalytic\ mechanism of the vertebrate mitochondrial enzyme.\ \ citrate (SI)-synthase activity ; GO:0004108 \N tricarboxylic acid cycle ; GO:0006099 20683 IPR002015 A weakly conserved repeat module of unknown function, which occursin two regulatory subunits of the 26S-proteasome and in one subunit\ of the APC-complex (cyclosome) [MEDLINE:97348748].\ \ \N \N \N 20684 IPR002016 Peroxidases are haem-containing enzymes that use hydrogen peroxide asthe electron acceptor to catalyse a number of oxidative reactions.\ Most haem peroxidases follow the reaction scheme:\

\
Fe³⁺ + H₂O₂            --> [Fe⁴⁺=O]R' (Compound I) + H₂O\

\ \ \ \

\
[Fe⁴⁺=O]R' + substrate --> [Fe⁴⁺=O]R (Compound II) + oxidised substrate\

\ \ \ \

\
[Fe⁴⁺=O]R  + substrate -->  Fe³⁺ + H₂O + oxidised substrate\

\ \

In this mechanism, the enzyme reacts with one equivalent of H₂O₂ to give \ [Fe⁴⁺=O]R' (compound I). This is a two-electron oxidation/reduction \ reaction where H₂O₂ is reduced to water and the enzyme is oxidised. One \ oxidising equivalent resides on iron, giving the oxyferryl [MEDLINE:94341255] \ intermediate, while in many peroxidases the porphyrin (R) is oxidised to \ the porphyrin pi-cation radical (R'). Compound I then oxidises an organic \ substrate to give a substrate radical [MEDLINE:95006313].

\ \

Haem peroxidases include two superfamilies: one found in bacteria, fungi, plants and the second found in animals. The first one can be\ viewed as consisting of 3 major classes PUB00001075. Class\ I, the intracellular peroxidases, includes: yeast cytochrome c peroxidase\ (CCP), a soluble protein found in the mitochondrial electron transport\ chain, where it probably protects against toxic peroxides; ascorbate\ peroxidase (AP), the main enzyme responsible for hydrogen peroxide removal\ in chloroplasts and cytosol of higher plants PUB00001075; and bacterial catalase-\ peroxidases, exhibiting both peroxidase and catalase activities. It is\ thought that catalase-peroxidase provides protection to cells under\ oxidative stress [MEDLINE:92062697].

Class II consists of secretory fungal peroxidases: ligninases, or lignin \ peroxidases (LiPs), and manganese-dependent peroxidases (MnPs). These are\ monomeric glycoproteins involved in the degradation of lignin. In MnP,\ Mn²⁺ serves as the reducing substrate [MEDLINE:94220348]. Class II proteins contain four\ conserved disulphide bridges and two conserved calcium-binding sites.

Class III consists of the secretory plant peroxidases, which have multiple \ tissue-specific functions: e.g., removal of hydrogen peroxide from\ chloroplasts and cytosol; oxidation of toxic compounds; biosynthesis of the\ cell wall; defence responses towards wounding; indole-3-acetic acid (IAA) \ catabolism; ethylene biosynthesis; and so on PUB00005929. Class III proteins are \ also monomeric glycoproteins, containing four conserved disulphide bridges \ and two calcium ions, although the placement of the disulphides differs \ from class II enzymes.

The crystal structures of a number of these proteins show that they share the same architecture - two all- domains between which the haem group is embedded.

\ \ peroxidase activity ; GO:0004601 \N peroxidase reaction ; GO:0006804 20690 IPR002022

Pectate lyase EC: 4.2.2.2 is an enzyme involved in the maceration and soft rotting of plant tissue. Pectate lyase is responsible for the eliminative cleavage of pectate,\ yielding oligosaccharides with 4-deoxy--D-mann-4-enuronosyl groups\ at their non-reducing ends. The protein is maximally expressed late in\ pollen development. It has been suggested that the pollen expression of \ pectate lyase genes might relate to a requirement for pectin degradation\ during pollen tube growth [MEDLINE:91322485].

\ \

The structure and the folding kinetics of one member of this family, pectate lyase C\ (pelC)1 from Erwinia chrysanthemi has been investigated in some detail [MEDLINE:21924508],[MEDLINE:93276270]. PelC contains a parallel -helix folding motif. The majority of the regular secondary structure is composed of parallel -sheets (about\ 30%). The individual strands of the sheets are connected by unordered loops of varying length. The backbone is then formed by a large helix composed of -sheets. There are two disulfide bonds in pelC and 12 proline residues. One of these prolines, Pro220, is involved in a cis peptide bond. he folding mechanism of pelC involves two slow phases that have been attributed to proline isomerization.

\ \

The allergens in this family include allergens with the following designations: Amb a 1, Amb a 2, Amb a 3, Cha o 1, Cup a 1, Cry j 1, Jun a 1.

\ \

Two of the major allergens in the pollen of short ragweed (Ambrosia \ artemisiifolia) are Amb aI and Amb aII. The primary structure of Amb aII\ has been deduced and has been shown to share ~65% sequence identity with\ the Amb I multigene family of allergens [MEDLINE:92013060]. Members of the Amb aI/aII\ family include tobacco pectate lyase, which is similar to the deduced amino\ acid sequences of two pollen-specific pectate lyase genes identified in\ tomato\ \ \ \ [MEDLINE:93043039]; Cry jI, a major allergenic glycoprotein of Cryptomeria japonica \ (Japanese cedar) - the most common pollen allergen in Japan [MEDLINE:95003748]; and P56\ and P59, which share sequence similarity with pectate lyases of plant \ pathogenic bacteria [MEDLINE:91322485].

\ \ \ \ \N \N \N 20689 IPR002021 The nucleocapsid protein is referred to as NP. NP is is the majorstructural component of the nucleocapsid. The protein is approx.\ 58 kDa. 2600 NP molecules go to tightly encapsidate the viral RNA.\ NP interacts with several other viral encoded proteins, all of which are \ involved in controlling replication: NP-NP, NP-P, NP-(PL), \ and NP-V [MEDLINE:97240424], [MEDLINE:96400146], [MEDLINE:93381779].\ \ structural molecule activity ; GO:0005198 viral nucleocapsid ; GO:0019013 \N 20677 IPR002009 This family consists of bromovirus coat proteins. RNA-protein interactions stabilize many viruses and also the nucleoprotein cores of enveloped animal viruses (e.g. retroviruses). The nucleoprotein particles are frequently pleomorphic and generally unstable due to the lack of strong protein-protein interactions in their capsids.

The structure\ is known for cowpea chlorotic mottle virus\ \ \ \ [MEDLINE:95261705]. It shows novel quaternary structure interactions based on interwoven carboxyterminal polypeptides that extend from canonical capsid -barrel subunits. Additional particle stability is provided by intercapsomere contacts between metal ion\ mediated carboxyl cages and by protein interactions with regions of ordered RNA.

\ \ structural molecule activity ; GO:0005198 viral capsid ; GO:0019028 \N 20678 IPR002010 Members of this family export proteins, that do not possess signal peptides, through the membrane. Although the proteins that these\ exporters move may be different, the exporters are thought to \ function in similar ways [MEDLINE:95113771].\ FliR genes encode highly hydrophobic polypeptide. Sequence analysis of the fliR gene product has\ suggested the presence of eight transmembrane regions.\ \ \N membrane ; GO:0016020 protein targeting ; GO:0006605 20679 IPR002011 A number of growth factors stimulate mitogenesis by interacting with a familyof cell surface receptors which possess an intrinsic, ligand-sensitive,\ protein tyrosine kinase activity [MEDLINE:89024579]. These receptor tyrosine kinases (RTK)\ all share the same topology: an extracellular ligand-binding domain, a single\ transmembrane region and a cytoplasmic kinase domain. However they can be\ classified into at least five groups. The prototype for class II RTK's is the\ insulin receptor, a heterotetramer of two

and two

chains linked by\ disulfide bonds. The

and

chains are cleavage products of a\ precursor molecule. The

chain contains the ligand binding site, the

chain transverses the membrane and contains the tyrosine protein kinase\ domain.\ While only the insulin and the insulin growth factor I receptors are known to\ exist in the tetrameric conformation specific to class II RTK's, all the above\ proteins share extensive homologies in their kinase domain, especially around\ the putative site of autophosphorylation.\ \ ATP binding activity ; GO:0005524 membrane ; GO:0016020 transmembrane receptor protein tyrosine kinase signaling pathway ; GO:0007169 20680 IPR002012 The gonadotropin-releasing hormones (GnRH) (gonadoliberin) PUB00005538 are a familyof peptides that play a pivotal role in reproduction. The main function of\ GnRH is to act on the pituitary to stimulate the synthesis and secretion of\ luteinizing and follicle-stimulating hormones, but GnRH also acts on the\ brain, retina, sympathetic nervous system, gonads and placenta in certain\ species. There seems to be at least three forms of GnRH. The second form is\ expressed in midbrain and seems to be widespread. The third form has only been\ found so far in fish.\ GnRH is a C-terminal amidated decapeptide processed from a larger precursor\ protein. Four of the ten residues are perfectly conserved in all species\ where GnRH has been sequenced.\ \ hormone activity ; GO:0005179 extracellular ; GO:0005576 development ; GO:0007275 20681 IPR002013 Synaptic vesicles are recycled with remarkable speed and precision in nerve terminals. A major recycling pathway involves clathrin-mediated endocytosis at\ endocytic zones located around sites of release. Different 'accessory' proteins\ linked to this pathway have been shown to alter the shape and composition of lipid\ membranes, to modify membrane-coat protein interactions, and to influence actin\ polymerization. These include the GTPase dynamin, the lysophosphatidic acid acyl\ transferase endophilin, and the phosphoinositide phosphatase synaptojanin [MEDLINE:99069219]. \

The recessive suppressor of secretory defect in yeast Golgi and yeast\ actin function belongs to this family. This protein may be involved in the coordination of the activities of the secretory pathway and the actin cytoskeleton.

\ \

Human synaptojanin which may be localised on coated endocytic intermediates in\ nerve terminals also belongs to this family.

\ \ \N \N \N 20682 IPR002014

The VHS domain is a ~140 residues long domain, whose name is derivedfrom its occurrence in VPS-27, Hrs and STAM. Based on regions surrounding the domain, VHS-proteins can be divided into 4 groups [MEDLINE:21909369]:

STAM/EAST/Hbp which all share the domain composition VHS-SH3-ITAM and carry one or two ubiquitin-interacting motifs

Proteins with a FYVE domain (IPR000306 ) C-terminal to VHS which also carry one or two ubiquitin-interacting motifs

GGA proteins with a domain composition VHS-GAT (GGA and Tom1) homology domain

VHS domain alone or in combination with domains other than those listed above

The VHS domain is always found at the N-\ terminus of proteins suggesting that such topology is important for function. The domain is considered to have a general membrane targeting/cargo recognition role in vesicular trafficking [MEDLINE:20442079].

\ \

Resolution of the crystal structure of the VHS domain of Drosophila Hrs and\ human Tom1 revealed that it consists of eight helices arranged in a double-layer superhelix\ [MEDLINE:20155428]. The existence of conserved patches of residues on the domain surface suggests that VHS domains may be involved in protein-protein recognition and docking. Overall, sequence similarity is low (approx 25%) amongst domain family members

\ \ \ \ \ \N \N intracellular protein transport ; GO:0006886 20676 IPR002008

\ \ beta DNA polymerase activity ; GO:0003890 \N DNA repair ; GO:0006281 20671 IPR002003 Gas vesicles are small, hollow, gas filled protein structures found in severalcyanobacterial and archaebacterial microorganisms [MEDLINE:90104301]. They allow the\ positioning of the bacteria at the favorable depth for growth. Gas vesicles\ are hollow cylindrical tubes, closed by a hollow, conical cap at each end.\ Both the conical end caps and central cylinder are made up of 4-5 nm wide\ ribs that run at right angles to the long axis of the structure. Gas vesicles\ seem to be constituted of two different protein components: GVPa and GVPc.\ GVPc is a minor constituent of gas vesicles and seems to be located on the\ outer surface. Structurally, cyanobacterial GVPc consists of four or five\ tandem repeats of a 33 residue sequence flanked by sequences of 18 and 10\ residues at the N- and C-termini, respectively.\ \ \N \N \N 20672 IPR002004

This domain is found at the C terminus of polyadenylate-binding proteins and also in HECT domain IPR000569 containing proteins. It is probably involved in homodimerisation (either directly or indirectly).

\ \N \N \N 20673 IPR002005 Rab proteins constitute a family of small GTPases that serve a regulatoryrole in vesicular membrane traffic [MEDLINE:95045420], [MEDLINE:96062207]; C-terminal geranylgeranylation is\ crucial for their membrane association and function. This post-translational\ modification is catalysed by Rab geranylgeranyl transferase (Rab-GGTase), a \ multi-subunit enzyme that contains a catalytic heterodimer and an accessory\ component, termed Rab escort protein (REP)-1 [MEDLINE:95045420]. REP-1 presents newly-\ synthesised Rab proteins to the catalytic component, and forms a stable\ complex with the prenylated proteins following the transfer reaction. \

The mechanism of REP-1-mediated membrane association of Rab5 is similar\ to that mediated by Rab GDP dissociation inhibitor (GDI). REP-1 and Rab GDI \ also share other functional properties, including the ability to inhibit the\ release of GDP and to remove Rab proteins from membranes.

The crystal structure of the bovine -isoform of Rab GDI has been\ determined to a resolution of 1.81A [MEDLINE:96196507]. The protein is composed of two\ main structural units: a large complex multi-sheet domain I, and a smaller -helical domain II.

The structural organisation of domain I is closely related to FAD-containing\ monooxygenases and oxidases [MEDLINE:96196507]. Conserved regions common to GDI and the\ choroideraemia gene product, which delivers Rab to catalytic subunits of\ Rab geranylgeranyltransferase II, are clustered on one face of the domain\ [MEDLINE:96062207]. The two most conserved regions form a compact structure at the apex of\ the molecule; site-directed mutagenesis has shown these regions to play a\ critical role in the binding of Rab proteins [MEDLINE:96196507].

\ \ RAB GTPase activator activity ; GO:0005097 \N \N 20674 IPR002006 The core antigen of hepatitis viruses possesses a carboxylterminus rich in arginine. On this basis it was predicted\ that the core antigen would bind DNA [MEDLINE:81012115]. There is some\ experimental evidence to support this [MEDLINE:90012312].\ \ \N \N \N 20675 IPR002007

Peroxidases are haem-containing enzymes that use hydrogen peroxide asthe electron acceptor to catalyse a number of oxidative reactions.

\ \

Peroxidases are found in bacteria, fungi, plants and animals. On the basis\ of sequence similarity, a number of animal haem peroxidases can be\ categorised as members of a superfamily: myeloperoxidase (MPO); eosinophil\ peroxidase (EPO); lactoperoxidase (LPO); thyroid peroxidase (TPO);\ prostaglandin H synthase (PGHS); and peroxidasin [MEDLINE:94341255], [MEDLINE:95006313], [MEDLINE:88289715].

MPO plays a major role in the oxygen-dependent microbicidal system of neutrophils. EPO from eosinophilic granulocytes \ participates in immunological reactions, and potentiates tumor necrosis \ factor (TNF) production and hydrogen peroxide release by human monocyte-derived macrophages [MEDLINE:89352509], [MEDLINE:95293036]. In the main, MPO (and possibly EPO) utilises Cl^-ions and H₂O₂ to form hypochlorous acid (HOCl), which can effectively kill\ bacteria or parasites. In secreted fluids, LPO catalyses the oxidation of thiocyanate ions (SCN^-) by H₂O₂, producing the weak oxidising agent \ hypothiocyanite (OSCN^-), which has bacteriostatic activity [MEDLINE:83101416]. TPO uses \ I^- ions and H₂O₂ to generate iodine, and plays a central role in the \ biosynthesis of thyroid hormones T(3) and T(4).

To date, the 3D structures of MPO and PGHS have been reported. MPO is a \ homodimer: each monomer consists of a light (A or B) and a heavy (C or D) \ chain resulting from post-translational excision of 6 residues from the \ common precursor. Monomers are linked by a single inter-chain disulphide. \ Each monomer includes a bound calcium ion [MEDLINE:92318261]. PGHS exists as a symmetric \ dimer, each monomer of which consists of 3 domains: an N-terminal epidermal\ growth factor (EGF) like module; a membrane-binding domain; and a large\ C-terminal catalytic domain containing the cyclooxygenase and the peroxidase \ active sites. The catalytic domain shows striking structural similarity to \ MPO. The cyclooxygenase active site, which catalyses the formation of \ prostaglandin G2 (PGG2) from arachidonic acid, resides at the apex of a \ long hydrophobic channel, extending from the membrane-binding domain to the\ centre of the molecule. The peroxidase active site, which catalyses the\ reduction of PGG2 to PGH2, is located on the other side of the molecule, at\ the haem binding site [MEDLINE:94166877]. Both MPO and the catalytic domain of PGHS are \ mainly -helical, 19 helices being identified as topologically and\ spatially equivalent; PGHS contains 5 additional N-terminal helices that\ have no equivalent in MPO. In both proteins, three Asn residues in each\ monomer are glycosylated.

\ \ peroxidase activity ; GO:0004601 \N peroxidase reaction ; GO:0006804 20665 IPR001997 Calponin is a smooth muscle-specific, actin-, tropomyosin- and calmodulin-binding protein believed to be involved in regulation or modulation of contraction [MEDLINE:93380560], [MEDLINE:94193769]; interaction of the protein with actin inhibits actomyosin MgATPase activity. Multiple isoforms are found in smooth muscle [MEDLINE:94193769]. Calponin is a basic protein of ~34 Kd [MEDLINE:96132935]. The protein contains three repeats of a well-conserved 26-residue domain (see IPR000557).\ actin binding activity ; GO:0003779 \N smooth muscle contraction ; GO:0006939 20666 IPR001998

Xylose isomerase (EC: 5.3.1.5) [MEDLINE:89211422] is an enzyme found in microorganisms which catalyzes the interconversion of D-xylose to D-xylulose. It can also isomerize D-ribose to D-ribulose and D-glucose to D-fructose. The enzyme is a homotetramer, which is stabilised by cobalt, and requires magnesium for its catalytic activity. Each subunit contains 2 domains: the core domain is a parallel - barrel; the C-terminal domain is a loop structure consisting of 5 helices and is involved in intermolecular contacts between adjacent subunits [MEDLINE:89362453]. The active site lies in a deep pocket near the C-terminal ends of the strands of the barrel domain and includes residues from a second subunit. The tetramer is effectively a dimer of "active" dimers, the active sites being composed of residues from both subunits [MEDLINE:89362453].

Xylose isomerase also exists in plants\ \ \ \ [MEDLINE:96203931] where it is homodimeric and is manganese-dependent.

\ \ xylose isomerase activity ; GO:0009045 \N carbohydrate metabolism ; GO:0005975 20667 IPR001999

The osteonectin like domain, of unknown function, is found in extracellular proteins strongly expressed in tissues undergoing morphogenesis. It is a 240 amino acids domain, highly conserved, localized in the C-terminal part of the protein [MEDLINE:94164428].

This domain has a N-terminal section of about 90 residues that contains 11 conserved cysteines, a central section that is probably in an -helical conformation, and a C-terminal section that contains two EF-hand type calcium-binding regions [MEDLINE:96133731] and three conserved cysteines. This topology is schematically represented below.

\ +----+\ | |\ xCxCxCxxCCxCxxxCxxCxCxxxxxCxCxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx(Ca)xCxxC(Ca)Cxx\ \ C: conserved cysteines involved in disulfide bonds.\ Ca: EF-hand region (see IPR002048).\

\ \ \N \N \N 20668 IPR002000

Lysosome-associated membrane glycoproteins (lamp) [MEDLINE:92042016] are integral membrane proteins, specific to lysosomes, and whose exact biological function is not yet clear. Structurally, the lamp proteins consist of two internally homologous lysosome-luminal domains separated by a proline-rich hinge region; at the C-terminal extremity there is a transmembrane region (TM) followed by a very short cytoplasmic tail (C). In each of the duplicated domains, there are two conserved disulfide bonds. This structure is schematically represented in the figure below.

\
   +-----+            +-----+         +-----+            +-----+\
   |     |            |     |         |     |            |     |\
  xCxxxxxCxxxxxxxxxxxxCxxxxxCxxxxxxxxxCxxxxxCxxxxxxxxxxxxCxxxxxCxxxxxxxx\
  +--------------------------++Hinge++--------------------------++TM++C+\

In mammals, there are two closely related types of lamp: lamp-1 and lamp-2. In chicken lamp-1 is known as LEP100.

\ \

CD69 (also called gp110 or macrosialin) [MEDLINE:93252841] is a heavily glycosylated integral membrane protein whose structure consists of a mucin-like domain followed by a proline-rich hinge; a single lamp-like domain; a transmembrane region and a short cytoplasmic tail.

\ \

CD molecules are leucocyte antigens on cell surfaces. CD antigens nomenclature is updated at http://www.ncbi.nlm.nih.gov/PROW/guide/45277084.htm \

\ \ \ \N membrane ; GO:0016020 \N 20669 IPR002001

Insect diuretic hormones regulate fluid and ion secretion, and the receptors\ with which they interact are attractive targets for new insect control\ agents [MEDLINE:96189577]. Diuretic hormone receptors from the moth, Manduca sexta, and the\ house cricket, Acheta domesticus, share 53% sequence identity and have been\ shown to be members of the secretin-like family of GPCRs [MEDLINE:94103310]. The receptors\ bind diuretic hormone with high affinity and stimulate adenylate cyclase\ with high potency.

\ \ diuretic hormone receptor activity ; GO:0008036 membrane ; GO:0016020 \N 20670 IPR002002

The insect octopamine receptor mediates the attenuation of adenylate cyclase\ activity. Sequence and pharmacological comparisons indicate that the\ octopamine receptor is unique, but closely related to mammalian adrenergic\ receptors, perhaps as an evolutionary precursor [MEDLINE:90198291], [MEDLINE:91006061].

\ \ octopamine receptor activity ; GO:0004989 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20658 IPR001989 In Escherichia coli and related bacteria, the pflA protein (or act) [MEDLINE:89030680] is involved (EC: 1.97.1.4) in the activation of pyruvate formate-lyase (gene pflB) under anaerobic conditions by generation of an organic free radical, using S-adenosylmethionine and reduced flavodoxin as cosubstrates to produce 5'-deoxy-adenosine. The activity of pflA is iron-dependent. A protein highly similar to pflA and termed pflC [MEDLINE:95291446] is probably involved in the activation of a second pyruvate format lyase (gene pflD). The pflA/pflC proteins belong to a family that also includes phage T4 and Escherichia coli nrdG which are involved [MEDLINE:95155298] in the generation of the free radical for the anaerobic ribonucleoside-triphosphate reductase (gene nrdD or sunY). It also includes Escherichia coli hypothetical protein yjjW, Haemophilus influenzae hypothetical protein HI0520 and Methanococcus jannaschii hypothetical protein MJ0021. All these proteins possess, in their N-terminal section, a highly conserved region which contains three clustered cysteines which could be involved in iron-binding.\ oxidoreductase activity ; GO:0016491 \N oxygen and reactive oxygen species metabolism ; GO:0006800 20664 IPR001996

The first domain (IIA) carries the first permease-specific phoshorylation site, a histidine, which is phosphorylated by phospho-HPr. The second domain (IIB) is phosphorylated by phospho-IIA on a cysteinyl or histidyl residue, depending on the permease. Finally, the phosphoryl group is transferred from the IIB domain to the sugar substrate in a process catalyzed by the IIC domain; this process is coupled to the transmembrane transport of the sugar.

\ \ sugar porter activity ; GO:0005351 membrane ; GO:0016020 phosphoenolpyruvate-dependent sugar phosphotransferase system ; GO:0009401 20659 IPR001990

Granins (chromogranins or secretogranins) [MEDLINE:91272289] are a family of acidic proteins present in the secretory granules of a wide variety of endocrine and neuro-endocrine cells. The exact function(s) of these proteins is not yet known but they seem to be the precursors of biologically active peptides and/or they may act as helper proteins in the packaging of peptide hormones and neuropeptides. Apart from their subcellular location and the abundance of acidic residues (Asp and Glu), these proteins do not share many structural similarities. Only one short region, located in the C-terminal section, is conserved in all these proteins.

Chromogranins and secretogranins together share a C-terminal motif, whereas chromogranins A and B share a region of high similarity in their N-terminal section; this region includes two cysteine residues involved in a disulfide bond.

\ \ \N \N \N 20660 IPR001991

It has been shown [MEDLINE:94304911] that integral membrane proteins that mediate the uptakeof a wide variety of molecules with the concomitant uptake of sodium ions\ (sodium symporters) can be grouped, on the basis of sequence and functional\ similarities into a number of distinct families. One of these families [MEDLINE:93066362] is\ known as the sodium:dicarboxylate symporter family (SDF).

\ \

Such re-uptake of neurotransmitters from the synapses, is thought to be an important mechanism for terminating their action, by removing these chemicals from the synaptic cleft, and transporting them into presynaptic nerve terminals, and surrounding neuroglia. this removal is also believed to prevent them accumulating to the point of reaching neurotoxic [MEDLINE:93078876], [MEDLINE:93078877].

\ \

The structure of these transporter proteins has been variously reported to\ contain from 8 to 10 transmembrane (TM) regions, although 10 now seems to\ be the accepted value.

\ \

Members of the family include: several mammalian excitatory amino acid transporters, and a number of bacterial transporters. They vary with regars to their dependence on transport of sodium, and other ions.

\ \ sodium:dicarboxylate/tricarboxylate symporter activity ; GO:0005311 membrane ; GO:0016020 dicarboxylic acid transport ; GO:0006835 20661 IPR001992 A number of bacterial proteins, some of which are involved in a general secretion pathway (GSP) for the export of proteins (also called the type II pathway) [MEDLINE:93174466], have been found to be evolutionary related. These are proteins of about 400 amino acids that are highly hydrophobic and which are thought to be integral protein of the inner membrane.\ \N membrane ; GO:0016020 protein secretion ; GO:0009306 20662 IPR001993 A variety of substrate carrier proteins that are involved in energy transfer are found in the inner mitochondrial membrane [MEDLINE:90223523], PUB00001076, PUB00001076, [MEDLINE:93253777], [MEDLINE:94265916], [MEDLINE:94120553]. Such proteins include:\ ADP,ATP carrier protein (ADP/ATP translocase); 2-oxoglutarate/malate carrier\ protein; phosphate carrier protein; tricarboxylate transport protein (or \ citrate transport protein); Graves disease carrier protein; yeast mito-\ chondrial proteins MRS3 and MRS4; yeast mitochondrial FAD carrier protein;\ and many others.\ \ binding activity ; GO:0005488 mitochondrial inner membrane ; GO:0005743 transport ; GO:0006810 20663 IPR001995

Aspartic proteinases (EC: 3.4.23.-) of vertebrate, fungal and retroviral origin have been characterised [MEDLINE:93088003].Aspartic proteases include pepsins, cathepsins, and renins.\ Most members of the pepsin family specifically cleave bonds in peptides that are at least six residues in length, with hydrophobic residues in both\ the P1 and P1' positions [MEDLINE:95405254]. Crystallography has shown the active site to form a groove across the junction of the two lobes, with an extended loop projecting over the cleft to form an 11-residue flap, which encloses substrates and inhibitors within the active site [MEDLINE:95405254]. Specificity is determined by several hydrophobic residues surrounding the catalytic asparagines, and by three residues in the flap.

Cysteine residues are well conserved within the pepsin family, pepsin itself containing three disulphide loops. The first loop is found in all but the fungal enzymes, and is usually around five residues in length, but is longer in barrierpepsin and candidapepsin; the second loop is also small and found only in the animal enzymes; and the third loop is the largest, found in all members of the family, except for the cysteine-free polyporopepsin . The loops are spread unequally throughout the two lobes, suggesting that they formed after the initial gene duplication and fusion event [MEDLINE:95405254].

This family includes the single domain aspartic proteases from retroviruses, retrotransposons, and badnaviruses (plant dsDNA viruses).

Retroviral apartyl protease is synthesised as part of the POL polyprotein that contains; an aspartyl protease, a reverse transcriptase, RNase H and integrase. POL polyprotein undergoes specific enzymatic cleavage to yield the mature proteins.

\ \ aspartic-type endopeptidase activity ; GO:0004190 \N proteolysis and peptidolysis ; GO:0006508 20655 IPR001985

S-adenosylmethionine decarboxylase (EC: 4.1.1.50) (AdoMetDC) [MEDLINE:99306040] catalyzes the removal of the carboxylate group of S-adenosylmethionine to form S-adenosyl-5'-3-methylpropylamine which then acts as the n-propylamine group donor in the synthesis of the polyamines spermidine and spermine from putrescine.

The catalytic mechanism of AdoMetDC involves a covalently-bound pyruvoyl group. This group is post-translationally generated by a self-catalyzed intramolecular proteolytic cleavage reaction between a glutamate and a serine. This cleavage generates two chains, (N-terminal) and (C-terminal). The N-terminal serine residue of the chain is then converted by nonhydrolytic serinolysis into a pyruvyol group.

\ \ adenosylmethionine decarboxylase activity ; GO:0004014 \N spermidine biosynthesis ; GO:0008295 20656 IPR001986

EPSP synthase (3-phosphoshikimate 1-carboxyvinyltransferase) (EC: 2.5.1.19) catalyzes the sixth step in the biosynthesis from chorismate of the aromatic amino acids (the shikimate pathway) in bacteria (gene aroA), plants and fungi (where it is part of a multifunctional enzyme which catalyzes five consecutive steps in this pathway) PUB00004745. EPSP synthase has been extensively studied as it is the target of the potent herbicide glyphosate which inhibits the enzyme.

The sequence of EPSP from various biological sources shows that the structure of the enzyme has been well conserved throughout evolution. Two strongly conserved regions are well defined. The first one corresponds to a region that is part of the active site and which is also important for the resistance to glyphosate PUB00004745. The second second one is located in the C-terminal part of the protein and contains a conserved lysine which seems to be important for the activity of the enzyme.

\ \ \N \N \N 20651 IPR001981 Colipase is a small protein cofactor needed by pancreatic lipase for efficient dietary lipid hydrolyisis. Efficient absorption of dietary fats is dependent on the action of pancreatic triglyceride lipase. Colipase binds to the C-terminal, non-catalytic domain of lipase, thereby stabilising as active conformation and considerably increasing the overall hydrophobic binding site. Structural studies of the complex and of colipase alone have revealed the functionality of its architecture [MEDLINE:97382932], [MEDLINE:20039906].

Colipase is a small protein with five conserved disulfide bonds. Structural analogies have been recognised between a developmental protein (Dickkopf), the pancreatic lipase C-terminal domain, the N-terminal domains of lipoxygenases and the C-terminal domain of -toxin. These non-catalytic domains in the latter enzymes are important for interaction with membrane. It has not been established if these domains are also involved in eventual protein cofactor binding as is the case for pancreatic lipase [MEDLINE:20039906].

\ \ enzyme activator activity ; GO:0008047 extracellular ; GO:0005576 lipid catabolism ; GO:0016042 20652 IPR001982 The LAGLIDADG and HNH domains of site-specific DNA endonucleases encoded by viruses, bacteriophages as well as archaeal, eukaryotic nuclear and organellar genomes are characterized by the sequence motifs 'LAGLIDADG' and 'HNH', respectively [MEDLINE:97331323], [MEDLINE:97402526]. Phylogenetic analysis of the two domains indicates a lack of exchange of endonucleases between different mobile elements (environments) and between hosts from different phylogenetic kingdoms. However, there does appear to have been considerable exchange of endonuclease domains amongst elements of the same type. Such events are suggested to be important for the formation of elements of new specficity [MEDLINE:98026854].

'Homing' is the lateral transfer of an intervening genetic sequence, either an intron or an intein, to a cognate allele that lacks that element. The end result of homing is the duplication of the intervening sequence. The process is initiated by site-specific endonucleases that are encoded by open reading frames within the mobile elements. These endonucleases may be contrasted with a variety of enzymes involved in nucleic acid strand breakage and rearrangement, particularly restriction endonucleases. They are encoded within\ the intervening sequence and there are interesting limitations on the position and length of their open reading frames, and therefore on their structures. These enzymes display a unique strategy of flexible recognition of very long DNA target sites. This strategy allows these sequences to minimize nonspecific cleavage within the host genome, while maximizing the ability of the endonuclease to cleave closely related variants of the homing site [MEDLINE:99415130].

\ \ endonuclease activity ; GO:0004519 \N intron homing ; GO:0006314 20653 IPR001983

Mammalian translationally controlled tumor protein (TCTP) (or P23) is a protein which has been found to be preferentially synthesized in cells during the early growth phase of some types of tumor [MEDLINE:90056510], [MEDLINE:88189840], but which is also expressed in normal cells. The physiological function of TCTP is still not known. It was first identified as a histamine-releasing factor, acting in IgE +-\ dependent allergic reactions. In addition, TCTP has been shown to bind to\ tubulin in the cytoskeleton, has a high affinity for calcium, is the binding\ target for the antimalarial compound artemisinin, and is induced in vitamin\ D-dependent apoptosis. TCTP production is thought to be controlled at the\ translational as well as the transcriptional level [MEDLINE:20408860].

TCTP is a hydrophilic protein of 18 to 20 Kd. TCTPs do not share significant sequence similarity with any other class of\ proteins. Recently, the structure of TCTP was determined and exhibited\ significant structural similarity to the human protein Mss4, which is a\ guanine nucleotide-free chaperone of the Rab protein [MEDLINE:21366089]. Close homologs have been found in plants [MEDLINE:92322983], earthworm [MEDLINE:98322115], Caenorhabditis elegans (F52H2.11), Hydra, Saccharomyces cerevisiae (YKL056c) [MEDLINE:94378723] and Schizosaccharomyces pombe (SpAC1F12.02c).

\ \ molecular_function unknown ; GO:0005554 cytoplasm ; GO:0005737 \N 20657 IPR001988 Caulimoviruses are encapsidated plant viruses that contain circular double-stranded DNA [MEDLINE:87295496]. Members of the group include cauliflower mosaic virus\ \ \ [MEDLINE:81001865], carnation etched ring virus\ \ \ \ PUB00001147, figwort mosaic virus\ \ \ \ PUB00001147 and soybean chlorotic mottle virus\ \ \ \ [MEDLINE:90098857]. The viral coat proteins are quite similar, containing a fairly hydrophilic N-terminal region and a highly-basic C-terminal domain, which may be involved in DNA-binding. The sequences contain the motif CxxCxxxHxxxC, which is similarly found in the nucleic acid binding protein of retroviruses [MEDLINE:87295496].\ \ structural molecule activity ; GO:0005198 viral capsid ; GO:0019028 \N 20654 IPR001984

\ \

Endopeptidase La (Lon) proteins belong to the S16 family of the ATP-dependent\ endopeptidase SF clan [MEDLINE:95147689], see protease database http://merops.sanger.ac.uk/merops.htm]. The active site contains a conserved serine\ residue, by contrast with the active site of the only other clan member,\ ClpP endopeptidase (S16), which contains catalytic serine and histidine\ residues [MEDLINE:95147689]. There are no sequence similarities around the active sites of\ these two clan members [MEDLINE:95147689].

\ \

Lon (La) protease was the first ATP-dependent protease to be purified from\ Escherichia coli\ \ \ \ [MEDLINE:98087697], [MEDLINE:88298842], [MEDLINE:94124005], [MEDLINE:94043004]. The enzyme is a homotetramer of 87kDa subunits, with one\ proteolytic and one ATP-binding site per monomer, making it structurally\ less complex than other known ATP-dependent proteases [MEDLINE:88298842]. Despite this\ relative structural simplicity, Lon recognises its substrates directly,\ without delegating the task of substrate recognition to other enzymes [MEDLINE:88298842].\ By contrast, ClpP endopeptidases are multimeric assemblies of two different\ types of subunit, one of which has ATPase activity, and the other has\ proteolytic activity [MEDLINE:98087697].

\ \ serine-type endopeptidase activity ; GO:0004252 \N proteolysis and peptidolysis ; GO:0006508 20645 IPR001975

\ \ \

This family contains the L40 ribosomal protein from both prokaryotes and eukaryotes. Bovine ribosomal protein L40 has been identified as a secondary RNA binding protein [MEDLINE:88203200]. L40 is fused to a ubiquitin protein [MEDLINE:96011832].

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 20646 IPR001976

\ \ \

This family contains the S24e ribosomal proteins from eukaryotes and archaebacteria. These proteins have 101 to 148 amino acids.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 20647 IPR001977

This family contains dephospho-CoA kinases (EC: 2.7.1.24), which catalyse the phosphorylation of the 3'-hydroxyl group of dephosphocoenzyme A to form Coenzyme A. This enzyme uses ATP in its reaction.

\ ATP binding activity ; GO:0005524 \N \N 20648 IPR001978 The troponin (Tn) complex regulates Ca²⁺ induced muscle contraction. Tn contains three subunits, Ca²⁺ binding (TnC), inhibitory (TnI), and tropomyosin binding (TnT). This family includes troponin T and troponin I. Troponin I binds to actin and troponin T binds to tropomyosin [MEDLINE:87144593], [MEDLINE:95155315], [MEDLINE:95324796].\ \N \N \N 20649 IPR001980

Temperature-sensitive mutants of Escherichia coli, defective in the transfer of 3-deoxy-D-manno-octulosonic acid (KDO) from CMP-KDO to a tetraacyldisaccharide 1,4'-bisphosphate precursor of lipid A, have been used to map KDO transferase activity on the E.coli chromosome [MEDLINE:91236744]. The KDO transferase gene, designated kdtA, was shown to code for a 43kDa polypeptide. Overexpression of this single gene product greatly stimulates incorporation of two stereochemically distinct KDO residues during lipopolysaccharide biosynthesis in extracts of E.coli [MEDLINE:91236744].

From these experiments this protein was thought to play a role in lipopolysaccharide biosynthesis, however now it is annotated as phosphopantetheine adenylyltransferase (EC: 2.7.7.3), which catalyses the reversible transfer of an adenylyl group from ATP to \ 4'-phosphopantetheine to give dephospho-CoA (DPCOA) and pyrophosphate in the fourth step of coenzyme A biosynthesis.

\ \ pantotheine-phosphate adenylyltransferase activity ; GO:0004595 \N coenzyme A biosynthesis ; GO:0015937 20650 IPR001981 Colipase is a small protein cofactor needed by pancreatic lipase for efficient dietary lipid hydrolyisis. Efficient absorption of dietary fats is dependent on the action of pancreatic triglyceride lipase. Colipase binds to the C-terminal, non-catalytic domain of lipase, thereby stabilising as active conformation and considerably increasing the overall hydrophobic binding site. Structural studies of the complex and of colipase alone have revealed the functionality of its architecture [MEDLINE:97382932], [MEDLINE:20039906].

\ \ enzyme activator activity ; GO:0008047 extracellular ; GO:0005576 lipid catabolism ; GO:0016042 20643 IPR001972

Synonym(s): Erythrocyte membrane protein band 7.2b

Stomatin is a 31 kDa membrane protein [MEDLINE:97292616]. It was named after the rare human disease, haemolytic anaemia hereditary stomatocytosis. The protein contains a single hydrophobic domain, close to the N-terminus, and is phosphorylated [MEDLINE:97292616].

Stomatin is believed to be involved in regulating monovalent cation transport through lipid membranes. Absence of the protein in hereditary stomatocytosis is believed to be the reason for the leakage of Na⁺ and K⁺ ions into and from erythrocytes [MEDLINE:97292616].

A second function of stomatin is to act as a cytoskeletal anchor. One possible example of this is its interaction with some anti-malarial drugs. Current opinion speculates that such drugs bind to high density lipoproteins in serum. The lipoproteins are delivered to erythrocytes, where it is believed they Interact with stomatin as a means of transfer to the intracellular parasite, via a pathway used for the uptake of exogenous phospholipid [MEDLINE:97244184].

Stomatin-like proteins have been identified in various organisms, including Caenorhabditis elegans and Mus musculus.

\ \ \N membrane ; GO:0016020 \N 20644 IPR001973

Purinoceptors have been classified as P1 or P2, depending on their\ preference for adenosine or adenine nucleotides respectively. Adenosine\ receptors (P1 purinoceptors) are characterised by their affinity for\ adenosine and by the ability of methylxanthines to act as antagonists PUB00005868.\ Adenosine has very low affinity for P2 purinoceptors.

With the recent discovery of several new members from a variety of species,\ the P2Y purinoceptor family now encompasses types P2Y1 to P2Y6 PUB00005868. P2Y2 and\ P2Y6 map to within less than 4cM on chromosome 11q13.5, and constitute the\ first described chromosomal clustering of this gene family [MEDLINE:97432828]. Phylogenetic\ analysis of the P2Y purinoceptor family demonstrates the presence of five\ evolutionary branches and suggests the occurrence of an ancient gene\ duplication event [MEDLINE:97432828].

cDNA encoding the P2Y6 receptor has been isolated and functionally\ characterised [MEDLINE:96064682]. The receptor shows 44 and 38% amino acid identity with\ rat P2U and chicken P2Y receptors respectively [MEDLINE:96064682]. P2Y6 is functionally\ coupled to phospholipase C but not to adenylate cyclase in C6 rat glioma\ cells transfected with the cloned P2 expression vector [MEDLINE:96064682]. P2Y6 mRNA is\ abundantly expressed in various rat tissues, including lung, stomach,\ intestine, spleen, mesentery, heart, and, most prominently, aorta [MEDLINE:96064682]. The\ receptor has pharmacological characteristics distinct from any P2 receptor\ subtype thus far identified and suggests the existence of a novel regulatory\ system by extracellular nucleotides [MEDLINE:96064682].

\ \ purinergic nucleotide receptor activity, G-protein coupled ; GO:0045028 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20641 IPR001970

\ \ \

NHE1 is found in virtually all tissues and cells, where it most likely\ fulfils 'housekeeping' functions, including the maintenance of cytosolic pH\ and of cellular volume. In epithelial cells, it is largely restricted to the\ basolateral membrane, which specific subcellular localisation is thought to\ be important to the functioning of these epithelia.

\ \ ion channel activity ; GO:0005216 membrane ; GO:0016020 sodium ion transport ; GO:0006814 20642 IPR001971

\ \ \ Ribosomal protein S11 [MEDLINE:89052875] plays an essential role in selecting the correct tRNA in protein biosynthesis. It is located on the large lobe of the small ribosomal subunit. On the basis of sequence similarities, S11 belongs to a family of eubacterial, archaebacterial and eukaryotic ribosomal proteins PUB00005070.\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 20638 IPR001967

Family S11 (D-Ala-D-Ala carboxypeptidase) is a bacterial serine protease. Proteolytic enzymes that exploit serine in their catalytic activity are ubiquitous, being found in viruses, bacteria and eukaryotes [MEDLINE:95147689]. They include a wide range of peptidase activity, including exopeptidase, endo-peptidase, oligopeptidase and omega-peptidase activity. Over 20 families (denoted S1 - S27) of serine protease have been identified, these being grouped into 6 clans (SA, SB, SC, SE, SF and SG) on the basis of structural similarity and other functional evidence. Structures are known for four of the clans (SA, SB, SC and SE): these appear to be totally unrelated, suggesting at least four evolutionary origins of serine peptidases and possibly many more [MEDLINE:95147689].

Not with standing their different evolutionary origins, there are similarities in the reaction mechanisms of several peptidases. Chymotrypsin, subtilisin and carboxypeptidase C clans have a catalytic triad of serine, aspartate and histidine in common: serine acts as a nucleophile, aspartate as an electrophile, and histidine as a base [MEDLINE:95147689]. The geometric orientations of the catalytic residues are similar between families, despite different protein folds. The linear arrangements of the catalytic residues commonly reflect clan relationships. For example the catalytic triad in the chymotrypsin clan (SA) is ordered HDS, but is ordered DHS in the subtilisin clan (SB) and SDH in the carboxypeptidase clan (SC) [MEDLINE:95147689], [MEDLINE:93176119].

Bacterial cell walls are complex structures containing amino acids and amino sugars, with alternating chains of N-acetylglucosamine and N-acetyl-muramic acid units linked by short peptides [MEDLINE:95147689]: the link peptide in Escherichia coli is L-alanyl-D-isoglutamyl-L-meso-diaminopimelyl-D-alanine. The chains are usually cross-linked between the carboxyl of D-alanine and the free amino group of diaminopimelate. During the synthesis of peptidoglycan, the precursor has the described tetramer sequence with an added C-terminal D-alanine [MEDLINE:95147689].

D-Ala-D-Ala carboxypeptidase is involved in the metabolism of cell components [MEDLINE:92074811]; it is synthesised with a leader peptide to target it to the cell membrane [MEDLINE:95147689]. After cleavage of the leader peptide, the enzyme is retained in the membrane by a C-terminal anchor. There are three families of serine-type D-Ala-D-Ala peptidase, which are also known as low molecular weight penicillin-binding proteins.

Family S11 contains only D-Ala-D-Ala peptidases, unlike families S12 and S13, which contain other enzymes, such as class C -lactamases and D-amino-peptidases [MEDLINE:95147689]. Although these enzymes are serine proteases, some members of family S11 are partially inhibited by thiol-blocking agents [MEDLINE:92028812].

\ \ serine carboxypeptidase activity ; GO:0004185 \N proteolysis and peptidolysis ; GO:0006508 20640 IPR001969

\ \ aspartic-type endopeptidase activity ; GO:0004190 \N proteolysis and peptidolysis ; GO:0006508 20639 IPR001968

Glycoside hydrolase family 56 CAZY:GH_56).

\ \

The venom of honeybees contains several biologically-active peptides and\ two enzymes, one of which is a hyaluronidase [MEDLINE:93234539]. The amino acid sequence\ of bee venom hyaluronidase contains 349 amino acids, and includes four\ cysteines and a number of potential glycosylation sites [MEDLINE:93234539]. The sequence\ shows a high degree of similarity to PH-20, a membrane protein of mammalian\ sperm involved in sperm-egg adhesion, supporting the view that hyaluronidases\ play a role in fertilisation [MEDLINE:93234539].

PH-20 is required for sperm adhesion to the egg zona pellucida; it is\ located on both the sperm plasma membrane and acrosomal membrane [MEDLINE:91100409]. The\ amino acid sequence of the mature protein contains 468 amino acids, and\ includes six potential N-linked glycosylation sites and twelve cysteines,\ eight of which are tightly clustered near the C-terminus [MEDLINE:91100409].

\ \ hyaluronoglucosaminidase activity ; GO:0004415 \N carbohydrate metabolism ; GO:0005975 20633 IPR001962 This domain is always found associated with (IPR000583) catalyzes the assembly of asparagine from aspartate, Mg(2+)ATP, and glutamine.The three-dimensional architecture of the N-terminal domain of asparagine synthetase B is similar to that observed for glutamine phosphoribosylpyrophosphate amidotransferase while the molecular motif of the C-domain is reminiscent to that observed for GMP synthetase [MEDLINE:20056034].\ \ asparagine synthase (glutamine-hydrolyzing) activity ; GO:0004066 \N asparagine biosynthesis ; GO:0006529 20634 IPR001963 Glycoprotein VP7, also known as outer shell glycoprotein, is a serotype-specific antigen, and is the major neutralisation antigen. It is found in the dsRNA rotaviruses.\ \N \N \N 20635 IPR001964 The nucleotide sequence of the RNA of potato leafroll luteovirus (PLRV) has been determined [MEDLINE:89171329], [MEDLINE:89279282]. The sequence contains six large ORFs. The 3' coding region encodes three polypeptides: a 23K coat protein, a 17K polypeptide encoded in a different frame, and a 53K polypeptide, immediately following the coat protein sequence in the same frame. It has been suggested that the 53K polypeptide is translated by readthrough of the amber termination codon of the coat protein gene. The amino acid sequences encoded within the 3' region show many similarities to analogous polypeptides of barley yellow dwarf virus, PAV strain (BYDV), and beet western yellows virus (BWYV). It is possible that the ORF5 protein is a VPG-precursor from which, at the onset of RNA synthesis, the VPG molecule is released, in a similar fashion to that proposed for cowpea mosaic virus.\ \N \N \N 20636 IPR001965

The plant homeodomain (PHD) finger [MEDLINE:95216093],PUB00005675 is a C4HC3 zinc-finger-like motif found in nuclear proteins thought to be involved in chromatin-mediated transcriptional regulation. The PHD finger motif is reminiscent of, but distinct from the C3HC4 type RING finger.

The function of this domain is not yet known but in analogy with the LIM domain it could be involved in protein-protein interaction and be important for the assembly or activity of multicomponent complexes involved in transcriptional activation or repression. Alternatively, the interactions could be intra-molecular and be important in maintaining the structural integrity of the protein. In similarity to the RING finger and the LIM domain, the PHD finger is thought to bind two zinc ions.

\ \ DNA binding activity ; GO:0003677 \N regulation of transcription, DNA-dependent ; GO:0006355 20637 IPR001966

Bombesins are peptide neurotransmitters whose biological activity resides\ in a common C-terminal sequence, WAXGHXM PUB00005871. In the periphery, bombesin-related peptides stimulate smooth muscle and glandular secretion. In the\ brain, these peptides are believed to play a role in homeostasis, thermoregulation and metabolism, and have been reported to elicit analgesia and\ excessive grooming, together with central regulation of a variety of\ peripheral effects.

Mammalian bombesins are encoded by 2 genes. The preproGRP gene transcript\ encodes a precursor of 147 amino acids, which gives GRP and GRP18-27. The\ preproNMB gene transcript encodes a precursor of 117 amino acids, which is\ metabolised to neuromedin B. Receptors for these peptides have widespread\ distribution in peripheral tissue. High levels are found in smooth muscle\ and in the brain.

The gastrin-releasing peptide receptor has a wide distribution in peripheral\ tissue. High levels are found in smooth muscle (e.g., intestine, stomach\ and bladder) and in secretory glands (e.g., pancreas). In the brain, it is\ found in high levels in the hypothalamus, and is present in other areas in\ lower levels (e.g., the olfactory tract, dendate gyrus and cortex). It\ is also found in various cell lines (e.g., Swiss 3T3 fibroblasts and small-cell lung carcinomas). GRP receptors activate the phosphoinositide\ pathway via a pertussis-toxin-insensitive G-protein, probably of the Gq/G11\ class PUB00005871.

\ \ bombesin receptor activity ; GO:0004946 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20631 IPR001959 Probable transposase family which is found in a number of uncharacterised bacterial proteins. A novel insertion sequence (IS)-like element of the thermophilic bacterium PS3 that promotes expression of the\ alanine carrier protein-encoding gene [MEDLINE:96001252] belongs to this family.\ \ \N \N \N 20632 IPR001960

The WASP family proteins are closely associated with cytoskeletal regulation and are believed to regulate actin assembly downstream of the cdc42 and phosphatidylinositol bisphosphate signalling pathways. Their N-terminal WH1 domains bind proline rich sequences in the WASP interacting protein [MEDLINE:21909373].

WASP is the protein that is defective in Wiskott-Aldrich syndrome (WAS)[MEDLINE:96193767]. The majority of point mutations occur within the amino-terminal WH1 domain. The metabotropic glutamate receptors mGluR1alpha and mGluR5 bind a protein called homer, which is a WH1 domain homologue [MEDLINE:97459929], [MEDLINE:98088883]

\ \ \N \N \N 20630 IPR001958 The transposon Tn10-encoded tetracycline resistance (Tcr) protein functions as a metal-tetracycline/H⁺ antiporter [MEDLINE:90368755], [MEDLINE:84109550]. The nucleotide sequence of the Tn10 tetA gene, which alone is sufficient to confer tetracycline resistance, has been determined [MEDLINE:84109550]. The sequence similarity between the Tn10 tetA gene and the pBR322 Tcr determinant indicates that these phenotypically distinct Tcr determinants must have evolved from a common ancestral sequence [MEDLINE:84109550]. The markedly hydrophobic character of the predicted amino acid sequences of the Tn10 tetA and pBR322 tet-coded proteins suggests that a substantial portion of these proteins may be embedded within the cytoplasmic membrane [MEDLINE:84109550]. The Ser65-Asp66 dipeptide is conserved in all known tetracycline antiporter proteins. Site-directed mutagenesis studies have shown that a negative charge at position 66 is essential for tetracycline transport [MEDLINE:90368755], and that the region that includes the dipeptide plays an important role in metal-tetracycline transport; it perhaps acts as a gate that opens on the charge-charge interaction between Asp66 and the metal-tetracycline.\ tetracycline:hydrogen antiporter activity ; GO:0015520 integral to membrane ; GO:0016021 tetracycline transport ; GO:0015904 20629 IPR001957

The bacterial dnaA protein [MEDLINE:94153987], [MEDLINE:92140023], [MEDLINE:90117642] plays an important role in initiating and regulating chromosomal replication. DnaA is an ATP- and DNA-binding protein. It binds specifically to 9 bp nucleotide repeats known as dnaA boxes which are found in the chromosome origin of replication (oriC).

DnaA is a protein of about 50 kDa that contains two conserved regions: the first is located in the N-terminal half and corresponds to the ATP-binding domain, the second is located in the C-terminal half and could be involved in DNA-binding. The protein may also bind the RNA polymerase subunit, the dnaB and dnaZ proteins, and the groE gene products (chaperonins) [MEDLINE:91033012].

\ \ ATP binding activity ; GO:0005524 \N regulation of DNA replication ; GO:0006275 20626 IPR001954

Gluten is the protein component of wheat flour. It consists of numerous proteins, which are of 2 different types responsible for different physical properties of dough: the glutenins, which are primarily responsible for the elasticity, and the gliadins, which contribute to the extensibility. The glutenins themselves are of 2 different types, termed low and high [MEDLINE:86041882] molecular weight subunits. The latter have unusual structures: a central region contains multiple tandem repeats of blocks of amino acids, forming a loose helix based on reverse turns, and is flanked by globular regions, which can be cross-linked by disulphide bonds. The result is an elastic network in which the elasticity may derive from the cross-linking, the helical structure, or a combination of these [MEDLINE:89098419].

The gliadins are also of different types (e.g., / or gamma) and, like the glutenins, contain repetitive sequences [MEDLINE:85234522] that form loose helical structures, but are usually associated with more extensive non-repetitive regions, which are compact and globular [MEDLINE:86301876].

\ \ nutrient reservoir activity ; GO:0045735 \N \N 20627 IPR001955

Pancreatic hormone (PP) [MEDLINE:81052382] is a peptide synthesized in pancreatic islets of Langherhans, which acts as a regulator of pancreatic and gastrointestinal functions.

The hormone is produced as a larger propeptide, which is enzymatically cleaved to yield the mature active peptide: this is 36 amino acids in length [MEDLINE:87175708] and has an amidated C-terminus [MEDLINE:90092485]. The hormone has a globular structure, residues 2-8 forming a left-handed poly-proline-II-like helix, residues 9-13 a turn, and 14-32 an -helix,held close to the first helix by hydrophobic interactions [MEDLINE:87175708]. Unlike glucagon, another peptide hormone, the structure of pancreatic peptide is preserved in aqueous solution [MEDLINE:91296574]. Both N- and C-termini are required for activity: receptor binding and activation functions may reside in the N- and C-termini respectively [MEDLINE:87175708].

\ \ \ hormone activity ; GO:0005179 extracellular ; GO:0005576 \N 20625 IPR001953

\ \

NHE2, which shares around 50% amino acid identity with NHE1, has a limited\ expression pattern, being found preferentially in the gastrointestinal tract\ and the kidney. It is also much less sensitive to the inhibitory diuretic\ amiloride than the more ubiquitous NHE1. The targeting of NHE2 in polarised\ epithelial cells is controversial, some studies reporting basolateral, and\ others reporting apical localisation. When transfected into mutagenised\ cells devoid of endogenous NHE activity, NHE2 is capable of regulating pH,\ cellular volume, and proliferation, in a manner similar to NHE1.

\ \ ion channel activity ; GO:0005216 membrane ; GO:0016020 sodium ion transport ; GO:0006814 20628 IPR001956

This domain is involved in cellulose binding [MEDLINE:93146373] and is foundassociated with a wide range of bacterial glycosyl hydrolases. The structure for\ this domain is known [MEDLINE:97076134]; it forms a sandwich.

\ \ \N \N carbohydrate metabolism ; GO:0005975 20622 IPR001950 In budding yeast (Saccharomyces cerevisiae), SUI1 is a translation initiation factor that functions in concert with eIF-2 and the initiator tRNA-Met in directing the ribosome to the proper start site of translation [MEDLINE:92107175]. SUI1 is a protein of 108 residues. Close homologs of SUI1 have been found [MEDLINE:94121644] in mammals, insects and plants. SUI1 is also evolutionary related to hypothetical proteins from Escherichia coli (yciH), Haemophilus influenzae (HI1225) and Methanococcus vannielii.\ translation initiation factor activity ; GO:0003743 \N translational initiation ; GO:0006413 20623 IPR001951 Histone H4 is one of the four histones, along with H2A, H2B and H3, which forms the eukaryotic nucleosome core. Along with H3, it plays a central role in nucleosome formation. The sequence of histone H4 has remained almost invariant in more then 2 billion years of evolution [MEDLINE:94167243], [MEDLINE:82245291], [MEDLINE:88122601].\ DNA binding activity ; GO:0003677 nucleus ; GO:0005634 chromosome organization and biogenesis (sensu Eukarya) ; GO:0007001 20624 IPR001952

Alkaline phosphatase (EC: 3.1.3.1) (ALP) [MEDLINE:90336967] is a zinc and magnesium-containing metalloenzyme which hydrolyzes phosphate esters, optimally at high pH. It is found in nearly all living organisms, with the exception of some plants. In Escherichia coli, ALP (gene phoA) is found in the periplasmic space. In yeast it (gene PHO8) is found in lysosome-like vacuoles and in mammals, it is a glycoprotein attached to the membrane by a GPI-anchor.

In streptomyces species alkaline phosphatase is involved in the synthesis of streptomycin (SM), an antibiotic, express a phosphatase (EC: 3.1.3.39) (gene strK) which is highly related to ALP. It specifically cleaves both streptomycin-6-phosphate and, more slowly, streptomycin-3''-phosphate [MEDLINE:91375432].

In mammals, four different isozymes are currently known [MEDLINE:91139124]. Three of them are tissue-specific: the placental, placental-like (germ cell) and intestinal isozymes. The fourth form is tissue non-specific and was previously known as the liver/bone/kidney isozyme.

Alkaline phosphatase exists as a dimer, each monomer binding 2 zinc atoms and one magnesium atom, which are essential for enzymic activity, and folds into a 10-stranded -sheet structure [MEDLINE:91093215].

\ \ \N \N metabolism ; GO:0008152 20621 IPR001949 Respiratory-chain NADH dehydrogenase (EC: 1.6.5.3) PUB00001096, PUB00001096 (also known as complex I or NADH-ubiquinone oxidoreductase) is an oligomeric enzymatic complex located in the inner mitochondrial membrane which also seems to exist in the chloroplast and in cyanobacteria (as a NADH-plastoquinone oxidoreductase). Among the 25 to 30 polypeptide subunits of this bioenergetic enzyme complex there is one with a molecular weight of 51 kDa (in mammals), which is the second largest subunit of complex I and is a component of the iron-sulfur (IP) fragment of the enzyme. It seems to bind to NAD, FMN, and a 2Fe-2S cluster. The 51 kDa subunit and the bacterial hydrogenase

subunit contain three regions of sequence similarities. The first one most probably corresponds to the NAD-binding site, the second to the FMN-binding site, and the third one, which contains three cysteines, to the iron-sulfur binding region.\ NADH dehydrogenase (ubiquinone) activity ; GO:0008137 \N oxidative phosphorylation, NADH to ubiquinone ; GO:0006120 20619 IPR001947

Scorpion venoms contain a variety of peptides toxic to mammals, insects and crustaceans. Among these peptides there is a family of short toxins (30 to 40 residues) [MEDLINE:95091651], [MEDLINE:95118979] including charybdotoxin, kaliotoxin [MEDLINE:92112881], noxiustoxin PUB00006076 and iberiotoxin PUB00006076, [MEDLINE:92399426]. Charybdotoxin consists of a single polypeptide chain and is a potent, selective inhibitor of calcium-activated potassium channels in pituitary and aortic smooth muscle cells - the toxin reversibly blocks channel activity by interacting at the external pore of the channel protein[MEDLINE:88217894].

The tertiary structure of the toxins comprises a 3-stranded -sheet and a short helix, and is stabilised by a number of disulphide bridges [MEDLINE:92399426] as shown in the following schematic representation:\

\ +---------------------+\ | |\ | |\ xxxxxxxCxxxxxCxxxCxxxxxxxxxxxCxxxxCxCxxx\ | | | |\ | +----------------+ |\ +----------------------+\ \ 'C': conserved cysteine involved in a disulfide bond.\

\ \ toxin activity ; GO:0015070 \N pathogenesis ; GO:0009405 20620 IPR001948

Metalloproteases can be split into five clans, and futher sub-divided into families, on the basis of their metal binding residues.

Aminopeptidase I is a metallopeptidase that belongs to the M18 protease\ family, which is part of the MH clan [MEDLINE:95405261], see protease Database http://merops.sanger.ac.uk/merops.htm]. Proteins of this clan have two\ catalytic zinc ions at the active site, bound by His/Asp, Asp, Glu, Asp/Glu\ and His. The catalysed reaction involves the release of an N-terminal aminoacid,\ usually neutral or hydrophobic, from a polypeptide.

\ \

The yeast sequence has been deduced, and the mature protein shown to consist\ of 469 amino acids [MEDLINE:89214116]. A 45-residue presequence contains both\ positively- and negatively-charged and hydrophobic residues, which could be arranged\ in an N-terminal amphiphilic -helix [MEDLINE:89214116]. The presequence differs from\ signal sequences that direct proteins across bacterial plasma membranes and\ endoplasmic reticulum or into mitochondria. It is unclear how this unique\ presequence targets aminopeptidase I to yeast vacuoles, and how this\ sorting utilises classical protein secretory pathways [MEDLINE:89214116].

\ \ aminopeptidase I activity ; GO:0004250 vacuole ; GO:0005773 proteolysis and peptidolysis ; GO:0006508 20616 IPR001944

Glycoside hydrolase family 35 CAZY:GH_35).

\ \

Mammalian -galactosidase is a lysosomal enzyme (gene GLB1) which cleaves the terminal galactose from gangliosides, glycoproteins, and glycosaminoglycans and whose deficiency is the cause of the genetic disease Gm(1) gangliosidosis (Morquio disease type B).

\ \ beta-galactosidase activity ; GO:0004565 beta-galactosidase complex ; GO:0009341 carbohydrate metabolism ; GO:0005975 20617 IPR001945

Defects in DNA repair proteins can give rise, in humans, to the autosomal recessive disorders xeroderma pigmentosum (XP) and Cockayne's syndrome [MEDLINE:94212451], [MEDLINE:93247645]. XP is characterised by a high incidence of sunlight-induced skin cancer, the effect of skin-cell hypersensitivity to UV resulting from defects in the nucleotide excision pathway. Seven XP complementation groups have been identified: XP-A to XP-G.

The XP group D gene product (XPD) is a helicase that is required for nucleotide excision repair, and is also one of the components of basal transcription factor TFIIH [MEDLINE:97255961], [MEDLINE:95004586]. DNA repair defects in the XPD group are associated with the clinical features of XP and trichothiodystrophy (TTD), which is characterised by sulphur-deficient brittle hair and a variety of other associated abnormalities, but no skin cancer [MEDLINE:95004586].

XPD belongs to a family of ATP-dependent helicases that are characterised by a 'D-E-A-H' motif [MEDLINE:92066492]. This resembles the 'D-E-A-D-box' of other known helicases, which represents a special version of the B motif of ATP-binding proteins. In XPD, His replaces the second Asp.

\ \ ATP binding activity ; GO:0005524 nucleus ; GO:0005634 nucleotide-excision repair ; GO:0006289 20618 IPR001946

A wide distribution of -2A receptor mRNA has been demonstrated by\ Northern analysis, high levels occurring in rat CNS (e.g., hippocampus,\ cerebral cortex, brainstem, pituitary gland and cerebellum), and in\ peripheral tissues (e.g., kidney, aorta, skeletal muscle, spleen and lung). The receptor inhibits adenylyl cyclase and L-type calcium channels,\ and activates potassium channels through pertussis-toxin-insensitive\ G-proteins belonging to the Gi/G0 class PUB00005869.

\ \ alpha2-adrenergic receptor activity ; GO:0004938 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20614 IPR001941 Pro-opiomelanocortin is present in high levels in the pituitary and is processed into 3 major peptide families: adrenocorticotrophin (ACTH);

- and gamma-melanocyte- stimulating hormones (MSH); and

-endorphin [MEDLINE:91093046] . ACTH regulates the synthesis and release of glucocorticoids and, to some extent, aldosterone in the adrenal cortex. It is synthesised and released in response to corticotrophin-releasing factor at times of stress (i.e. heat, cold, infection, etc.), its release leading to increased metabolism. The action of MSH in man is poorly understood, but it may be involved in temperature regulation [MEDLINE:91093046]. Full activity of ACTH resides in the first 20 N-terminal amino acids, the first 13 of which are identical to

-MSH [MEDLINE:91093046], [MEDLINE:88268753].\ hormone activity ; GO:0005179 extracellular ; GO:0005576 \N 20615 IPR001943 During the process of Escherichia coli nucleotide excision repair, DNA damagerecognition and processing are achieved by the action of the uvrA, uvrB,\ and uvrC gene products [MEDLINE:93221456]. UvrB and UvrC share a common domain of around 35\ amino acids, the so called UVR domain. This domain in UvrB can interact with\ the homologous domain in UvrC throughout a putative coiled coil structure.\ This interaction is important for the incision of the damaged strand [MEDLINE:96107206].\ \ nuclease activity ; GO:0004518 \N nucleotide-excision repair ; GO:0006289 20613 IPR001940

\ \

The Escherichia coli htrA gene product (or DegP protein) is essential for bacterial\ survival at temperatures above 42 degrees [MEDLINE:89057448], [MEDLINE:90202693] and for digesting misfolded protein in the periplasm. Mature DegP from E. coli has 448 residues, of which His105, Asp135, and Ser210 form the catalytic triad [MEDLINE:89057448]. The protein has an N-terminal sequence typical of a leader\ peptide. Structural analysis indicates that bacterial HtrA is a serine protease\ belonging to the family of cage-forming proteases and that only unfolded polypeptides can be threaded in\ extended conformation into the cage to access the proteolytic sites. Disulfide bonds of partially unfolded substrates impede protein breakdown and represent a conformational\ constraint for entering the inner cavity. This preference for unfolded polypeptides\ might be also a reason for the ATP-independent mode of action and for the increased proteolytic activity at\ higher temperatures [MEDLINE:22297619].

The HtrA family shares a modular architecture composed of an N-terminal segment believed to have regulatory\ functions, a conserved trypsin-like protease domain, and one or two PDZ domains which mediate specific protein-protein interactions and bind preferentially to the\ C-terminal three to four residues of the target protein. HtrA belongs to the trypsin clan SA. SA proteases have a two-domain structure with each domain forming a six-stranded \ barrel. The active site cleft is located at the interface of the two perpendicularly arranged barrel domains. The active site is constructed by several loops located at the\ C-terminal side of both barrel domains. The functional unit of HtrA appears to be a trimer, which is stabilized exclusively by residues of the protease\ domains. The basic trimer has a\ funnel-like shape with the protease domains located at its top and the PDZ domains (IPR001478) protruding to the outside. Once substrates have been bound, they have to be delivered\ into the interior of the funnel and the proteolytic sites. In contrast to other protease-chaperone systems, ATP\ does not drive binding and release of substrates [MEDLINE:22297619].

The degQ and degS genes of E.coli encode proteins of 455 and 355 residues\ that are homologues of the DegP protease [MEDLINE:96165272]. Purified DegQ protein has the\ properties of a serine endoprotease, and is processed by the removal of a\ 27-residue N-terminal signal sequence. Deletion studies suggest that DegQ,\ like DegP, functions as a periplasmic protease in vivo [MEDLINE:96165272].

\ \ \ serine-type endopeptidase activity ; GO:0004252 \N proteolysis and peptidolysis ; GO:0006508 20610 IPR001936

Ras proteins are membrane-associated molecular switches that bind GTP and GDP and slowly hydrolyze GTP to GDP [MEDLINE:91095015]. This intrinsic GTPase activity of ras is stimulated by a family of proteins collectively known as 'GAP' or GTPase-activating proteins [MEDLINE:91355280], [MEDLINE:95031997]. As it is the GTP bound form of ras which is active, these proteins are said to be down-regulators of ras.

The Ras GTPase-activating proteins are quite large (from 765 residues for sar1 to 3079 residues for IRA2) but share only a limited (about 250 residues) region of sequence similarity, referred to as the 'catalytic domain' or rasGAP domain.

Note: There are distinctly different GAPs for the rap and rho/rac subfamilies of ras-like proteins (reviewed in reference [MEDLINE:94081948]) that do not share sequence similarity with ras GAPs.

\ \ \N \N \N 20611 IPR001937

Galactose-1-phosphate uridyl transferase (EC: 2.7.7.10) (galT) catalyzes the transfer of an uridyldiphosphate group on galactose (or glucose) 1-phosphate. During the reaction, the uridyl moiety links to a histidine residue. In the Escherichia coli enzyme, it has been shown [MEDLINE:89016576] that two histidine residues separated by a single proline residue are essential for enzyme activity.

On the basis of sequence similarities, two apparently unrelated families seem to exist. Class-I enzymes are found in eukaryotes as well as some bacteria such as Escherichia coli or Streptomyces lividans, while class-II enzymes have been found so far only in bacteria such as Bacillus subtilis or Lactobacillus helveticus\ \ \ \ [MEDLINE:91294192].

\ \ UTP-hexose-1-phosphate uridylyltransferase activity ; GO:0003982 \N galactose metabolism ; GO:0006012 20612 IPR001938 Pathogenesis related (PR) proteins, which are induced by various agents ranging from ethylene to pathogens, are structurally diverse and apparently ubiquitous in plants\ \ \ [MEDLINE:93099273]: they include thaumatin, osmotin, tobacco major and minor PR proteins,

-amylase/trypsin inhibitor, and P21 and PWIR2 soybean and wheat leaf proteins. The proteins are involved in systematically acquired resistance and stress response in plants, although their precise role is unknown [MEDLINE:93099273]. Thaumatin is an intensely sweet tasting protein (about 100,000 times sweeter than sucrose [MEDLINE:82262799]) found in the West African shrub Thaumatococcus danielli: it is induced by attack by viroids, which are single-stranded unencapsulated RNA molecules that do not code for protein. Like other PR proteins, thaumatin is predicted to have a mainly

structure, with a high content of

-turns and little helix [MEDLINE:93099273].\ Tobacco cells exposed to gradually increased salt concentrations develop a greatly increased tolerance to salt, due to the expression of osmotin PUB00004573, a member of the PR protein family. Wheat plants attacked by barley powdery mildew express a PR protein (PWIR2), which results in resistance against that infection PUB00004573. The similarity between this and other PR proteins to the maize

-amylase/trypsin inhibitor has suggested that PR proteins may act as some form of inhibitor [MEDLINE:91322503].\ \ \N \N \N 20609 IPR001935 The calcitonin (CT) gene is alternatively expressed in a tissue-specific manner, producing either the calcium regulatory hormone CT in the thyroid, or the neuropeptide calcitonin gene related peptide (CGRP) in the brain [MEDLINE:85180007]. In medullary carcinoma of the thyroid, both peptides are produced [MEDLINE:85180007]. The calcitonin regulatory hormone is a peptide of 32 residues that causes a rapid but short-lived drop in calcium and phosphate levels in the blood by promoting the incorporation of these ions in the bones [MEDLINE:89076193]. The structure of salmon calcitonin has been studied by 2D NMR in SDS micelles [MEDLINE:92031485]. The main conformational feature of the hormone is an

-helix from residues 6-22, which includes an amphipathic segment. Two cysteine residues (at positions 1 and 7) form an N-terminal loop, and a C-terminal decapeptide forms a loop that folds back towards the helix [MEDLINE:92031485].\ hormone activity ; GO:0005179 extracellular ; GO:0005576 \N 20606 IPR001931

\ \ \

A number of eukaryotic ribosomal proteins can be grouped on the basis of\ sequence similarities. These proteins have 82 to 87 amino acids. The amino termini are all N -acetylated. The N-terminal halves of the protein molecules are highly conserved in contrast to the carboxy-terminal parts [MEDLINE:86104253].

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 20607 IPR001932

This domain is found in protein phosphatase 2C, as well as other proteins eg. pyruvate dehydrogenase (lipoamide)]-phosphatase (EC: 3.1.3.43) and adenylate cyclase (EC: 4.6.1.1).

Protein phosphatase 2C (PP2C) is one of the four major classes of mammalian\ serine/threonine specific protein phosphatases (EC: 3.1.3.16). PP2C [MEDLINE:92201367] is a\ monomeric enzyme of about 42 Kd which shows broad substrate specificity and\ is dependent on divalent cations (mainly manganese and magnesium) for its\ activity. Its exact physiological role is still unclear. Three isozymes are\ currently known in mammals: PP2C-, - and -gamma. In yeast, there are\ at least four PP2C homologs: phosphatase PTC1 [MEDLINE:93360976] which has weak tyrosine\ phosphatase activity in addition to its activity on serines, phosphatases PTC2\ and PTC3, and hypothetical protein YBR125c. Isozymes of PP2C are also known\ from Arabidopsis thaliana (ABI1, PPH1), Caenorhabditis elegans (FEM-2,\ F42G9.1, T23F11.1), Leishmania chagasi and Paramecium tetraurelia.\ In Arabidopsis thaliana, the kinase associated protein phosphatase (KAPP) [MEDLINE:95063913]\ is an enzyme that dephosphorylates the Ser/Thr receptor-like kinase RLK5 and\ which contains a C-terminal PP2C domain.

PP2C does not seem to be evolutionary related to the main family of serine/\ threonine phosphatases: PP1, PP2A and PP2B . However, it is significantly\ similar to the catalytic subunit of pyruvate dehydrogenase phosphatase\ (EC: 3.1.3.43) (PDPC) [MEDLINE:93378941], which catalyzes dephosphorylation and concomitant\ reactivation of the subunit of the E1 component of the pyruvate\ dehydrogenase complex. PDPC is a mitochondrial enzyme and, like PP2C, is\ magnesium-dependent.

\ \ enzyme activity ; GO:0003824 \N \N 20608 IPR001933

Neuropeptide Y (NPY) is one of the most abundant peptides in mammalian\ brain, inducing a variety of behavioural effects (e.g., stimulation of food\ intake, anxiety, facilitation of learning and memory, and regulation of the\ cardiovascular and neuroendocrine systems). In the periphery, NPY\ stimulates vascular smooth muscle contraction and modulates hormone\ secretion. NPY has been implicated in the pathophysiology of hypertension,\ congestive heart failure, affective disorders and appetite regulation PUB00005893.

Several pharmacologically distinct neuropeptide Y receptors have been\ characterised, designated NPY Y1-Y6. Y4 receptors show highest similarity\ to Y1 receptors from human, rat and mouse PUB00005893. It is believed that they\ may have potential roles in central nervous system, cardiovascular and\ gastrointestinal function [MEDLINE:96070761].

\ \ neuropeptide Y receptor activity ; GO:0004983 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20598 IPR001922

D2 receptors have a similar pharmacological profile to D3 and D4 receptors.\ They are present in high levels in the principal dopamine projection areas\ (including the caudate-putamen, nucleus accumbens and olfactory tubercle);\ they are found in cell bodies of dopaminergic neurons in the substantia\ nigra and ventral tegmental area; and, in the periphery, they are found in\ the pituitary, heart and blood vessels PUB00005878.

\ \ dopamine receptor activity ; GO:0004952 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20599 IPR001923

Prostanoids (prostaglandins (PG) and thromboxanes (TX)) mediate a wide variety of actions and play important physiological roles in the cardiovascular and immune systems, and in pain sensation in peripheral systems PUB00005901. PGI2 and TXA2 have opposing actions, involving regulation of the interaction of platelets with the vascular endothelium, while PGE2, PGI2 and PGD2 are powerful vasodilators and potentiate the action of various autocoids to induce plasma extravasation and pain sensation. To date, evidence for at least 5 classes of prostanoid receptor has been obtained. However, identification of subtypes and their distribution is hampered by expression of more than one receptor within a tissue, coupled with poor selectivity of available agonists and antagonists.

EP2 receptors mediate vasodilation, bronchodilation and relaxation of\ intestinal smooth muscle, and stimulate fluid secretion in the intestine. The receptors activate adenylate cyclase through Gs PUB00005901.

\ \ prostaglandin E receptor activity ; GO:0004957 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20597 IPR001921

\ \ \

The genomic structure and sequence of the human ribosomal protein L7a has been determined [MEDLINE:92096469]. The gene contains 8 exons and 7 introns, encompassing 3179 bp. The human gene resembles other mammalian ribosomal protein genes in so far as it contains a short first exon, a short 5' untranslated leader and its transcriptional start sites at C residues embedded in a poly-pyrimidine tract [MEDLINE:92096469].

The sequence of a gene for ribosomal protein L4 of S.cerevisiae has also been determined, which, unlike most of its other ribosomal protein genes, has no intron [MEDLINE:90221868]. The single open reading frame is highly similar to mammalian ribosomal protein L7a.

There appear to be two genes for L4, both of which are active [MEDLINE:90221868]. Yeast cells containing a disruption of the L4-1 gene form smaller colonies than either wild-type or disrupted L4-2 strains. Disruption of both L4 genes is lethal, probably resulting from an inability of the organism to produce functional ribosomes. [MEDLINE:91260682]

Several other ribosomal proteins have been found to share sequence similarity with L7a, including yeast NHP2 [MEDLINE:91289691], B.subtilis hypothetical protein ylxQ, Halobacterium marismortui Hs6, and M.jannaschii MJ1203.

This InterPro entry focus on regions that characterise the ribosomal L7A proteins but distinguish them from the rest of the HMG-like family.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 20604 IPR001929 Germins [MEDLINE:94164428] are a family of homopentameric cereal glycoproteins expressed during germination which may play a role in altering the properties of cell walls during germinative growth. It has been shown that wheat and barley germins act as oxalate oxidases (EC: 1.2.3.4), an enzyme that catalyzes the oxidative degradation of oxalate to carbonate and hydrogen peroxide [MEDLINE:98210240].Germins are highly similar to Slime mold spherulins 1a and 1b and Germin-like proteins from various plants.\ \N \N \N 20605 IPR001930

Metalloproteases can be split into five clans, and futher sub-divided into families, on the basis of their metal binding residues.

Membrane alanine aminopeptidase (EC: 3.4.11.2)\ is part of the HEXXH⁺E\ group; it consists entirely of aminopeptidases, spread across a wide\ variety of species [MEDLINE:95405261]. Functional studies show that CD13/APN catalyzes the removal of single amino acids from the amino terminus of small peptides and probably plays a role in their final digestion; one family member (leukotriene-A4 hydrolase) is known to hydrolyse the epoxide leukotriene-A4\ to form an inflammatory mediator [MEDLINE:95405261]. This hydrolase has been shown to\ have aminopeptidase activity [MEDLINE:91058588], and the zinc ligands of the M1 family\ were identified by site-directed mutagenesis on this enzyme [MEDLINE:95405261] CD13 participates in trimming peptides bound to MHC class II molecules [MEDLINE:96305201] and cleaves MIP-1 chemokine, which alters target cell specificity from basophils to eosinophils [MEDLINE:96195223]. CD13 acts as a receptor for specific strains of RNA viruses (coronaviruses) which cause a relatively large percentage of upper respiratory\ trace infections.

\ \

CD molecules are leucocyte antigens on cell surfaces. CD antigens nomenclature is updated at http://www.ncbi.nlm.nih.gov/PROW/guide/45277084.htm \

\ \ \ membrane alanyl aminopeptidase activity ; GO:0004179 \N proteolysis and peptidolysis ; GO:0006508 20600 IPR001925

The major protein of the outer mitochondrial membrane of eukaryotes is a porin that forms a voltage-dependent anion-selective channel (VDAC) that behaves as a general diffusion pore for small hydrophilic molecules [MEDLINE:94304912], [MEDLINE:93032135], [MEDLINE:90151906], [MEDLINE:87308079]. The channel adopts an open conformation at low or zero membrane potential and a closed conformation at potentials above 30-40 mV.

This protein contains about 280 amino acids and its sequence is composed of between 12 to 16 -strands that span the mitochondrial outer membrane. Yeast contains two members of this family (genes POR1 and POR2); vertebrates have at least three members (genes VDAC1, VDAC2 and VDAC3) [MEDLINE:96411667].

\ \ voltage-dependent ion-selective channel activity ; GO:0008308 mitochondrial outer membrane ; GO:0005741 anion transport ; GO:0006820 20601 IPR001926 Pyridoxal-5'-phosphate-dependent enzymes (B6 enzymes) catalyze manifold reactions in the metabolism of amino acids. Most of these enzymes can be assigned to one of three different families of homologous proteins, the

and gamma families. The

and gamma family might be distantly related with one another, but are clearly not homologous with the

family. The

family includes L- and D-serine dehydratase, threonine dehydratase, the

subunit of tryptophan synthase, threonine synthase and cysteine synthase. These enzymes catalyze

-replacement or

-elimination reactions [MEDLINE:94155902].

Comparison of sequences from eukaryotic, archebacterial, and eubacterial species indicates that the functional specialization of most B6 enzymes has occurred already in the universal ancestor cell. The cofactor pyridoxal-5-phosphate must have emerged very early in biological evolution; conceivably, organic cofactors and metal ions were the first biological catalysts [MEDLINE:20260389].

The 3D\ structure of the -subunit of tryptophan synthase has been solved. The\ subunit has two domains that are approximately the same size and similar to\ each other in folding pattern. Each has a core containing a four-stranded\ parallel -sheet with three helices on its inner side and one on the outer\ side. The cofactor is bound at the interface between the domains [MEDLINE:95267813].

\ \ lyase activity ; GO:0016829 \N amino acid metabolism ; GO:0006520 20602 IPR001927

It has been shown [MEDLINE:94304911] that integral membrane proteins that mediate the intake of a wide variety of molecules with the concomitant uptake of sodium ions (sodium symporters) can be grouped, on the basis of sequence and functional similarities into a number of distinct families. One of these families is known as the sodium: galactoside symporter family (SGF).

Like sugar transport proteins, these integral membrane proteins are predicted to comprise twelve membrane spanning domains.

\ \ \ transporter activity ; GO:0005215 membrane ; GO:0016020 sodium ion transport ; GO:0006814 20603 IPR001928

Endothelins are synthesised by proteolysis of large preproendothelins, which are cleaved to 'big endothelins' before being processed to the mature peptide.

Sarafotoxins (SRTX) and bibrotoxin (BTX) are cardiotoxins from the venom of snakes of the Atractaspis family, structurally and functionally [MEDLINE:89369759], [MEDLINE:92023522] similar to endothelin.

As shown in the following schematic representation, these peptides which are 21 residues long contain two intramolecular disulfide bonds.\

\ +-------------+\ | |\ CxCxxxxxxxCxxxCxxxxxx\ | |\ +-------+\ 'C': conserved cysteine involved in a disulfide bond.\

\ \ toxin activity ; GO:0015070 \N \N 20590 IPR001913

Equine arteritis virus small envelope glycoprotein (Gs) is a class I transmembrane protein which adopts a number of different conformations [MEDLINE:97093422], [MEDLINE:95264432].

\ \N \N \N 20591 IPR001915

Metalloproteases can be split into five clans, and futher sub-divided into families, on the basis of their metal binding residues.

This is family M48 in the peptidase classification. The members of this set of proteins are mostly described as probable protease htpX homolog (EC: 3.4.24.-) or CAAX prenyl protease 1, which proteolytically removes the C-terminal three residues of farnesylated proteins. They are intergral membrane proteins associated with the endoplasmic reticulum and golgi, binding one zinc ion per subunit.

\ \ \ metalloendopeptidase activity ; GO:0004222 membrane ; GO:0016020 proteolysis and peptidolysis ; GO:0006508 20592 IPR001916

Glycoside hydrolase family 22 CAZY:GH_22) and -lactalbumins. Asp and/or the carbonyl oxygen of the C-2 acetamido group \ of the substrate acts as the catalytic nucleophile/base.

\ \

Lysozyme type C and -lactalbumin and are similar both in terms of primary \ sequence and structure, and probably evolved from a common ancestral \ protein. There is, however, no similarity in function as lactalbumin \ promotes the conversion of galactosyltransferase to lactose synthase and is\ essential for milk production [MEDLINE:84185596], while lysozyme catalyses the hydrolysis \ of bacterial cell wall polysaccharides; it has also been recruited for a \ digestive role in certain ruminants and colobine monkeys [MEDLINE:89291894]. Another \ significant difference between the two enzymes is that all lactalbumins have \ the ability to bind calcium [MEDLINE:87065037], while this property is restricted to only \ a few lysozymes [MEDLINE:88030086].

The binding site was deduced using high resolution \ X-ray structure analysis and was shown to consist of three aspartic acid \ residues. It was first suggested that calcium bound to lactalbumin \ stabilised the structure, but recently it has been claimed that calcium \ controls the release of lactalbumin from the golgi membrane and that the \ pattern of ion binding may also affect the catalytic properties of the \ lactose synthetase complex.

\ \ \N extracellular ; GO:0005576 \N 20589 IPR001912

\ \ \

Ribosomal protein S4 is one of the proteins from the small ribosomal subunit. In Escherichia coli, S4 is known to bind directly to 16S ribosomal RNA. Mutations in S4 have been shown to increase translational error frequencies [MEDLINE:91252202], PUB00005070.\ S4 is a protein of 171 to 205 amino-acid residues (except for NAM9, which is much larger). The crystal structure of a bacterial S4 protein revealed a two domain molecule. The first domain is composed of four helices in the known structure. The second domain is in the middle of the first one and displays some structural homology with the ETS DNA binding domain PUB00005070.\ This family includes small ribosomal subunit S4 from prokaryotes and S9 from animals.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 20594 IPR001918 The sequence Arg-Gly-Asp, found in fibronectin, is crucial for its interaction with its cell surface receptor, an integrin [MEDLINE:86133544], [MEDLINE:92023518]. What has been called the 'RGD' tripeptide is also found in the sequences of a number of other proteins, where it has been shown to play a role in cell adhesion. These proteins are: some forms of collagens, fibrinogen, vitronectin, von Willebrand factor (VWF), snake disintegrins, and slime mold discoidins. The 'RGD' tripeptide is also found in other proteins where it may also, but not always, serve the same purpose.

Note: No protein matches are shown due to the low specificity of this rule.

\ \ \N \N cell adhesion ; GO:0007155 20595 IPR001919

The microbial degradation of cellulose and xylans requires several types of enzyme such as endoglucanases (EC: 3.2.1.4), cellobiohydrolases (EC: 3.2.1.91) (exoglucanases), or xylanases (EC: 3.2.1.8) [MEDLINE:91359927].Structurally, cellulases and xylanases generally consist of a catalytic domain joined to a cellulose-binding domain (CBD) by a short linker sequence rich in proline and/or hydroxy-amino acids.

The CBD domain is found either at the N-terminal or at the C-terminal extremity of these enzymes. As it is shown in the following schematic representation, there are two conserved cysteines in this CBD domain - one at each extremity of the domain - which have been shown [MEDLINE:92104156] to be involved in a disulfide bond. There are also four conserved tryptophan, two are involved in cellulose binding.\ The CBD of a number of bacterial cellulases has been shown to consist of about 105 amino acid residues [MEDLINE:92253551].

\ +-------------------------------------------------+\ | |\ xCxxxxWxxxxxNxxxWxxxxxxxWxxxxxxxxWNxxxxxGxxxxxxxxxxCx\ \ 'C': conserved cysteine involved in a disulfide bond.\

\ \ hydrolase activity, hydrolyzing O-glycosyl compounds ; GO:0004553 \N carbohydrate metabolism ; GO:0005975 20596 IPR001920

Aspartate racemase (EC: 5.1.1.13) and glutamate racemase (EC: 5.1.1.3) are two evolutionary related bacterial enzymes that do not seem to require a cofactor for their activity [MEDLINE:93229497]. Glutamate racemase, which interconverts L-glutamate into D-glutamate, is required for the biosynthesis of peptidoglycan and some peptide-based antibiotics such as gramicidin S.In addition to characterized aspartate and glutamate racemases, this family also includes a hypothetical protein from Erwinia carotovora and one from Escherichia coli (ygeA).

Two conserved cysteines are present in the sequence of these enzymes. They are expected to play a role in catalytic activity by acting as bases in proton abstraction from the substrate.

\ \ racemase and epimerase activity, acting on amino acids and derivatives ; GO:0016855 \N metabolism ; GO:0008152 20593 IPR001917

Aminotransferases share certain mechanistic features with other pyridoxal-phosphate dependent enzymes, such as the covalent binding of the pyridoxal-phosphate group to a lysine residue. On the basis of sequence similarity, these various enzymes can be grouped into subfamilies. One of these, is called class-II. It consists of Serine palmitoyltransferase (EC: 2.3.1.50), Histidinol-phosphate aminotransferase (EC: 2.6.1.9), Glycine acetyltransferase EC: 2.3.1.29), 5-aminolevulinic acid synthase (EC: 2.3.1.37) and 8-amino-7-oxononanoate synthase (EC: 2.3.1.47).

\ transferase activity ; GO:0016740 \N metabolism ; GO:0008152 20587 IPR001910

Inosine-uridine preferring nucleoside hydrolase (EC: 3.2.2.1) (IU-nucleoside hydrolase or IUNH) is an enzyme first identified in protozoan [MEDLINE:96214502] that catalyzes the hydrolysis of all of the commonly occuring purine and pyrimidine nucleosides into ribose and the associated base, but has a preference for inosine and uridine as substrates. This enzyme is important for these parasitic organisms, which are deficient in de novo synthesis of purines, to salvage the host purine nucleosides.IUNH from Crithidia fasciculata has been sequenced and characterized, it is an homotetrameric enzyme of subunits of 34 Kd. An histidine has been shown to be important for the catalytic mechanism, it acts as a proton donor to activate the hypoxanthine leaving group.

A highly conserved region located in the N-terminal extremity contains four conserved aspartates that have been shown [MEDLINE:96214503] to be located in the active site cavity.

IUNH is evolutionary related to a number of uncharacterized proteins from various biological sources.

\ \ \N \N \N 20588 IPR001911

\ \ \

Evidence suggests that, in prokaryotes, the peptidyl\ transferase reaction is performed by the large subunit 23S rRNA, whereas\ proteins probably have a greater role in eukaryote ribosomes. Most of the\ proteins lie close to, or on the surface of, the 30S subunit, arranged\ peripherally around the rRNA [MEDLINE:97428328]. The small subunit ribosomal proteins can\ be categorised as primary binding proteins, which bind directly and\ independently to 16S rRNA; secondary binding proteins, which display no\ specific affinity for 16S rRNA, but its assembly is contingent upon the\ presence of one or more primary binding proteins; and tertiary binding\ proteins, which require the presence of one or more secondary binding\ proteins and sometimes other tertiary binding proteins.\ The small ribosomal subunit protein S21 contains 55-70 amino acid residues,\ and has only been found in eubacteria to date. Experimental evidence has\ revealed that S21 is well exposed on the surface of the Escherichia coli\ ribosome [MEDLINE:98058740], and is one of the 'split proteins': these are a discrete group\ that are selectively removed from 30S subunits under low salt conditions\ and are required for the formation of activated 30S reconstitution\ intermediate (RI*) particles.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 20584 IPR001907

The clp protease is an ATP-dependent protease that cleaves a number ofproteins, such as casein and albumin [MEDLINE:90324245]. It exists as a heterodimer of\ ATP-binding regulatory A and catalytic P subunits, both of which are\ required for effective levels of protease activity in the presence of\ ATP [MEDLINE:90324245], although the P subunit alone does possess some catalytic activity.

\ \

The clpP subunit is a serine protease that contains 2 residues (Ser and\ His) of the triad (Ser, His and Asp) normally found in serine proteases,\ although the sequence of clpP subunits shows no similarity to trypsin- or\ subtilisin-like enzymes [MEDLINE:90324245].

\ \

Proteases highly similar to ClpP have been found to be encoded in the genome\ of the chloroplast of plants and seem to be also present in other eukaryotes.\ The sequences around two of the residues involved in the catalytic triad (a\ serine and a histidine) are highly conserved.

\ \ endopeptidase Clp activity ; GO:0008462 \N proteolysis and peptidolysis ; GO:0006508 20585 IPR001908

\ \ \ melanocortin receptor activity ; GO:0004977 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20586 IPR001909

The Krueppel-associated box (KRAB) is a domain of around 75 amino acids that is found in the N-terminal part of about one third of eukaryotic Krueppel-type\ C2H2 zinc finger proteins (ZFPs). It is enriched in charged amino acids and can be divided into subregions A and B, which are predicted to fold into two amphipathic -helices. The KRAB A and B boxes can be separated by variable spacer segments and many KRAB proteins contain only the A box [MEDLINE:91219421].

The KRAB domain functions as a transcriptional repressor when tethered to the template DNA by a DNA-binding domain. A sequence of 45 amino acids in the KRAB A subdomain has been shown to be necessary and sufficient for transcriptional repression. The B box does not repress by itself but does potentiate the repression exerted by the KRAB A subdomain [MEDLINE:94240165], [MEDLINE:94240166]. Gene silencing requires the binding of the KRAB domain to the RING-B box-coiled coil (RBCC) domain of the KAP-1/TIF1- corepressor. As KAP-1 binds to the heterochromatin proteins HP1, it has been proposed that the KRAB-ZFP-bound target gene could be silenced following recruitment to heterochromatin [MEDLINE:20120851], [MEDLINE:20309743].

KRAB-ZFPs probably constitute the single largest class of transcription factors within the human genome [MEDLINE:99287584]. Although the function of KRAB-ZFPs is largely unknown, they appear to play important roles during cell differentiation and development. The KRAB domain is generally encoded by two exons. The regions coded by the two exons are known as KRAB-A and KRAB-B.

\ \ nucleic acid binding activity ; GO:0003676 intracellular ; GO:0005622 regulation of transcription, DNA-dependent ; GO:0006355 20581 IPR001904

Paxillin is a cytoskeletal protein involved in actin-membrane attachment at sites of cell adhesion to the extracellular matrix (focal adhesion) [MEDLINE:95197488], [MEDLINE:95051116]. Extensive tyrosine phosphorylation occurs during integrin-mediated cell adhesion, embryonic development, fibroblast transformation and following stimulation of cells by mitogens that operate through the 7TM family of G-protein-coupled receptors [MEDLINE:95051116]. Paxillin binds in vitro to the focal adhesion protein vinculin, as well as to the SH3 domain of c-Src, and, when tyrosine phosphorylated, to the SH2 domain of v-Crk [MEDLINE:95051116]. An N-terminal region has been identified that supports the binding of both vinculin and the focal adhesion tyrosine kinase, pp125Fak [MEDLINE:95051116].

Paxillin is a 68 kDa protein containing multiple domains, including four tandem C-terminal LIM domains (each of which binds 2 zinc ions); an N-terminal proline-rich domain, which contains a consensus SH3 binding site; and three potential Crk-SH2 binding sites [MEDLINE:95197488]. The predicted structure of paxillin suggests that it is a unique cytoskeletal protein capable of interaction with a variety of intracellular signalling and structural molecules important in growth control and the regulation of cytoskeletal organisation [MEDLINE:95197488], [MEDLINE:95051116].

\ \ \N cytoskeleton ; GO:0005856 cell-matrix adhesion ; GO:0007160 20582 IPR001905

A number of evolutionarily-related proteins have been found to be involved in the transport of ammonium ions across membranes [MEDLINE:94341258], [MEDLINE:96214991].

Members of this family include:\

Yeast ammonium transporters MEP1, MEP2 and MEP3.
Arabidopsis thaliana high affinity ammonium transporter (gene AMT1).
>Corynebacterium glutamicum ammonium and methylammonium transport system.
Escherichia coli putative ammonium transporter amtB.
Bacillus subtilis nrgA.
Mycobacterium tuberculosis hypothetical protein MtCY338.09c.
Synechocystis strain PCC 6803 hypothetical proteins sll0108, sll0537 and sll1017.
Methanococcus jannaschii hypothetical proteins MJ0058 and MJ1343.
Caenorhabditis elegans hypothetical proteins C05E11.4, F49E11.3 and M195.3.

As expected by their transport function, these proteins are highly hydrophobic\ and seem to contain from 10 to 12 transmembrane domains.

\ \ ammonium transporter activity ; GO:0008519 membrane ; GO:0016020 transport ; GO:0006810 20583 IPR001906

Tpsa includes vetispiridiene synthase Q39979
Tpsb includes (-)-limonene synthase, Q39979/>.
Tpsc includes copalyl diphosphate synthase (kaurene synthase A), O04408.
Tpsd includes taxadiene synthase, O04408/>, pinene synthase, O24475.
Tpse includes ent-kaurene synthase B O24475/>.
Tpsf includes linalool synthase Q9ZPN5.

\ \

In the fungus Phaeosphaeria sp.L487 the synthesis of ent-kaurene from geranylgeranyl dophosphate is promoted by a single bifunctional protein [MEDLINE:97413762].

\ \ lyase activity ; GO:0016829 \N metabolism ; GO:0008152 20576 IPR001899

Viruses, parasites and bacteria are covered in protein and sugar molecules that help them gain entry into a host by counteracting the host's defenses. One such molecule is the M protein produced by certain streptococcal bacteria. M proteins embody a motif that is now known to be shared by many Gram-positive bacterial surface proteins. The motif includes a conserved hexapeptide, which precedes a hydrophobic C-terminal membrane anchor, which itself precedes a cluster of basic residues [MEDLINE:90264329], [MEDLINE:91141313].This structure is represented in the following schematic representation:

\ +--------------------------------------------+-+--------+-+\ | Variable length extracellular domain |H| Anchor |B|\ +--------------------------------------------+-+--------+-+\ \ 'H': conserved hexapeptide.\ 'B': cluster of basic residues.\

It has been proposed that this hexapeptide sequence is responsible for a post-\ translational modification necessary for the proper anchoring of the proteins\ which bear it, to the cell wall.

\ \ \ \N \N \N 20577 IPR001900 This group of bacterial and eukaryotic proteins is defined on sequence similarity. The size of these proteins range from 644 residues (rnb) to 1250 (SSD1). While their sequence is highly divergent they share a conserved domain in their C-terminal section [MEDLINE:97439408]. It is possible that this domain plays a role in a putative exonuclease function that would be common to all these proteins.\ ribonuclease activity ; GO:0004540 \N \N 20578 IPR001901

\ \

In eukaryotes, the evolutionary related protein sec61-gamma plays a role in protein translocation through the endoplasmic reticulum; it is part of a trimeric complex that also consist of sec61- and [MEDLINE:94150683]. Both secE and sec61-gamma are small proteins of about 60 to 90 amino acids that contain a single transmembrane region at their C-terminal extremity (Escherichia coli secE is an exception, in that it possess an extra N-terminal segment of 60 residues that contains two additional transmembrane domains) [MEDLINE:98053998].

\ \ \N membrane ; GO:0016020 intracellular protein transport ; GO:0006886 20579 IPR001902

A number of proteins involved in the transport of sulphate across a membraneas well as some yet uncharacterized proteins have been shown [MEDLINE:94188926], [MEDLINE:95342164] to be evolutionary related.\ These proteins are:\

Neurospora crassa sulphate permease II (gene cys-14).
Yeast sulphate permeases (genes SUL1 and SUL2).
Rat sulphate anion transporter 1 (SAT-1).
Mammalian DTDST, a probable sulphate transporter which, in Human, is involved in the genetic disease, diastrophic dysplasia (DTD).
Sulfate transporters 1, 2 and 3 from the legume Stylosanthes hamata.
Human pendrin (gene PDS), which is involved in a number of hearing loss genetic diseases.
Human protein DRA (Down-Regulated in Adenoma).
Soybean early nodulin 70.
Escherichia coli hypothetical protein ychM.
Caenorhabditis elegans hypothetical protein F41D9.5.

These proteins are highly hydrophobic and seem to contain about 12 transmembrane domains.

\ \ sulfate porter activity ; GO:0008271 membrane ; GO:0016020 sulfate transport ; GO:0008272 20580 IPR001903 Different families of ssRNA negative-strand viruses contain glycoproteins responsible for forming spikes on the surface of the virion. The glycoprotein spike is made up of a trimer of glycoproteins. These proteins are frequently abbreviated to G protein. Channel formed by glycoprotein spike is thought to function in a similar manner to Influenza virus M2 protein channel, thus allowing a signal to pass across the viral membrane to signal for viral uncoating [MEDLINE:92074232], [MEDLINE:97152510].\ \N \N \N 20573 IPR001896 This family of membrane/coat proteins are found in a number of different ssRNA plant virus families including potexviruses, hordeiviruses and carlaviruses.\ \N \N \N 20574 IPR001897

Porins are found in the outer membranes of Gram-negative bacteria,mitochondria and chloroplasts, where they form ion-selective channels for\ small hydrophilic molecules (up to ~600 D) [MEDLINE:91134313], [MEDLINE:92219987]. X-ray structure analyses\ of several bacterial porins [MEDLINE:91192174], [MEDLINE:92222788], [MEDLINE:95055730] have revealed a 16-stranded anti-parallel -barrel structure enclosing the transmembrane pore, by contrast with\ all other integral membrane proteins described to date, which are -helical. Three subunits form a trimer; the 3-fold axis is approximately\ parallel to the barrel axes and is assumed to be perpendicular to the\ membrane plane PUB00001081.

\ \ \ transporter activity ; GO:0005215 membrane ; GO:0016020 transport ; GO:0006810 20575 IPR001898

Integral membrane proteins that mediate the intake of a wide variety ofmolecules with the concomitant uptake of sodium ions (sodium symporters) can\ be grouped, on the basis of sequence and functional similarities into a number\ of distinct families. One of these families currently consists of the\ following proteins:\

Mammalian sodium/sulphate cotransporter [MEDLINE:93376745].
Mammalian renal sodium/dicarboxylate cotransporter [MEDLINE:96199379], which transports succinate and citrate.
Mammalian intestinal sodium/dicarboxylate cotransporter.
Chlamydomonas reinhardtii putative sulphur deprivation response regulator SAC1 [MEDLINE:96208501].
Caenorhabditis elegans hypothetical proteins B0285.6, F31F6.6, K08E5.2 and R107.1.
Escherichia coli hypothetical protein yfbS.
Haemophilus influenzae hypothetical protein HI0608.
Synechocystis strain PCC 6803 hypothetical protein sll0640.
Methanococcus jannaschii hypothetical protein MJ0672.

These transporters are proteins of from 430 to 620 amino acids which are\ highly hydrophobic and which probably contain about 12 transmembrane regions.

\ \ transporter activity ; GO:0005215 membrane ; GO:0016020 sodium ion transport ; GO:0006814 20563 IPR001887 Barnase is the extracellular ribonuclease of Bacillus amyloliquefaciens, and barstar its specific intracellular inhibitor [MEDLINE:90162921], [MEDLINE:89012012]. Expression of barstar is necessary to counter the lethal effect of expressed active barnase. Barnase hydrolyses phosphodiester bonds in RNA, poly- and oligo-ribonucleotides, resulting in 3'-nucleoside monophosphates via 2',3'-cyclo-phospate intermediates. It is a small single-chain protein that has neither disulphide bonds nor non-peptide components. The NMR structure [MEDLINE:91363360] contains 2

-helices and a 5-stranded anti-parallel

-sheet. The protein core is formed by the packing of the first

-helix onto the

-sheet.\ endoribonuclease activity ; GO:0004521 \N \N 20564 IPR001888 Autonomous mobile genetic elements such as transposon or insertion sequences (IS)encode an enzyme, transposase, that is required for excising and inserting\ the mobile element. Transposases have been grouped into various families [MEDLINE:94316508], [MEDLINE:92149305], [MEDLINE:92039004]. This family includes the mariner transposase [MEDLINE:97050851].\ \ \N \N \N 20565 IPR001889

The thymidine kinase from herpes virus catalyses the reaction:

ATP + THYMIDINE = ADP + THYMIDINE 5'-PHOSPHATE.

The enzyme is not subject to feedback inhibition by its product and the crystal structure of the enzyme from HSV type 1 has been reported [MEDLINE:96003730].

\ \ ATP binding activity ; GO:0005524 \N TMP biosynthesis ; GO:0006230 20566 IPR001890

This family is composed of small proteins of unknown function.

\ molecular_function unknown ; GO:0005554 \N \N 20567 IPR001891

Malic enzymes (malate oxidoreductases) catalyse the oxidative decarboxylation of malate to form pyruvate PUB00001542, a reaction important in a number of metabolic pathways - e.g. carbon dioxide released from the reaction may be used in sugar production during the Calvin cycle of photosynthesis PUB00001542. There are 3 forms of the enzyme [MEDLINE:91131600]: an NAD-dependent form that decarboxylates oxaloacetate; an NAD-dependent form that does not decarboxylate oxalo-acetate; and an NADPH-dependent form [MEDLINE:94132054]. Other proteins known to be similar to malic enzymes are the Escherichia coli scfA protein; an enzyme from Zea mays (Maize), formerly thought to be cinnamyl-alcohol dehydrogenase [MEDLINE:91355904]; and the hypothetical Saccharomyces cerevisiae protein YKL029c.

Studies on the duck liver malic enzyme reveals that it can be alkylated by bromopyruvate, resulting in the loss of oxidative decarboxylation and the subsequent enhancement of pyruvate reductase activity [MEDLINE:92002141]. The alkylated form is able to bind NADPH but not L-malate, indicating impaired substrate-or divalent metal ion-binding in the active site [MEDLINE:92002141]. Sequence analysis has highlighted a cysteine residue as the point of alkylation, suggesting that it may play an important role in the activity of the enzyme [MEDLINE:92002141], although it is absent in the sequences from some species.

There are three well conserved regions in the enzyme sequences. Two of them seem to be involved in the binding NAD or NADP. The significance of the third one, located in the central part of the enzymes, is not yet known.

\ \ malic enzyme activity ; GO:0004470 \N malate metabolism ; GO:0006108 20568 IPR001891

\ \ malic enzyme activity ; GO:0004470 \N malate metabolism ; GO:0006108 20569 IPR001892

\ \ \

Ribosomal protein S13 is one of the proteins from the small ribosomal subunit. In Escherichia coli, S13 is known to be involved in binding fMet-tRNA and, hence, in the initiation of translation. It is a basic protein of 115 to 177 amino-acid residues. This family of ribosomal proteins is present in procaryotes and eukaryotes [MEDLINE:91337062], PUB00005070.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 20562 IPR001885

Lipoxygenases (EC: 1.13.11.-) are a class of iron-containing dioxygenaseswhich catalyzes the hydroperoxidation of lipids, containing a cis,cis-1,4-\ pentadiene structure. They are common in plants where they may be involved in\ a number of diverse aspects of plant physiology including growth and\ development, pest resistance, and senescence or responses to wounding PUB00005925. In\ mammals a number of lipoxygenases isozymes are involved in the metabolism of\ prostaglandins and leukotrienes PUB00005925. Sequence data is available for the\ following lipoxygenases:

\ \ \

Plant lipoxygenases (EC: 1.13.11.12\ \ \ \ IPR001246). Plants express a variety of cytosolic\ isozymes as well as what seems to be a chloroplast isozyme [MEDLINE:94148883] .

Mammalian arachidonate 5-lipoxygenase (EC: 1.13.11.34\ \ \ \ IPR001246/>).

Mammalian arachidonate 12-lipoxygenase (EC: 1.13.11.31\ \ \ \ IPR001885).

Mammalian erythroid cell-specific 15-lipoxygenase (EC: 1.13.11.33\ \ \ \ IPR001885/>).

\ \ \

The iron atom in lipoxygenases is bound by four ligands, three of which are\ histidine residues [MEDLINE:93276267]. Six histidines are conserved in all lipoxygenase\ sequences, five of them are found clustered in a stretch of 40 amino acids.\ This region contains two of the three zinc-ligands; the other histidines have\ been shown [MEDLINE:92232702] to be important for the activity of lipoxygenases.

\ \ lipoxygenase activity ; GO:0016165 \N leukotriene metabolism ; GO:0006691 20572 IPR001895

Ras proteins are membrane-associated molecular switches that bind GTP and GDP and slowly hydrolyze GTP to GDP [MEDLINE:91095015]. The balance between the GTP bound (active) and GDP bound (inactive) states is regulated by the opposite action of proteins activating the GTPase activity and that of proteins which promote the loss of bound GDP and the uptake of fresh GTP [MEDLINE:94081948], PUB00001017. The latter proteins are known as guanine-nucleotide dissociation stimulators (GDSs) (or also as guanine-nucleotide releasing (or exchange) factors (GRFs)). Proteins that act as GDS can be classified into at least two families, on the basis of sequence similarities, the CDC24 family (see IPR001331) and the CDC25 family.

The size of the proteins of the CDC25 family range from 309 residues (LTE1) to 1596 residues (sos). The sequence similarity shared by all these proteins is limited to a region of about 250 amino acids generally located in their C-terminal section (currently the only exceptions are sos and ralGDS where this domain makes up the central part of the protein). This domain has been shown, in CDC25 an SCD25, to be essential for the activity of these proteins.

\ \ guanyl-nucleotide exchange factor activity ; GO:0005085 \N intracellular signaling cascade ; GO:0007242 20570 IPR001893

This cysteine rich repeat contains four cysteines. It is found in multiple copies in a protein that binds to fibroblast growth factors [MEDLINE:93078761]. The repeat is also found in the golgi apparatus protein 1 precursor (MG-160/ESL-1, Q9Z1E9).

\ \N \N \N 20571 IPR001894

The precursor sequences of a number of antimicrobial peptides secreted by neutrophils (polymorphonuclear leukocytes) upon activation have been found to be evolutionarily related and are collectively known as cathelicidins [MEDLINE:96049543].

Structurally, these proteins consist of three domains: a signal sequence, a conserved region of about 100 residues that contains four cysteines involved in two disulfide bonds, and a highly divergent C-terminal section of variable size. It is in this C-terminal section that the antibacterial peptides are found; they are proteolytically processed from their precursor by enzymes such as elastase. This structure is shown in the following schematic representation:

\
   +---+--------------------------------+--------------------+\
   |Sig| Propeptide     C  C  C  C      | Antibacterial pep. |\
   +---+----------------|--|--|--|------+--------------------+\
                        |  |  |  |\
                        +--+  +--+\
\
'C': conserved cysteine involved in a disulfide bond.\

\ \ antimicrobial peptide activity ; GO:0003795 extracellular ; GO:0005576 defense response ; GO:0006952 20552 IPR001874 3-dehydroquinate dehydratase (EC: 4.2.1.10), or dehydroquinase, catalyzes the conversion of 3-dehydroquinate into 3-dehydroshikimate. It is the third step in the shikimate pathway for the biosynthesis of aromatic amino acids from chorismate. Two classes of dehydroquinases exist, known as types I and II. Class-II enzymes are homododecameric enzymes of about 17 kDa. They are found in some bacteria such as actinomycetales\ \ \ [MEDLINE:91375423], [MEDLINE:94224145] and some fungi where they act in a catabolic pathway that allows the use of quinic acid as a carbon source.\ \ \ 3-dehydroquinate dehydratase activity ; GO:0003855\ \N \N aromatic amino acid family biosynthesis ; GO:0009073 20553 IPR001875

The apoptotic signal coming from ligand-induced oligomerization of death receptors is mediated by a number of adaptor proteins containing specialized interaction domains. Besides the death effector domain (DED), this group is formed by the death domain (DD, see IPR000488).

The death effector domain was first described in the FADD/Mort1 protein [MEDLINE:95277837] and later shown to also occur in several other proteins [MEDLINE:97242415], [MEDLINE:97360133]. The DED typically associates with other DED-containing proteins, forming either dimers or trimers [MEDLINE:97242415], [MEDLINE:97360133], [MEDLINE:96279827]. It has been predicted that the DED is related in structure and sequence to both DD and CARD domains, which work in similar pathways and show similar interaction properties [MEDLINE:97318595].

\ \ apoptosis regulator activity ; GO:0016329 \N apoptosis ; GO:0006915 20554 IPR001876

Ran is an evolutionary conserved member of the Ras superfamily that regulates all receptor-mediated transport between the nucleus and the cytoplasm. Ran binding protein 2 (RanBP2) is a 358-kDa nucleoporin located on the cytoplasmic side of the nuclear pore complex which plays a role in nuclear protein import [MEDLINE:22014335]. RanBP2 contains multiple zinc fingers which mediate binding to RanGDP [MEDLINE:99254072].

\ \ \N \N \N 20555 IPR001877 Proteins that transport heavy metals in micro-organisms and mammals share similarities in their sequences and structures. Some of these proteins are involved in bacterial resistance to toxic metals, such as lead and cadmium, \ while others are involved in inherited human syndromes, such as Wilson and Menkes diseases [MEDLINE:94378325].\

Copper-transporting ATPase 1 (ATP7A and ATP7B) is thought to function in\ the export of copper, and possibly other metals, from the cytoplasm to an\ intracellular organelle. The protein functions as a monomer and is an\ integral membrane protein, with 8 predicted transmembrane (TM) domains,\ possibly inserted into the membrane of a subcellular compartment. ATP7A is\ found in most tissues, except liver. Defects in the protein, resulting in\ defective absorption and transport of copper, are associated with Menkes\ syndrome (also known as kinky hair disease), an X-linked recessive disease\ characterised by progressive neurodegeneration and connective-tissue\ disturbances, focal cerebral and cerebellar degeneration, early retardation\ in growth, peculiar hair, hipopigmentation, vascular complications and death\ in early childhood.

Defects in ATP7B are associated with Wilson disease, an autosomal recessive\ disorder of copper metabolism in which copper cannot be incorporated into\ ceruloplasmin in liver, and cannot be excreted from the liver into the bile.\ Copper thus accumulates in the liver, and ultimately in the brain and kidney,\ leading to neurological manifestations and signs of cirrhosis.

\ \ \ ATP binding activity ; GO:0005524 membrane ; GO:0016020 copper ion transport ; GO:0006825 20556 IPR001878 The 18 residues CCHC Zinc finger domain is mainly found in the Nucleocapsid protein of retrovirus. It is required for viral genome packaging and for early infection process [MEDLINE:90147677], [MEDLINE:99175320]. It is also found in eukaryotic proteins involved in RNA binding or single strand DNA binding.\ nucleic acid binding activity ; GO:0003676 \N \N 20557 IPR001879

This domain is found in the extracellular part of some hormone receptors including the calcitonin receptor; corticotropin releasing factor receptor 1; diuretic hormone receptor; glucagon-like peptide 1 receptor; and parathyroid hormone peptide receptor.

\ G-protein coupled receptor activity ; GO:0004930 membrane ; GO:0016020 \N 20558 IPR001881

A sequence of about forty amino-acid residues long found in the sequence of epidermal growth factor (EGF) has been shown [MEDLINE:91145344], [MEDLINE:85063790], PUB00004964, PUB00004964, [MEDLINE:88196363], PUB00001077 to be present in a large number of membrane-bound and extracellular, mostly animal proteins. Many of these proteins require calcium for their biological function and a calcium-binding site has been found to be located at the N-terminus of some EGF-like domains PUB00001077. Calcium-binding may be crucial for numerous protein-protein interactions.

For human coagulation factor IX it has been shown [MEDLINE:95330802] that the calcium-ligands form a pentagonal bipyramid. The first, third and fourth conserved negatively charged or polar residues are side chain ligands. Latter is possibly hydroxylated (see IPR000152. A conserved aromatic residue as well as the second conserved negative residue are thought to be involved in stabilizing the calcium-binding site.

Like in non-calcium binding EGF-like domains there are six conserved cysteines and the structure of both types is very similar as calcium-binding induces only strictly local structural changes [MEDLINE:92406922].

\
                             +------------------+        +---------+\
                             |                  |        |         |\
               nxnnC-x(3,14)-C-x(3,7)-CxxbxxxxaxC-x(1,6)-C-x(8,13)-Cx\
                   |                  | \
                   +------------------+\
\
'n': negatively charged or polar residue [DEQN]\
'b': possibly -hydroxylated residue [DN]\
'a': aromatic amino acid\
'C': cysteine, involved in disulfide bond\
'x': any amino acid.\

\ \ calcium ion binding activity ; GO:0005509 \N \N 20561 IPR001884

Eukaryotic initiation factor 5A (eIF-5A) (formerly known as eIF-4D) [MEDLINE:93349426], [MEDLINE:91246178] is a small protein whose precise role in the initiation of protein synthesis is not known. It appears to promote the formation of the first peptide bond. eIF-5A seems to be the only eukaryotic protein to contain an hypusine residue.Hypusine is derived from lysine by the post-translational addition of a butylamino group (from spermidine) to the epsilon-amino group of lysine. The hypusine group is essential to the function of eIF-5A.

A hypusine-containing protein has been found in archaebacteria such as Sulfolobus acidocaldarius or Methanococcus jannaschii; this protein is highly similar to eIF-5A and could play a similar role in protein biosynthesis.

\ \ translation initiation factor activity ; GO:0003743 \N translational initiation ; GO:0006413 20560 IPR001883

At least eight sub-types of metabotropic receptor (MGR1-8) have been\ identified in cloning studies. The sub-types differ in their agonist\ pharmacology and signal transduction pathways PUB00005885.

MGR7 mRNA has a widespread distribution in many neuronal cells of the central nervous\ system, with highest levels in the hippocampal formation, cerebral cortex\ and cerebellum PUB00005885, [MEDLINE:94117433]; it is thus different from the more limitedly expressed\ MGR4 or MGR6 mRNA [MEDLINE:94117433]. MGR7 and MGR4 are believed to correspond to the\ putative L-2-amino-4-phosphonobutyrate receptor, which plays an important\ role in modulation of glutamate transmission in the CNS [MEDLINE:94117433].

\ \ metabotropic glutamate, GABA-B-like receptor activity ; GO:0008067 membrane ; GO:0016020 \N 20559 IPR001882 Biotin, which plays a catalytic role in some carboxyl transfer reactions, is covalently attached, via an amide bond, to a lysine residue in enzymes requiring this coenzyme [MEDLINE:89372795], [MEDLINE:88198199], [MEDLINE:85060474], [MEDLINE:92406744]. Sequence data reveal that the region around the biocytin (biotin-lysine) residue is well conserved and is evolutionary related to that around the lipoyl-binding lysine residue of 2-oxo acid dehydrogenase acyltransferases.\ biotin binding activity ; GO:0009374 \N \N 20546 IPR001866 E2 is an early regulatory protein found in the dsDNA papillomaviruses. E2 regulates viral transcription and DNA replication. It binds to the E2RE response element (5'-ACCNNNNNNGGT-3') present in multiple copies in the regulatory region. It can either activate or repress transcription, depending on E2RE's posiiton with regard to proximal promoter elements. Repression occurs by sterically hindering the assembly of the transcription initiation complex. The E1-E2 dimer complex binds to the origin of DNA replication [MEDLINE:93024918].\ DNA binding activity ; GO:0003677 \N regulation of transcription, DNA-dependent ; GO:0006355 20547 IPR001867

This domain is almost always found associated with the response regulator receiver domain (see IPR001789.

\ DNA binding activity ; GO:0003677 \N regulation of transcription, DNA-dependent ; GO:0006355 20548 IPR001869 Thiol-activated cytolysins [MEDLINE:91072294], PUB00006593 are toxins produced by a variety of Gram-positive bacteria and are characterized by their ability to lyse cholesterol-containing membranes, their reversible inactivation by oxidation and their capacity to bind to cholesterol. All these proteins contain a single cysteine residue, located in their C-terminal section, which has been shown PUB00006593 to be essential for the binding to cholesterol.\ cholesterol binding activity ; GO:0015485 \N pathogenesis ; GO:0009405 20549 IPR001870

The B30.2-like domain is a conserved domain of 160-170 amino acids which isfound in nuclear and cytoplasmic proteins, as well as transmembrane and\ secreted proteins. It was named after the B30-2 exon which maps within the\ human class I histocompatibility complex region and codes for a 166-amino-acid\ peptide similar to the C-terminal domain of human Sjoegren's syndrome nuclear\ antigen A/Ro (SS-A/Ro) and ret finger protein (RFP), Xenopus laevis nuclear factor 7\ (XNF7), and Bos taurus butyrophilin [MEDLINE:99083436]. The B30.2-like domain is found associated\ with different N-terminal domains: immunoglobulin domain in the case of\ butyrophilin, zinc-binding B-box domain in the case of RFP and SS-A/Ro and\ leucine zipper in the case of enterophilin. The function of the B30.2-like\ domain is not known, but the cytoplasmic B30.2-like domain of butyrophilin has\ been shown to interact with xanthine oxidase [MEDLINE:99083436].\

\ \ \N \N \N 20550 IPR001872

Bacterial cell walls contain large amounts of murein lipoprotein, a small protein that is both N-terminally bound to lipid and attached to membrane peptidoglycan (murein) through the epsilon-amino group of its C-terminal lysine residue [MEDLINE:95405254].Secretion of this lipoprotein is facilitated by the action of lipoprotein signal peptidase (also known as leader peptidase II), located in the inner membrane [MEDLINE:95405254], [MEDLINE:84162059]. The enzyme is inhibited by globomycin\ and also by pepstatin, suggesting that it is an aspartic peptidase [MEDLINE:95405254].

\ \

SPase II (EC: 3.4.23.36), also known as lipoprotein signal peptidase, recognizes a conserved sequence and cuts in front of a cysteine residue to which a glyceride-fatty acid lipid is attached. SPase II is an integral\ membrane protein that is anchored in the cytoplasmic membrane.

\ \

The catalytic residues have not been identified, but three conserved\ aspartates can be identified from sequence alignments.

\ \ aspartic-type endopeptidase activity ; GO:0004190 membrane ; GO:0016020 proteolysis and peptidolysis ; GO:0006508 20551 IPR001873

The apical membrane of many tight epithelia contains sodium channels thatare primarily characterised by their high affinity to the diuretic blocker\ amiloride [MEDLINE:94237395], [MEDLINE:97061613], [MEDLINE:97061613], [MEDLINE:96070858]. These channels mediate the first step of active sodium\ reabsorption essential for the maintenance of body salt and water\ homeostasis [MEDLINE:94237395]. In vertebrates, the channels control reabsorption of\ sodium in kidney, colon, lung and sweat glands; they also play a role in\ taste perception.

Members of the epithelial Na⁺ channel (ENaC) family fall into four\ subfamilies, termed , , gamma and delta [MEDLINE:97061613]. The proteins exhibit\ the same apparent topology, each with two transmembrane (TM) spanning\ segments, separated by a large extracellular loop. In most ENaC proteins\ studied to date, the extracellular domains are highly conserved and contain\ numerous cysteine residues, with flanking C-terminal amphipathic TM regions,\ postulated to contribute to the formation of the hydrophilic pores of the\ oligomeric channel protein complexes. It is thought that the well-conserved\ extracellular domains serve as receptors to control the activities of the\ channels.

Vertebrate ENaC proteins are similar to degenerins of Caenorhabditis elegans\ \ \ \ [MEDLINE:95014183]: deg-1, del-1, mec-4, mec-10 and unc-8. These proteins can be mutated to cause neuronal degradation, and are also thought to form sodium channels.

Structurally, the proteins that belong to this family consist of about 510\ to 920 amino acid residues. They are made of an intracellular N-terminus\ region followed by a transmembrane domain, a large extracellular loop, a\ second transmembrane segment and a C-terminal intracellular tail [MEDLINE:95014183].

\ \ sodium channel activity ; GO:0005272 membrane ; GO:0016020 sodium ion transport ; GO:0006814 20543 IPR001863

Glypicans [MEDLINE:96172815], [MEDLINE:95386580] are a family of heparan sulfate proteoglycans which are anchored to cell membranes by a glycosylphosphatidylinositol (GPI) linkage. Structurally, these proteins consist of three separate domains:

a) A signal sequence;
b) An extracellular domain of about 500 residues that contains 12 conserved cysteines probably involved in disulfide bonds and which also contains the sites of attachment of the heparan sulfate glycosaminoglycan side chains;
c) A C-terminal hydrophobic region which is post-translationally removed after formation of the GPI-anchor.

\ \ \N extracellular matrix ; GO:0005578 \N 20544 IPR001864

Trypanothione reductase from leishmania, and African and South American trypanosomes, has been purified and characterised [MEDLINE:91187059]. The enzymes have similar physical, mechanistic and kinetic properties, and are members of the flavoprotein disulphide oxidoreductase family. Trypanothione is the parasite analogue of glutathione, hence this enzyme is equivalent to glutathione reductase. It catalyses the reaction:

NADPH + trypanothione = NADP(+) + reduced trypanothione

Trypanothione reductase shows pronounced specificty for its disulphide substrates, trypanothione disulphide or glutathionylspermidine disulphide. The 3D structure of the enzyme has been determined and its mode of substrate binding revealed in detail [MEDLINE:94211757], offering hope for the design of drugs to combat Chagas disease. The structure belongs to the + class, i.e. with mainly anti-parallel -sheets separated by and regions. It contains an - sandwich characteristic of FAD/NAD-linked reductases and a C-terminal dimerisation domain.

\ \ disulfide oxidoreductase activity ; GO:0015036 \N electron transport ; GO:0006118 20545 IPR001865

\ \ \

Ribosomal S2 proteins have been shown to belong to a family that includes 40S ribosomal subunit 40kD proteins, putative laminin-binding proteins, NAB-1 protein and 29.3Kd protein from Haloarcula marismortui\ \ \ \ [MEDLINE:92184810], [MEDLINE:94164296]. The laminin-receptor proteins are thus predicted to be the eukaryotic homologue of the eubacterial S2 risosomal proteins [MEDLINE:95206934].

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 20539 IPR001858

Mammalian phosphatidylethanolamine-binding protein (also knowns as basic cytosolic 21 kDa protein) is an around 200 residue protein found in a variety of tissues [MEDLINE:95106305]. It binds hydrophobic ligands, such as phosphatidylethanolamine, but also seems [MEDLINE:95369465] to bind nucleotides such as GTP and FMN, it is suggested that it could act in membrane remodeling during growth and maturation.

This protein belongs to a family that includes proteins found in species ranging from plants to man.

\ \ \N \N \N 20540 IPR001859

\ \ \

Eukaryotic ribosomal P proteins have been classified according to their similarity to the mammalian P0, P1 and P2 proteins PUB00004501, all of which share a similar primary structure: an apparently globular N-terminal domain (which includes the protein core); an Ala-rich hinge region; and a highly-acidic Glu/Asp-rich C-terminal domain - this contains the ribosomal P consensus sequence EESDDDMGFGLFD, which protrudes from the ribosomal stalk.

The C-terminal regions of Trypanosoma cruzi P proteins are strongly immunogenic in Chagas disease. All 3 forms of the protein show the ability to generate autoimmune responses, but their antigenic properties differ as a result of discrepancies in their C-terminal sequences PUB00004501. The main linear epitope of the T.cruzi P1 and P2 proteins has been mapped to the 13-residue C-terminal sequence (R-13) EEEDDDMGFGLFD. This is identical to the eukaryotic P consensus, but has Ser substituted by Glu, yielding a more hydrophilic sequence, which is critical in determining the immunological reactivity of the T.cruzi R-13 epitope in Chagas disease.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 20541 IPR001860

Glycoside hydrolase family 34 CAZY:GH_34).

\ \

Neuraminidases cleave the terminal sialic acid residues from carbohydrate chains in glycoproteins. Sialic acid is a negatively charged sugar associated with the protein and lipid portions of lipoproteins. In Influenza virus, neuraminidases prevent self-aggregation by removing the carbohydrate from the viral envelope thus facilitating the mobility of the virus to and from the site of infection.\ Antiviral agents that inhibit influenza viral neuraminidase activity are of major importance in the control of influenza [MEDLINE:20024646].

\ \ exo-alpha-sialidase activity ; GO:0004308 membrane ; GO:0016020 carbohydrate metabolism ; GO:0005975 20542 IPR001862

The membrane-attack complex (MAC) of the complement system forms transmembrane channels. These channels disrupt the phospholipid bilayer of target cells, leading to cell lysis and death [MEDLINE:92126338], PUB00006592. A number of proteins participate in the assembly of the MAC. Freshly activated C5b binds to C6 to form a C5b-6 complex, then to C7 forming the C5b-7 complex. The C5b-7 complex binds to C8, which is composed of three chains (, , and gamma), thus forming the C5b-8 complex. C5b-8 subsequently binds to C9 PUB00006592, [MEDLINE:85257464], [MEDLINE:85063778] and acts as a catalyst in the olymerization of C9. Active MAC has a subunit composition of C5b-C6-C7-C8-C9{n}.

Perforin [MEDLINE:92126338], [MEDLINE:88334728] is a protein found in cytolytic T-cell and killer cells. In the presence of calcium, perforin polymerizes into transmembrane tubules and is capable of lysing, non-specifically, a variety of target cells [MEDLINE:90370039].

There are a number of regions of similarity in the sequences of complement components C6, C7, C8-, C8-, C9 and perforin.

\ \ \N \N \N 20536 IPR001855

Human, rabbit and\ guinea-pig -defensins, as well as human -defensin-2 (hBD2), induce the activation and degranulation of mast cells, resulting in the release of histamine and\ prostaglandin D2

\ \ antimicrobial peptide activity ; GO:0003795 extracellular ; GO:0005576 defense response ; GO:0006952 20537 IPR001856

mRNA for the SS3 receptor is widely distributed in mouse brain, with high\ levels in the forebrain, hippocampus and amygdala; moderate levels are also\ present in the substantia nigra . The receptors inhibit adenylyl cyclase\ through a pertussis-toxin-sensitive G-protein, probably belonging to the\ Gi/Go class PUB00005902.

\ \ somatostatin receptor activity ; GO:0004994 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20538 IPR001857

\ \ \

Ribosomal protein L19 is one of the proteins from the large ribosomal subunit [MEDLINE:94085364], [MEDLINE:91093287]. In Escherichia coli, L19 is known to be located at the 30S-50S ribosomal subunit interface [MEDLINE:78080790] and may play a role in the structure and function of the aminoacyl-tRNA binding site. It belongs to a family of ribosomal proteins, including L19 from eubacteria and red alga chloroplasts.

L19 is a protein of 120 to 130 amino-acid residues.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 20533 IPR001852

Snz1p is a highly conserved protein involved in growth arrest in S. cerevisiae [MEDLINE:97113448]. Sor1 (singlet oxygen resistance) is essential in pyridoxine (vitamin B6) synthesis in C. nicotianae and Aspergillus flavus. Pyridoxine\ quenches singlet oxygen at a rate comparable to that of vitamins C and E, two of the most highly efficient biological antioxidants, suggesting a previously unknown role for pyridoxine in\ active oxygen resistance. [MEDLINE:99362765].

\ \ molecular_function unknown ; GO:0005554 \N \N 20534 IPR001853 DSBA is a sub-family of the Thioredoxin family [MEDLINE:97293094]. The efficient and correct folding of bacterial disulfide bonded proteins in vivo is dependent upon a class of periplasmic oxidoreductase proteins called DsbA, after the Escherichia coli enzyme. The bacterial protein-folding factor DsbA is the most oxidizing of the thioredoxin family. DsbA catalyzes disulfide-bond formation during the folding of secreted proteins. The extremely oxidizing nature of DsbA has been proposed to result from either domain motion or stabilizing active-site interactions in the reduced form. DsbA's highly oxidizing nature is a result of hydrogen bond, electrostatic and helix-dipole interactions that favour the thiolate over the disulfide at the active site [MEDLINE:98322363]. In the pathogenic bacterium Vibrio cholerae, the DsbA homolog (TcpG) is responsible for the folding, maturation and secretion of virulence factors.

While the overall architecture of TcpG and DsbA is similar and the surface features are retained in TcpG, there are significant differences. For example, the kinked active site helix results from a three-residue loop in DsbA, but is caused by a proline in TcpG (making TcpG more similar to thioredoxin in this respect). Furthermore, the proposed peptide binding groove of TcpG is substantially shortened compared with that of DsbA due to a six-residue deletion. Also, the hydrophobic pocket of TcpG is more shallow and the acidic patch is much less extensive than that of E.coli DsbA [MEDLINE:97293094].

\ \ protein disulfide oxidoreductase activity ; GO:0015035 periplasmic space (sensu Gram-negative Bacteria) ; GO:0030288 \N 20535 IPR001854

\ \ \

Ribosomal protein L29 is one of the proteins from the large ribosomal subunit. L29 belongs to a family of ribosomal proteins of 63 to 138 amino-acid residues which, on the basis of sequence similarities PUB00005070, groups:\

Eubacterial L29.
Red Algal L29.
Bacterial L29.
Mammalian L35
Caenorhabditis elegans L35 (ZK652.4).
Yeast L35.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 20531 IPR001850 Flaviviruses produce a polyprotein from the ssRNA genome. The N-terminus of the NS3 protein (approx. 180 aa) is required for the processing of the polyprotein. NS3 also has conserved homology with NTP-binding proteins and DEAD family of RNA helicase [MEDLINE:95370229], [MEDLINE:91069238], [MEDLINE:94094568].\ ATP binding activity ; GO:0005524 \N \N 20532 IPR001851

The integral inner-membrane proteins translocate the substrate across the membrane. It has been shown [MEDLINE:86081738], [MEDLINE:95020621] that most of these proteins contain a conserved region located about 80 to 100 residues from their C-terminal extremity. This region seems [MEDLINE:92149312] to be located in a cytoplasmic loop between two transmembrane domains. Apart from the conserved region, the sequence of these proteins is quite divergent, however they can be classified into seven families which have been respectively termed: araH, cysTW, fecCD, hisMQ, livHM, malFG and oppBC.

\ \ transporter activity ; GO:0005215 membrane ; GO:0016020 transport ; GO:0006810 20530 IPR001849

The 'pleckstrin homology' (PH) domain is a domain of about 100 residues that occurs in a wide range of proteins involved in intracellular signaling or as constituents of the cytoskeleton [MEDLINE:93272305], [MEDLINE:93268380], [MEDLINE:94054654], [MEDLINE:95076505], [MEDLINE:95157628], [MEDLINE:95197706], [MEDLINE:96082954].

The function of this domain is not clear, several putative functions have been suggested:

binding to the

/gamma subunit of heterotrimeric G proteins,

binding to lipids, e.g. phosphatidylinositol-4,5-bisphosphate,

binding to phosphorylated Ser/Thr residues,

attachment to membranes by an unknown mechanism.

It is possible that different PH domains have totally different ligand requirements.

The 3D structure of several PH domains has been determined [MEDLINE:95360723]. All known cases have a common structure consisting of two perpendicular anti-parallel sheets, followed by a C-terminal amphipathic helix. The loops connecting the -strands differ greatly in length, making the PH domain relatively difficult to detect. There are no totally invariant residues within the PH domain.

Proteins reported to contain one more PH domains belong to the following families:

Pleckstrin, the protein where this domain was first detected, is the major substrate of protein kinase C in platelets. Pleckstrin is one of the rare proteins to contains two PH domains.
Ser/Thr protein kinases such as the Akt/Rac family, the -adrenergic receptor kinases, the mu isoform of PKC and the trypanosomal NrkA family.\
Tyrosine protein kinases belonging to the Btk/Itk/Tec subfamily.
Insulin Receptor Substrate 1 (IRS-1).
Regulators of small G-proteins like guanine nucleotide releasing factor GNRP (Ras-GRF) (which contains 2 PH domains), guanine nucleotide exchange proteins like vav, dbl, SoS and yeast CDC24, GTPase activating proteins like rasGAP and BEM2/IPL2, and the human break point cluster protein bcr.
Cytoskeletal proteins such as dynamin (see IPR001401 nuclear migration protein NUM1.
Mammalian phosphatidylinositol-specific phospholipase C (PI-PLC) (see IPR001401/>) isoforms gamma and delta. Isoform gamma contains two PH domains, the second one is split into two parts separated by about 400 residues.
Oxysterol binding proteins OSBP, yeast OSH1 and YHR073w.
Mouse protein citron, a putative rho/rac effector that binds to the GTP-bound forms of rho and rac.

yeast

Caenorhabditis elegans protein MIG-10.
Caenorhabditis elegans hypothetical proteins C04D8.1, K06H7.4 and ZK632.12.
Yeast hypothetical proteins YBR129c and YHR155w.

\ \ \N \N \N 20528 IPR001847 Proteases can be grouped into four classes according to the prominent functional groups at the active sites: viz., the Ser, Asp, Cys and\ metalloproteases. 3D structures are known for examples from all these\ classes: e.g., trypsin (Ser), pepsin (Asp), papain (Cys), and \ carboxypeptidase (Zn).

A number of viral proteases have been discovered and attempts have been\ made to assign them to one or other of the above classes, but the extent\ of the sequence similarity is very low. Studies with protease inhibitors suggest that the herpesvirus protease is\ a Ser protease belonging to either the trypsin-like or subtilisin-like\ families; it is not inhibited by inhibitors of Cys, Asp or metallo\ proteases.

\ \ serine-type endopeptidase activity ; GO:0004252 \N proteolysis and peptidolysis ; GO:0006508 20529 IPR001848

\ \ \

Evidence suggests that, in prokaryotes, the peptidyl transferase reaction is performed by the large subunit 23S rRNA, whereas proteins probably have a greater role in eukaryotic ribosomes. Most of the proteins lie close to, or on the surface of, the 30S subunit, arranged peripherally around the rRNA [MEDLINE:97428328]. The small subunit ribosomal proteins can be categorised as primary binding proteins, which bind directly and independently to 16S rRNA; secondary binding proteins, which display no specific affinity for 16S rRNA, but its assembly is contingent upon the presence of one or more primary binding proteins; and tertiary binding proteins, which require the presence of one or more secondary binding proteins and sometimes other tertiary binding proteins.

The small ribosomal subunit protein S10 consists of about 100 amino acid residues. In Escherichia coli, S10 is involved in binding tRNA to the ribosome, and also operates as a transcriptional elongation factor [MEDLINE:94293315]. Experimental evidence [MEDLINE:98058740] has revealed that S10 has virtually no groups exposed on the ribosomal surface, and is one of the "split proteins": these are a discrete group that are selectively removed from 30S subunits under low salt conditions and are required for the formation of activated 30S reconstitution intermediate (RI*) particles. S10 belongs to a family of proteins [MEDLINE:90192741] that includes: eubacteria S10; algal chloroplast S10; cyanelle S10; archaebacterial S10; Marchantia polymorpha and Prototheca wickerhamii mitochondrial S10; Arabidopsis thaliana mitochondrial S10 (nuclear encoded); vertebrate S20; plant S20; and yeast URP2.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 20526 IPR001845

Bacterial transcription regulatory proteins that bind DNA via a helix-turn-helix (HTH) motif can be grouped into families on the basis of sequence similarities. One such group, termed arsR, includes several proteins that appear to dissociate from DNA in the presence of metal ions: arsR, which functions as a transcriptional repressor of an arsenic resistance operon; smtB from Synechococcus PCC 7942, which acts as a transcriptional repressor of the smtA gene that codes for a metallothionein; cadC, a protein required for cadmium-resistance; and hypothetical protein yqcJ from Bacillus subtilis.

The HTH motif is thought to be located in the central part of these proteins [MEDLINE:93197158]. The motif is characterised by a number of well-conserved residues: at its N-terminal extremity is a cysteine residue; a second Cys is found in arsR and cadC, but not in smtA; and at the C-terminus lie one or two histidines. These residues may be involved in metal-binding (Zn in smtB; metal-oxyanions such as arsenite, antimonite and arsenate for arsR; and cadmium for cadC) [MEDLINE:93281406]. It is believed that binding of a metal ion could induce a conformational change that would prevent the protein from binding DNA [MEDLINE:93281406].

\ \ transcription factor activity ; GO:0003700 intracellular ; GO:0005622 regulation of transcription, DNA-dependent ; GO:0006355 20527 IPR001846

A family of growth regulators (originally called cef10, connective tissue growth factor, fisp-12, cyr61, or, alternatively, IG-M1 and IG-M2), all belong to immediate-early genes expressed after induction by growth factors or certain oncogenes. Sequence analysis of this family revealed the presence of four distinct modules. Each module has homologues in other extracellular mosaic proteins such as Von Willebrand factor, slit, thrombospondins, fibrillar collagens, IGF-binding proteins and mucins. Classification and analysis of these modules suggests the location of binding regions and, by analogy to better characterized modules in other proteins, sheds some light onto the structure of this new family [MEDLINE:93327926].

The vWF domain is found in various plasma proteins:\ complement factors B, C2, CR3 and CR4; the integrins (I-domains); collagen \ types VI, VII, XII and XIV; and other extracellular proteins [MEDLINE:94018965], [MEDLINE:94194513], [MEDLINE:91323531]. Although the majority of VWA-containing proteins are extracellular, the most ancient ones present in all eukaryotes are all intracellular proteins involved in functions such as transcription, DNA repair, ribosomal and membrane transport and the proteasome. A common feature appears to be involvement in multiprotein complexes. Proteins\ that incorporate vWF domains participate in numerous biological events\ (e.g. cell adhesion, migration, homing, pattern formation, and signal\ transduction), involving interaction with a large array of ligands [MEDLINE:94018965]. A number of human diseases arise from mutations in VWA domains. Secondary structure prediction from 75 aligned vWF sequences has revealed a largely alternating sequence of -helices and -strands [MEDLINE:94194513].

One of the functions of von Willebrand factor (vWF) is to serve as a carrier of clotting factor VIII (FVIII). The native conformation of the D' domain of vWF is not only required for factor VIII (FVIII) binding but also for normal multimerization and optimal secretion [MEDLINE:20269787].

\ \ \N \N \N 20525 IPR001844

The assembly of proteins has been thought to be the sole result of properties inherent in the primary sequence of polypeptides themselves. In some cases, however, structural information from other protein molecules is required for correct folding and subsequent assembly into oligomers [MEDLINE:88232881]. These 'helper' molecules are referred to as molecular chaperones, a subfamily of which are the chaperonins [MEDLINE:92256809]. They are required for normal cell growth (as demonstrated by the fact that no temperature sensitive mutants for the chaperonin genes can be found in the temperature range 20 to 43 degrees centigrade [MEDLINE:88232881]), and are stress-induced, acting to stabilise or protect disassembled polypeptides under heat-shock conditions [MEDLINE:92256809]. Type I chaperonins present in eubacteria, mitochondria and chloroplasts require the concerted action of 2 proteins, chaperonin 60 (cpn60) and chaperonin 10 (cpn10). Type II chaperonins, found in eukaryotic cytosol and in Archaebacteria, comprise only a cpn60 member.

The 10 kDa chaperonin (cpn10 - or groES in bacteria) exists as a ring-shaped oligomer of between 6 to 8 identical subunits, whereas the 60 kDa chaperonin (cpn60 - or groEL in bacteria) forms a structure comprising 2 stacked rings, each ring containing 7 identical subunits [MEDLINE:88232881]. These ring structures assemble by self-stimulation in the presence of Mg2+-ATP. The \ central cavity of the cylindrical cpn60 tetradecamer provides as isolated environment for protein folding whilst cpn-10 binds to cpn-60 and synchronizes the release of the folded protein in an Mg²⁺-ATP dependent manner [MEDLINE:92283754], [MEDLINE:92256809]. The binding of cpn10 to cpn60 inhibits the weak ATPase activity of cpn60.

The 60 kDa form of chaperonin is the immunodominant antigen of patients with Legionnaire's disease [MEDLINE:91169238], and is thought to play a role in the protection of the Legionella sp. bacteria from oxygen radicals within macrophages. This hypothesis is based on the finding that the cpn60 gene is upregulated in response to hydrogen peroxide, a source of oxygen radicals. Cpn60 has also been found to display strong antigenicity in many bacterial species [MEDLINE:92182006], and has the potential for inducing immune protection against unrelated bacterial infections. The RuBisCO subunit binding protein (which has been implicated in the assembly of RuBisCO) and cpn60 have been found to be evolutionary homologues, the RuBisCO subunit binding protein having the C-terminal Gly-Gly-Met repeat found in all bacterial cpn60 sequences. Although the precise function of this repeat is unknown, it is thought to be important as it is also found in 70 kDa heat-shock proteins [MEDLINE:91169238]. The crystal structure of E. coli GroEL has been resolved to 2.8A [MEDLINE:95021709].

\ \ \ \N \N \N 20520 IPR001839

Transforming growth factor- (TGF-) PUB00006591 is a multifunctional peptide that controls proliferation, differentiation and other functions in many cell types. TGF--1 is a peptide of 112 amino acid residues derived by proteolytic cleavage from the C-terminal of a precursor protein.

A number of proteins are known to be related to TGF--1 PUB00006591, [MEDLINE:92246938], [MEDLINE:94257860]. Proteins from the TGF- family are only active as homo- or heterodimer; the two chains being linked by a single disulfide bond. From X-ray studies of TGF--2 [MEDLINE:92335881], it is known that all the other cysteines are involved in intrachain disulfide bonds. As shown in the following schematic representation, there are four disulfide bonds in the TGF-'s and in inhibin chains, while the other members of this family lack the first bond.

\ \

\ interchain\ |\ +------------------------------------------|+\ | ||\ xxxxcxxxxxCcxxxxxxxxxxxxxxxxxxCxxCxxxxxxxxxxxxxxxxxxxCCxxxxxxxxxxxxxxxxxxxCxCx\ | | | | | |\ +------+ +--|----------------------------------------+ |\ +------------------------------------------+\ \ 'C': conserved cysteine involved in a disulfide bond.\

\ \ \N \N \N 20521 IPR001840

Complement components C3, C4 and C5 are large glycoproteins that have important functions in the immune response and host defence [MEDLINE:93056528]. They have a wide variety of biological activities and are proteolytically activated by cleavage at a specific site, forming a- and b-fragments [MEDLINE:89380278]. A-fragments form distinct structural domains of approximately 76 amino acids, coded for by a single exon within the complement protein gene. The C3a, C4a and C5a components are referred to as anaphylatoxins [MEDLINE:89380278], [MEDLINE:86136134]: they cause smooth muscle contraction, histamine release from mast cells, and enhanced vascular permeability [MEDLINE:86136134]; they also mediate chemotaxis, inflammation, and generation of cytotoxic oxygen radicals [MEDLINE:86136134]. The proteins are highly hydrophilic, with a mainly -helical structure held together by 3 disulphide bridges [MEDLINE:86136134].

\ \ complement activity ; GO:0003811 extracellular ; GO:0005576 complement activation ; GO:0006956 20522 IPR001841

The RING-finger is a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc, and is probably involved in mediating protein-protein interactions. [MEDLINE:93304824], [MEDLINE:96397942], [MEDLINE:96280420]. There are two different variants, the C3HC4-type and a C3H2C3-type, which is clearly related despite the different cysteine/histidine pattern. The latter type is sometimes referred to as 'RING-H2 finger'.

The RING domain is a protein interaction domain which has been implicated in a range of diverse biological processes.\ E3 ubiquitin-protein ligase activity is intrinsic to the RING domain of\ c-Cbl and is likely to be a general function of this domain; Various RING\ fingers exhibit binding to E2 ubiquitin-conjugating enzymes (Ubc's) [MEDLINE:20130827], [MEDLINE:99445925], [MEDLINE:20005208].\

\ \

Several 3D-structures for RING-fingers are known [MEDLINE:96397942], [MEDLINE:96280420]. The 3D structure of the zinc ligation system is unique to the RING domain and is refered to as the 'cross-brace' motif. The spacing of the cysteines in such a domain is C-x(2)-C-x(9 to 39)-C-x(1 to 3)-H-x(2 to 3)-C-x(2)-C-x(4 to 48)-C-x(2)-C. Metal ligand pairs one and three co-ordinate to bind one zinc ion, whilst pairs two and four bind the second, as illustrated in the following schematic representation:

\ x x x x x x\ x x x x\ x x x\ x x x x\ C C C C\ x \\ / x x \\ / x\ x Zn x x Zn x\ C / \\ C H / \\ C\ x x x x\ x x x x x x x x x x x x x\ \ 'C': conserved cysteine involved zinc binding.\ 'H': conserved histidine involved in zinc binding.\ 'Zn': zinc atom.

\ Note that in the older literature, some RING-fingers are denoted as LIM-domains. The LIM-domain Zn-finger is a fundamentally different family, albeit with similar Cys-spacing (see IPR001781).\ \ \N \N \N 20523 IPR001842

Metalloproteases can be split into five clans, and futher sub-divided into families, on the basis of their metal binding residues.

Fungalysin is a zinc-containing metallopeptidase that belongs to the M36\ family of clan MA. It is produced by fungi (Aspergillus and other\ species) to aid degradation of host lung cell walls on infection. The\ enzyme is a 42kDa single chain protein, with a pH optimum of 7.5-8.0 and\ optimal temperature of 60 celcius PUB00005938.

\ \ metalloendopeptidase activity ; GO:0004222 extracellular ; GO:0005576 proteolysis and peptidolysis ; GO:0006508 20524 IPR001843

Metalloproteases can be split into five clans, and futher sub-divided into families, on the basis of their metal binding residues.

Fragilysin is a zinc-containing enterotoxin that belongs to the M10C\ metallopeptidase family, which form part of the MB clan . It is produced\ by around 10% of pathogenic strains of the bacterium Bacteroides fragilis\ (which is found in mammalian large intestines in approximately the same\ quantities as Escherichia coli), and has been shown to cause diarrhoea.\ The fragilysin enterotoxin acts by proteolytically damaging the intestinal\ epithelium (at the tight junctions and basement membranes), causing the\ release of fluids into the intestinal lumen. In view of the intrinsic\ resistance of the intestinal tract to protease activity (it being constantly\ bathed in digestive proteases), an enzyme activity capable of puncturing\ the epithelium is considered rather unusual. However the exact mechanism of\ action of the protein is unknown PUB00005938.

\ \ metalloendopeptidase activity ; GO:0004222 extracellular ; GO:0005576 proteolysis and peptidolysis ; GO:0006508 20517 IPR001835

E.coli heat-labile enterotoxin is a bacterial protein toxin with an AB5 multimer structure, in which the B pentamer has a membrane-binding function and the A chain (IPR001144.

The A subunit has a less well-defined secondary structure. It predominantly interacts with the pentamer via the C-terminal A2 fragment, which runs through the charged central pore of the B subunits. A putative catalytic residue in the A1 fragment (Glu112) lies close to a hydrophobic region, which packs two loops together. It is thought that this region might be important for catalysis and membrane translocation [MEDLINE:93240541].

\ \ toxin activity ; GO:0015070 extracellular ; GO:0005576 pathogenesis ; GO:0009405 20518 IPR001837

\ \ \N \N \N 20519 IPR001838

\ \ inward rectifier potassium channel activity ; GO:0005242 membrane ; GO:0016020 potassium ion transport ; GO:0006813 20515 IPR001833 There has been a number of studies relative to the specificity of cAMP- and cGMP-dependent protein kinases [MEDLINE:80182327], [MEDLINE:84087865], [MEDLINE:86140057]. Both types of kinases appear to share a preference for the phosphorylation of serine or threonine residues found close to at least two consecutive N-terminal basic residues. It is important to note that there are quite a number of exceptions to this rule.

Note: No protein matches are shown due to the low specificity of this rule.

\ \ \N \N \N 20516 IPR001834

ferredoxin:NADP⁺ reductases (FNR) [MEDLINE:94299474].
plant and fungal NAD(P)H:nitrate reductases [MEDLINE:92084635], [MEDLINE:90371632].
NADH:cytochrome b5 reductases [MEDLINE:88007457].
NADPH:P450 reductases.
NADPH:sulphite reductases.
nitric oxide synthases.
phthalate dioxygenase reductase.
and various other flavoproteins.

NADH:cytochrome b5 reductase (CBR) serves as electron donor for cytochrome b5, a ubiquitous electron carrier (see IPR001199.

In biological nitrate assimilation, reduction of nitrate to nitrite is catalysed by the multidomain redox enzyme NAD(P)H:nitrate reductase (NR). Three forms of NR are known: an NADH-specific enzyme found in higher plants and algae (EC: 1.7.1.1); an NAD(P)H-bispecific enzyme found in higher plants, algae and fungi (EC: 1.7.1.2); and an NADPH-specific enzyme found only in fungi (EC: 1.7.1.3) [MEDLINE:90371632]. NR can be divided into 3 structure/function domains: the molybdopterin cofactor binds in the N-terminal domain; the central region is the cytochrome b domain, which is similar to animal cytochrome b5 (see IPR001199/>); and the C-terminal portion of the protein is occupied by the FAD/NAD(P)H binding domain, which is similar to CBR [MEDLINE:90371632]. The catalytic reduction of nitrate to nitrite can be viewed as a single polypeptide electron transport chain with electron flow from NAD(P)H -> FAD -> cytochrome b5 -> molybdopterin -> NO(3). Thus, the flavin domain of NR is functionally identical to CBR.

To date, the 3D-structures of the flavoprotein domain of Zea mays nitrate reductase [MEDLINE:95111952] and of pig NADH:cytochrome b5 reductase [MEDLINE:95200895] have been solved. The overall fold is similar to that of ferredoxin:NADP⁺ reductase [MEDLINE:94299474]: the FAD-binding domain (N-terminal) has the topology of an anti-parallel -barrel, while the NAD(P)-binding domain (C-terminal) has the topology of a classical pyridine dinucleotide-binding fold (i.e. a central parallel -sheet flanked by 2 helices on each side).

\ \ oxidoreductase activity ; GO:0016491 \N electron transport ; GO:0006118 20514 IPR001831

Like other lentiviruses, human immunodeficiency virus type 1 (HIV-1) encodes a trans-activating regulatory protein (Tat), which is essential for efficient transcription of the viral genome [MEDLINE:91354039], [MEDLINE:94336723]. Tat acts by binding to an RNA stem-loop structure, the trans-activating response element (TAR), found at the 5' ends of nascent HIV-1 transcripts. In binding to TAR, Tat alters the properties of the transcription complex, recruits a positive transcription elongation complex (P-TEFb) and hence increases the production of full-length viral RNA [MEDLINE:94336723]. Tat protein also associates with RNA polymerase II complexes during early transcription elongation afterthe promoter clearance and before the synthesis of full-length TAR RNA transcript. This interaction of Tat with RNA polymerase II elongation\ complexes is P-TEFb-independent. There are two Tat binding sites on each transcription elongation complex; one is located on\ TAR RNA and the other one on RNA polymerase II near the exit site for nascent mRNA transcripts which suggests that two Tat molecules are\ involved in performing various functions during a single round of HIV-1 mRNA synthesis [Zhou and Rana, J.Mol. Biol. 320(5) 925-942].

The minimum Tat sequence that can mediate specific TAR binding in vitro has been mapped to a basic domain of 10 amino acids, comprising mostly Arg and Lys residues. Regulatory activity, however, also requires the 47 N-terminal residues, which interact with components of the transcription complex and function as a transcriptional activation domain [MEDLINE:94336723], [MEDLINE:90352710], [MEDLINE:94166886].

\ \ transcription factor activity ; GO:0003700 host cell nucleus ; GO:0042025 regulation of transcription, DNA-dependent ; GO:0006355 20512 IPR001829

Most Gram-negative bacteria possess a supramolecular structure - the pili - on their surface, that mediates attachment to specific receptors. Many interactive subunits are required to assemble pili, but their assembly only takes place after translocation across the cytoplasmic membrane.

Periplasmic chaperones assist pili assembly by binding to the subunits, thereby preventing premature aggregation [MEDLINE:96324387], [MEDLINE:92074812]. This family of chaperones are structurally, and possibly evolutionarily, related to the immunoglobulin superfamily [MEDLINE:92224901]: they contain two globular domains, with a topology identical to an immunoglobulin fold.

\ \ chaperone activity ; GO:0003754 periplasmic space (sensu Gram-negative Bacteria) ; GO:0030288 cell wall organization and biogenesis ; GO:0007047 20513 IPR001830

Glycosyltransferase family 20 CAZY:GT_20).

\ \ \

Synthesis of trehalose in the yeast Saccharomyces cerevisiae is catalysed by the trehalose-6-phosphate (Tre6P) synthase/phosphatase complex, which is composed of at least three different subunits encoded by the genes TPS1, TPS2, and TSL1. Tps1 and Tps2 carry the catalytic activities of trehalose synthesis, namely Tre6P synthase (Tps1) and Tre6P phosphatase (Tps2), while TsI1 has regulatory functions. There is some evidence that TsI1 and Tps3\ may share a common function with respect to regulation and/or structural stabilization of the Tre6P synthase/phosphatase complex in exponentially growing, heat-shocked cells PUB00007032.

OtsA (trehalose-6-phosphate synthase) from Escherichia coli has homology to the full-length TPS1, the N-terminal part of TPS2 and an internal region of TPS3 (TSL1) of yeast [MEDLINE:94320793].

\ \ alpha,alpha-trehalose-phosphate synthase (UDP-forming) activity ; GO:0003825 \N trehalose biosynthesis ; GO:0005992 20509 IPR001827

The homeobox is a 60-residue motif first identified in a number of Drosophila homeotic and segmentation proteins, but now known to be well-conserved in many other animals, including vertebrates\ \ \ [MEDLINE:93032126], [MEDLINE:89323170], PUB00005540. Proteins containing homeobox domains are likely to play an important role in development - most are known to be sequence-specific DNA-binding transcription factors. The domain binds DNA through a helix-turn-helix (HTH) structure.

Many homeodomain-containing proteins have now been sequenced and, while the homeodomain flanking regions vary, characteristic conserved sequences upstream of the domain allow the proteins to be grouped into 3 subfamilies: the so-called antennapedia, engrailed and 'paired box' proteins. Antennapedia, which regulates the formation of leg structures in Drosophila, was one of the first homeotic genes studied and led to the discovery of the homeobox domain. Over expression of this gene in the wrong segment of the fruit fly can lead to the formation of leg structures in these segments. For example, over expression in the head segment can lead to the formation of legs instead of antennae (hence the name antennapedia). The sequences of the antennapedia proteins contain a conserved hexapeptide 5-16 residues upstream of the homeobox, the specific function of which is unclear. The six Drosophila proteins that belong to this group are antennapedia (Antp), abdominal-A (abd-A), deformed (Dfd), proboscipedia (pb), sex combs reduced (scr) and ultrabithorax (ubx) and are collectively known as the 'antennapedia' subfamily.

In vertebrates the corresponding Hox genes are known PUB00005540 as Hox-A2, A3, A4, A5, A6, A7, Hox-B1, B2, B3, B4, B5, B6, B7, B8, Hox-C4, C5, C6, C8, Hox-D1, D3, D4 and D8.

Caenorhabditis elegans lin-39 and mab-5 are also members of the 'antennapedia' subfamily.

Arg and Lys are most frequently found in the last position of the hexapeptide; other amino acids are found in only a few cases.

\ \ transcription factor activity ; GO:0003700 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 20510 IPR001828 This describes a ligand binding domain and includes extracellular ligand binding domains of a wide range of receptors, as well as the bacterial amino acid binding proteins of known structure [MEDLINE:94280862].\ \N \N \N 20511 IPR001829

\ \ chaperone activity ; GO:0003754 periplasmic space (sensu Gram-negative Bacteria) ; GO:0030288 cell wall organization and biogenesis ; GO:0007047 20507 IPR001824 A number of growth factors stimulate mitogenesis by interacting with a family of cell surface receptors which possess an intrinsic, ligand-sensitive, protein tyrosine kinase activity [MEDLINE:89024579]. These receptor tyrosine kinases (RTK) all share the same topology: an extracellular ligand-binding domain, a single transmembrane region and a cytoplasmic kinase domain. However they can be classified into at least five groups. The class III RTK's are characterized by the presence of five to seven immunoglobulin-like domains [MEDLINE:89163913] in their extracellular section. Their kinase domain differs from that of other RTK's by the insertion of a stretch of 70 to 100 hydrophilic residues in the middle of this domain. The receptors currently known to belong to class III are:

Platelet-derived growth factor receptor (PDGF-R). PDGF-R exists as a homo- or heterodimer of two related chains: and [MEDLINE:90220609].
Macrophage colony stimulating factor receptor (CSF-1-R) (also known as the fms oncogene).
Stem cell factor (mast cell growth factor) receptor (also known as the kit oncogene).
Vascular endothelial growth factor (VEGF) receptors Flt-1 and Flk-1/KDR [MEDLINE:93038639].
Fl cytokine receptor Flk-2/Flt-3 [MEDLINE:94084791].
The putative receptor Flt-4 [MEDLINE:93241723].

\ \ \ ATP binding activity ; GO:0005524 membrane ; GO:0016020 transmembrane receptor protein tyrosine kinase signaling pathway ; GO:0007169 20508 IPR001826

RHS elements are proteins of non-essential function believed to play an important role in the natural ecology of the cell. The protein sequences comprise highly conserved 141 kDa domain containing multiple tandem 22-residue repeats, followed by divergent C-terminal domains [MEDLINE:90094253], [MEDLINE:95020608]. The 22 residue repeats contain a YD dipeptide which is the most strongly conserved motif of the repeat.

\ \ \N \N \N 20504 IPR001819

Chromogranins and secretogranins are acidic proteins present in the secretory granules of endocrine and neuro-endocrine cells [MEDLINE:91272289], [MEDLINE:90056400]. Granins may be precursors of biologically-active peptides, or they may be helper proteins in the packaging of peptide hormones and neuropeptides - their precise role is unclear.

Chromogranins A and B are characterised by an N-terminal motif that includes 2 cysteine residues involved in disulphide bond formation.

\ \ \N \N \N 20505 IPR001820 Tissue inhibitors of metalloproteinases (TIMP) are a family of proteins [MEDLINE:90008902], [MEDLINE:91216377], [MEDLINE:92381050] that can form complexes with extracellular matrix metalloproteinases (such as collagenases) and irreversibly inactivate them. Members of this family are common in extracellular regions of vertebrate species [MEDLINE:95001883]. TIMP's are proteins of about 200 amino acid residues, 12 of which are cysteines involved in disulfide bonds [MEDLINE:90303199]. The basic structure of such a type of inhibitor is shown in the following schematic representation:

\
          +-----------------------------+         +--------------+\
          |                             |         |              |\
        CxCxCxxxxxxxxxxxxxxxxxCxxxxxxxxxCxxxxxxxCxCxCxCxCxxxxxCxxCxxx\
        |   |                 |                 |   | | |     |\
        |   +-----------------|-----------------+   +-+ +-----+\
        +---------------------+\
\
'C': conserved cysteine involved in a disulfide bond.\

\ \ metalloendopeptidase inhibitor activity ; GO:0008191 extracellular matrix ; GO:0005578 \N 20506 IPR001821

Hydrogenases catalyse the reversible oxidation of molecular hydrogen and play a vital role in anaerobic metabolism. Metal-containing hydrogenases are subdivided into three classes: Fe ('iron only') hydrogenases; Ni-Fe hydrogenases; and Ni-Fe-Se hydrogenases [MEDLINE:90198522]. Hydrogen oxidation is coupled to the reduction of electron acceptors (such as oxygen, nitrate, sulphate, carbon dioxide and fumarate), whereas proton reduction (hydrogen evolution) is essential in pyruvate fermentation or in the disposal of excess electrons.

The Ni-Fe hydrogenases, when isolated, are found to catalyse both hydrogen evolution and uptake, with low-potential multihaem cytochromes, such as cytochrome c3, acting as either electron donors or acceptors, depending on their oxidation state PUB00003575. Both periplasmic (soluble) and membrane-bound hydrogenases are known.

The Ni-Fe hydrogenases are heterodimeric proteins consisting of small (S) and large (L) subunits. The small subunit contains three iron-sulphur clusters (two [4Fe-4S] and one [3Fe-4S]); the large subunit contains a nickel ion PUB00003575, [MEDLINE:92215587]. Small subunits of membrane-bound Ni-Fe hydrogenases contain a C-terminal domain of about 40 residues that is absent in periplasmic forms.

The 3D structure of the Ni-Fe hydrogenase from Desulfovibrio gigas has been determined at 2.85A resolution [MEDLINE:95157629]. The small subunit consists of two domains, I(S) and II(S). The / twisted open sheet structure of the N-terminal I(S) domain is similar to that of flavodoxin; the C-terminal II(S) domain contains two -helices and has no -structure. The Fe-S clusters are distributed almost along a straight line, with the [3Fe-4S] cluster located half-way between the two [4Fe-4S] clusters. The two [4Fe-4S] clusters have been termed proximal (prox) and distal (dist), based on their distance to the Ni atom. Domain I(S) binds the [4Fe-4S]prox cluster, while domain II(S) binds the [4Fe-4S]dist and [3Fe-4S] clusters. The [4Fe-4S]prox cluster is coordinated by Cys-17, Cys-20, Cys-112 and Cys-148; [4Fe-4S]dist is coordinated by His-185, Cys-188, Cys-213 and Cys-219; and [3Fe-4S] is coordinated by Cys-228, Cys-246 and Cys-249. [4Fe-4S]dist is the first known example of a [4Fe-4S] cluster in protein structure ligated by a His side chain. A crown of acidic residues surrounds the partially-exposed His-185 and this might provide a recognition site for the redox partner (cytochrome c3) [MEDLINE:95157629]. A mechanism of electron transfer from the Ni active site through the Fe-S clusters to the cytochrome c3 has been suggested [MEDLINE:95157629]. The role of the [3Fe-4S] cluster is not clear: its high redox potential and its absence from some homologous hydrogenases put its involvement in electron transfer in doubt [MEDLINE:95157629].

\ \ hydrogenase activity ; GO:0008901 hydrogenase complex ; GO:0009375 electron transport ; GO:0006118 20502 IPR001818

Extracellular metalloproteases, such as collagenase and stromelysin, whichdegrade the extracellular matrix, are known as matrixins. They are zinc-dependent,\ calcium-activated proteases synthesised as inactive precursors\ (zymogens), which are proteolytically cleaved to yield the active enzyme\ [MEDLINE:90008879], [MEDLINE:90361016]. All matrixins and related proteins possess 2 domains: an N-terminal\ domain, and a zinc-binding active site domain. The N-terminal domain\ peptide, cleaved during the activation step, includes a conserved PRCGVPDV\ octapeptide, known as the cysteine switch, whose Cys residue chelates the\ active site zinc atom, rendering the enzyme inactive. The active enzyme\ degrades components of the extracellular matrix, playing a role in the\ initial steps of tissue remodelling during morphogenesis, wound healing,\ angiogenesis and tumour invasion [MEDLINE:90008879], [MEDLINE:90361016].

\ \ \ metalloendopeptidase activity ; GO:0004222 extracellular matrix ; GO:0005578 proteolysis and peptidolysis ; GO:0006508 20503 IPR001818

\ \ \ metalloendopeptidase activity ; GO:0004222 extracellular matrix ; GO:0005578 proteolysis and peptidolysis ; GO:0006508 20500 IPR001816

In prokaryotes elongation factor Ts (EF-Ts) is a component of the elongation cycle of protein biosynthesis. It associates with the EF-Tu.GDP complex and induces the exchange of GDP to GTP, it remains bound to the aminoacyl-tRNA.EF-Tu.GTP complex up to the GTP hydrolysis stage on the ribosome [MEDLINE:92345336].

EF-Ts is also a component of the chloroplast protein biosynthetic machinery and is encoded in the genome of some algal chloroplast [MEDLINE:94033298]. It is also present in mitochondria [MEDLINE:95340508].

\ \ \ translation elongation factor activity ; GO:0003746 \N translational elongation ; GO:0006414 20501 IPR001817

Vasopressin and oxytocin are members of the neurohypophyseal hormone family\ found in all mammalian species PUB00005908. They are present in high levels in the\ posterior pituitary. Vasopressin has an essential role in the control of\ the water content of the body, acting in the kidney to increase water and\ sodium absorption . In higher concentrations, vasopressin stimulates\ contraction of vascular smooth muscle, stimulates glycogen breakdown in the\ liver, induces platelet activation, and evokes release of corticotrophin\ from the anterior pituitary. Vasopressin and its analogues are used\ clinically to treat diabetes insipidus PUB00005908. Oxytocin stimulates contraction\ of uterine smooth muscle, and stimulates milk secretion in response to\ suckling by inducing contraction of myoepithelial cells in the mammary gland\ PUB00005908. Clinically, it is used to induce labour and promote lactation.

\ \ vasopressin receptor activity ; GO:0005000 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20499 IPR001815

Two additional clans (PA and PB) have been identified, these containing a\ mixture of serine, cysteine and threonine proteases. Clan PA contains a\ catalytically-active serine or cysteine nucleophilic residue as part of the\ ordered triad His, Asp, Ser (or Cys). Clan PB contains a serine, cysteine or\ threonine active residue at the N-terminus of the mature protease.

\ \

Capillovirus 36 kDa peptidases and non-peptidase homologues belong to the\ S35 serine protease family, which is part of the PA clan . In a number\ of capilloviruses that have been sequenced to date, an ORF has been\ identified that contains the consensus sequence Gly-Asp-Ser-Gly common\ to the active site of a number of serine proteases [MEDLINE:93033164]. Capilloviruses\ infect a number of different plant species, and can be detected by the\ presence of virions in leaf sap.

\ \ serine-type endopeptidase activity ; GO:0004252 \N proteolysis and peptidolysis ; GO:0006508 20498 IPR001814 Gene IV proteins are filamentous bacteriophage proteins [MEDLINE:81067903], [MEDLINE:85160831]. Their exact function is unknown, but they are thought to be involved in phage assembly and morphogenesis. The proteins are related to the bacterial general secretion pathway D (GSPD) family.\ molecular_function unknown ; GO:0005554 \N \N 20497 IPR001813

\ \ \

The 60S acidic ribosomal protein plays an important role in the elongation step of protein synthesis. This family includes archaebacterial L12, eukaryotic P0, P1 and P2 [MEDLINE:96282699].

The allergens in this family include allergens with the following designations: Alt a 6, Alt a 12, Cla h 3, Cla h 4 and Cla h 12.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 translational elongation ; GO:0006414 20496 IPR001812 The trypanosome parasite expresses these proteins to evade the immune response [MEDLINE:91039329]. The variant surface glycoprotein (VSG) of Trypanosoma brucei forms a coat on the surface of the parasite; by the expression of a series of antigenically distinct VSGs in the surface coat the parasite escapes the host immune response.

The 2.9A resolution crystal structure of the N-terminal domain of one variant, MITat 1.2, has been determined [MEDLINE:91039329]. The "top" of the protein, which in the surface coat may be exposed to the external environment, is formed from the ends of the two long helices, a short three-stranded -sheet, and a strand having irregular conformation that packs above these secondary structure elements. Two conserved disulfide bridges are in this part of the molecule. Several elements of the MITat 1.2 sequence, which contribute to the formation of the helix bundle structure, have been identified. These elements can be found in the sequences of several different VSGs, suggesting that to some extent the VSG structure is conserved in those variants [MEDLINE:98234224].

\ \ \N \N defense response ; GO:0006952 20495 IPR001811 Synonym(s): cytokine, intecrine

Many low-molecular weight factors secreted by cells including fibroblasts, macrophages and endothelial cells, in response to a variety of stimuli such as growth factors, interferons, viral transformation and bacterial products, are structurally related [MEDLINE:92000517], [MEDLINE:91145332], [MEDLINE:90076753]. Most members of this family of proteins seem to have mitogenic, chemotactic or inflammatory activities. These small cytokines are also called intercrines or chemokines. They are cationic proteins of 70 to 100 amino acid residues that share four conserved cysteine residues involved in two disulfide bonds, as shown in the following schematic representation:\

\ +------------------------------------+\ | |\ xxxxxxxxxxxxxxxxxxxxxxCxCxxxxxxxxxxxxxxxxxxxxxxxCxxxxxxxxxxxxCxxxxx\ | |\ +-------------------------+\ \ 'C': conserved cysteine involved in a disulfide bond.\

These proteins can be sorted into two groups based on the spacing of the two amino-terminal cysteines. In the first group (see IPR001089), they are adjacent (C-C).

\ \ \ chemokine activity ; GO:0008009 extracellular ; GO:0005576 immune response ; GO:0006955 20492 IPR001808 Numerous bacterial transcription regulatory proteins bind DNA via a helix-turn-helix (HTH) motif. These proteins are very diverse, but for convenience may be grouped into subfamilies on the basis of sequence similarity. One such family groups together a range of proteins, including anr, crp, clp, cysR, fixK, flp, fnr, fnrN, hlyX and ntcA [MEDLINE:91064083], [MEDLINE:93181282], [MEDLINE:91008963]. Within this family, the HTH motif is situated towards the C-terminus.\ \ transcription factor activity ; GO:0003700 intracellular ; GO:0005622 regulation of transcription, DNA-dependent ; GO:0006355 20493 IPR001809 The ospA and ospB genes encode the major outer membrane proteins of the Lyme disease spirochaete Borrelia burgdorferi\ \ \ [MEDLINE:89343634]. The deduced gene products OspA and OspB, contain 273 and 296 residues respectively [MEDLINE:89343634]. The two Osp proteins show a high degree of sequence similarity, indicating a recent evolutionary event. Molecular analysis and sequence comparison of OspA and OspB with other proteins has revealed similarity to the signal peptides of prokaryotic lipoproteins [MEDLINE:89343634], [MEDLINE:92219995].\ \ \N external outer membrane (sensu Gram-negative Bacteria) ; GO:0009279 \N 20494 IPR001810

The F-box domain was first described as a sequence motif found in cyclin-F that interacts with the protein SKP1 [MEDLINE:96319729], [MEDLINE:98004224]. This relatively conserved structural motif is present in numerous proteins and serves as a link between a target protein and a ubiquitin-conjugating enzyme. The SCF complex (e.g., Skp1-Cullin-F-box) plays a similar role as an E3 ligase in the ubiquitin protein degradation pathway [MEDLINE:98167912], [MEDLINE:98299162]. DifferentF-box proteins as a part of SCF complex recruit particular substrates for ubiquitination through specific proteinprotein interaction domains.

\ \

Many mammalian F-box domains contain leucine-rich or WD-40 repeats (IPR001680). However, several F-box\ proteins either have other previously described domains such as Sec7 domain found in FBS protein or do not contain defined proteinprotein\ interaction domains or motifs.

\ \ \N \N \N 20489 IPR001805

Adenosine kinase (ADK) phosphorylates adenosine and other related nucleosides [MEDLINE:96165550], [MEDLINE:97075030]. It is exclusive to eukaryotes [MEDLINE:97224402] and is a key enzyme in the purine salvage pathway. ADK catalyses the reaction:

 Adenosine + ATP = ADP + AMP

This reaction prevents toxic levels of adenosine building up within the cell. Experiments have been carried out on chick embryonic neurons to document the toxicity of adenosine, and the associated requirement for ADK [MEDLINE:98316912].

Adenosine and ATP have been connected with pain, and the control of pain PUB00001127, PUB00001127. Associated with this, adenosine has also been shown to have a number of anti-inflammatory activities PUB00001128. Human ADK bears little sequence similarity to other mammalian nucleoside kinases, but does share high similarity with some microbrial ribokinases and fructokinases, suggesting possible evolutionary connections PUB00001128, [MEDLINE:97075030].

\ \ adenosine kinase activity ; GO:0004001 \N purine salvage ; GO:0006166 20490 IPR001806 The Ras branch of the Ras superfamily consists of small GTPases most closely related to Ras and include the R-Ras, Rap, Ral, Rheb, Rin and Rit proteins. Although our understanding of Ras signaling and biology is now considerable, recent observations suggest that Ras function is more complex than previously believed. First, the three Ras proteins may not be functionally identical. Second, Ras function involves functional cross-talk with their close relatives [MEDLINE:20179483].\ \ GTP binding activity ; GO:0005525 \N small GTPase mediated signal transduction ; GO:0007264 20491 IPR001807

\ \

\ \ \

\ \ voltage-gated chloride channel activity ; GO:0005247 membrane ; GO:0016020 chloride transport ; GO:0006821 20488 IPR001804

3-isopropylmalate dehydrogenase (EC: 1.1.1.85) (IMDH) [MEDLINE:92085286], [MEDLINE:95291185] catalyzes the third step in the biosynthesis of leucine in bacteria and fungi, the oxidative decarboxylation of 3-isopropylmalate into 2-oxo-4-methylvalerate.

Tartrate dehydrogenase (EC: 1.1.1.93) [MEDLINE:94330710] catalyzes the reduction of tartrate to oxaloglycolate.

These enzymes are evolutionary related [MEDLINE:90046847], [MEDLINE:92085286], [MEDLINE:95291185], [MEDLINE:94330710]. The best conserved region of these enzymes is a glycine-rich stretch of residues located in the C-terminal section.

\ \ oxidoreductase activity ; GO:0016491 \N metabolism ; GO:0008152 20483 IPR001799

Ephrins are a family of proteins [MEDLINE:95140419] that are ligands of class V (EPH-related) receptor protein-tyrosine kinases (see IPR001426). These receptors and their ligands have been implicated in regulating neuronal axon guidance and in patterning of the developing nervous system and may also serve a patterning and compartmentalization role outside of the nervous system as well.

Ephrins are membrane-attached proteins of 205 to 340 residues. Attachment appears to be crucial for their normal function. Type-A ephrins are linked to the membrane via a glycosylphosphatidylinositol (GPI)-linkage, while type-B ephrins are type-I membrane proteins.

\ \ \ \N membrane ; GO:0016020 \N 20484 IPR001800

Members of this family are lipoproteins that are probably involved in evasion of the host immune system by pathogens [MEDLINE:98065943]. They are predominantly found in the Spirochaetaceae.

\ defense/immunity protein activity ; GO:0003793 external outer membrane (sensu Gram-negative Bacteria) ; GO:0009279 defense response ; GO:0006952 20485 IPR001801

The histone-like nucleoid-structuring (H-NS) protein belongs to a family of bacterial proteins that play a role in the formation of nucleoid structure and affect gene expression under certain conditions [MEDLINE:95180433].

\ \ DNA binding activity ; GO:0003677 intracellular ; GO:0005622 regulation of transcription, DNA-dependent ; GO:0006355 20486 IPR001802

An Heavy-Metal-Associated (HMA) domain (see IPR006121) has been found in the N-terminal regions of mercuric transport protein periplasmic component (gene merP) and plasmids carried by mercury-resistant Gram-negative bacteria, where it seems to be a mercury scavenger that specifically binds to one Hg²⁺ ion, passing this to mercuric reductase via the merT protein.

The structure of the mercuric ion-binding protein MerP from Shigella flexneri has been determined. The fold has been classed as a ferredoxin-like - sandwich, having a - - - architecture, with the two -helices overlaying a four-stranded anti-parallel -sheet [MEDLINE:97332449]. Structural differences between the reduced and mercury-bound forms of merP are localised to the metal-binding loop containing the consensus sequence GMTCXXC, the two cysteines of which are involved in bi-coordination of Hg²⁺ [MEDLINE:97332449].

\ \ mercury ion transporter activity ; GO:0015097 \N mercury ion transport ; GO:0015694 20487 IPR001803

Bluetongue virus (BTV) is a representative of the orbivirus genus of the Reoviridae\ \ \ [MEDLINE:95115758]. Orbiviruses infect mammalian hosts through insect vectors, causing economically-important diseases of domesticated animals\ \ \ \ [MEDLINE:95115758]. They possess a segmented, double-stranded RNA genome within a capsid that comprises four major polypeptides, designated VP2, VP3, VP5 and VP7. On entering a target cell, an outer layer, formed from VP2 and VP5, is removed, leaving an intact core within the cell [MEDLINE:95115758]. The core, which is 70nm across, contains 780 copies of VP7, which together form 260 trimeric 'bristly' capsomeres clothing an inner scaffold constructed from VP3 [MEDLINE:95115758].

The 3D structure of VP7 reveals two domains, one a -sandwich, the other a bundle of -helices, and a short C-terminal arm, which is thought to unite trimers during capsid formation [MEDLINE:95115758]. A concentration of methionine residues at the core of the molecule could provide plasticity, relieving structural mismatches during assembly [MEDLINE:95115758].

The 3D structure of baculovirus-expressed core protein VP7 of African horse sickness virus serotype 4 (AHSV-4) has been determined to 2.3A resolution [MEDLINE:96211513]. During crystallisation, the two-domain protein is cleaved, leaving only the top domain, in a manner reminiscent of bluetongue virus (BTV) VP7; this suggests that connections between top and bottom domains are relatively weak for these two distinct orbiviruses\ \ \ \ [MEDLINE:96211513]. The top domains of both BTV and AHSV VP7 are trimeric and structurally very similar. Electron density maps indicate an extra density feature along their molecular 3-fold axes, probably the result of an unidentified ion [MEDLINE:96211513]. The characteristics of the molecular surface indicate the possibility of attachment to the cell via attachment of an Arg-Gly-Asp (RGD) motif in the top domain of VP7 to a cellular integrin for both of these orbiviruses\ \ \ \ [MEDLINE:96211513].

\ \ structural molecule activity ; GO:0005198 viral capsid ; GO:0019028 \N 20481 IPR001795

The nucleotide sequence for the RNA of potato leafroll luteovirus (PLRV) has been determined [MEDLINE:89279282], [MEDLINE:89171329]. The sequence contains six large open reading frames (ORFs). The 5' coding region encodes two polypeptides of 28K and 70K, which overlap in different reading frames; it is suggested that the third ORF in the 5' block is translated by frameshift readthrough near the end of the 70K protein, yielding a 118K polypeptide [MEDLINE:89279282]. The C-terminal part of the 118K protein contains a consensus sequence for RNA-dependent RNA-polymerases [MEDLINE:89279282].

The genomic RNA sequence of cowpea southern bean mosaic virus (SBMV-C) has been determined [MEDLINE:88044510]. The genome contains four ORFs. The largest ORF encodes the two largest proteins translated in cell-free extracts from full-length virion RNA [MEDLINE:88044510]. Segments of the predicted amino acid sequence of this ORF resemble those of known viral RNA-polymerases, ATP-binding proteins and viral genome-linked proteins [MEDLINE:88044510].

The genome sequence of pea enation mosaic virus (PEMV) RNA 1 shows strong organisational relationships and sequence similarities to the beet western yellows-potato leafroll luteovirus subgroup [MEDLINE:91341468]. Sequence analysis reveals five predominant ORFs. The third ORF is characterised by a number of RNA-polymerase motifs and a helicase-like motif typical of RNA-dependent RNA-polymerases [MEDLINE:91341468]. It overlaps (out of frame) the ORF 2 product and is proposed to be expressed by a frameshift fusion of ORF 2 and ORF 3 [MEDLINE:91341468].

The PLRV sequence shows some similarities to the putative polymerase of SBMV\ \ \ \ [MEDLINE:88044510], and more extensive similarities to the corresponding beet western yellows virus polypeptide [MEDLINE:89057523].

\ \ RNA-directed RNA polymerase activity ; GO:0003968 \N transcription ; GO:0006350 20482 IPR001796

Dihydrofolate reductase (DHFR) (EC: 1.5.1.3) catalyses the NADPH-dependent reduction of dihydrofolate to tetrahydrofolate, an essential step in de novo synthesis both of glycine and of purines and deoxythymidine phosphate (the precursors of DNA synthesis) [MEDLINE:88145671], and important also in the conversion of deoxyuridine monophosphate to deoxythymidine monophosphate. Although DHFR is found ubiquitously in prokaryotes and eukaryotes, and is found in all dividing cells, maintaining levels of fully reduced folate coenzymes, the catabolic steps are still not well understood [MEDLINE:88254806].

Bacterial species possesses distinct DHFR enzymes (based on their pattern of binding diaminoheterocyclic molecules), but mammalian DHFRs are highly similar [MEDLINE:80049777]. The active site is situated in the N-terminal half of the sequence, which includes a conserved Pro-Trp dipeptide; the tryptophan has been shown [MEDLINE:83056867] to be involved in the binding of substrate by the enzyme. Its central role in DNA precursor synthesis, coupled with its inhibition by antagonists such as trimethoprim and methotrexate, which are used as anti-bacterial or anti-cancer agents, has made DHFR a target of anticancer chemotherapy. However, resistance has developed against some drugs, as a result of changes in DHFR itself [MEDLINE:90097935].

\ \ dihydrofolate reductase activity ; GO:0004146 \N nucleotide biosynthesis ; GO:0009165 20480 IPR001794 Friedreich ataxia is a progressive neurodegenerative disorder caused by loss of function mutations in the gene encoding frataxin (FRDA). Frataxin mRNA is predominantly expressed in tissues with a high metabolic rate (including liver, kidney, brown fat and heart). Mouse and yeast frataxin homologues contain a potential N-terminal mitochondrial targeting sequence, and human frataxin has been observed to co-localise with a mitochondrial protein. Furthermore, disruption of the yeast gene has been shown to result in mitochondrial dysfunction. Friedreich's ataxia is thus believed to be a mitochondrial disease caused by a mutation in the nuclear genome (specifically, expansion of an intronic GAA triplet repeat) [MEDLINE:96173952], [MEDLINE:96399023], [MEDLINE:97385237].\ \N mitochondrion ; GO:0005739 iron ion homeostasis ; GO:0006879 20479 IPR001793

Retinal pigment epithelium (RPE) hosts a putative GPCR. The RPE-retinal\ GPCR (RGR) covalently binds all-trans- and 11-cis-retinal after reduction\ by sodium borohydride [MEDLINE:95034741]. All-trans-retinal is bound preferentially over\ the 11-cis isomer. The human sequence is 86% identical to that of bovine\ RGR [MEDLINE:95034741], [MEDLINE:94081108], and a lysine residue, analogous to the retinaldehyde attachment\ site of rhodopsin, is conserved in TM domain 7 [MEDLINE:95034741]. The human gene, whose\ structure is distinct from that of the visual pigment genes, spans 14.8 kb\ and is split into 7 exons [MEDLINE:95034741]. This suggests that the rgr gene represents\ the earliest independent branch of the vertebrate opsin gene family [MEDLINE:95034741].\ Since the RGR gene product preferentially binds all-trans-retinal, it is\ thought that one of its functions may be to catalyse isomerisation of the\ chromophore by a retinochrome-like mechanism [MEDLINE:95034741].

\ \ G-protein coupled receptor activity ; GO:0004930 integral to membrane ; GO:0016021 phototransduction ; GO:0007602 20478 IPR001792

Acylphosphatase (EC: 3.6.1.7) is an enzyme of approximately 98 amino acid residues that specifically catalyses the hydrolysis of the carboxyl-phosphate bond of acylphosphates [MEDLINE:92147600], its substrates including 1,3-diphosphoglycerate and carbamyl phosphate [MEDLINE:89178637]. The enzyme has a mainly -sheet structure with 2 short -helical segments. It is distributed in a tissue-specific manner in a wide variety of species, although its physiological role is as yet unknown [MEDLINE:89178637]: it may, however, play a part in the regulation of the glycolytic pathway and pyrimidine biosynthesis [MEDLINE:88139273]. There are two known isozymes. One seems to be specific to muscular tissues, the other, called 'organ-common type', is found in many different tissues. While acylphosphatase have been so far only characterized in vertebrates, there are a number of bacterial and barchebacterial hypothetical proteins that are highly similar to that enzyme and that probably possess the same activity.

These proteins include:\

Escherichia coli putative acylphosphatase (EC: 3.6.1.7) (acylphosphate phosphohydrolase) (gene yccX).
Bacillus subtilis putative acylphosphatase (EC: 3.6.1.7) (acylphosphate phosphohydrolase) (gene yflL).
Archaeoglobus fulgidus hypothetical protein AF0818.

\ \ acylphosphatase activity ; GO:0003998 \N \N 20477 IPR001791

A homology domain first described in the long arm globular domain of laminin [MEDLINE:90368768]. Similar sequences also occurs in a large number of extracellular proteins. A general function of laminin-G repeats is not known, but in laminin it seems to bind to heparin [MEDLINE:93216822], [MEDLINE:98092298]. The structure of the laminin-G domain has been predicted to resemble that of pentraxin [MEDLINE:98153258].

Proteins with laminin-G domains include:\

Laminin.
Merosin.
Agrin.
Neurexins.
Vitamin K dependent protein S.
Sex steroid binding protein SBP/SHBG.
Drosophila proteins Slit, Crumbs, Fat.
several proteoglycan precursors.

\ \ \N \N \N 20474 IPR001788 This family may represent an RNA dependent RNA polymerase [MEDLINE:94094568]. The family contains the following proteins:

2A protein from bromoviruses\ \ \ \ [MEDLINE:94047331].
Putative RNA dependent RNA polymerase from tobamoviruses\ \ \ \ [MEDLINE:96323143].
Non structural polyprotein from togaviruses\ \ \ \ [MEDLINE:93188140].

\ \ RNA-directed RNA polymerase activity ; GO:0003968 \N transcription ; GO:0006350 20475 IPR001789 This domain receives the signal from the sensor partner in bacterial two-component systems. It is sometimes found N-terminal to a DNA binding effector domain [MEDLINE:95214091].\ DNA binding activity ; GO:0003677 \N regulation of transcription, DNA-dependent ; GO:0006355 20476 IPR001790

\ \ \

On the basis of sequence similarities the following prokaryotic and eukaryotic ribosomal proteins can be grouped:\

Bacterial 50S ribosomal protein L10;
Archaebacterial acidic ribosomal protein P0 homolog (L10E);
Eukaryotic 60S ribosomal protein P0 (L10E).

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 20471 IPR001784 The bunyaviruses are enveloped viruses with a genome consisting of 3 ssRNA segments (called L, M and S). The nucleocapsid protein is encode on the small (S) genomic RNA. The N protein is the major component of the nucleocapsids. This protein is thought to interact with the L protein, virus RNA and/or other N proteins [MEDLINE:95205077].\ \N viral nucleocapsid ; GO:0019013 \N 20472 IPR001786

At least eight sub-types of metabotropic receptor (MGR1-8) have been\ identified in cloning studies. The sub-types differ in their agonist\ pharmacology and signal transduction pathways PUB00005885.

MGR4 is brain-specific, showing a distinct distribution (excluding the cerebellum), being expressed\ in the thalamus, hypothalamus and caudate nucleus PUB00005885. In rat, the strongest\ MGR4 mRNA signal is found in the cerebellar granule cells [MEDLINE:96346635]. The principal\ difference from rat brain is the presence in human brain of MGR4 mRNA in\ the caudate nucleus and putamen [MEDLINE:96346635]. MGR4 inhibits adenylyl cyclase through\ a pertussis-toxin-sensitive G-protein, probably of the Gi/Go class PUB00005885.

\ \ metabotropic glutamate, GABA-B-like receptor activity ; GO:0008067 membrane ; GO:0016020 \N 20473 IPR001787

\ \ \

Ribosomal protein L21 is one of the proteins from the large ribosomal subunit. In Escherichia coli, L21 is known to bind to the 23S rRNA in the presence of L20. It belongs to a family of ribosomal proteins which, on the basis of sequence similarities, groups:\

Eubacterial L21.
Marchantia polymorpha chloroplast L21.
Cyanelle L21.
Plant chloroplast L21 (nuclear-encoded).

Eubacterial L21 is a protein of about 100 amino-acid residues, the mature form of the spinach chloroplast L21 has 200 residues.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 20470 IPR001783

The following proteins have been shown [MEDLINE:91142119], [MEDLINE:92219988] to be structurally and evolutionary related:

Riboflavin synthase chain (EC: 2.5.1.9) (RS-) (gene ribC in Escherichia coli, ribB in Bacillus subtilis and Photobacterium leiognathi, RIB5 in yeast). This enzyme synthesizes riboflavin from two moles of 6,7- dimethyl-8-(1'-D-ribityl)lumazine (Lum), a pteridine-derivative.
Photobacterium phosphoreum lumazine protein (LumP) (gene luxL). LumP is a protein that modulates the color of the bioluminescence emission of bacterial luciferase. In the presence of LumP, light emission is shifted to higher energy values (shorter wavelength). LumP binds non-covalently to 6,7-dimethyl-8-(1'-D-ribityl)lumazine.
Vibrio fischeri yellow fluorescent protein (YFP) (gene luxY). Like LumP, YFP modulates light emission but towards a longer wavelength. YFP binds non-covalently to FMN.

These proteins seem to have evolved from the duplication of a domain of about 100 residues. In its C-terminal section, this domain contains a conserved motif [KR]-V-N-[LI]-E which has been proposed to be the binding site for lumazine (Lum) and some of its derivatives. RS- which binds two molecules of Lum has two perfect copies of this motif, while LumP which binds one molecule of Lum, has a Glu instead of Lys/Arg in the first position of the second copy of the motif. Similarily, YFP, which binds to one molecule of FMN, also seems to have a potentially dysfunctional binding site by substitution of Gly for Glu in the last position of the first copy of the motif.

\ \ \N \N \N 20469 IPR001782

The flgH, flgI and fliF genes of Salmonella typhimurium encode the major proteins for the L, P and M rings of the flagellar basal body [MEDLINE:89291739]. In fact, the basal body consists of four rings (L,P,S and M) surrounding the flagellar rod, which is believed to transmit motor rotation to the filament [MEDLINE:90172414]. The M ring is integral to the inner membrane of the cell, and may be connected to the rod via the S (supramembrane) ring, which lies just distal to it. The L and P rings reside in the outer membrane and periplasmic space, respectively.

The sequences of the FlgH, FlgI and FliF gene products have been determined [MEDLINE:89291739]. FlgH and FlgI, which are exported across the cell membrane to their destinations in the outer membrane and periplasmic space, have typical N-terminal cleaved signal-peptide sequences [MEDLINE:89291739], [MEDLINE:87165756]. FlgH is predicted to have an extensive -sheet structure, in keeping with other outer membrane proteins, and FlgI is thought to have even more -structure content [MEDLINE:89291739]. Several aspects of the DNA sequence of these genes and their surrounds suggest complex regulation of the flagellar gene system.

\ \ structural molecule activity ; GO:0005198 periplasmic space (sensu Gram-negative Bacteria) ; GO:0030288 ciliary/flagellar motility ; GO:0001539 20467 IPR001780

\ \ \

A number of eukaryotic and archaebacterial ribosomal proteins can be grouped on the basis of sequence similarities. One of these families consists of:\

Vertebrate L35A.
Caenorhabditis elegans L35A (F10E7.7).
Yeast L37A/L37B (Rp47).
Plant L35A.
Pyrococcus woesei L35A homolog [MEDLINE:95206934].

These proteins have 87 to 110 amino-acid residues.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 20468 IPR001781

Recently [MEDLINE:90231440], [MEDLINE:93104672] a number of proteins have been found to contain a conserved cysteine-rich domain of about 60 amino-acid residues. These proteins are:

Caenorhabditis elegans mec-3; a protein required for the differentiation of the set of six touch receptor neurons in this nematode.
C. elegans. lin-11; a protein required for the asymmetric division of vulval blast cells.
Vertebrate insulin gene enhancer binding protein isl-1. Isl-1 binds to one of the two cis-acting protein-binding domains of the insulin gene.
Vertebrate homeobox proteins lim-1, lim-2 (lim-5) and lim3.
Vertebrate lmx-1, which acts as a transcriptional activator by binding to the FLAT element; a -cell-specific transcriptional enhancer found in the insulin gene.
Mammalian LH-2, a transcriptional regulatory protein involved in the control of cell differentiation in developing lymphoid and neural cell types.
Drosophila melanogaster protein apterous, required for the normal development of the wing and halter imaginal discs.
Vertebrate protein kinases LIMK-1 and LIMK-2.
Mammalian rhombotins. Rhombotin 1 (RBTN1 or TTG-1) and rhombotin-2 (RBTN2 or TTG-2) are proteins of about 160 amino acids whose genes are disrupted by chromosomal translocations in T-cell leukemia.
Mammalian and avian cysteine-rich protein (CRP), a 192 amino-acid protein of unknown function. Seems to interact with zyxin.
Mammalian cysteine-rich intestinal protein (CRIP), a small protein which seems to have a role in zinc absorption and may function as an intracellular zinc transport protein.
Vertebrate paxillin, a cytoskeletal focal adhesion protein.
Mouse testin which should not be confused with rat testin which is a thiol protease homolog (see IPR000169).
Sunflower pollen specific protein SF3.
Chicken zyxin. Zyxin is a low-abundance adhesion plaque protein which has been shown to interact with CRP.
Yeast protein LRG1 which is involved in sporulation [MEDLINE:94344779].
Yeast rho-type GTPase activating protein RGA1/DBM1.
C. elegans homeobox protein ceh-14.
C. elegans homeobox protein unc-97.
Yeast hypothetical protein YKR090w.
C. elegans hypothetical proteins C28H8.6.

These proteins generally have two tandem copies of a domain, called LIM (for Lin-11 Isl-1 Mec-3) in their N-terminal section. Zyxin and paxillin are exceptions in that they contains respectively three and four LIM domains at their C-terminal extremity. In apterous, isl-1, LH-2, lin-11, lim-1 to lim-3, lmx-1 and ceh-14 and mec-3 there is a homeobox domain some 50 to 95 amino acids after the LIM domains.

In the LIM domain, there are seven conserved cysteine residues and a histidine. The arrangement followed by these conserved residues is C-x(2)-C-x(16,23)-H-x(2)-[CH]-x(2)-C-x(2)-C-x(16,21)-C-x(2,3)-[CHD]. The LIM domain binds two zinc ions [MEDLINE:93281587]. LIM does not bind DNA, rather it seems to act as an interface for protein-protein interaction.

\ \ \N \N \N 20466 IPR001779

TWIK-1 was the first two P-domain K⁺ channel subunit cloned from human\ tissue PUB00009384. It is widely distributed, being particularly abundant in the\ brain and heart. It forms a weak inward rectifer K⁺ channel, and has been\ found to be inhibited by internal acidification; its activity is enhanced\ by protein kinase C phosphorylation.

\ \ potassium channel activity ; GO:0005267 membrane ; GO:0016020 potassium ion transport ; GO:0006813 20464 IPR001775

The general (type II) secretion pathway (GSP) within Gram-negative bacteria is a signal sequence-dependent process responsible for protein export [MEDLINE:93174466], [MEDLINE:95099573], [MEDLINE:92276315]. The process has two stages: exoproteins are first translocated across the inner membrane by the general signal-dependent export pathway (GEP), and then across the outer membrane by a species-specific accessory mechanism.

\ \ \N membrane ; GO:0016020 protein secretion ; GO:0009306 20465 IPR001778

The allergens in this family include allergens with the following designations: Lol p 5 and Poa p 9.

\ \

Grass pollen allergens are one of the major causes of type I allergies (including allergic rhinoconjunctivitis, allergic bronchial asthma and hayfever), afflicting 15-20% of a genetically predisposed population [MEDLINE:91093232]. The amino acid sequences of three Kentucky bluegrass (KBG, Poa pratensis) pollen allergen cDNA clones (KBG 41, 60 and 31), have been determined [MEDLINE:91093232]. The clones exhibit a high degree of sequence similarity to one another, minor similarity to other known allergens, and no similarity to other known proteins or genes. The predicted molecular masses of the proteins range from 28.3 to 37.8 kDa [MEDLINE:91093232]. Northern analysis indicates that expression of the genes is confined to pollen tissue. The results suggest that the clones code for a group of proteins that represent a new and previously uncharacterised group of grass pollen isoallergens, which have been designated Poa p 9 [MEDLINE:91093232].

The C-terminal fragment, conserved in Poa p 9 proteins, appears to contain epitopes unique to these proteins [MEDLINE:91268549]. The N-terminal region (IPR002914\ \ \ \ [MEDLINE:91268549]. Comparison of amino acid sequences of recombinant Poa p 9 proteins with those of Lol p 5 isoallergens revealed a low level of similarity between the N-terminal sequences of these proteins [MEDLINE:91268549].

\ \ \N \N \N 20463 IPR001774 Ligands of the Delta/Serrate/lag-2 (DSL) family and their receptors, members of the lin-12/Notch family, mediate cell-cell interactions that specify cell fate in invertebrates and vertebrates. In C. elegans, two DSL genes, lag-2 and apx-1,\ influence different cell fate decisions during development. [MEDLINE:96125168]. Molecular interaction between Notch and Serrate, another EGF-homologous transmembrane protein containing a region of striking similarity to Delta, has been shown and the same two EGF repeats of Notch may also constitute a Serrate binding domain [MEDLINE:92034990], [MEDLINE:95232495].\ \ \N membrane ; GO:0016020 cell communication ; GO:0007154 20462 IPR001772 Eukaryotic protein kinases PUB00001071, PUB00001071, [MEDLINE:92065854], [MEDLINE:92065863], [MEDLINE:88264399] are enzymesthat belong to a very extensive family of proteins which share a conserved catalytic core common with\ both serine/threonine and tyrosine protein kinases. There are a number of conserved regions in the\ catalytic domain of protein kinases. In the N-terminal extremity of the catalytic domain there is a\ glycine-rich stretch of residues in the vicinity of a lysine residue, which has been shown to be involved\ in ATP binding. In the central part of the catalytic domain there is a conserved aspartic acid residue\ which is important for the catalytic activity of the enzyme [MEDLINE:91320112].\

This domain is found in the C-terminal extremity of various serine/threonine-protein kinases from fungi, plants and animals.

\ \ ATP binding activity ; GO:0005524 \N protein amino acid phosphorylation ; GO:0006468 20461 IPR001771

Vasoactive intestinal polypeptide (VIP) has a wide physiological profile.\ In the periphery, it induces relaxation in smooth muscle; inhibits\ secretion in certain tissues, but stimulates secretion in others; and\ modulates activity of cells in the immune system PUB00005907. In the CNS, it has a\ range of both excitatory and inhibitory actions. VIP receptors are\ distributed widely in the periphery, and occur throughout the gastrointestinal tract and genitourinary system, other smooth muscles and\ secretory glands. In the CNS, they are found abundantly in, e.g. the cortex,\ hippocampus and thalamus PUB00005907. All VIP receptors activate adenylyl cyclase.

There are two structurally distinct receptors that recognise VIP peptides\ and pituitary adenylate cyclase activating polypeptide (PACAP) with similar\ affinities (PACAP/VIPR-1, PACAP/VIPR-2), as well as a specific receptor for\ the PACAP peptide (PACAP-1). RNA transcripts for all three receptor types\ are found in human heart, brain and adipose tissue [MEDLINE:97087354]. VIPR-1 is\ constitutively expressed, while the expression of VIPR-2 is induced only\ following stimulation through the TCR-associated CD3 complex [MEDLINE:96378694]. VIP\ induces the expression of the VIPR-2 gene in the absence of additional\ stimuli. Differential expression and regulation of the two VIP receptors\ in T lymphocytes suggests different physiological roles in mediating the\ immunomodulatory activities of VIP and related neuropeptides [MEDLINE:96378694].

\ \ vasoactive intestinal polypeptide receptor activity ; GO:0004999 membrane ; GO:0016020 G-protein coupled receptor protein signaling pathway ; GO:0007186 20458 IPR001767 Hedgehog proteins are involved in intracellular signalling required for a variety of patterning events during development. The hint domain is found in these proteins, as well as several proteins which contain inteins and undergo protein splicing [MEDLINE:97474313]. This entry is specific to hedgehog protein.\ \ \N \N development ; GO:0007275 20459 IPR001769 Peptidase family C25 is a protein family found in the bacteria. Porphyromonas gingivalis (Bacteroides gingivalis) a gram-negative anaerobic bacterial species strongly associated with adult periodontitis. One of its distinguishing characteristics and putative virulence properties is the ability to agglutinate erythrocytes [MEDLINE:97047672]. It is a highly proteolytic organism which metabolizes small peptides and amino acids. Indirect evidence suggests that the proteases produced by this microorganism constitute an important virulence factor [MEDLINE:92347990]. Protease-encoding genes have been shown to contain multiple copies of repeated nucleotide sequences. These conserved sequences have also been found in hemagglutinin genes [MEDLINE:98298016].\ cysteine-type peptidase activity ; GO:0008234 \N proteolysis and peptidolysis ; GO:0006508 20460 IPR001770

Guanine nucleotide binding proteins (G-proteins) are a family of membrane-associated proteins that couple extracellularly-activated integral-membrane receptors to intracellular effectors, such as ion channels and enzymes that vary the concentration of second messenger molecules [MEDLINE:92366949], [MEDLINE:91354032], [MEDLINE:91227903]. G-proteins are composed of 3 subunits (, and gamma) which, in the resting state, associate as a trimer at the inner face of the plasma membrane. The subunit has a molecule of guanosine diphosphate (GDP) bound to it: stimulation of the G-protein by an activated receptor leads to its exchange for GTP (guanosine triphosphate). This results in the separation of the from the and gamma subunits, which always remain tightly associated as a dimer. Both the and -gamma subunits are then able to interact with effectors, either individually or in a cooperative manner.

The intrinsic GTPase activity of the subunit hydrolyses the bound GTP to GDP. This returns the subunit to its inactive conformation and allows it to reassociate with the -gamma subunit, thus restoring the system to its resting state.

Although originally thought to be a passive attenuator and membrane anchor for the activated subunit, the -gamma subunit is now recognised as playing an active role in a number of different G-protein-coupled signalling events [MEDLINE:94019765]. It has been shown to modulate the activity of some isoforms of adenylyl cyclase, phospholipase C, and some ion channels. It is involved in receptor phosphorylation via specific kinases, and has been implicated in the p21ras-dependent activation of the MAP kinase cascade. It is also highly likely that it contributes to the recognition of specific receptors by the G-protein. No atomic structure is yet available for -gamma subunits, but it has been proposed that they interact both with each other and with other proteins via a coiled coil motif in their N-terminal regions [MEDLINE:93093151].

Five distinct mammalian G-protein gamma subunits have been cloned, and others have been identified but not fully characterised [MEDLINE:93320117], [MEDLINE:93176189]: they have also been identified in Drosophila and Loligo forbesi. The proteins contain 70-90 amino acids, with apparent molecular weights of 6-12 kDa. Their primary structures are notably more variable than those of the subunits. Gamma subunits are post-translationally modified by isoprenylation and carboxyl-methylation of a cysteine residue 4 amino acids from the C-terminus - this appears to be essential for the interaction of the -gamma subunit with the membrane and with other proteins.

The Caenorhabditis elegans protein egl-10, which is a regulator of G-protein signalling, contains a G-protein gamma-like domain.

\ \ signal transducer activity ; GO:0004871 heterotrimeric G-protein complex ; GO:0005834 G-protein coupled receptor protein signaling pathway ; GO:0007186 20456 IPR001765 Carbonic anhydrases (EC: 4.2.1.1)(CA) are zinc metalloenzymes which catalyze the reversible hydration of carbon dioxide.In Escherichia coli, CA (gene cynT) is involved in recycling carbon dioxide formed in the bicarbonate-dependent decomposition of cyanate by cyanase (gene cynS). By this action, it prevents the depletion of cellular bicarbonate [MEDLINE:92156106]. In photosynthetic bacteria and plant chloroplast, CA is essential to inorganic carbon fixation [MEDLINE:92262454].\ Prokaryotic and plant chloroplast CA are structurally and evolutionary related and form a family distinct from the one which groups the many different forms of eukaryotic CA's (see IPR001148).\ Hypothetical proteins yadF from Escherichia coli and HI1301 from Haemophilus influenzae also belong to this family.\ \ zinc ion binding activity ; GO:0008270 \N carbon utilization ; GO:0015976 20457 IPR001766 The fork head protein of Drosophila, a transcription factor that promotes terminal rather than segmental development, contains neither homeodomains nor zinc-fingers characteristic of other transcription factors [MEDLINE:89249328]. Instead, it contains a distinct type of DNA-binding region, containing around 100 amino acids, which has since been identified in a number of transcription factors (including Drosophila FD1-5, mammalian HNF-3, human HTLF, yeast HCM1, etc.). This is referred to as the fork head domain but is also known as a 'winged helix' [MEDLINE:89249328], [MEDLINE:93323996], [MEDLINE:92409595].The fork head domain binds B-DNA as a monomer [MEDLINE:93323996], but shows no similarity to previously identified DNA-binding motifs. Although the domain is found in several different transcription factors, a common function is their involvement in early developmental decisions of cell fates during embryogenesis [MEDLINE:92409595].\ \ transcription factor activity ; GO:0003700 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 20454 IPR001763

Rhodanese, a sulfurtransferase involved in cyanide detoxification (see IPR001307, including

Cdc25 phosphatase catalytic domain.
non-catalytic domains of eukaryotic dual-specificity MAPK-phosphatases.
non-catalytic domains of yeast PTP-type MAPK-phosphatases.
non-catalytic domains of yeast Ubp4, Ubp5, Ubp7.
non-catalytic domains of mammalian Ubp-Y.
Drosophila heat shock protein HSP-67BB.
several bacterial cold-shock and phage shock proteins.
plant senescence associated proteins.
catalytic and non-catalytic domains of rhodanese (see IPR001307/>).

Rhodanese has an internal duplication. This domain is found as a single copy in other proteins, including phosphatases and ubiquitin C-terminal hydrolases [MEDLINE:96355461].

\ \ \N \N \N 20455 IPR001764

\ Glycoside hydrolase family 3 CAZY:GH_3); glucan

-1,3-glucosidase (EC: 3.2.1.58); cellodextrinase (EC: 3.2.1.74); exo-1,3-1,4-glucanase (EC: 3.2.1.-).\ \ These enzymes are two-domain globular proteins that are N-glycosylated at three sites [MEDLINE:99148125]. This domain is often\ N-terminal to the glycoside hydrolase family 3, C terminal domain IPR002772. \ \ hydrolase activity, hydrolyzing O-glycosyl compounds ; GO:0004553 \N carbohydrate metabolism ; GO:0005975 20453 IPR001762

The adhesion of platelets to the extracellular matrix, and platelet-platelet interactions, are essential in thrombosis and haemostasis [MEDLINE:91315404]. Platelets adhere to damaged blood vessels, release biologically active chemicals, and aggregate, a function that is inhibited in normal blood [MEDLINE:91315404]. The binding of fibrinogen to the glycoprotein IIb/IIIa complex of activated platelets is essential to platelet aggregation and is induced by many agonists, including ADP, collagen, thrombin, epinephrine and prostaglandin endoperoxide analogue.

Snake venoms affect blood coagulation and platelet function in a complex manner [MEDLINE:92095959]: some induce aggregation and release reactions, and some inhibit them [MEDLINE:91315404]. Disintegrin, a component of some snake venoms, rather than inhibiting the release reactions, operates by inhibiting platelet aggregation, blocking the binding of fibrinogen to the receptor-glyco-protein complex of activated platelets [MEDLINE:92095959]. They act by binding to the integrin glycoprotein IIb-IIIa receptor on the platelet surface and inhibit aggregation induced by ADP, thrombin, platelet-activating factor and collagen. The role of disintegrin in preventing blood coagulation renders it of medical interest, particularly with regard to its use as an anti-coagulant [MEDLINE:93054601].

Disintegrins are peptides of about 70 amino acid residues that contain many cysteines all involved in disulfide bonds [MEDLINE:91242430]. Disintegrins contain an Arg-Gly-Asp (RGD) sequence, a recognition site of many adhesion proteins. The RGD sequence of disintegrins is postulated to interact with the glycoprotein IIb-IIIa complex.

The sequences of disintegrins from different snake species are known. These proteins are known as: albolabrin, applagin, barbourin, batroxostatin, bitistatin, echistatin, elegantin, eristicophin, flavoridin, halysin, kistrin, tergeminin and triflavin.

Some other proteins are known to contain a disintegrin domain:

Some snake venom zinc metalloproteinases [MEDLINE:92384940] consist of an N-terminal catalytic domain fused to a disintegrin domain. Such is the case for trimerelysin I (HR1B) , atrolysin e (Ht-e) and trigramin. It has been suggested that these proteinases are able to cleave themselves from the disintegrin domains and that the latter may arise from such a post-translational processing.
The -subunit of guinea pig sperm surface protein PH30 [MEDLINE:92204234]. PH30 is a protein involved in sperm-egg fusion. The subunit contains a disintegrin at the N-terminal extremity.
Mammalian epididymial apical protein 1 (EAP I) [MEDLINE:93038491]. EAP I is associated with the sperm membrane and may play a role in sperm maturation. Structurally, EAP I consists of an N-terminal domain, followed by a zinc metalloproteinase domain, a disintegrin domain, and a large C-terminal domain that contains a transmembrane region.

The schematic representation of the structure of a typical disintegrin is shown below:

\
                                   +---+\
       +--------+             +----|---|--------------------+\
       |        |             |    |   |                    |\
  xxxxxCxCxxxxxxCCxxxxCxxxxxxxCxxxxCCxxCxxxxxxxxCxxxRGDxxxxxCxxxxxxCxxxxxxx\
         |       |    |             |           |                  |\
         +-------+    +-------------+           +------------------+\
\
'C': conserved cysteine involved in a disulfide bond.\

\ \ \N \N \N 20452 IPR001761

This family includes the periplasmic binding proteins, and the LacI family transcriptional regulators. The periplasmic binding proteins are the primary receptors for chemotaxis and transport of many sugar based solutes. The LacI family of proteins consist of transcriptional regulators related to the lac repressor. In this case, generally the sugar binding domain binds a sugar which changes the DNA binding activity of the repressor domain (lacI) [MEDLINE:92260530], [MEDLINE:96239623].

\ \N \N \N 20450 IPR001759

Pentaxins (or pentraxins) [MEDLINE:84048773], [MEDLINE:95290124] are a family of proteins which show, under electron microscopy, a discoid arrangement of five noncovalently bound subunits. Proteins of the pentaxin family are involved in acute immunological responses [MEDLINE:95290124]. Three of the principal members of the pentaxin family are serum proteins: namely, C-reactive protein (CRP) [MEDLINE:98277135], serum amyloid P component protein (SAP) [MEDLINE:98183432], and female protein (FP) [MEDLINE:98246516].

CRP is expressed during acute phase response to tissue injury or inflammation in mammals. The protein resembles antibody and performs several functions associated with host defence: it promotes agglutination, bacterial capsular swelling and phagocytosis, and activates the classical complement pathway through its calcium-dependent binding to phosphocholine. CRPs have also been sequenced in an invertebrate, the Atlantic horseshoe crab, where they are a normal constituent of the hemolymph.

SAP is a vertebrate protein that is a precursor of amyloid component P. It is found in all types of amyloid deposits, in glomerular basement menbrane and in elastic fibres in blood vessels. SAP binds to various lipoprotein ligands in a calcium-dependent manner, and it has been suggested that, in mammals, this may have important implications in atherosclerosis and amyloidosis.

FP is a SAP homologue found in the Syrian hamster. The concentration of this plasma protein is altered by sex steroids and stimuli that elicit an acute phase response.

Pentaxin proteins expressed in the nervous system are neural pentaxin I (NPI) and II (NPII) [MEDLINE:97038700]. NPI and NPII are homologous and can exist within one species. It is suggested that both proteins mediate the uptake of synaptic macromolecules and play a role in synaptic plasticity. Apexin, a sperm acrosomal protein, is a homologue of NPII found in guinea pigs\ \ \ \ [MEDLINE:95096120].

PTX3 (or TSG-14) protein is a cytokine-induced protein that is homologous to CRPs and SAPs, but its function is not yet known.

\ \ \N \N \N 20451 IPR001760

Visual pigments [MEDLINE:87293932], [MEDLINE:87218500] are the light-absorbing molecules that mediate vision. They consist of an apoprotein, opsincalently linked to the chromophore cis-retinal. Vision is effected through the absorption of a photon by cis-retinal which is isomerized to trans-retinal. This isomerization leads to a change of conformation of the protein. Opsins are integral membrane proteins that belong to the rhodopsin-like superfamily of G-protein-coupled receptors (GPCRs). The activating ligands of the different superfamily members vary widely in structure and character, yet the proteins appear faithfully to have conserved a basic structural framework, believed to consist of 7 transmembrane (TM) helices. Although the sequences of these proteins are very diverse, reflecting to some extent this broad range of activating ligands, nevertheless, motifs have been identified in the TM regions that are characteristic of virtually the entire superfamily [MEDLINE:93234436], [MEDLINE:94224751]. Amongst the exceptions are the olfactory receptors, which cluster together in a subfamily, which lacks significant matches with domains 2, 4 and 6. Interestingly, the opsins also seem to be emerging as increasingly atypical of the superfamily, clustering most strongly, in phylogenetic analyses, with the olfactory receptors [MEDLINE:94224751].

The retinal is covalently linked to the above proteins through a protonated Schiff base with a conserved lysine residue located in the middle of the seventh transmembrane helix.

In vertebrates four different pigments are generally found. Rod cells, which mediate vision in dim light, contain the pigment rhodopsin. Cone cells, which function in bright light, are responsible for color vision and contain three or more color pigments (for example, in mammals: red, blue and green).

In Drosophila, the eye is composed of 800 facets or ommatidia. Each ommatidium contains eight photoreceptor cells (R1-R8): the R1 to R6 cells are outer cells, R7 and R8 inner cells. Each of the three types of cells (R1-R6, R7 and R8) expresses a specific opsin.

Proteins evolutionary related to opsins include squid retinochrome, also known as retinal photoisomerase, which converts various isomers of retinal into 11-cis retinal and mammalian retinal pigment epithelium (RPE) RGR [MEDLINE:95034741], a protein that may also act in retinal isomerization.

\ \ rhodopsin-like receptor activity ; GO:0001584 integral to membrane ; GO:0016021 vision ; GO:0007601 20448 IPR001757

P-type (or E1-E2-type) ATPases constitute a superfamily of cation transport enzymes, present both in prokaryota and eukaryota, whose members mediate membrane flux of all common biologically relevant cations [MEDLINE:94043000]. The enzymes, that form an aspartyl phosphate intermediate in the course of ATP hydrolysis, can be divided into 4 major groups [MEDLINE:94202222]: (1) Ca²⁺-transporting ATPases; (2) Na⁺/K⁺- and gastric H⁺/K⁺-transporting ATPases; (3) plasma membrane H⁺-transporting ATPases (proton pumps) of plants, fungi and lower eukaryotes; and (4) all bacterial P-type ATPases, except the Mg²⁺-ATPase of S.typhimurium, which is more similar to the eukaryotic sequences. However, great variety of sequence analysis methods results in diversity of classification. According to PRINTS signatures, P-type ATPase superfamily is divided into six groups (each of them has its own IPR number). And the entries of these groups can match the previous classification in the following way: IPR006069 fit group 4. Graduation into four major groups is more biologically relevant, as it correlates with cation specificities and biological sources of P-type ATPase.

\ \ P-type ATPase activity ; GO:0015662 membrane ; GO:0016020 cation transport ; GO:0006812 20449 IPR001758

EP4 receptors are found in high levels in the intestine, and in lower\ levels in the lung, kidney, thymus, uterus and brain; they are not found in\ the liver, heart, retina or in skeletal muscle. The receptors activate\ adenylate cyclase.

\ \ prostaglandin E receptor activity ; GO:0004957 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20446 IPR001754

Orotidine 5'-phosphate decarboxylase (EC: 4.1.1.23) (OMPdecase) [MEDLINE:88216255], [MEDLINE:92112814] catalyzes the last step in the de novo biosynthesis of pyrimidines, the decarboxylation of OMP into UMP. In higher eukaryotes OMPdecase is part, with orotate phosphoribosyltransferase, of a bifunctional enzyme, while the prokaryotic and fungal OMPdecases are monofunctional protein.

Some parts of the sequence of OMPdecase are well conserved across species. The best conserved region is located in the N-terminal half of OMPdecases and is centered around a lysine residue which is essential for the catalytic function of the enzyme.

\ \ orotidine-5'-phosphate decarboxylase activity ; GO:0004590 \N 'de novo' pyrimidine base biosynthesis ; GO:0006207 20447 IPR001756 Proteins that transport heavy metals in micro-organisms and mammals share similarities in their sequences and structures. Some of these proteins are involved in bacterial resistance to toxic metals, such as lead and cadmium, \ while others are involved in inherited human syndromes, such as Wilson and Menkes diseases [MEDLINE:94378325].\

\ \

Copper-transporting ATPase from Helicobacter pylori is an integral membrane, with 8 predicted transmembrane (TM) domains. The protein, which contains a single copy of the HMA domain, catalyses the reaction:

 ATP + H₂O = ADP + orthophosphate

\ \ ATP binding activity ; GO:0005524 membrane ; GO:0016020 copper ion transport ; GO:0006825 20445 IPR001753

Enoyl-CoA hydratase (EC: 4.2.1.17) (ECH) [MEDLINE:90032688] and 3-2trans-enoyl-CoA isomerase (EC: 5.3.3.8) (ECI) [MEDLINE:92068378] are two enzymes involved in fatty acid metabolism. ECH catalyzes the hydratation of 2-trans-enoyl-CoA into 3-hydroxyacyl-CoA and ECI shifts the 3- double bond of the intermediates of unsaturated fatty acid oxidation to the 2-trans position.

Most eukaryotic cells have two fatty-acid -oxidation systems, one located in mitochondria and the other in peroxisomes. In mitochondria, ECH and ECI are separate yet structurally related monofunctional enzymes. Peroxisomes contain a trifunctional enzyme [MEDLINE:90153855] consisting of an N-terminal domain that bears both ECH and ECI activity, and a C-terminal domain responsible for 3-hydroxyacyl-CoA dehydrogenase (HCDH) activity.

In Escherichia coli (gene fadB) and Pseudomonas fragi (gene faoA), ECH and ECI are also part of a multifunctional enzyme which contains both a HCDH and a 3-hydroxybutyryl-CoA epimerase domain [MEDLINE:90370500].

A number of other proteins have been found to be evolutionary related to the ECH/ECI enzymes or domains:\

3-hydroxbutyryl-coa dehydratase (EC: 4.2.1.55) (crotonase), a bacterial enzyme involved in the butyrate/butanol-producing pathway.
Naphthoate synthase (EC: 4.1.3.36) (DHNA synthetase) (gene menB) [MEDLINE:92332443], a bacterial enzyme involved in the biosynthesis of menaquinone (vitamin K2). DHNA synthetase converts O-succinyl-benzoyl-CoA (OSB-CoA) to 1,4-dihydroxy-2- naphthoic acid (DHNA).
4-chlorobenzoate dehalogenase (EC: 3.8.1.6) [MEDLINE:92304934], a Pseudomonas enzyme which catalyzes the conversion of 4-chlorobenzoate-CoA to 4-hydroxybenzoate-CoA.
A Rhodobacter capsulatus protein of unknown function (ORF257) [MEDLINE:92077430].
Bacillus subtilis putative polyketide biosynthesis proteins pksH and pksI.
Escherichia coli carnitine racemase (gene caiD) [MEDLINE:95115548].
Escherichia coli hypothetical protein ygfG.
Yeast hypothetical protein YDR036c.

\ \ enzyme activity ; GO:0003824 \N metabolism ; GO:0008152 20442 IPR001750 This domain is found in the NADH:ubiquinone oxidoreductase (complex I) which catalyses the transfer of two electrons from NADH to ubiquinone in a reaction that is associated with proton translocation across the membrane [MEDLINE:93110040].\ NADH dehydrogenase (ubiquinone) activity ; GO:0008137 \N oxidative phosphorylation, NADH to ubiquinone ; GO:0006120 20443 IPR001751 The S-100 domain is a subfamily of the EF-hand calcium binding proteins.S-100s are small dimeric acidic calcium and zinc-binding proteins PUB00006587 abundant in the brain. They have two different types of calcium-binding sites: a low affinity one with a special structure and a 'normal' EF-hand type high affinity site. The vitamin-D dependent intestinal calcium-binding proteins (ICaBP or calbindin 9 Kd) also belong to this family of proteins, but it does not form dimers. In the past years the sequences of many new members of this family have been determined (for reviews see PUB00006587, [MEDLINE:89299102], [MEDLINE:95278932]); in most cases the function of these proteins is not yet known, although it is becoming clear that they are involved in cell growth and differentiation, cell cycle regulation and metabolic control. A number of these proteins are known to bind calcium while others are not (p10 for example).\ \ calcium ion binding activity ; GO:0005509 \N \N 20444 IPR001752

Kinesin [MEDLINE:96124206], [MEDLINE:90328765], PUB00005510 is a microtubule-associated force-producing protein that may play a role in organelle transport. The kinesin motor activity is directed toward the microtubule's plus end. Kinesin is an oligomeric complex composed of two heavy chains and two light chains. The maintenance of the quaternary structure does not require interchain disulphide bonds.

The heavy chain is composed of three structural domains: a large globular N-terminal domain which is responsible for the motor activity of kinesin (it is known to hydrolyze ATP, to bind and move on microtubules), a central -helical coiled coil domain that mediates the heavy chain dimerization; and a small globular C-terminal domain which interacts with other proteins (such as the kinesin light chains), vesicles and membranous organelles.

A number of proteins have been recently found that contain a domain similar to that of the kinesin 'motor' domain PUB00005510, [MEDLINE:91368358]:\

Drosophila melanogaster claret segregational protein (ncd). Ncd is required for normal chromosomal segregation in meiosis, in females, and in early mitotic divisions of the embryo. The ncd motor activity is directed toward the microtubule's minus end.
Homo sapiens CENP-E [MEDLINE:91368358]. CENP-E is a protein that associates with kinetochores during chromosome congression, relocates to the spindle midzone at anaphase, and is quantitatively discarded at the end of the cell division. CENP-E is probably an important motor molecule in chromosome movement and/or spindle elongation.
H.sapiens mitotic kinesin-like protein-1 (MKLP-1), a motor protein whose activity is directed toward the microtubule's plus end.
Saccharomyces cerevisiae KAR3 protein, which is essential for S. cerevisiae nuclear fusion during mating. KAR3 may mediate microtubule sliding during nuclear fusion and possibly mitosis.
S. cerevisiae CIN8 and KIP1 proteins which are required for the assembly of the mitotic spindle. Both proteins seem to interact with spindle microtubules to produce an outwardly directed force acting upon the poles.
Emericella nidulans bimC, which plays an important role in nuclear division.
E. nidulans klpA.
Caenorhabditis elegans unc-104, which may be required for the transport of substances needed for neuronal cell differentiation.
C. elegans osm-3.
Xenopus laevis Eg5, which may be involved in mitosis.
Arabidopsis thaliana KatA, KatB and katC.
Chlamydomonas reinhardtii FLA10/KHP1 and KLP1. Both proteins seem to play a role in the rotation or twisting of the microtubules of the flagella.
C. elegans hypothetical protein T09A5.2.

The kinesin motor domain is located in the N-terminal part of most of the above proteins, with the exception of KAR3, klpA, and ncd where it is located in the C-terminal section.

The kinesin motor domain contains about 330 amino acids. An ATP-binding motif of type A is found near position 80 to 90, the C-terminal half of the domain is involved in microtubule-binding.

\ \ ATP binding activity ; GO:0005524 microtubule associated complex ; GO:0005875 \N 20440 IPR001748 A Xenopus protein known as G10 [MEDLINE:89306617] has been found to be highly conserved in a wide range of eukaryotic species. The function of G10 is still unknown. G10 is a protein of about 17 to 18 kDa (143 to 157 residues) which is hydrophilic and whose C-terminal half is rich in cysteines and could be involved in metal-binding.\ molecular_function unknown ; GO:0005554 nucleus ; GO:0005634 \N 20441 IPR001749

Glucose-dependent insulinotropic polypeptide (GIP) plays an important role\ in the regulation of postprandial insulin secretion and proinsulin gene\ expression of pancreatic -cells [MEDLINE:96013879]. The human GIP-receptor encodes a\ 7TM protein that is similar to the human glucagon-like peptide 1(GLP-1)\ receptor. It is hoped that an understanding of GIP-receptor regulation and\ signal transduction will shed light on the hormone's failure to exert its\ biological action at the pancreatic B-cell in type II diabetes mellitus.

\ \ gastric inhibitory peptide receptor activity ; GO:0016519 membrane ; GO:0016020 G-protein coupled receptor protein signaling pathway ; GO:0007186 20437 IPR001743 The exact function of the photosystem II reaction center T protein is unknown. It probably consists of a single transmembrane spanning helix. The photosystem II reaction center T protein, appears to be (i) a novel photosystem II subunit and (ii) required for maintaining optimal photosystem II activity under adverse growth conditions [MEDLINE:94298765].\ \ \N membrane ; GO:0016020 photosynthesis ; GO:0015979 20438 IPR001746 These occlusion proteins are major components of the virus occlusion bodies, large proteinaceous structures (polyhedra) that protect the virus from the outside environment for extended periods until they are ingested by insect larvae. They occur in various viruses including the single nucleocapsid nuclear polyhedrosis virus (SNPV) and granulosis virus.\ structural molecule activity ; GO:0005198 \N \N 20439 IPR001747

This family contains regions from vitellogenin, microsomal triglyceride transfer protein and apolipoprotein B-100. These proteins are all involved in lipid transport [MEDLINE:98362593].

This family contains the LV1n chain from lipovitellin, the predominantlipoprotein found in the yolk of egg-laying animals involved in lipid and metal storage. LV1n forms two domains and portions of two more:\ the N-sheet, the helical segment, one -strand of the A-sheet, and all but two -strands of the C-sheet. The N-sheet domain mainly consists of 11 -strands wrapped around an uncharged helix of 14 residues, although another -strand and 3 more small helices\ are included. There are two disulfide bonds within this region; one is conserved in the\ homologous proteins MTP and apoB. A drawn out loop containing two -strands helps to link the N-sheet to both the C- and A-sheets. In addition, a\ depression in the N-sheet globular domain accepts the loops of several -strands from the C- and A-sheets forming multiple interactions. Past comments have\ suggested the region has the appearance of and may function as a flexible "ball-and-socket" joint accommodating the lipid as the lipoprotein assembles [MEDLINE:22131001].

\ \ \ lipid transporter activity ; GO:0005319 \N lipid transport ; GO:0006869 20433 IPR001738

Rab proteins constitute a family of small GTPases that serve a regulatory role in vesicular membrane traffic [MEDLINE:95045420], [MEDLINE:93292071]; C-terminal geranylgeranylation is crucial for their membrane association and function. This post-translational modification is catalysed by Rab geranylgeranyl transferase (Rab-GGTase), a multi-subunit enzyme that contains a catalytic heterodimer and an accessory component, termed Rab escort protein (REP)-1 [MEDLINE:95045420], [MEDLINE:93292071]. REP-1 presents newly-synthesised Rab proteins to the catalytic component, and forms a stable complex with the prenylated proteins following the transfer reaction.

cDNA cloning of component A of rat Rab geranylgeranyl transferase (REP) confirms its resemblance to Rab3A guanine nucleotide dissociation inhibitor (GDI) and its identity with the human choroideremia gene product [MEDLINE:93292071]. A genetic defect in REP underlies human choroideremia. Choroideraemia (or tapetochoroidal dystrophy) is a common form of X-linked blindness characterised by progressive dystrophy of the choroid, retinal pigment epithelium and retina [MEDLINE:91015386], [MEDLINE:95072565], [MEDLINE:92196072].

\ \ RAB escort protein activity ; GO:0005084 RAB-protein geranylgeranyltransferase complex ; GO:0005968 intracellular protein transport ; GO:0006886 20434 IPR001739

The Methyl-CpG binding domain (MBD) binds to DNA that contains one or more symmetrically methylated CpGs [MEDLINE:94232813]. DNA methylation in animals is associated with alterations in chromatin structure and silencing of gene expression. MBD has negligible non-specific affinity for DNA. In vitro foot-printing with MeCP2 showed the MBD can protect a 12 nucleotide region surrounding a methyl CpG pair [MEDLINE:94232813]. MBDs are found in several Methyl-CpG binding proteins and also DNA demethylase [MEDLINE:99158138].

\ DNA binding activity ; GO:0003677 \N \N 20435 IPR001740

F4/80 is a monoclonal antibody that recognises a murine macrophage-restricted cell surface glycoprotein and has been extensively used to\ characterise macrophage populations in a wide range of immunological studies\ [MEDLINE:96132946]. Little is known about its possible role in macrophage differentiation\ and function. The sequence of the F4/80 protein is similar to two protein\ superfamilies: the N-terminal region contains seven epidermal growth factor\ (EGF)-like domains, while the C-terminal region contains seven hydrophobic\ regions whose signature is consistent with membership of the secretin-like\ superfamily of GPCRs. The EGF and GPCR domains are separated from each other\ by a serine/threonine-rich domain, a feature reminiscent of mucin-like,\ single-span, integral membrane glycoproteins with adhesive properties [MEDLINE:95324926].\ Because of its unique characteristics, this putative EGF module-containing,\ mucin-like hormone receptor has been named EMR1 [MEDLINE:95324926]. The EMR1 gene has been\ localised to human chromosome 19p13.3 [MEDLINE:95324926].

\ \ G-protein coupled receptor activity ; GO:0004930 membrane ; GO:0016020 \N 20436 IPR001742 This family contains the outer capsid, VP2 proteins from the orbiviruses; these are dsRNA viruses belonging to the Reoviridae. VP2 acts as an anchor for VP1 and VP3 and contains a non-specific DNA and RNA binding domain in the N-terminus [MEDLINE:97456499], [MEDLINE:97428566].\ structural molecule activity ; GO:0005198 viral capsid ; GO:0019028 \N 20431 IPR001736 Phosphatidylcholine-hydrolyzing phospholipase D (PLD) isoforms are activated by ADP-ribosylation factors (ARFs). PLD produces phosphatidic acid from phosphatidylcholine, which may be essential for the formation of certain types of transport vesicles or may be constitutive vesicular transport to signal transduction pathways. PC-hydrolyzing PLD is a homologue of cardiolipin synthase, phosphatidylserine synthase, bacterial PLDs, and viral proteins. Each of these appears to possess a domain duplication which is apparent by the presence of two motifs containing well-conserved histidine, lysine, and/or asparagine residues which may contribute to the active site aspartic acid. An Escherichia coli endonuclease (nuc) and similar proteins appear to be PLD homologues but possess only one of these motifs [MEDLINE:96303814], [MEDLINE:96334293], [MEDLINE:94327597], [MEDLINE:97386825].\ enzyme activity ; GO:0003824 \N metabolism ; GO:0008152 20432 IPR001737

A number of enzymes responsible for the dimethylation of adenosines inribosomal RNAs (EC: 2.1.1.48) have been found [MEDLINE:94343533], PUB00006589 to be evolutionary related.\ These enzymes are:\

Bacterial 16S rRNA dimethylase (gene ksgA), which acts in the biogenesis of ribosomes by catalyzing the dimethylation of two adjacent adenosines in the loop of a conserved hairpin near the 3'-end of 16S rRNA. Inactivation of ksgA leads to resistance to the aminoglycoside antibiotic kasugamycin.
Yeast 18S rRNA dimethylase (gene DIM1), which is functionally similar to ksgA and that dimethylates twin adenosines in the 3'-end of 18S rRNA.
Bacterial 'erm' methylases. These enzymes confer resistance to macrolide-lincosamide-streptogramin B (MLS) antibiotics - such as erythromycin - by dimethylating the adenine residue at position 2058 of 23S rRNA thus resulting in a reduced affinity between ribosomes and the MLS antibiotics.
Caenorhabditis elegans hypothetical protein EO2H1.1.

The best conserved region in these enzymes is located in the N-terminal\ section and corresponds to a region that is probably involved in S-adenosyl\ methionine (SAM) binding (see IPR000051).

\ \ rRNA methyltransferase activity ; GO:0008649 \N rRNA modification ; GO:0000154 20429 IPR001734

Sodium/substrate symport (or cotransport) is a widespread mechanism of solute transport across cytoplasmic membranes of pro- and eukaryotic cells. Thereby theenergy stored in an inwardly directed electrochemical sodium gradient (sodium motive force, SMF) is used to drive solute accumulation against a concentration\ gradient. The SMF is generated by primary sodium pumps (e.g. sodium/potassium ATPases, sodium translocating respiratory chain complexes) or via the action of\ sodium/proton antiporters. Sodium/substrate transporters are grouped in different families based on sequence similarities [MEDLINE:91227628], [MEDLINE:94304911].

One of these families, known as the sodium:solute symporter family (SSF), contains over a hundred members of pro- and eukaryotic origin [MEDLINE:22241627]. The average hydropathy plot for SSSF proteins predicts 11 to 15 putative transmembrane domains (TMs) in -helical conformation. A secondary structure model of PutP from Escherichia coli suggests the protein contains 13 TMs with the N-terminus located\ on the periplasmic side of the membrane and the C-terminus facing the cytoplasm. The results support the idea of a common topological motif for members of the SSSF. Transporters with a C-terminal extension are proposed to have\ an additional 14th TM.

An ordered binding model of sodium/substrate transport suggests that sodium binds to\ the empty transporter first, thereby inducing a conformational alteration which increases the affinity of the transporter for the solute. The formation of the ternary\ complex induces another structural change that exposes sodium and substrate to the other site of the membrane. Substrate and sodium are released and the empty\ transporter re-orientates in the membrane allowing the cycle to start again.

\ \ transporter activity ; GO:0005215 membrane ; GO:0016020 transport ; GO:0006810 20430 IPR001735

By contrast with vertebrate rhodopsin, which is found in rod cells, insectphotoreceptors are found in the ommatidia that comprise the compound eyes.\ Each Drosophila eye has 800 ommatidia, each of which contains 8 photoreceptor cells (designated R1-R8): R1-R6 are outer cells, while R7 and R8\ are inner cells. Opsins RH1 and RH2 have absorption maxima at 480nm and\ 420nm respectively [MEDLINE:85176937], [MEDLINE:85176938], [MEDLINE:86133563].

\ \ rhodopsin-like receptor activity ; GO:0001584 integral to membrane ; GO:0016021 phototransduction ; GO:0007602 20428 IPR001733

Eukaryotic microsomal signal peptidase is involved in the removal of signal\ peptides from secretory proteins as they pass into the endoplasmic reticulum\ lumen [MEDLINE:95147689]. The peptidase is more complex than its mitochondrial and\ bacterial counterparts, containing a number of subunits, ranging from two\ in the chicken oviduct peptidase, to five in the dog pancreas protein [MEDLINE:95147689].\ A number of these have been shown to be similar and form the eukaryotic\ signal peptidase (S26) family. They share sequence similarity with the\ bacterial leader peptidases (family S26A), although activity here is mediated\ by a serine/histidine dyad rather than a serine/lysine dyad [MEDLINE:95147689]. Archaeal signal peptidases may belong to this group.

\ \ \ peptidase activity ; GO:0008233 membrane ; GO:0016020 proteolysis and peptidolysis ; GO:0006508 20426 IPR001732

The UDP-glucose/GDP-mannose dehydrogenases are a small group of enzymes which possesses the ability to catalyze the NAD-dependent 2-fold oxidation of an alcholol to an acid without the release of an aldehyde intermediate [MEDLINE:89255437], [MEDLINE:97166186].

The enzymes have a wide range of functions. In plants UDP-glucose dehydrogenase, EC: 1.1.1.22, is an important enzyme in the synthesis of hemicellulose and pectin [MEDLINE:22027154], which are the components of newly formed cell walls; while in zebrafish UDP-glucose dehydrogenase is required for cardiac valve formation [MEDLINE:21425345]. In Xanthomonas campestris, a plant pathogen, UDP-glucose dehydrogenase is required for virulence [MEDLINE:21438997].

\ \

GDP-mannose dehydrogenase, EC: 1.1.1.132, catalyzes the formation of GDP-mannuronic acid, which is the monomeric unit from which the exopolysaccharide alginate is formed. Alginate is secreted by a number of bacteria, which include, the pathogenic bacterium Pseudomonas aeruginosa and Azotobacter vinelandii . In Pseudomonas aeruginosa alginate is believed to play an important role in the bacteria's resistance to antibiotics and the host immune response [MEDLINE:22131025], while in Azotobacter vinelandii it is essential for the encystment process [MEDLINE:99084950].

\ \ \N \N electron transport ; GO:0006118 20425 IPR001732

\ \

\ \ \N \N electron transport ; GO:0006118 20427 IPR001732

\ \

\ \ \N \N electron transport ; GO:0006118 20424 IPR001731 Delta-aminolevulinic acid dehydratase (EC: 4.2.1.24) (ALAD) [MEDLINE:89252914] catalyzes the second step in the biosynthesis of heme, the condensation of two molecules of 5-aminolevulinate to form porphobilinogen. The enzyme is an oligomer composed of eight identical subunits. Each of the subunits binds an atom of zinc or of magnesium (in plants). A lysine has been implicated in the catalytic mechanism [MEDLINE:86323088]. The sequence of the region in the vicinity of the active site residue is conserved in ALAD from various prokaryotic and eukaryotic species. Inactivating mutations in the human enzyme are responsible for an inherited porphyria, and enzyme inactivation has also been implicated in acute lead poisoning. The enzyme has also been reported to be a regulatory component within the 26S proteasome.\ porphobilinogen synthase activity ; GO:0004655 \N heme biosynthesis ; GO:0006783 20422 IPR001729 Pulmonary surfactant associated proteins promote alveolar stability by lowering the surface tension at the air-liquid interface in the peripheral air spaces. SP-C, a component of surfactant, is a highly hydrophobic peptide of 35 amino acid residues which is processed from a larger precursor protein. SP-C is post-translationally modified by the covalent attachment of two palmitoyl groups on two adjacent cysteines [MEDLINE:90222154], [MEDLINE:91200266].\ \ \N extracellular ; GO:0005576 respiratory gaseous exchange ; GO:0007585 20423 IPR001730

Cysteine protease activity is dependent on an active dyad of cysteine and histidine, the order and spacing of these residues varying in the known families. Nearly half of all cysteine proteases are found exclusively in viruses [MEDLINE:95147707]. Cysteine protease families have been grouped into five clans (designated CA, CB, CC, CD and CE) on the basis of structural and functional similarity. Families C1, C2 and C10, which belong to the CA clan, have a Cys/His catalytic diad, and are loosely termed papain-like. Families in the CB clan have a His/Cys diad, and contain enzymes from RNA viruses distantly related to chymotrypsin. Enzymes in clan CC are also from RNA viruses, but have a papain-like Cys/His active site. The remaining two clans, CD and CE, contain only one family each. Some families have not yet been asigned to a clan [MEDLINE:95147707], PUB00004506.

Two additional clans (PA and PB) have been identified, these containing a mixture of serine, cysteine and threonine proteases. Clan PA contains a catalytically-active serine or cysteine nucleophilic residue as part of the ordered triad His, Asp, Ser (or Cys). Clan PB contains a serine, cysteine or threonine active residue at the N-terminus of the mature protease. Nuclear inclusion A (NIA) proteases from potyviruses belong to the C4 cysteine protease family, which is part of the PB clan PUB00004506, PUB00004506. Potyviruses include plant viruses in which the single-stranded RNA encodes a polyprotein with NIA protease activity, where proteolytic cleavage is specific for Gln+Gly sites. The NIA protease acts on the polyprotein, releasing itself by Gln+Gly cleavage at both the N- and C-termini. It further processes the polyprotein by cleavage at five similar sites in the C-terminal half of the sequence. In addition to its C-terminal protease activity, the NIA protease contains an N-terminal domain that has been implicated in the transcription process PUB00004506.

This peptidase is present in the nuclear inclusion protein of potyviruses.

\ \ cysteine-type peptidase activity ; GO:0008234 \N proteolysis and peptidolysis ; GO:0006508 20419 IPR001726

DNA\ carries the biological information that instructs cells how to existin an ordered fashion: accurate replication is thus one of the most\ important events in the cell life cycle. This function is mediated by\ DNA-directed DNA-polymerases, which add nucleotide triphosphate (dNTP)\ residues to the 5'-end of the growing DNA chain, using a complementary \ DNA as template. Small RNA molecules are generally used as primers for\ chain elongation, although terminal proteins may also be used. Three motifs, A, B and C, as defined by Delarue et al. [MEDLINE:90319059], are seen to be conserved across all DNA-polymerases, with motifs A and C also seen in RNA- polymerases. They are centered on invariant residues, and their structural significance was implied from the Klenlow (E.coli) structure: motif A contains a strictly-conserved aspartate at the junction of a -strand and an -helix; motif B contains an -helix with positive charges; and motif C has a doublet of negative charges, located in a -turn- secondary structure [MEDLINE:90319059].

\ \ DNA nucleotidylexotransferase activity ; GO:0003912 \N \N 20420 IPR001727

A number of uncharacterized proteins share regions of similarities. These include,

Yeast hypothetical protein YBR187w.
Fission yeast hypothetical protein SpAC17G8.08c.
Mouse protein pFT27.
Synechocystis strain PCC 6803 hypothetical protein sll0615.

These are hydrophobic proteins of 200 to 320 amino acids that seem to contain six or seven transmembrane domains.

\ \ molecular_function unknown ; GO:0005554 membrane ; GO:0016020 \N 20421 IPR001728

\ \ \

In common with other members of the steroid hormone receptor family, thyroid hormone receptors (TRs) contain 2 major highly-conserved domains, involved in DNA- and ligand-binding respectively. Except for a conserved 12 residue motif adjacent to the DNA-binding domain, the N-terminal domains are divergent between - and -TR isoforms (but are conserved within isoforms). The DNA-binding domain is the most highly conserved feature of the family; it contains 2 zinc-binding modules, which are sometimes referred to as zinc fingers (see IPR001628 is thought to contain the binding site for transcriptional co-repressor proteins that mediate the transcriptional repression function of unliganded receptors.\ For more information see the TRR resource PUB00005673.

\ \ thyroid hormone receptor activity ; GO:0004887 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 20418 IPR001724

Family 58 (CAZY:GH_58).\ Bacteriophage E specifically recognises and infects strains of E.coli\ that display the -2,8-linked polysialic acid K1 capsule [MEDLINE:95351985], [MEDLINE:93322313].\ Bacteriophage E endosialidase is thought to be responsible for initial\ absorption of the phage to the host bacterium [MEDLINE:95351985]. The native enzyme is\ probably a trimer of identical 74 kD subunits. Within the K1E endosialidase\ sequence, a central region of 500 amino acids shows 84% identity to K1F\ endosialidase [MEDLINE:95351985]. Both enzymes contain two copies of a sialidase sequence\ motif common to many bacterial and viral sialidases. These motifs flank\ the region of greatest identity between the two endosialidases, suggesting\ that this domain is involved in binding and hydrolysis of the polysialic\ acid substrate [MEDLINE:95351985].

\ \ endo-alpha-sialidase activity ; GO:0016996 \N carbohydrate metabolism ; GO:0005975 20413 IPR001719

DNA damaging agents such as the antitumor drugs bleomycin and neocarzinostatin or those that generate oxygen radicals produce a variety of lesions in DNA. Amongst these is base-loss which forms apurinic/apyrimidinic (AP) sites or strand breaks with atypical 3'termini. DNA repair at the AP sites is initiated by specific endonuclease cleavage of the phosphodiester backbone. Such endonucleases are also generally capable of removing blocking groups from the 3'terminus of DNA strand breaks.

AP endonucleases can be classified into two families on the basis of sequence similarity. What we call family 2 groups the enzymes listed below [MEDLINE:90272680], [MEDLINE:95390957].\

Bacterial endonuclease IV (EC: 3.1.21.2) (gene nfo).
Mycobacterium leprae probable endonuclease (gene end) [MEDLINE:93188701].
Yeast apurinic endonuclase APN1 (EC: 4.2.99.18).
Caenorhabditis elegans hypothetical protein APN-1 or T05H10.2.

APN1 and nfo have been shown [MEDLINE:92078146] to be transition metalloproteins that seem to bind zinc and manganese.

\ \ endonuclease activity ; GO:0004519 intracellular ; GO:0005622 DNA repair ; GO:0006281 20414 IPR001720 PI3 kinases are enzymes that phosphorylate phosphoinositides on the 3-hydroxyl group of the inositol ring. The precise functions of the three products of PI3 kinase (PI-3-P, PI-3,4-P and PI-3,4,5-P) are not yet known, but it is suggested that they function as second messengers in signal transduction events in organisms ranging from yeast to mammals. There are several forms of PI3 kinase. One of these is the mammalian enzyme, a heterodimer of a 110 kDa catalytic subunit and an 85 kDa regulatory subunit, which allows it to bind to activated tyrosine protein kinases. PI3 kinase P85

subunits contain an N-terminal SH3 domain (see IPR001452.\ \ 1-phosphatidylinositol 3-kinase complex ; GO:0005942\ phosphatidylinositol 3-kinase activity ; GO:0016303 \N \N 20415 IPR001721 Threonine dehydratases including Serine/threonine dehydratase (see IPR001926.\ \ threonine dehydratase activity ; GO:0004794 \N isoleucine biosynthesis ; GO:0009097 20416 IPR001722

Glycoside hydrolase family 7 CAZY:GH_7). These enzymes were formerly known as cellulase family C.

\ \

Exoglucanases and cellobiohydrolases [MEDLINE:91359927] play a role in the conversion of cellulose to glucose by cutting the dissaccharide\ cellobiose from the nonreducing end of the cellulose polymer chain.\ Structurally, cellulases and xylanases generally consist of a catalytic\ domain joined to a cellulose-binding domain (CBD) via a linker region that\ is rich in proline and/or hydroxy-amino acids. In type I exoglucanases, the\ CBD domain is found at the C-terminal extremity of these enzyme (this short\ domain forms a hairpin loop structure stabilised by 2 disulphide bridges).

\ \ hydrolase activity, hydrolyzing O-glycosyl compounds ; GO:0004553 \N carbohydrate metabolism ; GO:0005975 20417 IPR001723

\ \ \

\ \ ligand-dependent nuclear receptor activity ; GO:0004879 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 20412 IPR001718

Chemokines are proteins that have important physiological and pathophysiological roles in a wide range of acute and chronic inflammatory\ processes PUB00005876. Their sequences are similar and are characterised by a\ 4-cysteine motif: the family can be divided according to whether the\ first 2 Cys residues are adjacent (the C-C family), or separated by an\ intervening residue (the C-x-C family). C-C chemokines are chemoattractant\ for monocytes but not for neutrophils. The C-C family includes human\ monocyte chemotactic protein-1 (MCP-1), regulated on activation, normal\ T cell expressed and secreted (RANTES) and macrophage inflammatory proteins\ (MIP-1a and MIP-1b) PUB00005876.

C-C chemokine receptors are found in monocytes, lymphocytes, basophils and\ eosinophils; mRNA is also found in some cell lines. MCP-1 and MIP-1a\ induce activation in low nanomolar concentrations and are highly selective\ relative to C-x-C receptors. Calcium mobilisation has been demonstrated in\ monocytes and in cells expressing the recombinant C-C receptor via an\ uncharacterised G-protein; pertussis toxin inhibits some of its actions PUB00005876.\ C-C CKR-7 (formerly designated Epstein-Barr virus induced, EBI-1, receptor)\ is expressed exclusively in B- and T-lymphocyte cell lines and in lymphoid\ tissues . The receptor is likely to be a mediator of EBV effects on B\ lymphocytes, or of normal lymphocyte functions PUB00005876. C-C CKR-7 is unique in\ that both of its introns interrupt the coding region of the first extracellular domain [MEDLINE:95154835]. The gene is encoded on human chromosome 17q12-q21.2 [MEDLINE:95154835].\ Murine C-C CKR-7 cDNA has also been isolated and encodes a protein with 86%\ identity to the human homologue.

\ \ C-C chemokine receptor activity ; GO:0016493 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20410 IPR001715

Actinin-type (including spectrin, fimbrin, ABP-280) (see IPR001589).
Calponin-type (see IPR001589/>).

A comprehensive review of proteins containing this type of actin-binding domains is given in [MEDLINE:96000088].

\ \ \N \N \N 20411 IPR001717

\ \

Naturally-occuring mutations have been characterised in the AE1 gene, which\ give rise to forms of several human diseases: included are spherocytosis,\ affecting red blood cells, and familial distal renal tubular acidosis, a\ kidney disease associated with the formation of kidney stones [MEDLINE:99280171].

\ \ \ inorganic anion exchanger activity ; GO:0005452 membrane ; GO:0016020 anion transport ; GO:0006820 20407 IPR001712

The Flagellar/Hr/Invasion Proteins Export Pore (FHIPEP) family [MEDLINE:94075235], [MEDLINE:93302711] consists of a number of proteins that constitute the type III secretion (or signal peptide-independent) pathway apparatus [MEDLINE:95099573], [MEDLINE:92276315]. This mechanism translocates proteins lacking an N-terminal signal peptide across the cell membrane in one step, as it does not require an intermediate periplasmic process to cleave the signal peptide. It is a common pathway amongst Gram-negative bacteria for secreting toxic and flagellar proteins.

The pathway apparatus comprises three components: two within the inner membrane and one within the outer [MEDLINE:93302711]. An FHIPEP protein is located within the inner membrane, although it is unknown which component it constitutes. FHIPEP proteins have all about 700 amino-acid residues. Within the sequence, the N terminus is highly conserved and hydrophobic, suggesting that this terminus is embedded within the membrane, with 6-8 transmembrane (TM) domains, while the C terminus is less conserved and appears to be devoid of TM regions. It is possible that members of the FHIPEP family serve as pores for the export of specific proteins.

\ \ \N membrane ; GO:0016020 protein secretion ; GO:0009306 20408 IPR001713

Stefin A is a member of the cystatin superfamily, which are tight, reversibly-binding inhibitors of the papain-like cysteine proteases [MEDLINE:95173977]. The inhibitors are involved in the control mechanism responsible for protein breakdown, and are thought to help protect cells from inappropriate endogenous or external proteolysis [MEDLINE:91309737].

\ \

The stefin family includes proteins that lack disulphide bonds and carbohydrates. The most abundant source of stefin A is poly-morphonuclear leucocytes from the liver, but it is also found in extracts of squamous epithelia from the mouth and oesophagus, and has been localised to the cytoplasm of the strata corneum and granulosum of the epidermis. The selective distribution of the inhibitor correlates with tissues that constitute a 'first line of defence' against pathogenic organisms. Stefin A may thus provide a protective function as an inhibitor of cysteine proteases utilised as invasive tools by many infectious agents [MEDLINE:95173977].

\ \

The structure of stefin A contains a 5-stranded anti-parallel -sheet, wrapped around a central helix. The loops formed between the strands are involved in inhibitor binding, one of these containing a QVVAG sequence, which is highly conserved in most members of the cystatin superfamily [MEDLINE:91309737].

\ \ \ \N \N \N 20409 IPR001714

Methionine aminopeptidase ((EC: 3.4.11.18) (MAP) is responsible for the removal of the amino-terminal (initiator) methionine from nascent eukaryotic cytosolic and cytoplasmic prokaryotic proteins if the penultimate amino acid is small and uncharged. All MAP studied to date are monomeric proteins that require cobalt ions for activity.

Two subfamilies of MAP enzymes are known to exist [MEDLINE:95372350], [MEDLINE:96368275]. While being evolutionary related, they only share a limited amount of sequence similarity mostly clustered around the residues shown to be involved in cobalt-binding.

\ \

The first family consists of enzymes from prokaryotes as well as eukaryotic MAP-1, while the second group is made up of archebacterial MAP and eukaryotic MAP-2. The second subfamily also includes proteins which do not seem to be MAP, but that are clearly evolutionary related such as mouse proliferation-associated protein 1 and fission yeast curved DNA-binding protein.

These proteins belong to family M24A and M24C in the classification of peptidases [MEDLINE:95405261].

\ \ \ methionyl aminopeptidase activity ; GO:0004239 \N proteolysis and peptidolysis ; GO:0006508 20404 IPR001709

Flavoprotein pyridine nucleotide cytochrome reductases [MEDLINE:92084635] (FPNCR) catalyse the interchange of reducing equivalents between one-electron carriers and the two-electron-carrying nicotinamide dinucleotides. The enzymes include ferredoxin:NADP⁺reductases (FNR) [MEDLINE:94299474], plant and fungal NAD(P)H:nitrate reductases [MEDLINE:92084635], [MEDLINE:90371632], NADH:cytochrome b5 reductases [MEDLINE:86195916], NADPH:P450 reductases [MEDLINE:91344276], NADPH:sulphite reductases [MEDLINE:89380164], nitric oxide synthases [MEDLINE:91287795], phthalate dioxygenase reductase [MEDLINE:94129395], and various other flavoproteins.

Despite functional similarities, FPNCRs show no sequence similarity to NADPH:adrenodoxin reductases [MEDLINE:89170752], nor to \ bacterial ferredoxin:NAD⁺reductases and their homologues [MEDLINE:90204534]. To date, 3D-structures of 4 members of the family have been solved: spinach ferredoxin:NADP⁺ reductase [MEDLINE:91095975]; Pseudomonas cepacia phthalate dioxygenase reductase [MEDLINE:94129395]; the flavoprotein domain of corn nitrate reductase [MEDLINE:95111952]; and pig NADH:cytochrome b5 reductase [MEDLINE:95196874]. In all of them, the FAD-binding domain (N-terminal) has the topology of an anti-parallel -barrel, while the NAD(P)-binding domain (C-terminal) has the topology of a classical pyridine dinucleotide-binding fold (i.e. a central parallel -sheet with 2 helices on each side) [MEDLINE:94129395]. In spite of such structural similarities, the level of amino acid identity between family members is at or below the limit of significance (e.g., nitrate reductase is only 15% identical to FNR) [MEDLINE:95111952].

\ \ oxidoreductase activity ; GO:0016491 \N electron transport ; GO:0006118 20405 IPR001710

Adrenomedullin is a hypotensive peptide, first identified in human pheochromocytoma arising from adrenal medulla [MEDLINE:93249425], [MEDLINE:93384621]. The protein is ~185 amino acids in length, and includes a 21-residue putative N-terminal signal sequence [MEDLINE:93384621]. The active peptide, which is expressed in adrenal glands, lung, kidney, heart, spleen, duodenum and submandibular glands, is thought to function as a hormone in circulation control.

The adrenomedullin precursor is believed to contain 2 cleavage sites, one of which produces the active adrenomedullin hormone, and the other, a 20-residue peptide (proadrenomedullin N-terminal 20 peptide, or proam-n20) of unknown function [MEDLINE:93343928].

\ \ hormone activity ; GO:0005179 extracellular ; GO:0005576 \N 20406 IPR001711

Phosphatidylinositol-specific phospholipase C (EC: 3.1.4.11), an eukaryotic intracellular enzyme, plays an important role in signal transduction processes [MEDLINE:91182830] (see IPR001192.

In mammals, there are at least 6 different isoforms of PI-PLC, they differ in their domain structure, their regulation, and their tissue distribution. Lower eukaryotes also possess multiple isoforms of PI-PLC.

All eukaryotic PI-PLCs contain two regions of homology, sometimes referred to as 'X-box' (see IPR001192/>) and 'Y-box'. The order of these two regions is always the same (NH2-X-Y-COOH), but the spacing is variable. In most isoforms, the distance between these two regions is only 50-100 residues but in the gamma isoforms one PH domain, two SH2 domains, and one SH3 domain are inserted between the two PLC-specific domains. The two conserved regions have been shown to be important for the catalytic activity. At the C-terminal of the Y-box, there is a C2 domain (see IPR000008) possibly involved in Ca-dependent membrane attachment.

\ \ \ 1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase activity ; GO:0004435\ \N \N intracellular signaling cascade ; GO:0007242 20403 IPR001708 Stage III sporulation protein J (SP3J) is a probable lipoprotein, rich in basic and hydrophobic amino acids. Mutations in the protein abolish the transcription of prespore-specific genes transcribed by the sigma G form of RNA polymerase [MEDLINE:93139756]. SP3J could be involved in a signal transduction pathway coupling gene expression in the prespore to events in the mother cell, or it may be necessary for essential metabolic interactions between the two cells [MEDLINE:93139756]. The protein shows a high degree of similarity to B.subtilis YQJG, to yeast OXA1 and also to bacterial 60 kDa inner-membrane proteins [MEDLINE:93315143], [MEDLINE:95350630], [MEDLINE:92204018], [MEDLINE:94350801]. These are integral membrane proteins of uncharacterised function that contain several potential transmembrane domains - one of these is located at the N-terminus, the rest residing within the C-terminal portion of the protein.\ \N membrane ; GO:0016020 signal transduction ; GO:0007165 20402 IPR001707

Chloramphenicol acetyltransferase (CAT) (EC: 2.3.1.28) [MEDLINE:91328788] catalyzes the acetyl-CoA dependent acetylation of chloramphenicol (Cm), an antibiotic which inhibits prokaryotic peptidyltransferase activity. Acetylation of Cm by CAT inactivates the antibiotic. A histidine residue, located in the C-terminal section of the enzyme, plays a central role in its catalytic mechanism.

There is a second family of CAT [MEDLINE:92234946], evolutionary unrelated to the main family described above. These CAT belong to the bacterial hexapeptide-repeat containing-transferases family (see IPR001451).

The crystal structure of the type III enzyme from Escherichia coli with chloramphenicol bound has been determined. CAT is a trimer of identical subunits (monomer Mr 25,000) and the trimeric structure is stabilized by a number of hydrogen bonds, some of which result in the extension of a -sheet across the subunit interface. Chloramphenicol binds in a deep pocket located at the boundary between adjacent subunits of the trimer, such\ that the majority of residues forming the binding pocket belong to one subunit while the catalytically essential histidine belongs to the adjacent subunit. His195 is appropriately positioned to act as a general base catalyst in the reaction, and the required tautomeric stabilization is provided by an unusual interaction with a main-chain carbonyl oxygen [MEDLINE:90250768].

\ \ chloramphenicol O-acetyltransferase activity ; GO:0008811 \N \N 20401 IPR001706

\ \ \

L35 is a basic protein of 60 to 70 amino-acid residues from the large (50S) subunit [MEDLINE:87101185]. Like many basic polypeptides, L35 completely inhibits ornithine decarboxylase when present unbound in the cell, but the inhibitory function is abolished upon its incorporation into ribosomes [MEDLINE:87101185]. It belongs to a family of ribosomal proteins, including L35 from eubacteria, plants, red algae and cyanelles - in lower plants it is found in the chloroplast, but is located in the nucleus in higher plants, suggesting chloroplast-to-nucleus relocation during the evolution of higher plants\ \ \ \ [MEDLINE:91104876].

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 20399 IPR001704

Orexins (also known as hypocretins) are recently identified neuropeptides that are specifically localised to the hypothalamus. They are thought to interact with autonomic, neurendocrine and neuroregulatory systems, and play an important role in the regulation of feeding behaviour [MEDLINE:99110962], [MEDLINE:98081872]. When applied to hypothalamic neurones, these peptides are neuroexcitatory, which action is probably mediated by their binding to a new family of G-protein-coupled receptors (orexin receptors 1 and 2), which were previously orphan [MEDLINE:98150861].

To date, two orexins have been characterised (orexin-A and -B), both encoded by a single mRNA transcript (prepro-orexin): orexin-A is a 33-residue peptide with two intramolecular disulphide bonds in the N-terminal region; and orexin-B is a linear 28-residue peptide. These peptides have 46% identity at the amino acid sequence level, and show some similarity to the glucagon/vasoactive intestinal polypeptide/secretin peptide family.

\ \ \ \N \N feeding behavior ; GO:0007631 20400 IPR001705

\ \ \

Ribosomal protein L33 is one of the proteins from the large ribosomal subunit. In Escherichia coli, L33 has been shown to be on the surface of 50S subunit. L33 belongs to a family of ribosomal proteins which, on the basis of sequence similarities [MEDLINE:92075758], [MEDLINE:94156176], PUB00005070, groups:\

Eubacterial L33.
Algal and plant chloroplast L33.
Cyanelle L33.

L33 is a small protein of 49 to 66 amino-acid residues.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 20398 IPR001703

A number of serum transport proteins are known to be evolutionarily related, including albumin, -fetoprotein, vitamin D-binding protein and afamin [MEDLINE:90112461], [MEDLINE:86216223], [MEDLINE:94299534]. Albumin is the main protein of plasma; it binds water, cations (such as Ca²⁺, Na⁺ and K⁺), fatty acids, hormones, bilirubin and drugs - its main function is to regulate the colloidal osmotic pressure of blood. Vitamin D-binding protein binds to vitamin D and its metabolites, as well as to fatty acids. The biological role of afamin (-albumin) has not yet been characterised.

Alpha-fetoprotein (AFP) (-fetoglobulin) is a foetal plasma protein that binds various cations, fatty acids and bilirubin [MEDLINE:79001617], [MEDLINE:80001710]. The protein appears in the plasma of 4-week old fetuses, reaches its highest levels in the 12th-16th week of gestation, dropping to trace amounts after birth. It is also found at high levels in the plasma and ascitic fluid of adults with hepatoma [MEDLINE:77242506].

The amino acid sequence contains a 19-amino acid signal peptide [MEDLINE:83273664], and a 591-residue mature protein [MEDLINE:91242409]. Fifteen regularly-spaced disulphide bridges generate a 3-domain folding structure, each domain containing ~190 amino acids, with 5 or 6 internal disulphide bonds, as shown schematically below. Sequence comparisons indicate that the greatest level of conservation resides in domain 3 and the lowest in domain 1 [MEDLINE:79001617].

\
                   +---+          +----+                        +-----+\
                   |   |          |    |                        |     |\
xxCxxxxxxxxxxxxxxxxCCxxCxxxxCxxxxxCCxxxCxxxxxxxxxCxxxxxxxxxxxxxxCCxxxxCxxxx\
  |                 |       |     |              |               |\
  +-----------------+       +-----+              +---------------+\

In addition to the monomeric form of AFP, dimeric and trimeric forms occur, which dissociate only on exposure to disulphide-reducing reagents, suggesting that polymer formation is mediated by inter-molecular disulphide bond formation [MEDLINE:77242506].

\ \ \ carrier activity ; GO:0005386 extracellular space ; GO:0005615 transport ; GO:0006810 20396 IPR001701

Glycoside hydrolase family 9 CAZY:GH_9). These enzymes were formerly known as cellulase family E.

\ \ hydrolase activity, hydrolyzing O-glycosyl compounds ; GO:0004553 \N carbohydrate metabolism ; GO:0005975 20397 IPR001702

The outer membrane of Gram-negative bacteria acts as a molecular filter for hydrophilic compounds. Proteins, known as porins [MEDLINE:88329047], are responsible for the 'molecular sieve' properties of the outer membrane. Porins form large water-filled channels which allows the diffusion of hydrophilic molecules into the periplasmic space. Some porins form general diffusion channels that allows any solutes up to a certain size (that size is known as the exclusion limit) to cross the membrane, while other porins are specific for a solute and contain a binding site for that solute inside the pores (these are known as selective porins). As porins are the major outer membrane proteins, they also serve as receptor sites for the binding of phages and bacteriocins.

General diffusion porins generally assemble as trimer in the membrane and the transmembrane core of these proteins is composed exclusively of strands [MEDLINE:91134313]. It has been shown [MEDLINE:92114794] that a number of general porins are evolutionary related, these porins are:\

Enterobacteria phoE.
Enterobacteria ompC.
Enterobacteria ompF.
Enterobacteria nmpC.
Bacteriophage PA-2 LC.
Neisseria PI.A.
Neisseria PI.B.

\ \ transporter activity ; GO:0005215 membrane ; GO:0016020 transport ; GO:0006810 20395 IPR001700

Members of this family include:

subunit from eubacteria
subunits from chloroplasts

The subunit of RNA polymerase consists of two independently folded domains, referred to as amino-terminal and carboxyl terminal domains. The amino terminal domain is involved in the interaction with the other subunits of the RNA polymerase. The carboxyl-terminal domain interacts with the DNA and activators. The amino acid sequence of the subunit is conserved in prokaryotic and chloroplast RNA polymerases. There are three regions of particularly strong conservation, two in the amino-terminal and one in the carboxyl-terminal [MEDLINE:98322352], [MEDLINE:96095212], [MEDLINE:95337664], [MEDLINE:97203125].

\ \ DNA-directed RNA polymerase activity ; GO:0003899 \N transcription ; GO:0006350 20392 IPR001698

The subunit is a protein of about 280 amino acid residues whose sequence is well conserved in eukaryotic species [MEDLINE:90190869].

\ \ F-actin capping activity ; GO:0003782 actin capping protein complex ; GO:0008290 actin cytoskeleton organization and biogenesis ; GO:0030036 20393 IPR001699

Transcription factors of the T-box family are required both for early cell-fate decisions, such as those necessary for formation of the basic vertebrate body plan, and for differentiation and organogenesis [MEDLINE:22088482]. The T-box is defined as the minimal region within the T-box protein that is both necessary and sufficient for sequence-specific\ DNA binding, all members of the family so far examined bind to the DNA consensus sequence TCACACCT. The T-box is a relatively large DNA-binding domain, generally comprising about a third of the entire protein (17-26 kDa).

T-box proteins tend to be expressed in specific organs or cell types, especially during development, and they are generally required for the development of\ those tissues, for example, Brachyury is expressed in posterior mesoderm and in the developing notochord, and it is required for\ the formation of these cells in mice[MEDLINE:97339734].

\ \ transcription factor activity ; GO:0003700 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 20394 IPR001700

Members of this family include:

subunit from eubacteria
subunits from chloroplasts

\ \ DNA-directed RNA polymerase activity ; GO:0003899 \N transcription ; GO:0006350 20390 IPR001697

Pyruvate kinase (EC: 2.7.1.40) (PK) catalyses the final step in glycolysis [MEDLINE:90336973], the conversion of phosphoenolpyruvate to pyruvate with concomitant phosphorylation of ADP to ATP:

 ADP + phosphoenolpyruvate = ATP + pyruvate

The enzyme, which is found in all living organisms, requires both magnesium and potassium ions for its activity [MEDLINE:86220125]. In vertebrates, there are four tissue-specific isozymes: L (liver), R (red cells), M1 (muscle, heart and brain), and M2 (early foetal tissue). In Escherichia coli, there are two isozymes: PK-I (gene pykF) and PK-II (gene pykA). All isozymes appear to be tetramers of identical subunits of ~500 residues.

The structure of cat muscle pyruvate kinase has been determined [MEDLINE:86220125]. The protein comprises three domains each belonging to the - class; one of these adopts a 3-layer(aba) sandwich architecture; the other two form -barrels.

\ \ pyruvate kinase activity ; GO:0004743 \N glycolysis ; GO:0006096 20391 IPR001697

Pyruvate kinase (EC: 2.7.1.40) (PK) catalyses the final step in glycolysis [MEDLINE:90336973], the conversion of phosphoenolpyruvate to pyruvate with concomitant phosphorylation of ADP to ATP:

 ADP + phosphoenolpyruvate = ATP + pyruvate

\ \ pyruvate kinase activity ; GO:0004743 \N glycolysis ; GO:0006096 20387 IPR001694

Respiratory-chain NADH dehydrogenase (EC: 1.6.5.3) PUB00001096, PUB00001096 (also known as complex I or NADH-ubiquinone oxidoreductase) is an oligomeric enzymatic complex located in the inner mitochondrial membrane which also seems to exist in the chloroplast and in cyanobacteria (as a NADH-plastoquinone oxidoreductase). Among the 25 to 30 polypeptide subunits of this bioenergetic enzyme complex there are fifteen which are located in the membrane part, seven of which are encoded by the mitochondrial and chloroplast genomes of most species. The most conserved of these organelle-encoded subunits is known as subunit 1 (gene ND1 in mitochondrion, and NDH1 in chloroplast) and seems to contain the ubiquinone binding site.

The ND1 subunit is highly similar to subunit 4 of Escherichia coli formate hydrogenlyase (gene hycD), subunit C of hydrogenase-4 (gene hyfC). Paracoccus denitrificans NQO8 and Escherichia coli nuoH NADH-ubiquinone oxidoreductase subunits also belong to this family [MEDLINE:93389724].

\ \ \N membrane ; GO:0016020 electron transport ; GO:0006118 20388 IPR001695

Lysyl oxidase (EC: 1.4.3.13) (LOX) [MEDLINE:93385183] is an extracellular copper-dependent enzyme that catalyzes the oxidative deamination of peptidyl lysine residues in precursors of various collagens and elastins, yielding -aminoadipic-delta-semialdehyde. The deaminated lysines are then able to form semialdehyde cross-links, resulting in the formation of insoluble collagen and elastin fibres in the extracellular matrix [MEDLINE:93024096].

The active site of LOX resides towards the C terminus: this region also binds a single copper atom in an octahedral coordination complex involving at least 3 His residues [MEDLINE:92332554]. Four histidine residues are clustered in a central region of the enzyme. This region is thought to be involved in cooper-binding and is called the 'copper-talon' [MEDLINE:93385183].

\ \ copper ion binding activity ; GO:0005507 \N \N 20389 IPR001696

\ \

\ \ \ \ voltage-gated sodium channel activity ; GO:0005248 voltage-gated sodium channel complex ; GO:0001518 sodium ion transport ; GO:0006814 20386 IPR001693

Calcitonin [MEDLINE:89076193] is a 32 amino acid polypeptide hormone that causes a rapid but short-lived drop in the level of calcium and phosphate in the blood, by promoting the incorporation of these ions in the bones, type. Alternative splicing of the gene coding for calcitonin produces a distantly related peptide of 37 amino acids, called calcitonin gene-related peptide (CGRP), type. CGRP induces vasodilatation in a variety of vessels, including the coronary, cerebral and systemic vasculature. Its abundance in the CNS also points toward a neurotransmitter or neuromodulator role.

Islet amyloid polypeptide (IAPP) [MEDLINE:90170905] (also known as diabetes-associated peptide (DAP), or amylin) is a peptide of 37 amino acids that selectively inhibits insulin-stimulated glucose utilization and glycogen deposition in muscle, while not affecting adipocyte glucose metabolism. Structurally, IAPP is closely related to CGRP.

Two conserved cysteines in the N-terminal of these peptides are known to be involved in a disulfide bond. The C-terminal residue of all three peptides is amidated.

\ xCxxxxxCxxxxxxxxxxxxxxxxxxxxxxxxxxxx-NH(2)\ | | Amide group\ +-----+\ \ 'C': conserved cysteine involved in a disulfide bond.\

\ \ \ hormone activity ; GO:0005179 extracellular ; GO:0005576 \N 20385 IPR001692

Histidinol dehydrogenase (EC: 1.1.1.23) (HDH) catalyzes the terminal step in the biosynthesis of histidine in bacteria, fungi, and plants', the four-electron oxidation of L-histidinol to histidine.

In 4-electron dehydrogenases, a single active site catalyses 2 separate oxidation steps: oxidation of the substrate alcohol to an intermediate aldehyde; and oxidation of the aldehyde to the product acid, in this case His [MEDLINE:87026557]. The reaction proceeds via a tightly- or covalently-bound inter-mediate, and requires the presence of 2 NAD molecules [MEDLINE:87026557]. By contrast with most dehydrogenases, the substrate is bound before the NAD coenzyme [MEDLINE:87026557]. A Cys residue has been implicated in the catalytic mechanism of the second oxidative step [MEDLINE:87026557].

In bacteria HDH is a single chain polypeptide; in fungi it is the C-terminal domain of a multifunctional enzyme which catalyzes three different steps of histidine biosynthesis; and in plants it is expressed as nuclear encoded protein precursor which is exported to the chloroplast [MEDLINE:91239521].

\ \ histidinol dehydrogenase activity ; GO:0004399 \N histidine biosynthesis ; GO:0000105 20384 IPR001690

Bacterial species have many methods of controlling gene expression and cellgrowth. Regulation of gene expression in response to changes in cell density is termed quorum sensing [MEDLINE:20076909], [MEDLINE:99145603]. Quorum-sensing bacteria produce, release and respond to hormone-like molecules (autoinducers) that accumulate in the external environment as the cell population grows. Once a threshold of these molecules is reached, a signal transduction cascade is triggered that ultimately leads to behavioural changes in the bacterium [MEDLINE:99145603]. Autoinducers are thus clearly important mediators of molecular communication.

Conjugal transfer of Agrobacterium octopine-type Ti plasmids is activated \ by octopine, a metabolite released from plant tumours [MEDLINE:94245603]. Octopine causes conjugal donors to secrete a pheromone, Agrobacterium autoinducer (AAI),\ and exogenous AAI further stimulates conjugation. The putative AAI synthase and an AAI-responsive transcriptional regulator have been found to be encoded by the Ti plasmid traI and traR genes, respectively. TraR and TraI are similar to the LuxR and LuxI regulatory proteins of Vibrio fischeri, and AAI is similar in structure to the diffusable V.fischeri autoinducer, the inducing ligand of LuxR. TraR activates target genes in the presence of AAI and also activates traR and traI themselves, creating two positive-feedback loops. TraR-AAI-mediated activation in wild-type Agrobacterium strains is enhanced by culturing on solid media, suggesting a possible role in cell density sensing [MEDLINE:94245603].

Production of light by the marine bacterium Vibrio fischeri and by recombinant hosts containing cloned lux genes is controlled by the density\ of the culture [MEDLINE:88096578]. Density-dependent regulation of lux gene expression has been shown to require a locus consisting of the luxR and luxI genes.

In these and other Gram-negative bacteria, N-(3-oxohexanoyl)-L-homoserine lactone (OHHL) acts as the autoinducer by binding to transcriptional regulatory proteins and activating them [MEDLINE:95058194]. OHHL and related molecules, such as N-butanoyl- (BHL), N-hexanoyl- (HHL) and N-oxododecanoyl- (PAI) homoserine lactones, are produced by a family of proteins that share a high level of sequence similarity.

Proteins which currently members of this family include:\

luxI from Vibrio fischeri.
ahyI and asaI from Aeromonas, which synthesize BHL and whose target are ahyR and asaR.
carI from Erwinia carotovora. The target of OHHL is carR which activates genes involved in the biosynthesis of carbapenem antibiotics.
eagI from Enterobacter agglomerans. The target of OHHL is not yet known.
esaI from Erwinia stewartii.
expI from Erwinia carotovora.
lasI from Pseudomonas aeruginosa, which synthesizes PAI and whose target is lasR which activates the transcription of the elastase gene.
rhlI (or vsmI) from Pseudomonas aeruginosa, which synthesizes BHL and HHL and whose target is rhlR.
swrI from Serratia liquefaciens, which synthesizes BHL.
yenI from Yersinia enterocolitica.

\ \ \N \N signal transduction ; GO:0007165 20383 IPR001689

The flagellar motor switch in Escherichia coli and Salmonella typhimurium regulates the direction of flagellar rotation and hence controls swimming behaviour [MEDLINE:94040782]. The switch is a complex apparatus that responds to signals transduced by the chemotaxis sensory signalling system during chemotactic behaviour [MEDLINE:94040782]. CheY, the chemotaxis response regulator, is believed to act directly on the switch to induce tumbles in the swimming pattern, but no physical interactions of CheY and switch proteins have yet been demonstrated.

The switch complex comprises at least three proteins - FliG, FliM and FliN. It has been shown that FliG interacts with FliM, FliM interacts with itself, and FliM interacts with FliN [MEDLINE:96200097]. Several residues within the middle third of FliG appear to be strongly involved in the FliG-FliM interaction, with residues near the N or C termini being less important [MEDLINE:96200097]. Such clustering suggests that FliG-FliM interaction plays a central role in switching.

Analysis of the FliG, FliM and FliN sequences shows that none are especially hydrophobic or appear to be integral membrane proteins [MEDLINE:89255090]. This result is consistent with other evidence suggesting that the proteins may be peripheral to the membrane, possibly mounted on the basal body M ring [MEDLINE:89255090], [MEDLINE:92335286].

\ \ motor activity ; GO:0003774 flagellar basal body (sensu Bacteria) ; GO:0009425 chemotaxis ; GO:0006935 20381 IPR001687

From sequence comparisons and crystallographic data analysis it has been shown [MEDLINE:84236073], [MEDLINE:85231195], [MEDLINE:86149249], [MEDLINE:87175567], [MEDLINE:91118233], [MEDLINE:93188011] that an appreciable proportion of proteins that bind ATP or GTP share a number of more or less conserved sequence motifs. The best conserved of these motifs is a glycine-rich region, which typically forms a flexible loop between a -strand and an -helix. This loop interacts with one of the phosphate groups of the nucleotide. This sequence motif is generally referred to as the 'A' consensus sequence [MEDLINE:84236073] or the 'P-loop' [MEDLINE:91118233].There are numerous ATP- or GTP-binding proteins in which the P-loop is found.\ We list below a number of protein families for which the relevance of the presence of such motif has been noted:\

Not all ATP- or GTP-binding proteins are picked-up by this motif. A number of proteins escape detection because the structure of their ATP-binding site is completely different from that of the P-loop. Examples of such proteins are the E1-E2 ATPases or the glycolytic kinases. In other ATP- or GTP-binding proteins the flexible loop exists in a slightly different form; this is the case for tubulins or protein kinases.

Note: No protein matches are shown due to the low specificity of this rule.

\ \ ATP binding activity ; GO:0005524 \N \N 20382 IPR001688

The major physiological role of calcitonin is to inhibit bone resorption\ thereby leading to a reduction in plasma Ca²⁺ PUB00005874. Further, it enhances\ excretion of ions in the kidney, prevents absorption of ions in the\ intestine, and inhibits secretion in endocrine cells (e.g. pancreas and\ pituitary). In the CNS, calcitonin has been reported to be analgesic\ and to suppress feeding and gastric acid secretion. It is used to treat\ Paget's disease of the bone. Calcitonin receptors are found predominantly\ on osteoclasts or on immortal cell lines derived from these cells. It is\ found in lower amounts in the brain (e.g. in hypothalamus and pituitary\ tissues) and in peripheral tissues (e.g. testes, kidney, liver and\ lymphocytes). It has also been described in lung and breast cancer cell\ lines. The predominant signalling pathway is activation of adenylyl cyclase\ through Gs, but calcitonin has also been described to have both stimulatory\ and inhibitory actions on the phosphoinositide pathway.

\ \ calcitonin receptor activity ; GO:0004948 membrane ; GO:0016020 \N 20377 IPR001682 Cation channels are transport proteins responsible for the movement of cations through the membrane. These proteins contain 6 transmembrane helices in which the last two helices flank a loop which determines ion selectivity. In some sub-families (e.g. Na channels) the domain is repeated four times, whereas in others (e.g. K channels) the protein forms as a tetramer in the membrane. This pore region is found in calcium and sodium channels, which are responsible for the transport of these ions through the membrane. The pore region is generally conserved and is essential for the specificity of the channel.\ cation channel activity ; GO:0005261 membrane ; GO:0016020 cation transport ; GO:0006812 20378 IPR001683

The PX (phox) domain [MEDLINE:97084820] occurs in a variety of eukaryotic proteins associated with intracellular signaling pathways.PX domains are important phosphoinositide-binding modules that have varying lipid-binding specificities [MEDLINE:21881635].\ The PX domain is approximately 120 residues long [MEDLINE:21267481],\ and folds into a three-stranded �-sheet followed by three -helices and a proline-rich region that immediately preceeds a membrane-interaction loop and spans approximately eight hydrophobic and polar residues. \ The PX domain of p47phox binds to the SH3 domain in the same protein\ [MEDLINE:21267481]. This SH3 binding function may play a regulatory role in either blocking PI binding or enhancing it (Matt Cheever pers. obs.). Given that only one SH3-PX domain interaction has been found, the issue of whether SH3 domain binding is a general feature of PX domains is yet to be resolved.

\ \

Among these proteins are: the phox proteins p40phox (see IPR000919.

\ \ \N \N intracellular signaling cascade ; GO:0007242 20379 IPR001684

\ \ \

L27 is a protein from the large (50S) subunit; it is essential for ribosome function, but its exact role is unclear. It belongs to a family of ribosomal proteins, including L27 from eubacteria and plant and red alga chloroplasts, and YmL2 protein (gene MRPL2 or MRP7) from yeast mitochondria. The schematic relationship between these groups of proteins is shown below.\

\ Eub. L27 Nxxxxxxxxx\ Algal L27 Nxxxxxxxxx\ Plant L27 tttttNxxxxxxxxxxxxx\ Yeast MRP7 tttNxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx\ \ 't': transit peptide.\ 'N': N-terminal of mature protein.\

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 20376 IPR001681

Neuropeptide receptors are present in very small quantities in the cell\ and are embedded tightly in the plasma membrane. The neuropeptides exhibit\ a high degree of functional diversity through both regulation of peptide\ production and through peptide-receptor interaction [MEDLINE:90036822]. The mammalian\ tachykinin system consists of 3 distinct peptides: substance P, substance\ K and neuromedin K. All possess a common spectrum of biological activities,\ including sensory transmission in the nervous system and contraction/\ relaxation of peripheral smooth muscles, and each interacts with a\ specific receptor type.

\ \ tachykinin receptor activity ; GO:0004995 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20380 IPR001686

Presenilins are polytopic transmembrane (TM) proteins, mutations in which are associated with the occurrence of early-onset familial Alzheimer's disease, a rare form of the disease that results from a single-gene mutation [MEDLINE:98180715]. The physiological functions of presenilins are unknown, but they may be related to developmental signalling, apoptotic signal transduction, or processing of selected proteins. That presenilin homologues have been identified in species that do not have an Alzhemier's disease correlate suggests that they may have functions unrelated to the disease, homologues having been identified in mouse, Drosophila and C.elegans.

Sel-12, a worm homologue of the mammalian presenilins (with which it shares ~50% amino acid identity), has been shown to facilitate the function of the Notch receptor (LIN-12 protein), which plays a role in cell-cell signalling during cell differentiation in development. Intriguingly, presenilin 1 (one of the two two presenilin genes present in human) is able to restore function in a C.elegans mutant lacking sel-12, suggesting presenilin may also be involved in cell-cell signalling in higher species [MEDLINE:96032531].

\ \ \N membrane ; GO:0016020 intracellular signaling cascade ; GO:0007242 20375 IPR001680

Beta-transducin (G-) is one of the three subunits (, , and gamma) of the guanine nucleotide-binding proteins (G proteins) which act as intermediaries in the transduction of signals generated by transmembrane receptors [MEDLINE:87297448] (see IPR001632). The subunit binds to and hydrolyzes GTP; the functions of the and gamma subunits are less clear but they seem to be required for the replacement of GDP by GTP as well as for membrane anchoring and receptor recognition.

In higher eukaryotes G- exists as a small multigene family of highly conserved proteins of about 340 amino acid residues. Structurally G- consists of eight tandem repeats of about 40 residues, each containing a central Trp-Asp motif (this type of repeat is sometimes called a WD-40 repeat). Such a repetitive segment has been shown [MEDLINE:92279208], [MEDLINE:92354695], \ [MEDLINE:94376869], [MEDLINE:99257314] to exist in a number of other proteins, including G--like peptides, yeast STE4, MSI1, CDC4, CDC20, MAK11, PRP4, PWP1 and TUP1, slime-mold AAC3 and coronin, and Drosophila Groucho protein. The number of repeats within these proteins varies between 5 (PRP4, TUP1, and Groucho) and 8 (G-, STE4, MSI1, AAC3, CDC4, PWP1, etc.). In G- and G- like proteins, the repeats span the entire length of the sequence, while in other proteins, they make up the N-terminal, the central or the C-terminal section.

\ \ \N \N \N 20371 IPR001676

Capsid proteins of picornaviruses. Picornaviruses are non-enveloped plus-strand ssRNA animal viruses with icosahedral capsids. They include rhinovirus (common cold) and poliovirus.

Common structure is an 8-stranded sandwich. Variations (one or two extra strands) occur.

\ \ structural molecule activity ; GO:0005198 viral capsid ; GO:0019028 \N 20372 IPR001677

Bacterial transferrin binding proteins act as transferrin receptors and are required for transferrin utilisation. Transferrins are iron-binding glycoproteins that control the level of free iron in biological fluids.

\ transferrin receptor activity ; GO:0004998 membrane ; GO:0016020 \N 20373 IPR001678

The following proteins seems to be evolutionary related:

Mammalian proliferating-cell nucleolar antigen p120 (gene NOL1) which may play a role in the regulation of the cell cycle and the increased nucleolar activity that is associated with the cell proliferation.
Yeast nucleolar protein NOP2 (or YNA1) which could be involved in nucleolar function during the onset of growth, and in the maintenance of nucleolar structure.
Yeast NCL1.
Bacterial protein sun (also known as fmu).
Escherichia coli hypothetical protein yebU.
Mycobacterium tuberculosis hypothetical protein MtCY21B4.24.
Methanococcus jannaschii hypothetical protein MJ0026.

NOL1 is a protein of 855 residues, NOP2 consists of 618 residues, NCL1 of 684, sun is a protein of about 430 to 450 residues and MJ026 has 274 residues. They share a conserved central domain which contains some highly conserved regions.

\ \ \N \N \N 20374 IPR001679

This family is predominantly composed of NAD-dependent bacterial DNA ligases. They are proteins of about 75 to 85 Kd whose sequence is well conserved [MEDLINE:92406015], [MEDLINE:93300828]. They also show similarity to yicF, an Escherichia coli hypothetical protein of 63 Kd.

\ \ DNA ligase (NAD+) activity ; GO:0003911 \N DNA repair ; GO:0006281 20370 IPR001675

Glycosyltransferase family 29 (CAZY:GT_29). These enzymes use a nucleotide monophosphosugar as the donor (CMP-NeuA) instead of a nucleotide diphosphosugar.

\ \

Sialyltransferase may be responsible for the synthesis of the sequence NEUAC-Alpha-2,3-GAL-Beta-1,3-GALNAC-, found on sugar chains O-linked to thr or ser and also as a terminal sequenec on certain gagnliosides. These enzymes catalyse sialyltransfer reactions during glycosylation, and are type II membrane proteins.

\ \ sialyltransferase activity ; GO:0008373 membrane ; GO:0016020 protein amino acid glycosylation ; GO:0006486 20368 IPR001673

Several Dictyostelium species have proteins that contain conserved repeats. These proteins have been variously described as extracellular matrix protein B', cyclic nucleotide phosphodiesterase inhibitor precursor', prestalk protein precursor', 'putative calmodulin-binding protein CamBP64', and cysteine-rich, acidic integral membrane protein precursor' as well as 'hypothetical protein'. The repeats are not confined to Dictyostelium spp, they occur in the Ascomycete Trichoderma harzianum in one of the conidiospore surface proteins, Q9Y7V5.

\ \N \N \N 20369 IPR001674 The amidotransferase family of enzymes utilizes the ammonia derived from the hydrolysis of glutamine for a subsequent chemical reaction catalyzed by the same enzyme. The ammonia intermediate does not dissociate into solution during the chemical transformations [MEDLINE:99315161].GMP synthetase is a glutamine amidotransferase from the de novo purine biosynthetic pathway. The C-terminal domain is specific to the GMP synthases EC: 6.3.5.2. In prokaryotes this domain mediates dimerisation. Eukaryotic GMP synthases are monomers. This domain in eukaryotes includes several large insertions that may form globular domains [MEDLINE:96133732].\ \ ATP binding activity ; GO:0005524 \N GMP biosynthesis ; GO:0006177 20366 IPR001671

Adrenocorticotrophin (ACTH), melanocyte-stimulating hormones (MSH) and -endorphin are peptide products of pituitary pro-opiomelanocortin.\ ACTH regulates synthesis and release of glucocorticoids and aldosterone\ in the adrenal cortex; it also has a trophic action on these cells.\ ACTH and -endorphin are synthesised and released in response to\ corticotrophin-releasing factor at times of stress (heat, cold, infections,\ etc.) - their release leads to increased metabolism and analgesia res..\ MSH has a trophic action on melanocytes, and regulates pigment production\ in fish and amphibia PUB00005891. The ACTH receptor is found in high levels in\ the adrenal cortex - binding sites are present in lower levels in the\ CNS. The MSH receptor is expressed in high levels in melanocytes,\ melanomas and their derived cell lines PUB00005891. Receptors are found in low\ levels in the CNS. MSH regulates temperature control in the septal region\ of the brain and releases prolactin from the pituitary.

\ \ \ melanocortin receptor activity ; GO:0004977 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20365 IPR001670

Alcohol dehydrogenase (EC: 1.1.1.1) (ADH) catalyzes the reversible oxidation of ethanol to acetaldehyde with the concomitant reduction of NAD PUB00006085. Currently three, structurally and catalytically, different types of alcohol dehydrogenases are known:

Zinc-containing 'long-chain' alcohol dehydrogenases.
Insect-type, or 'short-chain' alcohol dehydrogenases.
Iron-containing alcohol dehydrogenases.

Iron-containing ADH's have been found in yeast (gene ADH4) PUB00006085, as well as in Zymomonas mobilis (gene adhB) [MEDLINE:88038383]. These two iron-containing ADH's are closely related to the following enzymes:\

Escherichia coli propanediol oxidoreductase (EC: 1.1.1.77) (gene fucO) [MEDLINE:89291720], an enzyme involved in the metabolism of fucose and which also seems to contain ferrous ion(s).
Clostridium acetobutylicum NADPH- and NADH-dependent butanol dehydrogenases (EC: 1.1.1.-) (genes adh1, bdhA and bdhB) [MEDLINE:93054325], an enzyme which has activity using butanol and ethanol as substrates.
Escherichia coli adhE [MEDLINE:91200315], an iron-dependent enzyme which harbor three different activities: alcohol dehydrogenase, acetaldehyde dehydrogenase (acetylating) (EC: 1.2.1.10) and pyruvate-formate-lyase deactivase.
Bacterial glycerol dehydrogenase (EC: 1.1.1.6) (gene gldA or dhaD) [MEDLINE:94179122].
Clostridium kluyveri NAD-dependent 4-hydroxybutyrate dehydrogenase (4hbd) (EC: 1.1.1.61).
Citrobacter freundii and Klebsiella pneumoniae 1,3-propanediol dehydrogenase (EC: 1.1.1.202) (gene dhaT).
Bacillus methanolicus NAD-dependent methanol dehydrogenase (EC: 1.1.1.244) [MEDLINE:92355510].
Escherichia coli and Salmonella typhimurium ethanolamine utilization protein eutG.
Escherichia coli hypothetical protein yiaY.

\ \ oxidoreductase activity ; GO:0016491 \N metabolism ; GO:0008152 20367 IPR001672

Phosphoglucose isomerase (EC: 5.3.1.9) (PGI) [MEDLINE:81273331], [MEDLINE:92277670] is a dimeric enzyme that catalyzes the reversible isomerization of glucose-6-phosphate and fructose-6-phosphate. PGI is involved in different pathways: in most higher organisms it is involved in glycolysis; in mammals it is involved in gluconeogenesis; in plants in carbohydrate biosynthesis; in some bacteria it provides a gateway for fructose into the Entner-Doudouroff pathway. The multifunctional protein , PGI, is also known as neuroleukin, autocrine motility factor, and differentiation and maturation mediator and has different roles inside and outside the cell. In the cytoplasm, it catalyzes the second step in glycolysis. Outside the cell, it serves as a nerve growth factor and cytokine [MEDLINE:20120584].

PGI from Bacillus stearothermophilus has an open twisted / structural motif consisting of two globular domains and two protruding parts. It has been suggested that the top part of the large domain together with one of the protruding loops might participate in inducing the neurotrophic activity [MEDLINE:99254054]. The structure of rabbit muscle phosphoglucose isomerase complexed with various inhibitors shows that the enzyme is a dimer with two /-sandwich domains in each subunit. The location of the bound D-gluconate 6-phosphate inhibitor leads to the identification of residues involved in substrate specificity. In addition, the positions of amino acid residues that are substituted in the genetic disease nonspherocytic hemolytic anemia suggest how these substitutions can result in altered catalysis or protein stability [MEDLINE:20120584], 20390074].

\ \ glucose-6-phosphate isomerase activity ; GO:0004347 \N glycolysis ; GO:0006096 20364 IPR001669

The arginine dihydrolase (AD) pathway is found in many prokaryotes and some primitive eukaryotes, an example of the latter being Giardia lamblia [MEDLINE:98162867]. The three-enzyme anaerobic pathway breaks down L-arginine to form 1 mol of ATP, carbon dioxide and ammonia. In simpler bacteria, the first enzyme, arginine deiminase, can account for up to 10% of total cell protein [MEDLINE:98162867].

Most prokaryotic arginine deiminase pathways are under the control of a repressor gene, termed ArgR [MEDLINE:92260526] ]. This is a negative regulator, and will only release the arginine deiminase operon for expression in the presence of arginine [MEDLINE:99069319]. The crystal structure of apo-ArgR from Bacillus stearothermophilus has been determined to 2.5A by means of X-ray crystallography [MEDLINE:99260735]. The protein exists as a hexamer of identical subunits, and is shown to have six DNA-binding domains, clustered around a central oligomeric core when bound to arginine. It predominantly interacts with A.T residues in ARG boxes. This hexameric protein binds DNA at its N terminus to repress arginine biosyntheis or activate arginine catabolism. Some species have several ArgR paralogs. In a neighbor-joining tree, some of these paralogous sequences show long branches and differ significantly from the well-conserved C-terminal region.

\ \ transcription factor activity ; GO:0003700 \N regulation of transcription, DNA-dependent ; GO:0006355 20362 IPR001668 With some plasmids, recombination can occur in a site specific manner that is independent of RecA. In such cases, the recombination event requires another protein called Pre. Pre is a plasmid recombination enzyme. This protein is also known as Mob (conjugative mobilization) [MEDLINE:89359109].\ \ DNA binding activity ; GO:0003677 extrachromosomal circular DNA ; GO:0005727 DNA recombination ; GO:0006310 20363 IPR001669

\ \ transcription factor activity ; GO:0003700 \N regulation of transcription, DNA-dependent ; GO:0006355 20360 IPR001666 Phosphatidylinositol transfer protein (PITP) is a ubiquitous cytosolic protein, thought to be involved in transport of phospholipids from their site of synthesis in the endoplasmic reticulum and Golgi to other cell membranes [MEDLINE:95292332]. More recently, PITP has been shown to be an essential component of the polyphosphoinositide synthesis machinery and is hence required for proper signalling by epidermal growth factor and f-Met-Leu-Phe, as well as for exocytosis. The role of PITP in polyphosphoinositide synthesis may also explain its involvement in intracellular vesicular traffic [MEDLINE:95292332].\ \ \N intracellular ; GO:0005622 transport ; GO:0006810 20361 IPR001667 This is a family of predicted phosphoesterases that includes Drosophila prune protein and bacterial RecJ exonuclease [MEDLINE:98138617]. The RecJ protein of Escherichia coli plays an important role in a number of DNA repair and recombination pathways. RecJ catalyzes processive degradation of single-stranded DNA in a 5'-to-3' direction. Sequences highly related to those encoding RecJ can be found in many\ of the eubacterial genomes sequenced to date [MEDLINE:20100748].\ \ \ \N \N \N 20359 IPR001665

Cysteine protease activity is dependent on an active dyad of cysteine andhistidine, the order and spacing of these residues varying in the known\ families. Nearly half of all cysteine proteases are found exclusively\ in viruses [MEDLINE:95147707]. Cysteine protease families have been grouped into five\ clans (designated CA, CB, CC, CD and CE) on the basis of structural and\ functional similarity. Families C1, C2 and C10, which belong to the CA clan,\ have a Cys/His catalytic diad, and are loosely termed papain-like. Families\ in the CB clan have a His/Cys diad, and contain enzymes from RNA\ distantly related to chymotrypsin. Enzymes in clan CC are also from RNA\ viruses, but have a papain-like Cys/His active site. The remaining two\ clans, CD and CE, contain only one family each. Some families have not\ yet been assigned to a clan [MEDLINE:95147707], PUB00004506.

\ \

Caliciviruses are positive-stranded ssRNA viruses that cause gastroenteritis. The calicivirus genome contains two open reading frames, ORF1 and ORF2.\ ORF1 encodes a non-structural polypeptide, which has RNA helicase, cysteine\ protease and RNA polymerase activity PUB00004506. The regions of the polyprotein in\ which these activities lie are similar to proteins produced by the picornaviruses\ \ \ \ [MEDLINE:92201399].\ ORF2 encodes a structural, capsid protein. Two different\ families of caliciviruses can be distinguished on the basis of sequence\ similarity, namely the Norwalk-like viruses or small round structured\ viruses (SRSVs), and those classed as non-SRSVs.

\ \

Calicivirus proteases from the SRSV group, which are members of the PA\ protease clan, constitute family C37 of the cysteine proteases (proteases\ from non-SRSVs belong to the C24 family). As mentioned above, the protease\ activity resides within a polyprotein. The enzyme cleaves the polyprotein\ at sites N-terminal to itself, liberating the polyprotein helicase.

\ \ cysteine-type endopeptidase activity ; GO:0004197 \N proteolysis and peptidolysis ; GO:0006508 20356 IPR001662 Eukaryotic elongation factor 1 (EF-1) is responsible for the GTP-dependent binding of aminoacyl-tRNAs to the ribosomes [MEDLINE:91118231]. EF-1 is composed of four subunits: the

chain which binds GTP and aminoacyl-tRNAs, the gamma chain that probably plays a role in anchoring the complex to other cellular components and the

and delta (or

') chains. The gamma chain is a protein of about 410 to 440 residues.\ translation elongation factor activity ; GO:0003746 eukaryotic translation elongation factor 1 complex ; GO:0005853 translational elongation ; GO:0006414 20357 IPR001663 Bacterial ring hydroxylating dioxygenases are multicomponent 1,2-dioxygenase complexes that convert closed-ring structures to non-aromatic cis-diols [MEDLINE:91358314]. The complex has both hydroxylase and electron transfer components. The hydroxylase component is itself composed of two subunits: an

-subunit of about 50 kDa, and a

-subunit of about 20 kDa. The electron transfer component is either composed of two subunits: a ferredoxin and a ferredoxin reductase or by a single bifunctional ferredoxin/reductase subunit. Sequence analysis of hydroxylase subunits of ring hydroxylating systems (including toluene, benzene and napthalene 1,2-dioxygenases) suggests they are derived from a common ancestor [MEDLINE:91358314]. The

-subunit binds both a Rieske-like 2Fe-2S cluster and an iron atom: conserved Cys and His residues in the N-terminal region may provide 2Fe-2S ligands, while conserved His and Tyr residues may coordinate the iron. The

subunit may be responsible for the substrate specificity of the dioxygenase system [MEDLINE:91358314].\ iron ion binding activity ; GO:0005506 \N aromatic compound metabolism ; GO:0006725 20358 IPR001664

IF proteins are members of a very large multigene family of proteins which has been subdivided in five major subgroups:\

Type I: Acidic cytokeratins.
Type II: Basic cytokeratins.
Type III: Vimentin, desmin, glial fibrillary acidic protein (GFAP), peripherin, and plasticin.
Type IV: Neurofilaments L, H and M, -internexin and nestin.
Type V: Nuclear lamins A, B1, B2 and C.

All IF proteins are structurally similar in that they consist of: a central rod domain comprising some 300 to 350 residues which is arranged in coiled-coiled -helices, with at least two short characteristic interruptions; a N-terminal non-helical domain (head) of variable length; and a C-terminal domain (tail) which is also non-helical, and which shows extreme length variation between different IF proteins.

While IF proteins are evolutionary and structurally related, they have limited sequence homologies except in several regions of the rod domain.

\ \ \ \N \N \N 20353 IPR001659 A phycobilisome is an accessory light energy harvesting structure on the outer face of the thylakoid membranes in cyanobacteria and red algae. Phycobilisomes are mainly composed of phycobiliproteins (such as allophycocyanin, phycocyanin and phycoerythrin) together with linker polypeptides.\ \N light-harvesting complex (sensu Viridiplantae) ; GO:0009503 photosynthesis ; GO:0015979 20354 IPR001660 The sterile

motif (SAM) domain is a putative protein interaction module present in a wide variety of proteins [MEDLINE:97160498] involved in many biological processes. The SAM domain that spreads over around 70 residues is found in diverse\ eucaryotic organisms [MEDLINE:99101382]. SAM domains have been shown to homo- and hetero-oligomerize [MEDLINE:98001597], nevertheless with a\ low affinity constant [MEDLINE:99132419], and to mediate specific protein-protein interactions.\ \ Structural analyses show that the SAM domain is arranged in a small five-helix bundle with two large interfaces [MEDLINE:98001597]. In\ the case of the SAM domain of EphB2, each of these interfaces is able to form dimers. The presence of these two\ distinct intermonomers binding surface suggest that SAM could form extended polymeric structures [MEDLINE:99132419].\ \ \ \ \N \N \N 20355 IPR001661

Glycoside hydrolase family 37 CAZY:GH_37\ comprises enzymes with only one known activity; trehalase (EC: 3.2.1.28).

\ \

Trehalase is the enzyme responsible for the degradation of the disaccharide ,-trehalose yielding two glucose subunits [MEDLINE:93186779]. It is an enzyme found in a wide variety of organisms and whose sequence has been highly conserved throughout evolution.

\ \ alpha,alpha-trehalase activity ; GO:0004555 \N trehalose metabolism ; GO:0005991 20352 IPR001658

Gonadotrophin-releasing hormone (GnRH) is an important hypothalamic\ regulator of reproductive processes . Its major site of action is in\ the regulation of synthesis and release of gonadotrophins (FSH and LH)\ from the anterior pituitary. GnRH agonists are of potential therapeutic\ use in the suppression of prostate cancer and endometriosis PUB00005887. GnRH\ receptors are found in the anterior pituitary, placenta, ovary, testis,\ prostate, breast, and in certain tumours and immortalised cell lines.\ They are also present in the nervous system and gonads of certain species.

\ \ gonadotropin-releasing hormone receptor activity ; GO:0004968 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20351 IPR001657 The hedgehog protein precursor, HH, is involved in segment polarity and cell to cell communication, and plays important roles in both early embryogenesis and metamorphosis [MEDLINE:93185922], [MEDLINE:93083438], [MEDLINE:93008241], [MEDLINE:94040725]. The protein is expressed in embryo stripes [MEDLINE:93185922], and in several groups of cells belonging to the foregut, hindgut and various other unidentified tissues. Maximum expression is seen in embryos 6-12 hours after fertilisation, and in pupae 1-24 hours after puparium formation.\ \ \N \N development ; GO:0007275 20345 IPR001650

The domain, which defines this group of proteins is found in a wide variety of helicases and helicase related proteins. It may be that this is not an autonomously folding unit, but an integral part of the helicase.

\ ATP binding activity ; GO:0005524 \N \N 20346 IPR001651 Gastrin and cholecystokinin (CCK) PUB00005877 are structurally and functionally related peptide hormones that function as hormonal regulators of various digestive processes and feeding behaviors . They are known to induce gastric secretion, stimulate pancreatic secretion, increase blood circulation and water secretion in the stomach and intestine, and stimulate smooth muscle contraction. Originally found in the gut, these hormones have since been shown to be present in various parts of the nervous system. Like many other active peptides they are synthesized as larger protein precursors that are enzymatically converted to their mature forms. They are found in several molecular forms due to tissue-specific post-translational processing. The biological activity of gastrin and CCK is associated with the last five C-terminal residues. One or two positions downstream, there is a conserved sulfated tyrosine residue. The amphibian caerulein skin peptide, the cockroach leukosulfakinin I and II (LSK) peptides, the drosophila putative CCK-homologs Drosulfakinins I and II, cionin, a chicken gastrin/cholecystokinin-like peptide and cionin, a neuropeptide from the protochordate Ciona intestinalis belong to the same family.\ hormone activity ; GO:0005179 extracellular ; GO:0005576 \N 20347 IPR001653 Diaminopimelate epimerase (EC: 5.1.1.7) catalyzes the isomeriazation of L,L- to D,L-meso-diaminopimelate in the biosynthetic pathway leading from aspartate to lysine. This enzyme is a protein of about 30 kDa. Two conserved cysteines seem [MEDLINE:99060082] to function as the acid and base in the catalytic mechanism.\ diaminopimelate epimerase activity ; GO:0008837 \N lysine biosynthesis via diaminopimelate ; GO:0009089 20348 IPR001654 Herpesviruses have been implicated as a cause of tumours in a number of species. The common tumour condition of the fowl is caused by Marek's disease Herpesvirus (MDHV). Although infection is ubiquitous, only a proportion of fowl develop tumours, and the precise details of the process of tumour induction remains to be elucidated. Secretory glycoprotein GP57-65 precursor (glycoprotein A - GA) is thought to play an immunoevasive role in the pathogenesis of Marek's disease. It is a candidate for causing the early-stage immunosuppression that occurs after MDHV infection. The protein is predominantly secreted, but a small amount of mature GP57-65 is anchored in the plasma membrane, or held by other interactions. GA is similar to Herpesvirus glycoprotein C, and belongs to the immunoglobulin gene superfamily [MEDLINE:88230597], [MEDLINE:89269090].\ \N \N \N 20349 IPR001655

Phagocytes form the first line of defence against invasion by micro-organisms. Engulfing of bacteria by neutrophils is accompanied by the consumption of large amounts of oxygen - a so-called respiratory burst. Defects in phagocytosis involving the lack of a respiratory burst give rise to chronic granulomatous disease (CGD), in which patients are pre-disposed to infection, often from otherwise non-pathogenic bacteria [MEDLINE:96389574].

Regulation of the respiratory burst takes place at the phagocytic vacuole. The process is mediated by NADPH oxidase, which transports electrons across the plasma membrane to form superoxide (an oxygen molecule with an extra electron that is toxic to normal cells) in the vacuole interior. The electrons are carried across the membrane by a short electron transport chain in the form of an unusual flavocytochrome b [MEDLINE:96389574].

To conserve NADPH and avoid the toxic effects of superoxide, the oxidase remains inactive until it receives an appropriate stimulus. Activation involves the participation of a number of cytosolic proteins, some of which attach to the flavocytochrome. p47phox, p67phox (see IPR000108.

\ \ \N \N electron transport ; GO:0006118 20350 IPR001656 The uncharacterized hypothetical proteins ygbO from Escherichia coli, HI0701, the corresponding one from Haemophilus influenzae, HP0926 from Helicobacter pylori, YOR243c from Yeast chromosome XV, B0024.11 from Caenorhabditis elegans and MJ0588 and MJ1364 from Methanococcus jannaschii have been shown to share regions of similarities. They are hydrophilic proteins of from 39 to 77 Kd.\ molecular_function unknown ; GO:0005554 \N \N 20344 IPR001648

\ \ \

The small ribosomal subunit protein S18 is known to be involved in binding the aminoacyl-tRNA complex in E.coli\ \ \ \ [MEDLINE:89171319], and appears to be situated at the tRNA A-site. Experimental evidence has revealed that S18 is well exposed on the surface of the E.coli ribosome, and is a secondary rRNA binding protein [MEDLINE:98058740]. S18 belongs to a family of ribosomal proteins [MEDLINE:90192741] that includes: eubacterial S18; algal and plant chloroplast S18; and cyanelle S18.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 20340 IPR001644

The accumulation of phagocytic cells at the site of injury or infection is\ regulated by substances that stimulate chemotaxis, granule secretion,\ superoxide generation and upregulation of cell surface adhesion molecules\ in cells of the immune system PUB00005873. The chemoattractant substances include\ C5a, N-formylmethionyl-containing peptides, interleukin 8, leukotriene B4\ and platelet activating factor, many of which participate in anaphylactoid\ and septic shock . The C5a receptor is found on cells of the immune\ system (e.g., neutrophils, macrophages, mast cells and related cell lines),\ and is also present in smooth muscle. The amino acid sequence of the\ receptor contains several N-terminal acidic residues, which may be\ involved in binding the basic C5a peptide.

\ \ \ C3a anaphylatoxin receptor activity ; GO:0004943 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20341 IPR001645

Folylpolyglutamate synthase (EC: 6.3.2.17) (FPGS) is responsible for the addition of a polyglutamate tail to folate and folate derivatives, is an ATP-dependent enzyme isolated from eukaryotic and bacterial sources, where it plays a key role in the retention of the intracellular folate pool Its sequence is moderately conserved between prokaryotes (gene folC) and eukaryotes.

FPGS belongs to a protein family that contains a number of related peptidoglycan synthetases (Mur) (EC: 6.3.2.-) (see IPR000713).

A crystal structure of the MgATP complex of the enzyme from Lactobacillus casei reveals that folylpolyglutamate synthetase is a modular protein consisting of two domains, one with a typical mononucleotide-binding fold and the other strikingly similar to the folate-binding enzyme dihydrofolate reductase. The active site of the enzyme is located in a large interdomain cleft adjacent to an ATP-binding P-loop motif. Opposite this site, in the C domain, a cavity likely to be the folate binding site has been identified, and inspection of this cavity and the surrounding protein structure suggests that the glutamate tail of the substrate may project into the active site. A further feature of the structure is a well defined Omega loop, which contributes both to the active site and to interdomain interactions [MEDLINE:98283985].

\ \ ATP binding activity ; GO:0005524 \N folic acid and derivative biosynthesis ; GO:0009396 20342 IPR001646 These repeats were first identified in many cyanobacterial proteins but they are also found in bacterial as well as in plant proteins [MEDLINE:98316713]. The repeats were first identified in hglK [MEDLINE:96062225]. The function of these repeats is unknown. The structure of this repeat has been predicted to be a

-helix [MEDLINE:98318059]. The repeat can be approximately described as A(D/N)LXX, where X can be any amino acid.\ \N \N \N 20343 IPR001647 Numerous bacterial transcription regulatory proteins bind DNA via a helix-turn-helix (HTH) motif. These proteins are very diverse, but for convenience may be grouped into subfamilies on the basis of sequence similarity. One such family groups together a range of proteins, including acrR, betI, bm3R1, envR, qacR, mtrR, tcmR, tetC, tetR, ttk, ybiH, and yhgD [MEDLINE:95126562], [MEDLINE:94254732], [MEDLINE:93155125]. Many of these proteins function as repressors that control the level of susceptibility to hydrophobic antibiotics and detergents. They all have similar molecular weights - from 21 to 25 kDa. The helix-turn-helix motif is located in the initial third of the protein. The 3D structure of the homodimeric TetR protein complexed with 7-chloro-tetracycline-magnesium has been determined to 2.1 A resolution [MEDLINE:95222589]. TetR folds into 10

-helices with connecting turns and loops. The 3 N-terminal

-helices of the repressor form the DNA-binding domain: this structural motif encompasses an HTH fold with an inverse orientation compared with that of other DNA-binding proteins.\ transcription factor activity ; GO:0003700 \N regulation of transcription, DNA-dependent ; GO:0006355 20338 IPR001641

Aspartic proteases have a catalytic aspartate residue at their active site. More than 8 families (denoted A1-A9) have been identified, three of which (pepsin, retropepsin and cauliflower mosaic virus) have been grouped into a single clan (AA), as they are thought to share a common ancestry. The remaining five families have not yet been assigned to clans [MEDLINE:95405261], [MEDLINE:93176119].

Foamy virus (spumavirus) proteases belong to the A9 family of aspartic proteases. At the moment, it is not clear whether they share a common evolutionary origin with other aspartic proteases. Foamy viruses are single-stranded enveloped retroviruses that have been noted to infect monkeys, cats and humans. In the human virus, the aspartic protease is encoded by the retroviral gag gene [MEDLINE:88188241], and in monkeys by the pol gene [MEDLINE:91276270]. At present, the virus has not been proven to cause any particular disease. However, studies have shown human foamy virus causes neurological disorders in infected mice\ \ \ \ [MEDLINE:98210896].

\ \ aspartic-type endopeptidase activity ; GO:0004190 \N proteolysis and peptidolysis ; GO:0006508 20339 IPR001642

The neuromedin B receptor has been characterised in rat oesophagus and rat\ urinary bladder. It is widespread in the CNS, and is found in high\ levels in olfactory nucleus and thalamic regions, and in lower levels in\ the frontal cortex, dendate gyrus, amygdala and dorsal raphe. The\ receptor activates the phosphoinositide pathway through a pertussis-toxin-insensitive G-protein, probably of the Gq/G11 class PUB00005871.

\ \ bombesin receptor activity ; GO:0004946 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20333 IPR001636

Phosphoribosylaminoimidazole-succinocarboxamide synthase (EC: 6.3.2.6) (SAICAR synthetase) catalyzes the seventh step in the de novo purine biosynthetic pathway; the ATP-dependent conversion of 5'-phosphoribosyl-5-aminoimidazole-4-carboxylic acid and aspartic acid to SAICAR [MEDLINE:92245079].

In bacteria (gene purC), fungi (gene ADE1) and plants, SAICAR synthetase is a monofunctional protein; in animals it is the N-terminal domain of a bifunctional enzyme that also catalyze phosphoribosylaminoimidazole carboxylase (AIRC) activity (see IPR000031).

\ \ phosphoribosylaminoimidazole-succinocarboxamide synthase activity ; GO:0004639 \N purine nucleotide biosynthesis ; GO:0006164 20334 IPR001637 Glutamine synthetase (EC: 6.3.1.2) (GS) [MEDLINE:98219804] plays an essential role in the metabolism of nitrogen by catalyzing the condensation of glutamate and ammonia to form glutamine. Class I enzymes (GSI) are specific to prokaryotes, and are oligomers of 12 identical subunits. The activity of GSI-type enzyme is controlled by the adenylation of a tyrosine residue. The adenylated enzyme is inactive.

Recent reviews discuss: the discovery of the enzymatic synthesis of glutamine; the role of glutamine synthetase in defining the thermodynamics of ATPases; early isotopic tracer studies of the synthetase reaction; the proposed intermediacy of gamma-glutamyl-phosphate; the mechanism of\ methionine sulfoximine inhibition; stereochemical mapping of the enzyme's active site; detection of\ enzyme reaction cycle intermediates; borohydride trapping of gamma-glutamyl-P; positional\ isotope exchanges catalyzed by glutamine synthetase; regulation of bacterial enzyme; and how knowledge of the atomic structure of bacterial glutamine synthetase has clarified\ ligand binding interactions [MEDLINE:98219804], [MEDLINE:20175267].

\ \ glutamate-ammonia ligase activity ; GO:0004356 \N nitrogen metabolism ; GO:0006807 20335 IPR001638

In Gram-positive bacteria which are surrounded by a single membrane and have therefore no periplasmic region, the equivalent proteins are bound to the membrane via an N-terminal lipid anchor. These homolog proteins do not play an integral role in the transport process per se, but probably serve as receptors to trigger or initiate translocation of the solute throught the membrane by binding to external sites of the integral membrane proteins of the efflux system.

In addition, at least some solute-binding proteins function in the initiation of sensory transduction pathways.

On the basis of sequence similarities, the vast majority of these solute-binding proteins can be grouped [MEDLINE:93330183] into eight families or clusters, which generally correlate with the nature of the solute bound.

Family 3 groups together specific amino acids and opine-binding periplasmic proteins and a periplasmic homolog with catalytic activity.

\ \ transporter activity ; GO:0005215 periplasmic space (sensu Gram-negative Bacteria) ; GO:0030288 transport ; GO:0006810 20336 IPR001639

The general (type II) secretion pathway (GSP) within Gram-negative bacteria is a signal sequence-dependent process responsible for protein export [MEDLINE:93174466], [MEDLINE:95099573], [MEDLINE:92276315]. The process has two stages: exoproteins are first translocated across the inner membrane by the general signal-dependent export pathway (GEP), and then across the outer membrane by a species-specific accessory mechanism.

A number of molecules are involved in the GSP; one of these is known as the 'C' protein, the most probable location of which is the inner membrane [MEDLINE:90008916]. This suggests that protein C is part of the GEP apparatus, aiding trans-location of exoproteins from the cytoplasm to the periplasm, prior to transport across the outer membrane. The size of the 'C' protein is around 270 to 300 amino acids. It apparently contains a single transmembrane domain located in the N-terminal section. The short N-terminal domain is predicted to be cytoplasmic and the large C-terminal domain periplasmic.

The 'C' protein has been sequenced in a variety of bacteria such as Aeromonas (gene exeC); Erwinia (gene outC); Escherichia coli (gene yheE); Klebsiella pneumoniae (gene pulC); Pseudomonas aeruginosa (gene xcpS) or Vibrio cholerae (gene epsC).

\ \ protein transporter activity ; GO:0008565 type II protein secretion system complex ; GO:0015627 type II protein (Sec) secretion system ; GO:0015628 20337 IPR001640 Prolipoprotein diacylglyceryl transferase [MEDLINE:94327509] is the bacterial enzyme that catalyzes the first step in lipoprotein biogenesis, it transfers the n-acyl diglyceride group on what will become the N-terminal cysteine of membrane lipoproteins. Prolipoprotein diacylglyceryl transferase (gene lgt) is an integral membrane protein.\ transferase activity ; GO:0016740 membrane ; GO:0016020 protein-lipoylation ; GO:0009249 20332 IPR001635

During flagellar morphogenesis in Salmonella typhimurium and Escherichia coli, the fliK gene product is responsible for hook length control [MEDLINE:96213039]. The deduced amino acid sequences of FliK proteins from S.typhimurium and E.coli have molecular masses of 41,748 and 39,246 Da, respectively, and are fairly hydrophilic [MEDLINE:96213039]. Sequence comparison reveals around 50% identity, with greatest conservation in the C-terminal region, with 71% identity in the last 154 amino acids - mutagenesis of this conserved region completely abolishes motility. The central and C-terminal regions are rich in proline and glutamine respectively; it is thought that they may constitute distinct domains, separated by a linker region [MEDLINE:96213039].

It is considered unlikely that FliK functions as a molecular ruler for determining hook length, but that it is more likely to be employing a novel mechanism [MEDLINE:96213039].

\ \ motor activity ; GO:0003774 flagellar hook (sensu Bacteria) ; GO:0009424 flagella biogenesis ; GO:0009296 20331 IPR001634

In addition to their role in energy metabolism, purines (especially\ adenosine and adenine nucleotides) produce a wide range of pharmacological\ effects mediated by activation of cell surface receptors PUB00005868. Distinct\ receptors exist for adenosine. In the periphery, the main effects of\ adenosine include vasodilation, bronchoconstriction, immunosuppresion,\ inhibition of platelet aggregation, cardiac depression, stimulation of\ nociceptive afferents, inhibition of neurotransmitter release and\ inhibition of the release of other factors, e.g. hormones PUB00005868. In the CNS,\ adenosine exerts a pre- and post-synaptic depressant action, reducing motor\ activity, depressing respiration, inducing sleep and relieving anxiety. The\ physiological role of adenosine is thought to be to adjust energy demands\ in line with oxygen supply. Many of the clinical actions of methylxanthines\ are thought to be mediated through antagonism of adenosine receptors. Four\ subtypes of receptor have been identified, designated A1, A2A, A2B and A3.

\ \ adenosine receptor activity, G-protein coupled ; GO:0001609 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20330 IPR001633 This domain is found in diverse bacterial signaling proteins. It is called EAL after its conserved residues. The EAL domain is a good candidate for a diguanylate phosphodiesterase function [MEDLINE:21441661]. The domain contains many conserved acidic residues that could participate in metal binding and might form the phosphodiesterase\ active site. It often but not always occurs along with PAS IPR000014 domains that are also found in many signalling proteins.\ \ molecular_function unknown ; GO:0005554 \N \N 20329 IPR001632

Although originally thought to be a passive attenuator and membrane anchor for the activated subunit, the -gamma subunit is now recognised as playing an active role in a number of different G-protein-coupled signalling events [MEDLINE:94019765]. It has been shown to modulate the activity of some isoforms of adenylyl cyclase, phospholipase C, and some ion channels. It is involved in receptor phosphorylation via specific kinases, and has been implicated in the p21 ras-dependent activation of the MAP kinase cascade. It is also highly likely that it contributes to the recognition of specific receptors by the G-protein. No atomic structure is yet available for -gamma subunits, but it has been proposed that they interact both with each other and with other proteins via a coiled coil motif in their N-terminal regions [MEDLINE:93093151].

Four different G-protein subunits have been identified in mammals, and some have also been identified in certain invertebrate, plant and fungal species. Beta subunits contain around 340 amino acids, with apparent molecular weights of 35-36 kDa. Their sequences are highly conserved between species, implying that they perform a fundamentally important role in the organisation of G-protein linked systems [MEDLINE:92279208]. The sequences display tandem repeats of a 40-residue domain containing a characteristic Trp-Asp motif (the so-called WD-40 repeat [MEDLINE:92354695]) (see IPR001680).

\ \ signal transducer activity ; GO:0004871 heterotrimeric G-protein complex ; GO:0005834 G-protein coupled receptor protein signaling pathway ; GO:0007186 20328 IPR001631

Eukaryotic-like DNA topoisomerase I, otherwise known as relaxing enzyme, untwisting enzyme or swivelase, (EC: 5.99.1.2) is one of the two types of enzyme that catalyze the interconversion of topological DNA isomers and is vital for the processes of replication, transcription, and recombination [MEDLINE:90180672], [MEDLINE:95292060], [MEDLINE:89264463], [MEDLINE:95288784]. Topoisomerase I catalyses the ATP-independent breakage of single-stranded DNA, followed by passage and rejoining of another single-stranded DNA region [MEDLINE:89288043]. This reaction brings about the conversion of one topological DNA isomer into another: e.g., relaxation of positive and negative super-coils; interconversion of simple and knotted rings of single-stranded DNA; and intertwisting of single-stranded rings of complementary sequences [MEDLINE:89288043], [MEDLINE:91187651].

When a eukaryotic type 1 topoisomerase breaks a DNA backbone bond, it simultaneously forms a protein-DNA link where the hydroxyl group of a tyrosine residue is joined to a 3'-phosphate on DNA, at one end of the enzyme-severed DNA strand. In eukaryotes and poxvirus topoisomerases I, there are a number of conserved residues in the region around the active site tyrosine.

Vaccinia virus, a cytoplasmically-replicating poxvirus, encodes a type I DNA topoisomerase that is biochemically similar to eukaryotic-like DNA topoisomerases I, and which has been widely studied as a model topoisomerase. It is the smallest topoisomerase known and is unusual in that it is resistant to the potent chemotherapeutic agent camptothecin. The crystal structure of an amino-terminal fragment of vaccinia virus DNA topoisomerase I shows that the fragment forms a five-stranded, antiparallel -sheet with two short -helices and connecting loops. Residues that are conserved between all eukaryotic-like type I topoisomerases are not clustered in particular regions of the structure [MEDLINE:95086864].

Human topoisomerase I has been shown to be inhibited by camptothecin (CPT), a plant alkaloid with antitumour activity [MEDLINE:91187651]. The crystal structures of human topoisomerase I comprising the core and carboxyl-terminal domains in covalent and noncovalent complexes with 22-base pair DNA duplexes reveal an enzyme that "clamps" around essentially B-form DNA. The core domain and the first eight residues of the carboxyl-terminal domain of the enzyme, including the active-site nucleophile tyrosine-723, share significant structural similarity with the bacteriophage family of DNA integrases. A binding mode for the anticancer drug camptothecin has been proposed on the basis of chemical and biochemical information combined with the three-dimensional structures of topoisomerase I-DNA complexes [MEDLINE:98155246].

\ \ DNA topoisomerase type I activity ; GO:0003917 \N DNA unwinding ; GO:0006268 20327 IPR001631

\ \ DNA topoisomerase type I activity ; GO:0003917 \N DNA unwinding ; GO:0006268 20326 IPR001630

Transcription initiation is dictated by the presence and activity of specific nuclear factors that bind to DNA regulatory sequences and interact with the transcriptional machinery. The functions of some of these factors can be altered by phosphorylation, which affects both DNA binding and transcriptional activation [MEDLINE:91145994]. Phosphorylation is effected by specific protein kinases that have been activated by the stimulus of signal transduction pathways, resulting in the regulation of gene transcription by modulating the phosphorylation sites of transcription factors.

Cyclic AMP (cAMP) regulates the expression of many genes via a conserved gene promoter element CRE (cAMP response element) [MEDLINE:90287125], which has the sequence 5'-TGACGTCA-3' [MEDLINE:89143746]. The cAMP response element binding protein (CREB) is a nuclear factor that is regulated by protein kinase A phosphorylation. Transcription is stimulated on binding to the CRE of a phosphorylated CREB dimer, which is held together by leucine zippers. Dimerisation and transcriptional efficacy have been found to be stimulated by phosphorylation at several distinct sites, and it has thus been suggested [MEDLINE:90287125] that CREB may be regulated by multiple kinases. Sequence analysis of the gene has revealed a cluster of protein kinase A, protein kinase C, and casein kinase II consensus recognition sites near the N-terminus of the protein sequence, and the proximity of these sites to one another indicates the possibility of interaction in a positive or negative fashion to regulate CREB bioactivity.

The 'leucine zipper' (see IPR002158 gene regulatory proteins. The zipper consists of a periodic repetition of leucine residues at every seventh position, and regions containing them appear to span 8 turns of -helix. The leucine side chains that extend from one helix interact with those from a similar helix, hence facilitating dimerisation in the form of a coiled-coil. Leucine zippers are present in many gene regulatory proteins, including the CREB proteins, Jun/AP1 transcription factors, fos oncogene and fos-related proteins, C-myc, L-myc and N-myc oncogenes, and so on.

\ \ transcription factor activity ; GO:0003700 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 20325 IPR001628

Receptors for steroid, thyroid, and retinoid hormones belong to a family of nuclear trans-acting transcriptional regulatory factors [MEDLINE:96243403], [MEDLINE:88204933], PUB00005324, PUB00005324, [MEDLINE:92005700], [MEDLINE:92191987]. In vertebrates, these proteins regulate diverse biological processes such as pattern formation, cellular differentiation and homeostasis.

These proteins all share a conserved cysteine-rich DNA-binding region of some 65 residues. This region has been predicted to fold into two 'C4'-type zinc fingers.

A consensus representation of the DNA-binding domain is shown in the following figure:\

\ ----Zinc-finger---- ------Zinc-Finger------\ C.LC.D.AAG.HF...AC..CK.FF.R.........C.....C.I.K..R..C..CR..KC...GM\ I E SSC NY S A V Q R\ V TT T\

\ \ transcription factor activity ; GO:0003700 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 20322 IPR001624

Four genes from the major Bacillus subtilis chemotaxis locus have been shown to encode proteins that are similar to the Salmonella typhimurium FlgB, FlgC, FlgG and FliF proteins; a further gene product is similar to the Escherichia coli FliE protein [MEDLINE:91285431]. All of these proteins are thought to form part of the hook-basal body complex of the bacterial flagella [MEDLINE:91285431]. The FlgB, FlgC and FlgG proteins are components of the proximal and distal rods; FliF forms the M-ring that anchors the rod assembly to the membrane; but the role of FliE has not yet been determined [MEDLINE:91285431]. The similarity between the proteins in these two organisms suggests that the structures of the M-ring and the rod may be similar [MEDLINE:91285431]. Nevertheless, some differences in size and amino acid composition between some of the homologues suggest the basal body proteins may be organised slightly differently within B. subtilis [MEDLINE:91285431].

From gel electrophoresis and autoradiography of 35S-labelled S. typhimurium hook-basal body complexes and the deduced number of sulphur-containing residues in FliE, the stoichiometry of the protein in the hook-basal body complex has been estimated to be about nine subunits [MEDLINE:92202159]. FliE does not undergo cleavage of a signal peptide, nor does it show any similarity to the axial components like the rod or hook proteins, which are thought to be exported by the flagellum-specific export pathway [MEDLINE:92202159]. On this evidence, it has been suggested that FliE may be in the vicinity of the MS ring, perhaps acting as an adaptor protein between ring and rod substructures [MEDLINE:92202159].

\ \ structural molecule activity ; GO:0005198 flagellum (sensu Bacteria) ; GO:0009288 ciliary/flagellar motility ; GO:0001539 20323 IPR001626

\ A number of bacterial transport systems have been found to contain integral\ membrane components that have similar sequences PUB00009997: these systems fit the\ characteristics of ATP-binding cassette transporters [MEDLINE:92065822]. The\ proteins form homo- or hetero-oligomeric channels, allowing ATP-mediated \ transport. Hydropathy analysis of the proteins has revealed the presence\ of 6 possible transmembrane regions. These proteins belong to family 3 of ABC transporters.\ \ ATP binding activity ; GO:0005524 membrane ; GO:0016020 transport ; GO:0006810 20324 IPR001627

The Sema domain occurs in semaphorins, which are a large family of secreted and transmembrane proteins, some of which function as repellent signals during axon guidance. Sema domains also occur in a hepatocyte growth factor receptor, in SEX protein [MEDLINE:99091049] and in viral proteins.

CD100 (also called SEMA4D) is associated with PTPase and serine kinase activity. CD100 increases PMA, CD3 and CD2 induced T cell proliferation, increases CD45 induced T cell adhesion, induces B cell homotypic adhesion and down-regulates B cell expression of CD23.

\ \

CD molecules are leucocyte antigens on cell surfaces. CD antigens nomenclature is updated at http://www.ncbi.nlm.nih.gov/PROW/guide/45277084.htm \

\ \ \ \N \N \N 20321 IPR001623

The prokaryotic heat shock protein DnaJ interacts with the chaperone hsp70-like DnaK protein [MEDLINE:94287451]. Structurally, the DnaJ protein consists of an N-terminal conserved domain (called 'J' domain) of about 70 amino acids, a glycine-rich region ('G' domain') of about 30 residues, a central domain containing four repeats of a CXXCXGXG motif ('CRR' domain) and a C-terminal region of 120 to 170 residues.

Such a structure is shown in the following schematic representation:\

\
  +------------+-+-------+-----+-----------+--------------------------------+\
  | N-terminal | | Gly-R |     | CXXCXGXG  | C-terminal                     |\
  +------------+-+-------+-----+-----------+--------------------------------+\

It is thought that the 'J' domain of DnaJ mediates the interaction with the dnaK protein. The J- and CRR-domains are found in many prokaryotic and eukaryotic proteins [MEDLINE:92263470], either together or separately: e.g., those containing both J- and CRR-domains include yeast proteins MAS5/YDJ1, MDJ1, SCJ1, XDJ1 and YNL077w, plant dnaJ homologues from leek and cucumber, and human HDJ2; those with only the J-domain include R.fredii nolC, E.coli cbpA [MEDLINE:94134696], yeast proteins SEC63/NPL1, SIS1, CAJ1, YFR041c, YIR004w and YJL162c, P.falciparum ring-infected erythrocyte surface antigen, human HDJ1 and HSJ1, and Drosophila cysteine-string protein.

\ \ \N \N \N 20320 IPR001622

\ \ \ potassium channel activity ; GO:0005267 membrane ; GO:0016020 potassium ion transport ; GO:0006813 20319 IPR001621 Peroxidases are haem-containing enzymes that use hydrogen peroxide asthe electron acceptor to catalyse a number of oxidative reactions.\

Peroxidases are found in bacteria, fungi, plants and animals. Fungal ligninases, or lignin peroxidases (LiPs), and manganese-dependent peroxidases (MnPs), are extracellular haem enzymes involved in the degradation of lignin. In MnP, Mn²⁺ serves as the reducing substrate [MEDLINE:94220348].

It is commonly thought that the plant polymer lignin is the second most abundant organic compound on Earth, exceeded only by cellulose PUB00006588. Higher plants synthesise vast quantities of insoluble macromolecules, including lignins. Lignin is an amorphous three-dimensional aromatic biopolymer composed of oxyphenylpropane units. Biodegradation of lignins is slow - it is probable that their decomposition is the rate-limiting step in the biospheric carbon-oxygen cycle, which is mediated almost entirely by the catabolic activities of microorganisms. The white-rot fungi are able extensively to decompose all the important structural components of wood, including both cellulose and lignin. Under the proper environmental conditions, white-rot fungi completely degrade all structural components of lignin, with ultimate formation of CO₂ and H₂O PUB00006588. The first step in lignin degradation is depolymerisation, catalysed by the LiPs (ligninases). LiPs are secreted, along with hydrogen peroxide (H₂O₂), by white-rot fungi under conditions of nutrient limitation. The enzymes are not only important in lignin biodegradation, but are also potentially valuable in chemical waste disposal because of their ability to degrade environmental pollutants [MEDLINE:94220348],PUB00006588.

To date, 3D structures have been determined for LiP PUB00006588 and MnP [MEDLINE:95105154] from Phanerochaete chrysosporium, and for the fungal peroxidase from Arthromyces ramosus\ \ \ \ [MEDLINE:94118276]. All these proteins share the same architecture and consist of 2 all- domains, between which is embedded the haem group. The helical topography of LiPs is nearly identical to that of yeast cytochrome c peroxidase (CCP) [MEDLINE:95006313], despite the former having 4 disulphide bonds, which are absent in CCP (MnP has an additional disulphide bond at the C-terminus).

\ \ \ peroxidase activity ; GO:0004601 \N peroxidase reaction ; GO:0006804 20318 IPR001620

D3 receptors have a similar pharmacological profile to D2 receptors. They\ are expressed predominantly in the limbic area (including the olfactory\ tubercle, nucleus accumbens, islands of Calleja and hypothalamus), and they\ are present in lower levels in the caudate-putamen and cerebral cortex .\ The receptors are also found in dopamine cell bodies in the substantia\ nigra . The distribution of the receptors is consistent with a role in\ cognition and emotional functions; they may thus be the target of antipsychotic therapy involving dopamine antagonists PUB00005878.

\ \ dopamine receptor activity ; GO:0004952 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20317 IPR001619

Sec1-like molecules have been implicated in a variety of eukaryotic vesicle transport processes including neurotransmitter release by exocytosis. They regulate\ vesicle transport by binding to a t-SNARE from the syntaxin family. This process is thought\ to prevent SNARE complex formation, a protein complex required for membrane fusion.\ Whereas Sec1 molecules are essential for neurotransmitter release and other secretory\ events, their interaction with syntaxin molecules seems to represent a negative regulatory\ step in secretion [MEDLINE:20366578].

\ \ protein transporter activity ; GO:0008565 \N protein secretion ; GO:0009306 20315 IPR001615 Bacillus thuringiensis produces toxins active against insects [MEDLINE:96211639]. The toxin kills the larvae of dipteran insects by making pores in the epithelial cell membrane of the insect midgut. The crystal protein is produced during sporulation and is accumulated both as an inclusion and as part of the spore coat.\ pore-forming toxin activity ; GO:0015289 extracellular ; GO:0005576 pathogenesis ; GO:0009405 20316 IPR001616

Equine herpesvirus-1 (EHV-1)is a respiratory virus capable of causing abortion and neurological disease. Its complete DNA sequence has been determined [MEDLINE:92295566] and the constituent genes found to be arranged co-linearly with those in the genomes of other alphaherpesviruses, namely varicella-zoster virus and herpes simplex virus type-1 (HSV-1)\ \ \ [MEDLINE:92295566]. Comparisons of the predicted amino acid sequences have allowed functions of many EHV-1 proteins to be inferred.

For example, detailed analysis of HSV-1 and HSV-2 DNA has revealed an open reading frame sufficient to encode 626 amino acids for the HSV-1 alkaline exonuclease (620 amino acids for HSV-2) [MEDLINE:86144016]. Comparison of the predicted amino acid sequences of the viral enzymes has revealed significant differences in the N-terminal portions of the proteins; nevertheless, their three-dimensional structures are believed to be similar.

\ \ exonuclease activity ; GO:0004527 \N \N 20312 IPR001612

Caveolins [MEDLINE:96147209], [MEDLINE:96133891] are a family of integral membrane proteins which are the principal components of caveolae membranes. Cavoleae are flask-shaped plasma membrane invaginations whose exact cellular function is not yet clear. Caveolins may act as scaffolding proteins within caveolar membranes. They interact directly with G-protein subunits and can functionally regulate their activity.

Currently, three different forms of caveolins are known: caveolin-1 (or VIP21), caveolin-2 and caveolin-3 (or M-caveolin).

Caveolins are proteins of about 20 Kd, they form high molecular mass homo-oligomers. Structurally they seem to have N-terminal and C-terminal hydrophilic segments and a long central transmembrane domain that probably forms a hairpin in the membrane. Both extremities are known to face the cytoplasm.

\ \ \ \N \N \N 20313 IPR001613

Monoamine oxidases (MAO) A and B are encoded by two genes derived from a common ancestral gene [MEDLINE:93057796]. The enzymes catalyse the oxidative deamination of biogenic and xenobiotic amines and have important roles in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues [MEDLINE:88332342]. MAO-A preferentially oxidises biogenic amines such as 5-hydroxytryptamine, norepinephrine and epinephrine. MAO-A deficiency has been linked to Brunner's syndrome, a form of X-linked nondysmorphic mild mental retardation [MEDLINE:88332342].

The protein contains two similarly-sized subunits, one of which contains covalently-bound flavin adenine dinucleotide (FAD). The FAD binding site lies near the C terminus; at the N terminus are features characteristic of the ADP-binding fold, suggesting that this region is also involved in FAD binding [MEDLINE:88332342]. The A and B forms of the enzyme share 70% sequence identity; both contain the pentapeptide Ser-Gly-Gly-Cys-Tyr, the cysteine of which binds FAD [MEDLINE:88263063].

\ \ \ amine oxidase (flavin-containing) activity ; GO:0004041 \N electron transport ; GO:0006118 20314 IPR001614

The myelin sheath is a multi-layered membrane, unique to the nervous system, that functions as an insulator to greatly increase the velocity of axonal impulse conduction [MEDLINE:87166035]. Myelin proteolipid protein (PLP or lipophilin) [MEDLINE:91269299] is the major myelin protein from the central nervous system (CNS). It probably plays an important role in the formation or maintenance of the multilamellar structure of myelin. In man point mutations in PLP are the cause of Pelizaeus-Merzbacher disease (PMD), a neurologic disorder of myelin metabolism. In animals dismyelinating diseases such as mouse 'jimpy' (jp), rat md, or dog 'shaking pup' are also caused by mutations in PLP.

PLP is a highly conserved [MEDLINE:92126243] hydrophobic protein of 276 to 280 amino acids which seems to contain four transmembrane segments, two disulfide bonds and which covalently binds lipids (at least six palmitate groups in mammals) [MEDLINE:93099097].

PLP is highly related to M6, a neuronal membran glycoprotein [MEDLINE:94000809].

\ \ \N \N \N 20310 IPR001610

PAC motifs occur C-terminal to a subset of all known PAS motifs (see IPR000014.

\ \N \N signal transduction ; GO:0007165 20311 IPR001611

Leucine-rich repeats (LRRs) are 20-29-residue sequence motifs present in tandem arrays a number of proteins with diverse functions, such as hormone receptor interactions, enzyme inhibition, cell adhesion and cellular trafficking. A number of recent studies revealed the involvement of LRR proteins in early mammalian development, neural development, cell polarization, regulation of gene expression and apoptosis signalling. It was shown that LRRs may be critical to the morphology and dynamics of cytoskeleton. The primary function of these motifs appears to be to provide a versatile structural framework for the formation of protein-protein interactions.

\ Sequence analyses of LRR proteins suggested the existence of several different subfamilies of LRRs. The significance of this classification is that repeats from different subfamilies never occur simultaneously and have most probably evolved independently. It is, however, now clear that all major classes of LRR have curved horseshoe structures with a parallel sheet on the concave side and mostly helical elements on the convex side. At least six families of LRR proteins,\ characterized by different lengths and consensus sequences of the repeats, have been identified. Eleven-residue segments of the LRRs\ (LxxLxLxxN/CxL), corresponding to the �-strand and adjacent loop regions, are conserved in LRR proteins, whereas the remaining parts of the repeats (herein\ termed variable) may be very different . Despite the differences, each of the variable parts contains two half-turns\ at both ends and a "linear" segment (as the chain follows a linear path overall), usually formed by a helix, in the middle. The concave face and the adjacent loops are the most common protein interaction surfaces on LRR proteins. 3D structure of some LRR proteins-ligand complexes show that the concave surface of LRR domain is ideal for interaction with -helix, thus supporting earlier conclusions that the elongated and curved LRR structure provides an outstanding framework for achieving diverse protein-protein interactions [MEDLINE:21622566]. Molecular modeling suggests that the conserved pattern LxxLxL, which is shorter than the previously proposed LxxLxLxxN/CxL is sufficient to impart the characteristic horseshoe curvature to proteins with 20- to 30-residue repeats [MEDLINE:21964673].

\ \ \ \ \N \N \N 20307 IPR001607 This domain displays some similarities with the Zn binding domain of the insulinase family . It is found only in a small subfamily of ubiquitin thiolesterases [MEDLINE:98431658], [MEDLINE:98072201]. All members of this subfamily are isopeptidase-T that are known to cleave isopeptide bonds between ubiquitin moieties.\ \N \N \N 20308 IPR001608 A family of uncharacterized enzymes that bind to pyridoxal-5'-phosphate. Thestructure of yeast YBL036C shows the protein is composed of a single TIM barrel domain (the structure is from BNLs structural genomics project). Members of the family are found in prokaryotic and eukaryotic proteins including a proline synthetase associated protein in eubacteria\ \ \ \ [MEDLINE:91285432] and in human. YBL0413 from yeast is homologous to a protein of Pseudomonas aeruginosa that is likely to be involved in proline biosynthesis [MEDLINE:95176707].\ \ \N \N \N 20309 IPR001609

Muscle contraction is caused by sliding between the thick and thin filaments of the myofibril. Myosin is a major component of thick filaments and exists as a hexamer of 2 heavy chains [MEDLINE:92041767], 2 alkali light chains, and 2 regulatory light chains. The heavy chain can be subdivided into the N-terminal globular head and the C-terminal coiled-coil rod-like tail, although some forms have a globular region in their C-terminal. There are many cell-specific isoforms of myosin heavy chains, coded for by a multi-gene family [MEDLINE:90033298]. Myosin interacts with actin to convert chemical energy, in the form of ATP, to mechanical energy [MEDLINE:87092266]. The 3-D structure of the head portion of myosin has been determined [MEDLINE:93303624] and a model for actin-myosin complex has been constructed [MEDLINE:93303625].

The globular head is well conserved, some highly-conserved regions possibly relating to functional and structural domains [MEDLINE:83273600]. The rod-like tail starts with an invariant proline residue, and contains many repeats of a 28 residue region, interrupted at 4 regularly-spaced points known as skip residues. Although the sequence of the tail is not well conserved, the chemical character is, hydrophobic, charged and skip residues occuring in a highly ordered and repeated fashion [MEDLINE:83273600].

\ \ ATP binding activity ; GO:0005524 myosin ; GO:0016459 \N 20306 IPR001606 Members of the recently discovered ARID (AT-rich interaction domain) family of DNA-binding proteins are found in fungi and invertebrate and vertebrate metazoans. ARID-encoding genes are involved in a variety of biological processes including embryonic development, cell lineage gene regulation and cell cycle\ control. Although the specific roles of this domain and of ARID-containing proteins in transcriptional regulation are yet to be elucidated, they include both positive and negative transcriptional regulation and a likely involvement in the modification of chromatin structure [MEDLINE:20299265].\

The human SWI-SNF complex protein p270 is an ARID family member with non-sequence-specific DNA binding activity. The ARID consensus and other structural features are common to both p270 and yeast SWI1, suggesting that p270 is a human counterpart of SWI1 [MEDLINE:20221560]. The approximately 100-residue ARID sequence is present in a series of proteins strongly implicated in the regulation of cell growth, development, and tissue-specific gene expression. Although about a dozen ARID proteins can be identified from database searches, to date, only Bright (a regulator of B-cell-specific gene expression), dead ringer (a Drosophila melanogaster gene product required for normal development), and MRF-2 (which represses expression from the cytomegalovirus enhancer) have been analyzed directly in regard to their DNA binding properties. Each binds preferentially to AT-rich sites. In contrast, p270 shows no sequence preference in its DNA binding activity, thereby demonstrating that AT-rich binding is not an intrinsic property of ARID domains and that ARID family proteins may be involved in a wider range of\ DNA interactions [MEDLINE:20221560].

\ \ DNA binding activity ; GO:0003677 intracellular ; GO:0005622 \N 20303 IPR001602 This family contains small uncharacterised proteins of 14 to 16 kDa mainly from bacteria although the signatures also occur in a hypothetical protein from archaea and from yeast.\ molecular_function unknown ; GO:0005554 \N \N 20304 IPR001604 A family of bacterial and eukaryotic endonucleases (EC 3.1.30.-) share the following characteristics: they act on both DNA and RNA, cleave double-stranded and single-stranded nucleic acids and require a divalent ion such as magnesium for their activity. An histidine has been shown [MEDLINE:94359798] to be essential for the activity of the Serratia marcescens nuclease. This residue is located in a conserved region which also contains an aspartic acid residue that could be implicated in the binding of the divalent ion.\ endonuclease activity ; GO:0004519 \N \N 20302 IPR001601

\ \

Methyl-transferases are responsible for the transfer of methyl groups between two molecules. This profile recognises the methyl-transferase superfamily, which includes the CheR-type MCP methyl-transferases; O-methyl-transferases (family 2) and the NNMT/PNMT/TEMT family of methyl-transferases.

\ \ methyltransferase activity ; GO:0008168 \N \N 20305 IPR001605

Spectrin is the major constituent of the cytoskeletal network underlying the erythrocyte plasma membrane; it associates with band 4.1 and actin to form the cytoskeletal super-structure. The native spectrin molecule is a tetramer comprising two anti-parallel heterodimers joined head to head, such that the C terminus of the -subunit and the N terminus of the -subunit are included within the same molecule.

Spectrin is similar to -actinin and dystrophin, and contains a pleckstrin homology (PH) domain. The exact function of the PH domain is unknown, but evidence suggests that it contains an electrostatically-polarised pocket that facilitates binding of a ligand (e.g., a peptide). The PH domain contains a number of hydrophobic residues that form a hydrophobic core responsible for protein stability. The spectrin PH domain [MEDLINE:94268558], which has the familiar 7-stranded anti-parallel up and down -barrel capped by a C-terminal amphiphilic helical cap [MEDLINE:94268557], contains insertions that confer 2 additional turns of -helix in the loop between strands 3 and 4. The C-terminal helix is packed into a gorge between strands 1 and 2, and lies parallel to strand 7 [MEDLINE:96185451].

\ \ \N \N \N 20300 IPR001598 Autonomous mobile genetic elements such as transposon or insertion sequences (IS) encode an enzyme, called transposase, required for excising and inserting the mobile element. On the basis of sequence similarities, transposases can be grouped into various families. One of these families has been shown [MEDLINE:93094145], [MEDLINE:93329359] to consist of proteins of 340 to 380 amino acids.\ \ \N \N \N 20297 IPR001594 This domain is also known as NEW1 [MEDLINE:99250263], [MEDLINE:97315340]. The DHHC Zn-finger was first isolated in the Drosophila putative transcription factor DNZ1 [MEDLINE:99250263]. The function of this domain is unknown, but it has been predicted to be involved in protein-protein or protein-DNA interactions [MEDLINE:91369360].\ \N \N \N 20298 IPR001595

This family of lipoproteins is Mycoplasma specific, and includes a variety of hypothetical proteins [MEDLINE:97105885]. They all have a prokaryotic membrane lipoprotein lipid attachment site which is probable acts as a membrane anchor.

\ molecular_function unknown ; GO:0005554 \N \N 20299 IPR001597

Tryptophan indole-lyase (EC: 4.1.99.1) (tryptophanase) and tyrosine phenol-lyase (EC: 4.1.99.2) (-tyrosinase) are related pyridoxal-phosphate dependent homotetrameric enzymes PUB00003112. Tryptophan indole-lyase catalyzes the transformation of tryptophan into indole, pyruvate and ammonia and tyrosine phenol-lyase transforms tyrosine into phenol, pyruvate and ammonia.

Both enzymes are proteins that contains 450 to 470 amino acids. The pyridoxal-phosphate group is attached to a lysine residue in the central section of the sequence.

\ \ lyase activity ; GO:0016829 \N amino acid metabolism ; GO:0006520 20295 IPR001592

This protease is found in genome polyproteins of potyviruses. The genome polyprotein contains: N-terminal protein (P1), helper component protease(EC: 3.4.22.-)(HC-PRO), protein P3, 6KD protein (6K1), cytoplasmic inclusion protein (CI), 6KD protein 2 (6K2), genome-linked protein (VPG), nuclear inclusion protein A (EC: 3.4.22.-), nuclear inclusion protein B (EC: 2.7.7.48) and coat protein (CP).\ The coat protein is at the C-terminus of the polyprotein.

\ \ \N \N \N 20296 IPR001593

\ \ \

A number of eukaryotic and archaebacterial ribosomal proteins can be grouped on the basis of sequence similarities. One of these families consists of proteins that have from 220 to 250 amino acids.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 20301 IPR001599 The proteinase-binding

-actinin seems to reside in the first 250 residues of the protein. A similar actin-binding domain has been found in the N-terminal region of many different actin-binding proteins [MEDLINE:91280669], [MEDLINE:91369360], like the

chain of spectrin (or fodrin), dystrophin, the slime mold gelation factor (or ABP-120), filamin and fimbrin.\ actin binding activity ; GO:0003779 \N \N 20293 IPR001590

CD156 (also called ADAM8 (EC: 3.4.24.-) or MS2 human) has been implicated in extravasation of leukocytes.

The members of this family are enzymes that cleave peptides.\ These proteases require zinc for catalysis. Members of this\ family are also known as adamalysins.\ Most members of this family are snake venom endopeptidases,\ but there are also some mammalian proteins such as P78325,\ and fertilin P78325/>. Fertilin and closely related\ proteins appear to not have some active site residues and\ may not be active enzymes.

\ \

CD molecules are leucocyte antigens on cell surfaces. CD antigens nomenclature is updated at http://www.ncbi.nlm.nih.gov/PROW/guide/45277084.htm \

\ \ \ metalloendopeptidase activity ; GO:0004222 \N proteolysis and peptidolysis ; GO:0006508 20294 IPR001591 Orthomyxoviridae RNA polymerase with the subunit composition of PB1-PB2-PA is a unique multifunctional enzyme with the activities of both synthesis and cleavage of RNA, and is involved in both transcription and replication of the RNA genome. Transcription is initiated by using capped RNA fragments, which are generated after cleavage of host cell mRNA by the RNA polymerase-associated capped RNA endonuclease [MEDLINE:96399738]. It would appear that two separate sequences, one N-(242-282) and the other C-terminal (538-577) proximal segments of PB2 subunit, constitute the RNA cap-binding site of the\ influenza virus RNA polymerase [MEDLINE:99457299].\ \ RNA-directed RNA polymerase activity ; GO:0003968 \N transcription ; GO:0006350 20290 IPR001587 This domain is found in a family of proteins composed of uncharacterized proteins of about 50 to 77 kD. Their central region is well conserved and contains three conserved histidines. Most of these proteins are related at the N-terminal region to the

-lactamase family.\ molecular_function unknown ; GO:0005554 \N \N 20291 IPR001588

Caseins [MEDLINE:89264419] are the major protein constituent of milk. Caseins can be classified into two families; the first consists of the kappa-caseins, and the second groups the -s1, -s2, and -caseins. The / caseins are a rapidly diverging family of proteins. However two regions are conserved: a cluster of phosphorylated serine residues and the signal sequence.

Alpha-s2 casein is known as epsilon-casein in mouse, gamma-casein in rat and casein-A in guinea pig. Alpha-s1 casein is known as -casein in rat and rabbit and as casein-B in guinea pig.

\ \ \N \N \N 20289 IPR001586 Beta-lactamases (EC: 3.5.2.6) [MEDLINE:81101305], [MEDLINE:91186832] are enzymes which catalyze the hydrolysis of an amide bond in the

-lactam ring of antibiotics belonging to the penicillin/cephalosporin family. Four kinds of

-lactamase have been identified [MEDLINE:89271760]. This family represents the class-C enzymes, which are serine hydrolases.\ \ beta-lactamase activity ; GO:0008800 periplasmic space (sensu Gram-negative Bacteria) ; GO:0030288 antibiotic catabolism ; GO:0017001 20288 IPR001585

Transaldolase is evolutionary related [MEDLINE:95291446] to a bacterial protein of about 20 Kd (known as talC in Escherichia coli, IPR004731), whose exact function is not yet known.

\ \ aldolase activity ; GO:0016228 \N carbohydrate metabolism ; GO:0005975 20284 IPR001579

Chitinases (EC: 3.2.1.14) [MEDLINE:92387339] are enzymes that catalyze the hydrolysis of the -1,4-N-acetyl-D-glucosamine linkages in chitin polymers. From the view point of sequence similarity chitinases belong to either family 18 or 19 in the classification of glycosyl hydrolases [MEDLINE:92082464].

Chitinases of family 18 (also known as classes III or V) groups a variety of chitinases and other proteins. Site directed mutagenesis experiments [MEDLINE:93366760] and crystallographic data [MEDLINE:95219379], [MEDLINE:95219380] have shown that a conserved glutamate is involved in the catalytic mechanism and probably acts as a proton donor. This glutamate is at the extremity of the best conserved region in these proteins.

\ \ enzyme activity ; GO:0003824 \N carbohydrate metabolism ; GO:0005975 20285 IPR001580

Synonym(s): Calregulin, CRP55, HACBP

Calreticulin [MEDLINE:92359928] is a high-capacity calcium-binding protein which is present in most tissues and located at the periphery of the endoplasmic (ER) and the sarcoplamic reticulum (SR) membranes. It probably plays a role in the storage of calcium in the lumen of the ER and SR and it may well have other important functions.

Structurally, calreticulin is a protein of about 400 amino acid residues consisting of three domains:\

An N-terminal, probably globular, domain of about 180 amino acid residues (N-domain).
A central domain of about 70 residues (P-domain) which contains three repeats of an acidic 17 amino acid motif. This region binds calcium with a low-capacity, but a high-affinity.
A C-terminal domain rich in acidic residues and in lysine (C-domain). This region binds calcium with a high-capacity but a low-affinity.

Calreticulin is evolutionarily related to several other calcium-binding proteins, including Onchocerca volvulus antigen RAL-1, calnexin [MEDLINE:94262164] and calmegin [MEDLINE:94171811].

\ \ calcium ion storage activity ; GO:0005514 \N \N 20286 IPR001581

On the basis of functional and structural similarities, the small cytokines leukemia inhibitory factor (LIF) and oncostatin (OSM) can be classified into a single family [MEDLINE:92229820], [MEDLINE:92020908].

It has been said [MEDLINE:92020908] that LIF and OSM can be included in the IL-6 family of cytokines (see the relevant entry PDOC00227), but while all these cytokines seem to be structurally related, the sequence similarity is not high enough to allow the use of a single consensus pattern.

\ \ \ cytokine activity ; GO:0005125 extracellular ; GO:0005576 immune response ; GO:0006955 20287 IPR001584

Integrase comprises three domains capable of folding independently and whose three-dimensional structures are known. However, the manner in which the N-terminal, catalytic, and C-terminal domains interact in the holoenzyme remains obscure. Numerous studies indicate that the enzyme functions as a multimer, minimally a dimer. The integrase proteins from HIV-1 and ASV have been studied most carefully with respect to the structural basis of catalysis. Although the active site of ASV integrase does not undergo significant conformational changes on binding the required metal cofactor, that of HIV-1 IN does. This active site-mediated conformational change in HIV-1 reorganizes the catalytic core and C-terminal domains and appears to promote an interaction that is favorable for catalysis [MEDLINE:99312236].

Retroviral integrase is synthesised as part of the POL polyprotein that contains; an aspartyl protease, a reverse transcriptase, RNase H and integrase. POL polyprotein undergoes specific enzymatic cleavage to yield the mature proteins. The presence of retrovirus integrase-related gene sequences in eukaryotes is known. Bacterial transposases involved in the transposition of the insertion sequence also belong to this group.

HIV integrase catalyses the incorporation of virally derived DNA into the human genome. This unique step in the virus life cycle provides a variety of points for intervention and hence is an attractive target for the development of new therapeutics for the treatment of AIDS [MEDLINE:97304688]. Substrate recognition by the retroviral integrase enzyme is critical for retroviral integration. To catalyze this recombination event, integarse must recognize and act on two types of substrates, viral DNA and host DNA, yet the necessary interactions exhibit markedly different degrees of specificity [MEDLINE:99312237].

\ \ DNA binding activity ; GO:0003677 \N DNA recombination ; GO:0006310 20283 IPR001578

Cysteine protease activity is dependent on an active dyad of cysteine andhistidine, the order and spacing of these residues varying in the 20 or so\ known families. Families C1, C2 and C10 are loosely termed papain-like, and\ nearly half of all cysteine proteases are found exclusively in viruses [MEDLINE:95147707].

\ \ \

Ubiquitin is highly conserved, commonly found conjugated to proteins in\ eukaryotic cells, where it may act as a marker for rapid degradation, or\ it may have a chaperone function in protein assembly [MEDLINE:95147707]. The ubiquitin is\ released by cleavage from the bound protein by a protease [MEDLINE:95147707]. A number of\ deubiquitinising proteases are known: all are activated by thiol compounds\ [MEDLINE:95147707], [MEDLINE:86278072], and inhibited by thiol-blocking agents and ubiquitin aldehyde [MEDLINE:95147707], [MEDLINE:87175569],\ and as such have the properties of cysteine proteases [MEDLINE:95147707].

The deubiquitinsing proteases can be split into 2 size ranges (20-30 kDa\ and 100-200 kDa) [MEDLINE:95147707]: the yuh1 family of proteases fall into the first group.\ Yeast yuh1 protease is known to be active only against small ubiquitin\ conjugates, being inactive against conjugated -galactosidase [MEDLINE:95147707]. A\ mammalian homologue, UCH (ubiquitin conjugate hydrolase), is one of the most\ abundant proteins in the brain [MEDLINE:95147707]. Only one conserved cysteine can be\ identified, along with two conserved histidines. The spacing between the\ cysteine and the second histidine is thought to be more representative of\ the cysteine/histidine spacing of a cysteine protease catalytic dyad [MEDLINE:95147707].

\ \ ubiquitin C-terminal hydrolase activity ; GO:0004221 intracellular ; GO:0005622 ubiquitin-dependent protein catabolism ; GO:0006511 20282 IPR001577

Metalloproteases can be split into five clans, and futher sub-divided into families, on the basis of their metal binding residues.

Leishmanolysin is an enzyme found in the eukaryotes including Leishmania and related parasitic\ protozoa [MEDLINE:95405261]. The endopeptidase is the most abundant protein on the cell\ surface during the promastigote stage of the parasite, and is attached to\ the membrane by a glycosylphosphatidylinositol anchor [MEDLINE:95405261]. In the amastigote\ form, the parasite lives in lysosomes of host macrophages, producing a\ form of the protease that has an acidic pH optimum [MEDLINE:95405261]. This differs from\ most other metalloproteases and may be an adaptation to the environment in\ which the organism survives [MEDLINE:95405261]. The protein contains a catalytic HEXXH\ motif, in which the additional zinc-binding residue is unknown.

\ \ metalloendopeptidase activity ; GO:0004222 membrane ; GO:0016020 cell adhesion ; GO:0007155 20281 IPR001576 Phosphoglycerate kinase (EC: 2.7.2.3) (PGK) is an enzyme that catalyzes the formation of ATP to ADP and vice versa. In the second step of the second phase in glycolysis, 1,3-diphosphoglycerate is converted to3-phosphoglycerate, forming one molecule of ATP. If the reverse were to occur, one molecule of ADP would be formed. This reaction is essential in most cells for the generation of ATP in aerobes, for fermentation in anaerobes and for carbon fixation in plants. \

PGK is found in all living organisms and its sequence has been highly conserved throughout evolution. The enzyme exists as a monomer containing two nearly equally-sized domains that correspond to the N- and C-terminii of the protein (the last 15 C-terminal residues loop back into the N-terminal domain). 3-phosphoglycerate (3-PG) binds to the N-terminal, while the nucleotide substrates, MgATP or MgADP,\ bind to the C-terminal domain of the enzyme. This extended two domain structure is associated with large-scale 'hinge-bending' conformational changes, similar to those found in hexokinase [MEDLINE:20058829]. At the core of each domain is a 6-stranded parallel -sheet surrounded by -helices. Domain 1 has a parallel -sheet of six strands with an order of 342156, while domain 2 has a parallel -sheet of six strands with an order of 321456. Analysis of the reversible unfolding of yeast phosphoglycerate kinase leads to the conclusion that the two lobes are capable of folding independently, consistent with the presence of intermediates on the folding pathway with a single domain folded [MEDLINE:91077396].

Phosphoglycerate kinase (PGK) deficiency is associated with hemolytic anemia and mental disorders in man\ \ \ \ [MEDLINE:84202994].

\ \ phosphoglycerate kinase activity ; GO:0004618 \N glycolysis ; GO:0006096 20279 IPR001573 This domain is found in scaffold proteins that bind the regulatory subunit (RII) of protein kinase A with high affinity [MEDLINE:97123248]. Each AKAP protein (more than 36) allow subcellular targeting of protein kinase A through association with structural proteins, membranes or cellular organelles [MEDLINE:97123248]. The gravin, an autoantigen recognized by serum from myasthenia gravis patients contains 3 repeats of this domain [MEDLINE:97153077].\ protein transporter activity ; GO:0008565 \N protein targeting ; GO:0006605 20280 IPR001574 A number of bacterial and plant toxins act by inhibiting protein synthesis in eukaryotic cells. The toxins of the Shiga and ricin family inactivate 60S ribosomal subunits by an N-glycosidic cleavage which releases a specific adenine base from the sugar-phosphate backbone of 28S rRNA [MEDLINE:88111703], [MEDLINE:89231631], [MEDLINE:92075756]. Members of the family include shiga and shiga-like toxins, and type I (e.g. trichosanthin and luffin) and type II (e.g. ricin, agglutinin and abrin) ribosome inactivating proteins (RIPs). All these toxins are structurally related. RIPs have been of considerable interest because of their potential use, conjugated with monoclonal antibodies, as immunotoxins to treat cancers. Further, trichosanthin has been shown to have potent activity against HIV-1-infected T cells and macrophages [MEDLINE:94344957]. Elucidation of the structure-function relationships of RIPs has therefore become a major research effort. It is now known that RIPs are structurally related. A conserved glutamic residue has been implicated in the catalytic mechanism [MEDLINE:88190113]; this lies near a conserved arginine, which also plays a role in catalysis [MEDLINE:94016586].\ protein biosynthesis inhibitor activity ; GO:0017149 \N negative regulation of protein biosynthesis ; GO:0017148 20278 IPR001571

Vasoactive intestinal polypeptide (VIP) has a wide physiological profile.\ In the periphery, it induces relaxation in smooth muscle; inhibits\ secretion in certain tissues, but stimulates secretion in others; and\ modulates activity of cells in the immune system PUB00005907. In the CNS, it has a\ range of both excitatory and inhibitory actions. VIP receptors are\ distributed widely in the periphery, and occur throughout the gastrointestinal tract and genitourinary system, other smooth muscles and\ secretory glands. In the CNS, they are found abundantly in, e.g. the cortex,\ hippocampus and thalamus PUB00005907. All VIP receptors activate adenylyl cyclase.

\ \ vasoactive intestinal polypeptide receptor activity ; GO:0004999 membrane ; GO:0016020 G-protein coupled receptor protein signaling pathway ; GO:0007186 20276 IPR001570

Metalloproteases can be split into five clans, and futher sub-divided into families, on the basis of their metal binding residues.

The thermolysin family (M4), part of the MA clan (HEXXH⁺E), is composed\ only of secreted eubacterial endopeptidases [MEDLINE:95405261]. The zinc-binding residues\ are H-142, H-146 and E-166, with E-143 acting as the catalytic residue [MEDLINE:95405261].\ Thermolysin also contains 4 calcium-binding sites, which contribute to its\ unusual thermostability [MEDLINE:95405261]. The family also includes enzymes from a number\ of pathogens, including Legionella and Listeria, and the protein pseudolysin,\ all with a substrate specificity for an aromatic residue in the P1' position\ [MEDLINE:95405261]. Three-dimensional structure analysis has shown that the enzymes undergo\ a hinge-bend motion during catalysis [MEDLINE:95405261]. Pseudolysin has a broader\ specificity, acting on large molecules such as elastin and collagen,\ possibly due to its wider active site cleft [MEDLINE:95405261].

\ \ metalloendopeptidase activity ; GO:0004222 extracellular ; GO:0005576 proteolysis and peptidolysis ; GO:0006508 20277 IPR001570

Metalloproteases can be split into five clans, and futher sub-divided into families, on the basis of their metal binding residues.

\ \ metalloendopeptidase activity ; GO:0004222 extracellular ; GO:0005576 proteolysis and peptidolysis ; GO:0006508 20275 IPR001569

\ \ \

A number of eukaryotic and archaebacterial ribosomal proteins can be grouped on the basis of sequence similarities. One of these families consists of proteins of 56 to 96 amino-acid residues that share a highly conserved region located in the N-terminal part.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 20273 IPR001567

Metalloproteases can be split into five clans, and futher sub-divided into families, on the basis of their metal binding residues.

The Thimet oligopeptidase family, is a large family of mammalian and bacterial oligopeptidases that cleave medium sized peptides. The group also contains mitochondrial\ intermediate peptidase which is encoded by nuclear DNA but functions within the mitochondria to remove the leader sequence.

\ \ metalloendopeptidase activity ; GO:0004222 \N proteolysis and peptidolysis ; GO:0006508 20274 IPR001568

The fungal ribonucleases T2 from Aspergillus oryzae, M from Aspergillus saitoi and Rh from Rhizopus niveus are structurally and functionally related 30 Kd glycoproteins [MEDLINE:91035364] that cleave the 3'-5' internucleotide linkage of RNA via a nucleotide 2',3'-cyclic phosphate intermediates (EC: 3.1.27.1).

Two histidines residues have been shown [MEDLINE:90126828],[MEDLINE:92339548] to be involved in the catalytic mechanism of RNase T2 and Rh. These residues and the region around them are highly conserved in a number of other RNAses that have been found to be evolutionary related to these fungal enzymes.

\ \ endoribonuclease activity ; GO:0004521 \N \N 20272 IPR001566

This protein family forms a sub-family of proteins that contain the SAM (S-adenosylmethionine) binding motif IPR000051.

It is probable that ygcA/HI0333 and HI0958 are responsible for the methylation of U747 and U1939 in 23S rRNA. In tRNA (uracil-5-)-methyltransferase, a cysteine is known to participate in the catalytic mechanism by forming a covalent adduct to C6 of uracil.

\ \ RNA methyltransferase activity ; GO:0008173 \N RNA processing ; GO:0006396 20271 IPR001565

Synaptotagmins are synaptic vesicle membrane proteins found in abundance in nerve cells and some endocrine cells [MEDLINE:95211844], [MEDLINE:95050743]. The amino acid sequence of synaptotagmin comprises a single transmembrane region with a short vesicular N-terminal region, and a cytoplasmic C-terminal region containing 2 internal repeats similar to the C2 regulatory domain of protein kinase C. The protein is believed to be important in the docking and fusion of synaptic vesicles with the plasma membrane, i.e. with neurotransmitter release [MEDLINE:95211844], [MEDLINE:95050743].

The 2 synaptotagmin C2 domains have been shown to have different functions: C2A binds phospholipid in a calcium-dependent manner, while C2B binds inositol polyphosphate and phospholipid irrespective of the presence of Ca²⁺ [MEDLINE:95050743]. The structure of C2 domains in synaptotagmin I has been deduced: the C2 polypeptide forms an 8-stranded -sandwich constructed around a conserved 4-stranded motif, designated a C2 key [MEDLINE:95211844]. The calcium binding region is a cup-shaped depression formed by the N- and C-terminal loops of the C2-key motif, while the site of phospholipid interaction is thought to be a polybasic sequence on the hairpin loop connecting strands 3 and 4 [MEDLINE:95211844].

\ \ \ transporter activity ; GO:0005215 membrane ; GO:0016020 transport ; GO:0006810 20268 IPR001562 Kinases are generally multi-domain, multi-functional proteins. Protein tyrosine kinases (PTKs), serine/threonine kinases, and other signal transduction proteins, possess a region of unknown function related to pleckstrin, designated the PH domain. A point mutation affecting a conserved Arg in the PH domain of the cytoplasmic PTK Btk causes the human disease X-linked agammaglobulinemia and X-linked immunodeficiency in mice. Btk forms a family with 2 other PTKs, Isk/Tsk and Tec, in which the PH domain is followed by an SH3 domain. The conserved sequence between the 2 regions has tentatively been designated the TH (Tec homology) domain. The N-terminal 27 residues of the TH domain are highly conserved (the Btk motif), and are followed by a proline-rich (PRR) region: the Btk motif contains a conserved His and 3 Cys residues that are involved in zinc fingers (although these differ from known zinc finger topologies), while PRRs are commonly involved in protein-protein interactions. The Tec extension to the PH domain may be of functional importance in various signalling pathways in different species [MEDLINE:94350112]. A complete TH domain, containing both the Btk and PRR regions, has not been found outside the Btk family, and may be a hallmark of these cytoplasmic PTKs.\ \N \N intracellular signaling cascade ; GO:0007242 20269 IPR001563

All known carboxypeptidases are either metallo carboxypeptidases or serine carboxypeptidases (EC 3.4.16.5 and EC 3.4.16.6). The catalytic activity of the serine carboxypeptidases, like that of the trypsin family serine proteases, is provided by a charge relay system involving an aspartic acid residue hydrogen-bonded to a histidine, which is itself hydrogen-bonded to a serine [MEDLINE:90216664]. The sequences surrounding the active site serine and histidine residues are highly conserved in all the serine carboxypeptidases.

These proteins belong to family S10 in the classification of peptidases [MEDLINE:95147689].

\ \ serine carboxypeptidase activity ; GO:0004185 \N proteolysis and peptidolysis ; GO:0006508 20270 IPR001564

Nucleoside diphosphate kinases (EC: 2.7.4.6) (NDK) PUB00006586 are enzymes required for the synthesis of nucleoside triphosphates (NTP) other than ATP. They provide NTPs for nucleic acid synthesis, CTP for lipid synthesis, UTP for polysaccharide synthesis and GTP for protein elongation, signal transduction and microtubule polymerization.

In eukaryotes, there seems to be a small family of NDK isozymes each of which acts in a different subcellular compartment and/or has a distinct biological function. Eukaryotic NDK isozymes are hexamers of two highly related chains (A and B) PUB00006586. By random association (A6, A5B...AB5, B6), these two kinds of chain form isoenzymes differing in their isoelectric point.

NDK are proteins of 17 Kd that act via a ping-pong mechanism in which a histidine residue is phosphorylated, by transfer of the terminal phosphate group from ATP. In the presence of magnesium, the phosphoenzyme can transfer its phosphate group to any NDP, to produce an NTP.

NDK isozymes have been sequenced from prokaryotic and eukaryotic sources. It has also been shown [MEDLINE:91077931] that the Drosophila awd (abnormal wing discs) protein, is a microtubule-associated NDK. Mammalian NDK is also known as metastasis inhibition factor nm23. The sequence of NDK has been highly conserved through evolution. There is a single histidine residue conserved in all known NDK isozymes, which is involved in the catalytic mechanism [MEDLINE:91224972]. Our signature pattern contains this residue.

\ \ ATP binding activity ; GO:0005524 \N CTP biosynthesis ; GO:0006241 20267 IPR001561 Matrix protein (M1) of influenza virus is a bifunctional protein that mediates the encapsidation of RNA-nucleoprotein cores into the membrane envelope. It is therefore\ required that M1 binds both membrane and RNA simultaneously [MEDLINE:97307259].\ \ structural molecule activity ; GO:0005198 \N \N 20266 IPR001560

Bombesins are peptide neurotransmitters whose biological activity resides\ in a common C-terminal sequence, WAXGHXM PUB00005871. In the periphery, bombesin-related peptides stimulate smooth muscle and glandular secretion. In the\ brain, these peptides are believed to play a role in homeostasis, thermo-regulation and metabolism, and have been reported to elicit analgesia and\ excessive grooming, together with central regulation of a variety of\ peripheral effects.

The recently-identified BRS-3 bombesin receptor subtype is found in germ\ cells in testis and in uteri of pregnant animals; it is also present in a\ variety of lung carcinoma cell lines PUB00005871. The receptor is believed to play\ a role in sperm cell division and maturation. Its action is mediated by\ association with G-proteins that activate a phosphatidylinositol-calcium\ second messenger system.

\ \ bombesin receptor activity ; GO:0004946 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20264 IPR001558

Human immunodeficiency virus (HIV) negative factor (Nef protein) accelerates virulent progression of acquired immunodeficiency syndrome (AIDS) by its interaction with specific\ cellular proteins involved in signal transduction and host cell activation. Nef has been shown\ to bind specifically to a subset of the Src family of kinases [MEDLINE:98035457].

\ \ \ GTP binding activity ; GO:0005525 \N \N 20265 IPR001559

Synonym(s): Paraoxonase, A-esterase, Aryltriphosphatase, Phosphotriesterase, Paraoxon hydrolase

Bacteria such as Pseudomonas diminuta harbor a plasmid that carries the gene for Aryldialkylphosphatase (EC: 3.1.8.1). This enzyme has attracted interest because of its potential use in the detoxification of chemical waste and warfare agents and its ability to degrade agricultural pesticides such as parathion. It act specifically on synthetic organophosphate triesters and phosphorofluoridates. It does not seem to have a natural occuring substrate and may thus have optimally evolved for utilizing paraoxon.

Aryldialkylphosphatase belongs to a family [MEDLINE:98044654], [MEDLINE:98215634] of enzymes that possess a binuclear zinc metal center at their active site. The two zinc ions are coordinated by six different residues, six of which being histidines.

\ \ hydrolase activity, acting on ester bonds ; GO:0016788 \N catabolism ; GO:0009056 20261 IPR001555

Phosphoribosylglycinamide formyltransferase (EC: 2.1.2.2) (GART) [MEDLINE:90373777] catalyzes the third step in de novo purine biosynthesis, the transfer of a formyl group to 5'-phosphoribosylglycinamide. In higher eukaryotes, GART is part of a multifunctional enzyme polypeptide that catalyzes three of the steps of purine biosynthesis. In bacteria, plants and yeast, GART is a monofunctional protein of about 200 amino-acid residues.

In the Escherichia coli enzyme, an aspartic acid residue has been shown to be involved in the catalytic mechanism. The region around this active site residue is well conserved in GART from prokaryotic and eukaryotic sources.

Mammalian formyltetrahydrofolate dehydrogenase (EC: 1.5.1.6) [MEDLINE:91161584] is a cytosolic enzyme responsible for the NADP-dependent decarboxylative reduction of 10-formyltetrahydrofolate into tetrahydrofolate. It is a protein of about 900 amino acids consisting of three domains; the N-terminal domain (200 residues) is structurally related to GARTs.

Escherichia coli methionyl-tRNA formyltransferase (EC: 2.1.2.9) (gene fmt) [MEDLINE:92325012] is the enzyme responsible for modifying the free amino group of the aminoacyl moiety of methionyl-tRMA(fMet). The central part of fmt seems to be evolutionary related to GART's active site region.

\ \ \N \N \N 20262 IPR001556

\ \ \ bombesin receptor activity ; GO:0004946 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20263 IPR001557

L-lactate dehydrogenase (EC: 1.1.1.27) (LDH) [MEDLINE:88118943] catalyzes the reversible NAD-dependent interconversion of pyruvate to L-lactate. In vertebrate muscles and in lactic acid bacteria it represents the final step in anaerobic glycolysis. This tetrameric enzyme is present in prokaryotic and eukaryotic organisms. In vertebrates there are three isozymes of LDH: the M form (LDH-A), found predominantly in muscle tissues; the H form (LDH-B), found in heart muscle and the X form (LDH-C), found only in the spermatozoa of mammals and birds. In birds and crocodilian eye lenses, LDH-B serves as a structural protein and is known as epsilon-crystallin [MEDLINE:89017148].

L-2-hydroxyisocaproate dehydrogenase (EC: 1.1.1.-) (L-hicDH) [MEDLINE:90060838] catalyzes the reversible and stereospecific interconversion between 2-ketocarboxylic acids and L-2-hydroxy-carboxylic acids. L-hicDH is evolutionary related to LDH's.

\ \ L-lactate dehydrogenase activity ; GO:0004459 \N glycolysis ; GO:0006096 20260 IPR001554

Glycoside hydrolase family 14 CAZY:GH_14\ comprises enzymes with only one known activity; -amylase (EC: 3.2.1.2). A Glu residue has been proposed as a catalytic residue, but it is not known if it is the nucleophile or the proton donor.

\ \

Beta-amylase [MEDLINE:88299722], [MEDLINE:89113345] is an enzyme that hydrolyzes 1,4--glucosidic linkages in starch-type polysaccharide substrates so as to remove\ successive maltose units from the non-reducing ends of the chains. Beta-amylase is present in certain bacteria as well as in plants.

Three highly conserved sequence regions are found in all known -amylases.\ The first of these regions is located in the N-terminal section of the enzymes\ and contains an aspartate which is known [MEDLINE:89340383] to be involved in the catalytic\ mechanism. The second, located in a more central location, is centered around\ a glutamate which is also involved [MEDLINE:94229061] in the catalytic mechanism.

The 3D structure of a complex of soybean -amylase with an inhibitor\ (-cyclodextrin) has been determined to 3.0A resolution by X-ray\ diffraction [MEDLINE:93147073]. The enzyme folds into large and small domains: the large\ domain has a ( )8 super-secondary structural core, while the smaller\ is formed from two long loops extending from the -3 and -4 strands\ of the ( )8 fold [MEDLINE:93147073]. The interface of the two domains, together\ with shorter loops from the ( )8 core, form a deep cleft, in which\ the inhibitor binds [MEDLINE:93147073]. Two maltose molecules also bind in the cleft,\ one sharing a binding site with -cyclodextrin, and the other sitting\ more deeply in the cleft [MEDLINE:93147073].

\ \ beta-amylase activity ; GO:0016161 \N polysaccharide catabolism ; GO:0000272 20259 IPR001553

The recA gene product is a multifunctional enzyme that plays a role in homologous recombination, DNA repair and induction of the SOS response [MEDLINE:91375455]. In homologous recombination, the protein functions as a DNA-dependent ATPase, promoting synapsis, heteroduplex formation and strand exchange between homologous DNAs [MEDLINE:91375455]. RecA also acts as a protease cofactor that promotes autodigestion of the lexA product and phage repressors. The proteolytic inactivation of the lexA repressor by an activated form of recA may cause a derepression of the 20 or so genes involved in the SOS response, which regulates DNA repair, induced mutagenesis, delayed cell division and prophage induction in response to DNA damage [MEDLINE:91375455].

RecA is a protein of about 350 amino-acid residues. Its sequence is very well conserved [MEDLINE:97330595], [MEDLINE:96074319], [MEDLINE:96139045] among eubacterial species. It is also found in the chloroplast of plants\ \ \ [MEDLINE:92390390]. RecA-like proteins are found in archea and diverse eukaryotic organisms, like fission yeast, mouse or human. In the filament\ visualized by X-ray crystallography, �-strand 3, the loop C-terminal to �-strand 2, and -helix D of the core domain form one surface that packs against -helix A and �-strand 0 (the N-terminal domain) of an adjacent monomer during polymerization [Lusetti and Cox, Annu. Rev. Biochem. 2002. 71:71-100.]. The core ATP-binding site domain is well conserved, with 14 invariant residues. It contains the nucleotide binding loop between �-strand 1 and -helix C. The E. coli sequence GPESSGKT matches the consensus sequence of amino acids (G/A)XXXXGK(T/S) for the Walker A box (also\ referred to as the P-loop) found in a number of nucleoside triphosphate (NTP)-binding proteins. Another\ nucleotide binding motif, the Walker B box is found at �-strand 4 in the RecA structure. The Walker B\ box is characterized by four hydrophobic amino acids followed by an acidic residue (usually aspartate). Nucleotide specificity and additional ATP binding interactions are contributed by the amino acid residues at �-strand 2 and the loop C-terminal to that\ strand, all of which are greater than 90% conserved among bacterial RecA proteins.

\ \ DNA dependent ATPase activity ; GO:0008094 \N DNA recombination ; GO:0006310 20258 IPR001551

The ability of marijuana to activate the cannabinoid receptor provides a\ molecular explanation for its psychoactive effects and other CNS actions\ (which include hallucinations, memory deficits, altered time and space\ perception, CNS depression and appetite stimulation) PUB00005670. The endogenous\ ligand at the cannabinoid receptor is unknown, although it may be a\ derivative of arachidonic acid. The cannabinoid receptor is widespread\ throughout the CNS, high levels occurring in the dendate gyrus, hippocampus\ and cerebral cortex, with more moderate levels in the hypothalamus and\ amygdala. It is also present in various cell lines, and in the periphery\ it is found in the testis and vas deferens PUB00005670.

\ \ cannabinoid receptor activity ; GO:0004949 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20257 IPR001550 This is a family of bacterial proteins related to the Escherichia coli bglG protein. E. coli bglG protein mediates the positive regulation of the

-glucoside (bgl) operon by functioning as a transcriptional antiterminator [MEDLINE:90381772]. BglG is an RNA-binding protein that recognizes a specific sequence located just upstream of two termination sites within the operon. The activity of bglG is supressed by its phosphorylation [MEDLINE:90341774] by bglF (EII-bgl), the permease from the

-glucoside PTS system. BglG is highly similar to other proteins, which also probably act as transcriptional antiterminators.\ RNA binding activity ; GO:0003723 \N regulation of transcription, DNA-dependent ; GO:0006355 20255 IPR001547

Glycoside hydrolase family 5 CAZY:GH_5).

\ \

The microbial degradation of cellulose and xylans requires several types of enzymes. Fungi and bacteria produces a spectrum of cellulolytic enzymes (cellulases) and xylanases which, on the basis of sequence similarities, can be classified into families. One of these families is known as the cellulase family A [MEDLINE:90034189] or as the glycosyl hydrolases family 5 [MEDLINE:92082464]. One of the conserved regions in this family contains a conserved glutamic acid residue which is potentially involved [MEDLINE:91312880] in the catalytic mechanism.

\ \ hydrolase activity, hydrolyzing O-glycosyl compounds ; GO:0004553 \N carbohydrate metabolism ; GO:0005975 20256 IPR001548

Metalloproteases can be split into five clans, and futher sub-divided into families, on the basis of their metal binding residues.

Pepetidyl-dipeptidase A (angiotensin-converting enzyme) is a mammalian\ enzyme responsible for cleavage of dipeptides from the C-termini of\ proteins, notably converting angiotensin I to angiotensin II [MEDLINE:95405261]. The enzyme\ exists in two differentially transcribed forms, the most common of which\ is from lung endothelium; this contains two homologous domains that have\ arisen by gene duplication [MEDLINE:95405261]. The testis-specific form contains only the\ C-terminal domain, arising from a duplicated promoter region present in\ intron 12 of the gene [MEDLINE:95405261].

\ \

Both enzymatic forms are membrane proteins that are anchored by means of a\ C-terminal transmembrane domain. Both domains of the endothelial enzyme are\ active, but have differing kinetic constants [MEDLINE:95405261]. The catalytic residues and\ zinc ligands have been identified, showing that the enzyme belongs to the\ HEXXH⁺E sub-group of metalloproteases [MEDLINE:95405261], [MEDLINE:91225000]. A number of insect enzymes have\ been shown to be similar to peptidyl-dipeptidase A, these containing a\ single catalytic domain.

\ \ peptidyl-dipeptidase A activity ; GO:0004246 membrane ; GO:0016020 proteolysis and peptidolysis ; GO:0006508 20254 IPR001546

Little is known about the structure and function of the mating factor\ receptors, STE2 and STE3. It is believed, however, that they are integral\ membrane proteins that may be involved in the response to mating factors\ on the cell membrane PUB00001139, PUB00001139, [MEDLINE:88234520]. The amino acid sequences of both receptors\ contain high proportions of hydrophobic residues grouped into 7 domains,\ in a manner reminiscent of the rhodopsins and other receptors believed to\ interact with G-proteins. However, while a similar 3D framework has been\ proposed to account for this, there is no significant sequence similarity\ either between STE2 and STE3, or between these and the rhodopsin-type\ family: the receptors thus bear their own unique '7TM' signatures.

\ \

The STE3 gene in S.cerevisiae is the cell-surface receptor that binds the\ 13-residue lipopeptide a-factor. Several related fungal pheromone receptor\ sequences are known: these include pheromone B 1 and B 3, and\ pheromone B 1 receptors from Schizophyllum commune; pheromone receptor\ 1 from Ustilago hordei; and pheromone receptors 1 and 2 from Ustilago maydis.\ Members of the family share about 20% sequence identity.

Ustilago maydis, a tetrapolar fungal species, has two genetically unlinked\ loci that encode the distinct mating functions of cell fusion (the a locus)\ and subsequent sexual development and pathogenicity (the b locus) [MEDLINE:94316642].\ The a locus exists in two alleles, the mating type in each of which is\ determined by a set of two genes; one encodes a precursor for a lipopeptide\ mating factor, while the other specifies the receptor for the pheromone\ secreted by cells of opposite mating type [MEDLINE:92154661]. U.maydis thus employs a\ novel strategy to determine its mating type by providing the primary\ determinants of cell-cell recognition directly from the mating type locus\ [MEDLINE:92154661]. The bipolar species, Ustilago hordei, contains both a and b loci;\ physical linkage of these loci in this bipolar fungus accounts for its\ distinct mating system. [MEDLINE:94316642].

\ \ \ mating-type a-factor pheromone receptor activity ; GO:0004933 membrane ; GO:0016020 \N 20252 IPR001544

\ \ enzyme activity ; GO:0003824 \N metabolism ; GO:0008152 20253 IPR001545

The crystal structures of four growth factors; nerve growth factor, transforming growth factor-, platelet-derived growth factor, and human chorionic gonadotropin from four separate superfamilies revealed that these proteins are structurally related and share a common overall topology [MEDLINE:93258805]. These proteins show very little sequence homology, but they all have an unusual arrangement of six cysteines linked to form a "cystine-knot" conformation. The active forms of these proteins are dimers, either homo- or heterodimers [MEDLINE:95392154]. Because of their shape, there appears to be an intrinsic requirement for the cystine-knot growth factors to form dimers. This extra level of organization increases the variety of structures built around this simple structural motif [MEDLINE:96082952].

Glycoprotein hormones [MEDLINE:81280516], [MEDLINE:93075015] (or gonadotropins) are a family of proteins which include the mammalian hormones follitropin (FSH), lutropin (LSH), thyrotropin (TSH) and chorionic gonadotropin (CG), as well as at least two forms of fish gonadotropins. All these hormones consist of two glycosylated chains ( and ). In mammalian gonadotropins, the chain is identical in the four types of hormones but the chains, while homologous, are different.

The chains are proteins of about 100 to 140 amino acid residues which contain the cysteine-knot domain (see IPR006208, as shown in the following schematic representation.\

\
      +----------------------+\
      |         +------------|-----------------------------+\
      |       +-|------------|--------+                    |\
      |       | |            |        |                    |\
   xxxCxxxxxxxCxCxxCxCxxxxxxxCxxxxxxxxCxxxxxxxCxCxCxxCxxxxxCxxxxxxxxxxx\
                   | |                        | | |  |\
                   | |                        | | +--+\
                   +-|------------------------+ |\
                     +--------------------------+\
\
'C': conserved cysteine involved in a disulfide bond.\

\ \ hormone activity ; GO:0005179 extracellular ; GO:0005576 \N 20251 IPR001543 Proteins in this group are involved in a secretory pathway responsible for the surface presentation of invasion plasmid antigen needed for the entry of Salmonella and other species into mammalian cells[MEDLINE:93078625], [MEDLINE:97039726].They could play a role in preserving the translocation competence of the IPA antigens and are required for secretion of the three IPA proteins [MEDLINE:92193289].\ \ \N \N \N 20250 IPR001542

Arthropod defensins are a family of insect and scorpion cysteine-rich antibacterial peptides, primarily active against Gram-positive bacteria\ \ \ [MEDLINE:89098894], [MEDLINE:90293084], [MEDLINE:93228618], [MEDLINE:92105112], [MEDLINE:93049356]. All these peptides range in length from 38 to 51 amino acids. There are six conserved cysteines all involved in intrachain disulfide bonds.

A schematic representation of peptides from the arthropod defensin family is shown below.\

\ +----------------------------+\ | | \ xxCxxxxxxxxxxxxxxCxxxCxxxxxxxxxCxxxxxCxCxx\ | | | |\ +---|---------------+ |\ +-----------------+\ \ 'C': conserved cysteine involved in a disulfide bond.\ \

Although low level sequence similarities have been reported [MEDLINE:89098894] between the arthropod defensins and mammalian defensins, the topological arrangement of the disulfide bonds as well as the tertiary structure [MEDLINE:90382590] are completely different in the two families.

\ \ \N \N \N 20249 IPR001540

Glycoside hydrolase family 20 CAZY:GH_20). Carbonyl oxygen of the C-2 acetamido group of the substrate acts as the catalytic nucleophile/base in this family of enzymes.

\ \

In the brain and other tissues, -hexosaminidase A degrades GM2 gangliosides; specifically, the enzyme hydrolyses terminal non-reducing N-acetyl-D-hexosamine residues in N-acetyl--D-hexosaminides. There are 3 forms of -hexosaminidase: hexosaminidase A is a trimer, with one , one -A and one -B chain; hexosaminidase B is a tetramer of two -A and two -B chains; and hexosaminidase S is a homodimer of chains. The two chains are derived from the cleavage of a precursor. Mutations in the -chain lead to Sandhoff disease, a lysosomal storage disorder characterised by accumulation of GM2 ganglioside [MEDLINE:93363649].

\ \ beta-N-acetylhexosaminidase activity ; GO:0004563 \N carbohydrate metabolism ; GO:0005975 20248 IPR001540

Glycoside hydrolase family 20 CAZY:GH_20). Carbonyl oxygen of the C-2 acetamido group of the substrate acts as the catalytic nucleophile/base in this family of enzymes.

\ \

\ \ beta-N-acetylhexosaminidase activity ; GO:0004563 \N carbohydrate metabolism ; GO:0005975 20247 IPR001539

Porphyromonas gingivalis collagenase (gene prtC) [MEDLINE:92283742] is an enzyme that degrades type I collagen and that seems to require a metal cofactor. PrtC is evolutionary related to a number of uncharacterized proteins with a well conserved region containing two cysteines.

These proteins belong to family U32 in the classification of peptidases.

\ \ peptidase activity ; GO:0008233 \N proteolysis and peptidolysis ; GO:0006508 20245 IPR001537 The spoU gene of Escherichia coli codes for a protein that shows strong similarities to previously characterized 2'-O-methyltransferases [MEDLINE:97465955]. The Pet56 protein of Saccharomyces cerevisiae has been shown to be required for ribose methylation at a universally conserved nucleotide in the peptidyl transferase center of the mitochondrial large ribosomal RNA (21S rRNA). Cells reduced in this activity were deficient in formation of functional large subunits of the mitochondrial ribosome. The Pet56 protein catalyzes the site-specific formation of 2'-O-methylguanosine on in vitro transcripts of both mitochondrial 21S rRNA and E. coli 23S rRNA providing evidence for an essential modified nucleotide in rRNA [MEDLINE:94090319].\ RNA methyltransferase activity ; GO:0008173 \N RNA processing ; GO:0006396 20246 IPR001538

Mannose-6-phosphate isomerase or phosphomannose isomerase (EC: 5.3.1.8) (PMI) is the enzyme that catalyzes the interconversion of mannose-6-phosphate and fructose-6-phosphate. In eukaryotes PMI is involved in the synthesis of GDP-mannose, a constituent of N- and O-linked glycans and GPI anchors and in prokaryotes it participates in a variety of pathways, including capsular polysaccharide biosynthesis and D-mannose metabolism. PMI's belong to the cupin superfamily whose functions range from isomerase and epimerase activities involved in the modification of cell wall carbohydrates in bacteria and plants, to non-enzymatic storage proteins in plant seeds, and transcription factors linked to congenital baldness in mammals [MEDLINE:21108725]. Three classes of PMI have been defined [MEDLINE:94139717].

The type II phosphomannose isomerases are bifunctional enzymes EC: 5.3.1.8. This entry covers the isomerase region of the protein [MEDLINE:98173770]. The guanosine diphospho-D-mannose pyrophosphorylase region is described in another InterPro entry (see IPR005836).\ \ mannose-1-phosphate guanylyltransferase (GDP) activity ; GO:0008928 \N polysaccharide metabolism ; GO:0005976 20243 IPR001534

This new apparently nematode-specific protein family has been called family 2 [MEDLINE:98086477]. The proteins show weak similarity to transthyretin (formerly called prealbumin) which transports thyroid hormones. The specific function of this protein is unknown.

\ \ molecular_function unknown ; GO:0005554 \N \N 20244 IPR001535 Arenaviruses are single stranded RNA viruses. The arenavirus S RNAs that have been characterised include conserved terminal sequences, an ambisense arrangement of the coding regions for the precursor glycoprotein (GPC) and nucleocapsid (N) proteins and an intergenic region capable of forming a base-paired "hairpin" structure. The mature glycoproteins that result are G1 and G2 and the N protein [MEDLINE:91253262].

Tacaribe virus (TACV) is an arenavirus that is genetically and antigenically\ closely related to Junin virus (JUNV), the aetiological agent of Argentine\ haemorrhagic fever (AHF). It is well established that TACV protects experimental animals fully against an otherwise lethal challenge with JUNV. It has been established that it is the heterologous glycoprotein that protects against JUNV challenge. A recombinant vaccinia virus that expresses JUNV glycoprotein precursor (VV-GJun) protected seventy-two percent of the animals inoculated with two doses of VV-GJun against the lethal JUNV challenge [MEDLINE:20231938].

\ \ \N \N \N 20241 IPR001531

Bacillus cereus contains a monomeric phospholipase C (EC: 3.1.4.3) (PLC) of 245 amino-acid residues. Although PLC prefers to act on phosphatidylcholine, it also shows weak catalytic activity with sphingomyelin and phosphatidylinositol [MEDLINE:88296483]. Sequence studies have shown the protein to be similar both to toxin from Clostridium perfringens and Clostridium bifermentans, a phospholipase C involved in haemolysis and cell rupture [MEDLINE:89108574], and to lecithinase from Listeria monocytogenes, which aids cell-to-cell spread by breaking down the 2-membrane vacuoles that surround the bacterium during transfer [MEDLINE:92104678].

Each of these proteins is a zinc-dependent enzyme, binding 3 zinc ions per molecule [MEDLINE:90255924]. The enzymes catalyse the conversion of phosphatidylcholine and water to 1,2-diacylglycerol and choline phosphate [MEDLINE:88296483], [MEDLINE:89108574], [MEDLINE:90255924].

In B. cereus, there are nine residues known to be involved in binding the zinc ions: 5 His, 2 Asp, 1 Glu and 1 Trp. These residues are all conserved in the Clostridium -toxin.

\ \ zinc ion binding activity ; GO:0008270 \N \N 20242 IPR001533

DCoH is the dimerization cofactor of hepatocyte nuclear factor 1 (HNF-1) that functions as both a transcriptional coactivator and a pterin dehydratase [MEDLINE:97052967]. X-ray crystallographic studies have shown that the ligand binds at four sites per tetrameric enzyme, with little apparent conformational change in the protein.

\ \ \N \N \N 20240 IPR001530

Beet curly top (BCTV), bean summer death and tobacco yellow dwarf viruses belong to a third possible subgroup. Like MSV and WDV, BCTV is transmitted by a specific leafhopper species, yet like the whitefly-transmitted gemini-viruses it has a host range confined to dicotyledenous plants.

Sequence comparison of the whitefly-transmitted squash leaf curl\ \ \ \ [MEDLINE:91082449] and tomato yellow leaf curl viruses [MEDLINE:92107660], [MEDLINE:92024070] with the genomic components of TGMV and BGMV reveals a close evolutionary relationship [MEDLINE:91082449]. Amino acid sequence alignments of potato yellow mosaic viral (PYMV) proteins with those encoded by other geminiviruses show that PYMV is closely related to geminiviruses isolated from the New World, especially in the putative coat protein gene regions [MEDLINE:91311403].

\ \ \N \N \N 20238 IPR001528 Flaviviruses encode a single polyprotein. This is cleaved into three structural and seven non-structural proteins. The NS4B protein is small and poorly conserved among the Flaviviruses. NS4B contains multiple hydrophobic potential membrane spanning regions [MEDLINE:91069238]. NS4B may form membrane components of the viral replication complex and could be involved in membrane localisation of NS3 and NS5 (see IPR000208.\ \N \N \N 20239 IPR001529

In eukaryotes, there are three different forms of DNA-directed RNA polymerases (EC: 2.7.7.6) transcribing different sets of genes. Each class of RNA polymerase is an assemblage of ten to twelve different polypeptides. In archaebacteria, there is generally a single form of RNA polymerase which also consist of an oligomeric assemblage of 10 to 13 polypeptides.

It has recently been shown [MEDLINE:94089382], [MEDLINE:93109294] that small subunits of about 15 kDa, found in polymerase types I and II, are highly conserved. These proteins contain a probable zinc finger in their N-terminal region and a C-terminal zinc ribbon domain (see IPR001222).

\ \ DNA-directed RNA polymerase activity ; GO:0003899 \N transcription ; GO:0006350 20237 IPR001526

CD59 (also called 1F-5Ag , H19, HRF20, MACIF, MIRL, P-18 or protectin) inhibits formation of membrane attack complex (MAC), thus protecting cells from complement mediated lysis. It has a signaling role, as a GPI-anchored molecule, in T cell activation and appears to have some role in cell adhesion through CD2 (controversial). CD59 associates with C9, inhibiting incorporation into C5b-8 preventing terminal steps in polymerization of the (MAC) in plasma membranes. Genetic defects in GPI-anchor attachment that cause a reduction or loss of both CD59 and CD55 on erythrocytes produce the symptoms of the disease paroxysmal nocturnal hemoglobinuria (PNH).

\ \

A variety of GPI-linked cell-surface glycoproteins are composed of one or more copies of a conserved domain of about 100 amino-acid residues [MEDLINE:91210310], [MEDLINE:93352546]. Among these proteins, U-PAR contains three tandem copies of the domain, while all the others are made up of a single domain.

As shown in the following schematic, this conserved domain contains 10 cysteine residues involved in five disulfide bonds - in U-PAR, the first copy of the domain lacks the fourth disulfide bond.

\ +------+ +------------------------+ +---+\ | | | | | |\ xCxxCxxxxxxCxxxxxCxxxxxCxxxxxxxxxxxxxxxxxxCxxxxCxxxxxxxxxxxxxxCCxxxCxxxxxxxx\ | | | |\ +---------------------+ +--------------+\ \ 'C': conserved cysteine involved in a disulfide bond.\

\ \

CD molecules are leucocyte antigens on cell surfaces. CD antigens nomenclature is updated at http://www.ncbi.nlm.nih.gov/PROW/guide/45277084.htm \

\ \ \ \N \N \N 20236 IPR001525 C-5 cytosine-specific DNA methylases (EC: 2.1.1.73) (C5 Mtase) are enzymes that specifically methylate the C-5 carbon of cytosines in DNA to produce C5-methylcytosine [MEDLINE:89252879], [MEDLINE:94173650], [MEDLINE:89236399]. In mammalian cells, cytosine-specific methyltransferases methylate certain CpG sequences, which are believed to modulate gene expression and cell differentiation. In bacteria, these enzymes are a component of restriction-modification systems and serve as valuable tools for the manipulation of DNA [MEDLINE:95292061], [MEDLINE:94173650]. The structure of HhaI methyltransferase (M.HhaI) has been resolved to 2.5 A [MEDLINE:93345018]: the molecule folds into 2 domains - a larger catalytic domain containing catalytic and cofactor binding sites, and a smaller DNA recognition domain.\ DNA binding activity ; GO:0003677 \N DNA methylation ; GO:0006306 20234 IPR001523 The paired box is a conserved 124 amino acid N-terminal domain of unknown function that usually, but not always, precedes a homeobox domain (see IPR001356, the observed grouping of segments into pairs depending on the position of the segment in the segmental array, and not on the identity of the segment as in the case of homeotic genes. This implies that the genes affect different processes from those altered by homeotic genes.\ \N nucleus ; GO:0005634 development ; GO:0007275 20235 IPR001524

Glycoside hydrolase family 6 CAZY:GH_6). These enzymes were formerly known as cellulase family B.

\ \

The 3D structure of the enzymatic core of cellobiohydrolase II (CBHII) from\ the fungus Trichoderma reesei reveals an - protein with a fold\ similar to the ubiquitous barrel topology first seen in triose phosphate\ isomerase [MEDLINE:90333255]. The active site of CBHII is located at the C-terminal end of\ a parallel barrel, in an enclosed tunnel through which the cellulose\ threads. Two aspartic acid residues, located in the center of the tunnel\ are the probable catalytic residues [MEDLINE:90333255].

\ \ hydrolase activity, hydrolyzing O-glycosyl compounds ; GO:0004553 \N carbohydrate metabolism ; GO:0005975 20233 IPR001522

Fatty acid desaturases are enzymes that catalyze the insertion of a double bond at the delta position of fatty acids.

There seems to be two distinct families of fatty acid desaturases which do not seem to be evolutionary related: the first contains stearoyl-CoA desaturase (SCD) (EC: 1.14.19.1); the second includes plant stearoyl-acyl-carrier protein and cyanobacteria desA protein.

SCD is a key regulatory enzyme of unsaturated fatty acid biosynthesis. In association with cytochrome b5 and NADP-dependent cytochrome b5 reductase, it constitutes part of a microsomal membrane-bound 3-component system in animals and fungi [MEDLINE:89034247]. SCD contains 4 putative transmembrane (TM) regions that anchor it in the microsomal membrane. SCD uses oxygen and electrons from reduced cytochrome b5 [MEDLINE:91056050],[MEDLINE:87008535] to catalyse the insertion of a cis double bond between carbons 9 and 10 of a spectrum of fatty acids [MEDLINE:89034247],[MEDLINE:91056050],[MEDLINE:87008535]. The preferred substrates of SCD are palmitoyl-CoA and stearoyl-CoA, which are converted to palmitoleic (16:1) and oleic (18:1) acids respectively [MEDLINE:89034247],[MEDLINE:87008535]. These unsaturated molecules are the major storage form of fatty acids (as triacylglycerols) in adipocytes [MEDLINE:89034247].

\ \ iron ion binding activity ; GO:0005506 membrane ; GO:0016020 fatty acid biosynthesis ; GO:0006633 20232 IPR001521

Opsins are the photoreceptors of animal retinas PUB00005667: vertebrate rhodopsinis found in rod cells and mediates scotopic vision; red, green and blue\ opsins are found in cone cells and mediate photopic vision. Blue-sensitive\ opsin has an absorption maximum at 420nm. The ratio of blue cones to rods\ is ~1:200 PUB00005667. Deficiency in blue opsin results in tritanopia colour\ blindness.

\ \ \ rhodopsin-like receptor activity ; GO:0001584 integral to membrane ; GO:0016021 phototransduction ; GO:0007602 20230 IPR001519 Ferritin is one of the major non-heme iron storage proteins in animals, plants, and microorganisms [MEDLINE:87190419], [MEDLINE:87297437]. It consists of a mineral core of hydrated ferric oxide, and a multi-subunit protein shell\ which encloses the former and assures its solubility in an aqueous\ environment.\

In animals the protein is mainly cytoplasmic and there are generally two or\ more genes that encodes for closely related subunits (in mammals there are two\ subunits which are known as H(eavy) and L(ight)). In plants ferritin is found\ in the chloroplast [MEDLINE:91009326].

\ \ ferric iron binding activity ; GO:0008199 \N iron ion homeostasis ; GO:0006879 20231 IPR001520

The 5HT4 receptor is found in neurons in the CNS, with highest levels in\ colliculus and hippocampus . In the periphery, it is found in myenteric\ neurons in ileum and in smoothe muscle (e.g., rat oesophagus and heart\ muscle). The receptor is linked to the adenylyl cyclase pathway via\ Gs PUB00005889.

\ \ \N integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20229 IPR001518

Argininosuccinate synthase (EC: 6.3.4.5) (AS) is a urea cycle enzyme that catalyzes the penultimate step in arginine biosynthesis: the ATP-dependent ligation of citrulline to aspartate to form argininosuccinate, AMP and pyrophosphate [MEDLINE:91071613], [MEDLINE:88257029].

In humans, a defect in the AS gene causes citrullinemia, a genetic disease\ characterized by severe vomiting spells and mental retardation.

AS is a homotetrameric enzyme of chains of about 400 amino-acid residues. An arginine seems to be important for the enzyme's catalytic mechanism. The sequences of AS from various prokaryotes, archaebacteria and eukaryotes show significant similarity.

\ \ ATP binding activity ; GO:0005524 \N arginine biosynthesis ; GO:0006526 20227 IPR001516

This domain represents an N-terminal extension of IPR001750. It contains NADH-Ubiquinone chain 5 and eubacterial chain L.

This domain is found in the NADH:ubiquinone oxidoreductase (complex I) which catalyses the transfer of two electrons from NADH to ubiquinone in a reaction that is associated with proton translocation across the membrane [MEDLINE:93110040].

\ \ NADH dehydrogenase (ubiquinone) activity ; GO:0008137 \N oxidative phosphorylation, NADH to ubiquinone ; GO:0006120 20228 IPR001517

Barley yellow dwarf virus (BYDV) can be separated into two groups based on serological relationships, presumably governed by the viral capsid structure [MEDLINE:91108372]. Coding regions of coat proteins have been identified for the MAV-PS1, P-PAV (group 1) and NY-RPV (group 2) isolates of BYDV. Group 1 proteins show 71% sequence similarity to each other, 51% similarity to those of group 2, and a high degree of similarity to those from other luteoviruses (including coat proteins from beet western yellow virus (BWYV)\ \ \ [MEDLINE:89057523] and potato leafroll virus (PLRV)\ \ \ \ [MEDLINE:89279259], [MEDLINE:89279282]).

Among luteovirus coat protein sequences in general, several highly conserved domains can be identified, while other domains differentiate group 1 isolates from group 2 and other luteoviruses. Sequence comparisons between the genomes of PLRV, BWYV and BYDV have revealed ~65% protein sequence similarity between the capsid proteins of BWYV and PLRV and ~45% similarity between BYDV and PLRV\ \ \ \ [MEDLINE:91108372]. The N-terminal regions of these sequences, like those of many plant virus capsid proteins, is highly basic. These regions may be\ involved in protein-RNA interaction.

\ \ structural molecule activity ; GO:0005198 viral capsid ; GO:0019028 \N 20226 IPR001515

\ \ \

The L32e family consists of proteins that have 135 to 240 amino-acid residues.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 20224 IPR001513

In addition to their role in energy metabolism, purines (especially\ adenosine and adenine nucleotides) produce a wide range of pharmacological\ effects mediated by activation of cell surface receptors PUB00005868. Distinct\ receptors exist for adenosine. In the periphery, the main effects of\ adenosine include vasodilation, bronchoconstriction, immunosuppresion,\ inhibition of platelet aggregation, cardiac depression, stimulation of\ nociceptive afferents, inhibition of neurotransmitter release and\ inhibition of the release of other factors, e.g. hormones PUB00005868. In the CNS,\ adenosine exerts a pre- and post-synaptic depressant action, reducing motor\ activity, depressing respiration, inducing sleep and relieving anxiety. The\ physiological role of adenosine is thought to be to adjust energy demands\ in line with oxygen supply. Many of the clinical actions of methylxanthines\ are thought to be mediated through antagonism of adenosine receptors. Four\ subtypes of receptor have been identified, designated A1, A2A, A2B and A3.

\ \

A2A receptors have a limited distribution in the brain and are found in the\ striatum, olfactory tubercle and nucleus accumbens. In the periphery, A2\ receptors mediate vasodilation, immunosuppression, inhibition of platelet\ aggregation and gluconeogenesis PUB00005868. The receptors activate adenylyl\ cyclase through Gs.

\ \ A2A adenosine receptor activity, G-protein coupled ; GO:0001611 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20225 IPR001514

It has been shown [MEDLINE:90066488], [MEDLINE:90256750], [MEDLINE:93376499] that small subunits of about 30 to 40 kDa found in archebacterial and all three types of eukaryotic polymerases are highly conserved. Subunits known to belong to this family are:

Budding yeast RPC5 subunit (or RPC40) from RNA polymerases I and III.
Mammalian RPA40 from RNA polymerase I.
Budding yeast RPB3 subunit from RNA polymerase II.
Fission yeast rpb3 subunit from RNA polymerase II.
Mammalian RPB3 (or RPB33) (gene POLR2C) from RNA polymerase II.
Conjugation stage-specific protein cnjC from Tetrahymena thermophila, which may be a stage-specific RNA polymerase subunit.
Archebacterial RNA polymerase subunit D (gene rpoD).

\ \ DNA-directed RNA polymerase activity ; GO:0003899 nucleus ; GO:0005634 transcription ; GO:0006350 20222 IPR001510

Synonym(s): Poly(ADP) polymerase (PARP)

NAD(+) ADP-ribosyltransferase(EC: 2.4.2.30)[MEDLINE:88038784], [MEDLINE:94287450] is a eukaryotic enzyme that catalyzes the covalent attachment of ADP-ribose units from NAD(⁺) to various nuclear acceptor proteins. This post-translational modification of nuclear proteins is dependent on DNA. It appears to be involved in the regulation of various important cellular processes such as differentiation, proliferation and tumor transformation as well as in the regulation of the molecular events involved in the recovery of the cell from DNA damage.

Structurally, NAD(+) ADP-ribosyltransferase consists of three distinct domains: an N-terminal zinc-dependent DNA-binding domain, a central automodification domain and a C-terminal NAD-binding domain.

The DNA-binding region contains a pair of PARP-type zinc finger domains which have been shown to bind DNA in a zinc-dependent manner. The PARP-type zinc finger domains seem to bind specifically to single-stranded DNA and to act as a DNA nick sensor. DNA ligase III [MEDLINE:95280920] contains, in its N-terminal section, a single copy of a zinc finger highly similar to those of PARP.

\ \ DNA binding activity ; GO:0003677 nucleus ; GO:0005634 \N 20223 IPR001512

mRNA for the SS4 receptor is present in high levels in the pituitary but\ is absent from the brain and peripheral tissues . The receptors inhibit\ adenylyl cyclase through a pertussis-toxin-sensitive G-protein, probably\ belonging to the Gi/Go class PUB00005902.

\ \ \ somatostatin receptor activity ; GO:0004994 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20221 IPR001509 This family of proteins utilise NAD as a cofactor. The proteins in this family use nucleotide-sugar substrates for a variety of chemical reactions [MEDLINE:97317070].\ enzyme activity ; GO:0003824 \N nucleotide-sugar metabolism ; GO:0009225 20219 IPR001507

A large domain, containing around 260 amino acids, has been recognised in a variety of receptor-like eukaryotic glycoproteins [MEDLINE:92209715]. All of these proteins are mosaic proteins composed of various domains and that all have a large extracellular region followed by either a transmembrane region and a very short cytoplasmic region or by a GPI-anchor. The domain common to all these proteins is located in the C-terminal portion of the extracellular region, and contains 8 conserved Cys residues, which are probably involved in disulphide bond formation.

CD105 (also called endoglin) is the regulatory component of the TGF- receptor complex. It is a modulator of cellular responses to TGF- 1.

\ \

CD molecules are leucocyte antigens on cell surfaces. CD antigens nomenclature is updated at http://www.ncbi.nlm.nih.gov/PROW/guide/45277084.htm \

\ \ \N \N \N 20220 IPR001508

N-Methyl-D-aspartate (NMDA) receptors are members of the glutamate receptorchannel superfamily, which mediate most of the fast excitory synaptic\ transmissions in the central nervous system. The superfamily consists of 3\ subtypes: kainate receptors, AMPA receptors and NMDA receptors. The NMDA\ receptor is highly permeable to calcium ions and plays a key role in the\ plasticity of synapses, which is believed to underlie memory and learning,\ as well as the development of the nervous system. Abnormal activation has\ been suggested to lead to neuronal cell death observed in many acute and\ chronic disorders such as ischemia, stroke, Alzheimer's disease, and\ Huntingdon's disease [MEDLINE:92192280].

NMDA receptors possess 4 transmembrane (TM) helical domains in the C-terminal half of the sequence and require both glycine and glutamate for\ activation, resulting in influx of calcium ions into the cell [MEDLINE:92192280]. The\ receptors can also be activated by polyamine, they can be blocked by\ magnesium ions, inhibited by zinc ions, and modulated by arachidonic acid.\ Other non-NMDA glutamate receptors (e.g., kainate) are structurally similar\ to NMDA receptors, but are functionally distinct, possibly as a result of\ amino acid substitutions at important positions in the sequence.

\ \ \ glutamate-gated ion channel activity ; GO:0005234 membrane ; GO:0016020 ion transport ; GO:0006811 20218 IPR001506

Synonym(s): Astacus proteinase, Crayfish small-molecule proteinase

The astacin (EC: 3.4.24.21) family of metalloendopeptidases encompasses a range of proteins\ found in hydra to humans, in mature and developmental systems [MEDLINE:95400192]. Their\ functions include activation of growth factors, degradation of polypeptides,\ and processing of extracellular proteins [MEDLINE:95400192]. The proteins are synthesised\ with N-terminal signal and pro-enzyme sequences, and many contain multiple\ domains C-terminal to the protease domain. They are either secreted from\ cells, or are associated with the plasma membrane.

\ \

The astacin molecule adopts a kidney shape, with a deep active-site cleft\ between its N- and C-terminal domains [MEDLINE:93188025]. The zinc ion, which lies at the\ bottom of the cleft, exhibits a unique penta-coordinated mode of binding,\ involving 3 histidine residues, a tyrosine and a water molecule (which is\ also bound to the carboxylate side chain of Glu93) [MEDLINE:93188025]. The N-terminal\ domain comprises 2 -helices and a 5-stranded -sheet. The overall\ topology of this domain is shared by the archetypal zinc-endopeptidase\ thermolysin. Astacin protease domains also share common features with\ serralysins, matrix metalloendopeptidases, and snake venom proteases; they\ cleave peptide bonds in polypeptides such as insulin B chain and bradykinin,\ and in proteins such as casein and gelatin; and they have arylamidase\ activity [MEDLINE:95400192].

\ \ astacin activity ; GO:0008533 \N proteolysis and peptidolysis ; GO:0006508 20217 IPR001505

The Cu(A) centre contains a mixed valence binuclear copper binding site formed of about 50 amino acids containing two cysteines and histidines and one glutamate and methionine [MEDLINE:96029614]. The Cu(A) centre has been identified in subunit II of cytochrome c oxidase and nitrous oxide reductase [MEDLINE:92371427], [MEDLINE:92380183].

Cytochrome c oxidase (EC: 1.9.3.1) [MEDLINE:83257235], [MEDLINE:94364936] is an oligomeric enzymatic complex which is a component of the respiratory chain and is involved in the transfer of electrons from cytochrome c to oxygen. In eukaryotes this enzyme complex is located in the mitochondrial inner membrane; in aerobic prokaryotes it is found in the plasma membrane. The enzyme complex consists of 3-4 subunits (prokaryotes) to up to 13 polypeptides (mammals). Subunit II (see IPR002429) transfers the electrons from cytochrome c to the catalytic subunit I. It provides the substrate-binding site and contains a Cu(A) centre that is probably the primary acceptor in cytochrome c oxidase.

Nitrous oxide reductase (EC: 1.7.99.6) (gene nosZ) of Pseudomonas is part of the bacterial respiratory system which is activated under anaerobic conditions in the presence of nitrate or nitrous oxide. NosZ is a periplasmic homodimer that contains a dinuclear copper center, probably located in a 3-dimensional fold similar to the cupredoxin-like fold that has been suggested for the copper-binding site of subunit II [MEDLINE:92371427].

\ \ copper ion binding activity ; GO:0005507 \N \N 20216 IPR001504

\ \ bradykinin receptor activity ; GO:0004947 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20214 IPR001501

Hydrogenases are enzymes that catalyze the reversible activation of hydrogen and which occur widely in prokaryotes as well as in some eukaryotes. There are various types of hydrogenases, but all of them seem to contain at least one iron-sulfur cluster. They can be broadly divided into two groups: hydrogenases containing nickel and, in some cases, also selenium (the [NiFe] and [NiFeSe] hydrogenases) and those lacking nickel (the [Fe] hydrogenases).

The [NiFe] and [NiFeSe] hydrogenases are heterodimer that consist of a small subunit that contains a signal peptide and a large subunit. All the known large subunits seem to be evolutionary related [MEDLINE:90202716]; they contain two Cys-x-x-Cys motifs; one at their N-terminal end; the other at their C-terminal end. These four cysteines are involved in the binding of nickel [MEDLINE:95157629]. In the [NiFeSe] hydrogenases the first cysteine of the C-terminal motif is a selenocysteine which has experimentally been shown to be a nickel ligand [MEDLINE:89098869].

\ \ nickel ion binding activity ; GO:0016151 \N electron transport ; GO:0006118 20215 IPR001503

Glycosyltransferase family 10 CAZY:GT_10).

\ \

The galactoside 3-fucosyltransferases display similarities with the -2 and -6-fucosyltranferases PUB00007032. The biosynthesis of the carbohydrate antigen sialyl Lewis X (sLe(x)) is dependent on the activity of an galactoside 3-fucosyltransferase. This enzyme catalyses the transfer of fucose from GDP--fucose to the 3-OH of N-acetylglucosamine present in lactosamine acceptors [MEDLINE:97194928].

\ \ fucosyltransferase activity ; GO:0008417 membrane ; GO:0016020 protein amino acid glycosylation ; GO:0006486 20213 IPR001500 The name 'lipocalin' has been proposed [MEDLINE:87305323] forthe larger protein family, but cytosolic fatty-acid binding proteins are also included. The sequences of most members of the family, the core or kernal lipocalins, are characterized by\ three short conserved stretches of residues, while others, the outlier lipocalin group, share only one or two of these\ [MEDLINE:92028985], [MEDLINE:93264947]. Proteins known to belong to this family include

-1-microglobulin (protein HC);

-1-acid glycoprotein (orosomucoid) [MEDLINE:89113403]; aphrodisin; apolipoprotein D;

-lactoglobulin; complement\ component C8 gamma chain [MEDLINE:91187018]; crustacyanin [MEDLINE:91224133]; epididymal-retinoic acid binding protein\ (E-RABP) [MEDLINE:94348866]; insectacyanin; odorant-binding protein (OBP); human pregnancy-associated endometrial

-2\ globulin; probasin (PB), a rat prostatic protein; prostaglandin D synthase (EC: 5.3.99.2) [MEDLINE:92151289]; purpurin; Von\ Ebner's gland protein (VEGP) [MEDLINE:94237155]; and lizard epididymal secretory protein IV (LESP IV) [MEDLINE:93252911].\

Alpha-1-acid glycoprotein (orosomucin) (A1AG) is a major serum glycoprotein\ of unknown physiological function PUB00003097. It has been implicated in cellular\ inflammation by increasing tissue factor expression and tumour necrosis\ factor secretion of monocytes. The protein is associated with five\ asparaginyl-linked complex oligosaccaride chains, the proportions and\ identities of which are altered in several physiological and pathological\ conditions PUB00003097. A1AG is also clinically important as a non-specific drug\ binder in serum [MEDLINE:89113403]. It has recently been shown to bind to\ thalidomide, which may be involved in its inhibition of tumor necrosis\ factor production [MEDLINE:96353854].

\ \ \N \N \N 20212 IPR001499

The STE3 gene of Saccharomyces cerevisiae is the cell-surface receptor that binds the\ 13-residue lipopeptide a-factor. Several related fungal pheromone receptor\ sequences are known: these include pheromone B 1 and B 3, and\ pheromone B 1 receptors from Schizophyllum commune; pheromone receptor\ 1 from Ustilago hordei; and pheromone receptors 1 and 2 from Ustilago maydis.\ Members of the family share about 20% sequence identity.

\ \ mating-type factor pheromone receptor activity ; GO:0004932 membrane ; GO:0016020 \N 20211 IPR001498 This group contains a number of uncharacterised proteins from yeast and bacteria.\ molecular_function unknown ; GO:0005554 \N \N 20209 IPR001497

Synonym(s): 6-O-methylguanine-DNA methyltransferase, O-6-methylguanine-DNA-alkyltransferase

The repair of DNA containing O6-alkylated\ guanine is carried out by DNA-[protein]-cysteine S-methyltransferase (EC: 2.1.1.63). The major mutagenic and carcinogenic effect of methylating agents in DNA is the formation of O6-alkylguanine. The\ alkyl group at the O-6 position is transferred to a cysteine residue in the\ enzyme [MEDLINE:89024568]. This is a suicide reaction since the enzyme is irreversibly inactivated\ and the methylated protein accumulates as a dead-end product. Most, but not\ all of the methyltransferases are also able to repair O-4-methylthymine. DNA-[protein]-cysteine S-methyltransferases are widely distributed and are found in various prokaryotic and eukaryotic sources [MEDLINE:92253409].

\ \ methylated-DNA-[protein]-cysteine S-methyltransferase activity ; GO:0003908 \N DNA repair ; GO:0006281 20210 IPR001497

Synonym(s): 6-O-methylguanine-DNA methyltransferase, O-6-methylguanine-DNA-alkyltransferase

\ \ methylated-DNA-[protein]-cysteine S-methyltransferase activity ; GO:0003908 \N DNA repair ; GO:0006281 20206 IPR001494

The exchange of macromolecules between the nucleus and cytoplasm takes place through nuclear pore complexes. Active transport of large molecules through these pore complexes require carrier proteins that shuttle between the two components. Members of the importin-/karyopherin- family subunits act as carriers for many nuclear trafficking processes PUB00009772. Importin- binds cargo in the cytoplasm, the complex moves through the pore and cargo is released in the nucleus on binding of Ran-GTP to importin-.

Importin- is a helicoidal molecule constructed from 19 HEAT repeats, each formed from a pair of -helices. Many nuclear pore proteins contain FG sequence repeats, and interactions between\ repeats containing FxFG or GLFG cores and transport factors have been demonstrated. The crystal structure of residues 1-442 of importin- bound to a\ GLFG peptide indicates that this repeat core binds to the same primary site as FxFG cores, suggesting that functional differences between different repeats probably\ arise from differences in their spatial organization.

\ \ protein transporter activity ; GO:0008565 cytoplasm ; GO:0005737 protein-nucleus import, docking ; GO:0000059 20208 IPR001496

The SOCS box was first identified in SH2-domain-containing proteins of the suppressor of cytokines signaling (SOCS) family [MEDLINE:97345633] but was later also found in:

the WSB (WD-40-repeat-containing proteins with a SOCS box) family,
the SSB (SPRY domain-containing proteins with a SOCS box) family,
the ASB (ankyrin-repeat-containing proteins with a SOCS box) family,
and ras and ras-like GTPases [MEDLINE:98081836].

The SOCS box found in these proteins is an about 50 amino acid carboxy-terminal domain composed of two blocks of well-conserved residues separated by between 2 and 10 nonconserved residues [MEDLINE:98081836]. The C-terminal conserved region is an L/P-rich sequence of unknown function, whereas the N-terminal conserved region is a consensus BC box [MEDLINE:99088036], which binds to the Elongin BC complex [MEDLINE:99088036], [MEDLINE:99162559]. It has been proposed that this association could couple bound proteins to the ubiquitination or proteasomal compartments [MEDLINE:99162559].

\ \ \N \N intracellular signaling cascade ; GO:0007242 20207 IPR001495 In vivo, protein kinase C exhibits a preference for the phosphorylation of serine or threonine residues found close to a C-terminal basic residue [MEDLINE:87054002], [MEDLINE:86008331].\ The presence of additional basic residues at the N or C terminus of the\ target amino acid enhances the Vmax and Km of the phosphorylation reaction. \

Note: No protein matches are shown due to the low specificity of this rule.

\ \ \N \N \N 20204 IPR001492 Flagellin is the subunit which polymerizes to form the filaments of bacterial flagella. This N-terminal domain and the C-terminal IPR001029 always occur together.\ \ structural molecule activity ; GO:0005198 flagellar filament (sensu Bacteria) ; GO:0009420 ciliary/flagellar motility ; GO:0001539 20205 IPR001493 Presenilins are polytopic transmembrane (TM) proteins, mutations in whichare associated with the occurrence of early-onset familial Alzheimer's\ disease, a rare form of the disease that results from a single-gene\ mutation \ [MEDLINE:99007742], [MEDLINE:98180715]. \ The physiological functions of\ presenilins are unknown, but they may be related to developmental signalling,\ apoptotic signal transduction, or processing of selected proteins, such as the

-amyloid precursor protein(

In humans, there are two presenilin genes (PS1 and PS2)that share 67% amino acid identity,\ the greatest divergence between the two falling in the N-terminus and in the\ large hydrophilic loop towards the C-terminus of each molecule. Six to\ nine TM domains are predicted for each, and biochemical analysis has\ demonstrated that their C-termini are cytoplasmic; but the orientation of\ their N-termini and large hydrophilic loops remains to be resolved. They\ are expressed in almost all tissues, including the brain and, at a cellular\ level, they have been localised to the nuclear envelope, endoplasmic\ reticulum and Golgi apparatus.

Presenilin 2 (unlike presenilin 1) has been found to have pro-apoptotic \ actions, which are enhanced by the mutations that have been characterised\ in this protein; however, when compared to PS1 gene mutations, they are\ thought to be responsible for only a small percentage of early-onset\ familial Alzheimer's disease cases (ca. 1%) [MEDLINE:99007745].

\ \ \N membrane ; GO:0016020 intracellular signaling cascade ; GO:0007242 20203 IPR001491 Thrombomodulin is an endothelial cell thrombin receptor that converts thrombin from a procoagulant to an anticoagulant enzyme [MEDLINE:94029900], [MEDLINE:89008498]. Thrombomodulin forms a 1:1 stoichiometric complex with thrombin that is responsible for the conversion of\ protein C to the activated protein CA. Protein CA scissions the activated cofactors of the coagulation mechanism, factors VA and VIIIA, and thereby reduces the amount of thrombin generated.\

\ The thrombin-bound structures of peptide fragments from the fifth EGF-like\ domain of thrombomodulin have been determined by NMR and transferred NOE\ spectroscopy [MEDLINE:96276211]. The peptides assume an EGF-like structure, with an anti-parallel -sheet, which shows structural resilience in accommodating \ different numbers of residues within its disulphide loop. The key\ contacts with thrombin are hydrophobic interactions between the side chains\ of residues Ile 414 and Ile 424 of thrombomodulin and a hydrophobic pocket\ on the thrombin surface . The unique -sheet structures of the bound\ peptides are specified by the presence of disulphide bridges; corresponding\ linear thrombomodulin fragments fold into sheet structures with different\ backbone topologies.

\ \ transmembrane receptor activity ; GO:0004888 membrane ; GO:0016020 blood coagulation ; GO:0007596 20202 IPR001490 The genome polyprotein contains: caspid protein C, envelope glycoproteins E1 and E2, protein P7, nonstructural protein NS2, protease/helicase NS3, nonstructural proteins NS4A and NS4B (this family), NS5A and NS5B.\

The small proteins NS2A, NS2B, NS4A and NS4B are hydrophobic, suggesting a possible membrane-related function [MEDLINE:97368158].\ It is known that NS4B interacts with NS4A and NS3 to form a large\ replicase complex to direct the viral RNA replication [MEDLINE:97404652]. NS3 and NS5 may also play a role in the viral RNA replication.

\ \ \N \N \N 20201 IPR001489

Prokaryotic heat-stable enterotoxins are responsible for acute diarrhea [MEDLINE:87191003]. The active toxin is a short peptide of around twenty residues which contains\ six cysteines involved in three disulfide bonds.

\ \ toxin activity ; GO:0015070 extracellular ; GO:0005576 pathogenesis ; GO:0009405 20196 IPR001482 A number of bacterial proteins, some of which are involved in a general secretion pathway (GSP) for the export of proteins (also called the type II\ pathway) belong to this group [MEDLINE:93174466], [MEDLINE:95020523]. These proteins\ are probably located in the cytoplasm and, on the basis of the presence of a\ conserved P-loop region IPR001687, bind ATP.\ \ ATP binding activity ; GO:0005524 intracellular ; GO:0005622 transport ; GO:0006810 20197 IPR001483 Urotensin II, a small peptide that contains a disulfide bridge, was originally isolated from the caudal\ portion of the spinal cord of teleost and elasmobranch fish [MEDLINE:92319231]. The peptide has also\ been found in the brain of frogs\ \ \ \ [MEDLINE:93075134]. Urotensin II seems to be involved in smooth\ muscle stimulation.\ \ hormone activity ; GO:0005179 extracellular ; GO:0005576 \N 20198 IPR001484 Pyrokinins are insect neuropeptides that mediate visceral muscle contractile activity (myotropic activity) [MEDLINE:91239599]. They share an amide-blocked C-terminal pentapeptide sequence that is\ sufficient to elicit a significant myotropic activity. Pheromonotropin which controls sex\ pheromone production also belongs to this group [MEDLINE:92134266].\ \ neuropeptide hormone activity ; GO:0005184 \N muscle contraction ; GO:0006936 20199 IPR001486 Globins are heme-containing proteins involved in binding and/or transporting oxygen . Almost all globins belong to a large family IPR000971, the\ only exceptions are the following proteins which form a family of their own PUB00001080, PUB00001080. \ These proteins contain a conserved histidine which could be involved in heme-\ binding.\ \ \N \N oxygen transport ; GO:0015671 20195 IPR001481

EP3 receptors mediate contraction in a wide range of smooth muscles,\ including gastrointestinal and uterine PUB00005901. They also inhibit neurotransmitter release in central and autonomic nerves through a presynaptic action,\ and inhibit secretion in glandular tissues (e.g., acid secretion from\ gastric mucosa, and sodium and water reabsorption in the kidney) . mRNA\ is found in high levels in the kidney and uterus, and in lower levels in\ the brain, thymus, lung, heart, stomach and spleen. The receptors activate\ adenylate cyclase via an uncharacterised G-protein, probably of the Gi/Go\ class PUB00005901.

Sequence analysis shows the EP3 receptors to fall into distinct classes,\ based on their N- and C-terminal and loop signatures. For convenience, we\ have designated these classes types 1 to 3.

\ \ prostaglandin E receptor activity ; GO:0004957 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20200 IPR001487 Bromodomains are found in a variety of mammalian, invertebrate and yeast DNA-binding proteins [MEDLINE:92285152]. Bromodomains can interact withacetylated lysine [MEDLINE:97318593].\ In some proteins, the classical bromodomain has diverged to such an\ extent that parts of the region are either missing or contain an insertion\ (e.g., mammalian protein HRX, Caenorhabditis elegans hypothetical protein ZK783.4, yeast protein YTA7). The bromodomain may occur as a single copy, or in duplicate.\

The precise function of the domain is unclear, but it may be involved in\ protein-protein interactions and may play a role in assembly or activity\ of multi-component complexes involved in transcriptional activation [MEDLINE:96022440].

\ \ \N \N \N 20191 IPR001477 The mumps virus SH protein is a membrane protein and not essential for virus growth [MEDLINE:97076225]. Its function is unknown.\ \ molecular_function unknown ; GO:0005554 membrane ; GO:0016020 \N 20192 IPR001478 PDZ domains are found in diverse signaling proteins in bacteria, yeast,plant, insect and vertebrate. Many PDZ\ domain-containing proteins appear to be localised to highly specialised submembranous\ sites, suggesting their participation in cellular junction formation, receptor or channel\ clustering, and intracellular signalling events [MEDLINE:97194073], [MEDLINE:97348826].\ \ \N \N intracellular signaling cascade ; GO:0007242 20193 IPR001479 Pyrrolo-quinoline quinone (PQQ) is a redox coenzyme, which serves as a cofactor for a number of enzymes (quinoproteins) and particularly for some bacterial\ dehydrogenases [MEDLINE:89372803], [MEDLINE:90020466]. A number of bacterial quinoproteins belong to this family.\ \ \N periplasmic space (sensu Gram-negative Bacteria) ; GO:0030288 electron transport ; GO:0006118 20194 IPR001480 Members of this family are plant lectins. Curculin is a sweet-tasting and taste-modifying protein from the fruits of Curculigo latifolia. The three mannose-binding sites are devoid of mannose-binding activity [MEDLINE:97238475]. Other members of this family are mannose specific and have diverse functions. The lectin of the saffron plant (Crocus sativus L.) specifically interacts with a yeast mannan and is a major corm protein specifically expressed in this organ [MEDLINE:20156529].

The actin-binding\ and vesicle-associated protein comitin exhibits a mannose-specific\ lectin activity and may have a role in cell motility. It binds to vesicle membranes via mannose residues and, by way of its interaction with actin, links these membranes to the cytoskeleton.

\ \ sugar binding activity ; GO:0005529 \N \N 20188 IPR001474

GTP cyclohydrolase I (EC: 3.5.4.16) catalyzes the biosynthesis of formic acid and dihydroneopterin triphosphate from GTP. This reaction is the first step in\ the biosynthesis of tetrahydrofolate in prokaryotes, of tetrahydrobiopterin in\ vertebrates, and of pteridine-containing pigments in insects.\ The\ comparison of the sequence of the enzyme from bacterial and eukaryotic sources\ shows that the structure of this enzyme has been extremely well conserved\ throughout evolution [MEDLINE:95352066].

\ \ GTP cyclohydrolase I activity ; GO:0003934 \N biosynthesis ; GO:0009058 20189 IPR001475

The sulphonylurea receptor (SUR) is a member of the ATP-binding cassettesuperfamily that associates with certain K⁺ channel inward rectifier\ subunits to form ATP-sensitive K⁺ channels (KATP channels) [MEDLINE:95232532], [MEDLINE:96072967]. These are\ a family of K⁺ channels that are inhibited by intracellular ATP, which can\ couple metabolic state to cell excitability. Their presence on pancreatic\ islet cells allows the cells to function as metabolic sensors,\ regulating insulin release in relation to glucose metabolism. Furthermore,\ SUR is the site of action for the sulphonylurea oral hypoglycaemic agents\ that are used widely for the treatment of non-insulin dependent diabetes\ mellitus. When these agents bind to the sulphonlyurea receptor, they reduce\ KATP channel activity, stimulating insulin release.

\ \

As mentioned, SUR is a member of the ATP-binding cassette superfamily\ (traffic adenosine triphsophatase superfamily), other members including the\ P-glycoprotein multi-drug resistance (MDR) proteins and the cystic\ fibrosis transconductance regulators (CFTRs). This raises the possibility\ that SUR may transport some endogenous substance, as yet unidentified.\ Two closely related genes have been found to encode the sulphonylurea\ receptors, SUR1 and SUR2, there being three splice variants of the second\ form [MEDLINE:98346877]. They are thought to contain 13-17 transmembrane (TM) domains,\ with two potential nucleotide binding folds, and a large number of possible\ protein kinase A, or C phosphorylation sites.

\ \

Comparison of the properties of cloned and wild-type KATP channels suggests\ that splice variants of SUR2 (termed SUR2A and SUR2B) may form the cardiac\ and smooth muscle KATP channel isoforms, when combined with the inward\ rectifier subunit Kir 6.2.

\ \ sulfonylurea receptor activity ; GO:0008281 membrane ; GO:0016020 potassium ion transport ; GO:0006813 20190 IPR001476

The chaperonins are 'helper' molecules required for correct folding and subsequent assembly of some proteins [MEDLINE:92256809]. These are required for normal cell growth [MEDLINE:88232881], and are stress-induced, acting to stabilise or protect disassembled \ polypeptides under heat-shock conditions. Type I chaperonins present in eubacteria, mitochondria and chloroplasts require the concerted action of 2 proteins, chaperonin 60 (cpn60) and chaperonin 10 (cpn10) [MEDLINE:22241614].

The 10 kDa chaperonin (cpn10 - or groES in bacteria) exists as a ring-shaped oligomer of between six to eight identical subunits, while the 60 kDa \ chaperonin (cpn60 - or groEL in bacteria) forms a structure comprising 2 \ stacked rings, each ring containing 7 identical subunits [MEDLINE:88232881]. These ring \ structures assemble by self-stimulation in the presence of Mg²⁺-ATP. The \ central cavity of the cylindrical cpn60 tetradecamer provides as isolated environment for protein folding whilst cpn-10 binds to cpn-60 and synchronizes the release of the folded protein in an Mg²⁺-ATP dependent manner [MEDLINE:92283754]. The binding of cpn10 to \ cpn60 inhibits the weak ATPase activity of cpn60.

Escherichia coli GroES has also been shown to bind ATP cooperatively, and \ with an affinity comparable to that of GroEL [MEDLINE:94050183]. Each GroEL subunit contains three structurally distinct domains: an apical, an intermediate and an equatorial domain. The apical\ domain contains the binding sites for both GroES and the unfolded protein substrate. The equatorial domain contains the ATP-binding site and most of the oligomeric\ contacts. The intermediate domain links the apical and equatorial domains and transfers allosteric information between them. The GroEL oligomer is a tetradecamer,\ cylindrically shaped, that is organized in two heptameric rings stacked back to back. Each GroEL ring contains a central cavity, known as the 'Anfinsen cage',\ that provides an isolated environment for protein folding. The identical 10 kDa subunits of GroES form a dome-like heptameric oligomer in solution. ATP binding to GroES may\ be important in charging the seven subunits of the interacting GroEL ring\ with ATP, to facilitate cooperative ATP binding and hydrolysis for \ substrate protein release.

\ \ \N \N \N 20185 IPR001471

Pathogenesis-related genes transcriptional activator binds to the GCC-box pathogenesis-related promoter element and activates the plant's defense genes. Ethylene, chemically the simplest plant hormone, participates in a \ number of stress responses and developmental processes: e.g., fruit\ ripening, inhibition of stem and root elongation, promotion of seed\ germination and flowering, senescence of leaves and flowers, and sex\ determination [MEDLINE:95249975]. DNA sequence elements that confer ethylene \ responsiveness have been shown to contain two 11bp GCC boxes, which\ are necessary and sufficient for transcriptional control by ethylene.\ Ethylene responsive element binding proteins (EREBPs) have now been\ identified in a variety of plants. The proteins share a similar domain\ of around 59 amino acids, which interacts directly with the GCC box in\ the ERE.

\ \ transcription factor activity ; GO:0003700 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 20186 IPR001472 WARNING: This profile is a frequent hit producer. In theabsence of other evidence (experimental, co-occurrence with\ DNA-binding domains, etc.) a match to this entry should\ only be taken as a weak indication of nuclear \ localization. \

Note: No protein matches are shown due to the low specificity of this rule.

\ \ \N \N \N 20187 IPR001473 Clathrin is the major protein of the polyhedral coat of coated pits and vesicles. In yeast, it is involved in the retention of proteins in an intracellular membrane compartment, probably the trans-golgi. Clathrin has a triskeleton structure composed of three heavy chains and three light chains that are the basic subunits of the clathrin coat. The C-terminal domain forms the hub of the triskeleton and contains the trimerization domain and the light chain binding domain involved in the assembly of the clathrin lattice.\

The N-terminal of the heavy chain\ is known as the globular domain, and is composed of seven\ repeats which form a propeller [MEDLINE:99043510].

\ \ \N \N \N 20184 IPR001470 Chlorosomes, which are attached to the inner surface of the cytoplasmic membrane, consist of four polypeptides and associated pigments and lipids.\ The principal light-harvesting pigment of the green filamentous bacterium\ Chloroflexus aurantiacus is bacteriochlorophyll (Bchl) c. This pigment is\ either bound to, or constrained by, a small approximately 80-residue\ polypeptide designated Bchlc-binding protein. In C.aurantiacus, a C-terminal\ extension is believed to play a role in proper incorporation of the protein\ during chlorosome assembly [MEDLINE:90330558]. The protein has a high degree of similarity\ to Bchlc-binding proteins of other photosynthetic bacteria.\ \ \N \N photosynthesis ; GO:0015979 20183 IPR001469

\ \

\ \ \ \ \ \ \

This family represents subunits called delta and epsilon in human and metazoan species. In bacterial species the delta (D) subunit is the equivalent to the Oligomycin sensitive subunit (OSCP) in metazoans. The E. coli delta and metazoan OSCP subunits are found in Pfam family OSCP (OSCP).

\ \ hydrogen-transporting two-sector ATPase activity ; GO:0003936 \N proton transport ; GO:0015992 20182 IPR001469

\ \

\ \ \ \ \ \ \

\ \ hydrogen-transporting two-sector ATPase activity ; GO:0003936 \N proton transport ; GO:0015992 20181 IPR001468

Indole-3-glycerol phosphate synthase (EC: 4.1.1.48) (IGPS) catalyzes the fourth step in the biosynthesis of tryptophan, the ring closure of 1-(2-carboxy-phenylamino)-1-deoxyribulose into indol-3-glycerol-phosphate. In some bacteria, IGPS is a single chain enzyme. In others, such as Escherichia coli, it is the N-terminal domain of a bifunctional enzyme that also catalyzes N-(5'-phosphoribosyl)anthranilate isomerase (EC: 5.3.1.24) (PRAI) activity (see IPR001240 A structure of the IGPS domain of the bifunctional enzyme from the mesophilicbacterium Escherichia coli (eIGPS) has been compared with the monomeric indole-3-glycerol phosphate\ synthase from the hyperthermophilic archaeon Sulfolobus solfataricus (sIGPS). Both are single-domain\ (/)8 barrel proteins, with one (eIGPS) or two (sIGPS) additional helices inserted before the first strand [MEDLINE:96363663].

\ \ indole-3-glycerol-phosphate synthase activity ; GO:0004425 \N tryptophan metabolism ; GO:0006568 20179 IPR001465

Malate synthase (EC: 4.1.3.2) catalyzes the aldol condensation of glyoxylate with acetyl-CoA to form malate - the second step of the glyoxylate bypass and an\ alternative to the tricarboxylic acid cycle in bacteria, fungi and plants.

\ \ malate synthase activity ; GO:0004474 \N tricarboxylic acid cycle ; GO:0006099 20180 IPR001466

Beta-lactamase catalyses the opening and hydrolysis of the -lactam ring of -lactam antibiotics such as penicillins and cephalosporins [MEDLINE:91311684]. There\ are four groups, classed A, B, C and D according to sequence, substrate\ specificity, and kinetic behaviour: class A (penicillinase-type) is the\ most common [MEDLINE:91311684]. The genes for class A -lactamases are widely \ distributed in bacteria, frequently located on transmissable plasmids in\ Gram-negative organisms, although an equivalent chromosomal gene has been \ found in a few species [MEDLINE:89350885].

\ \

Class A, C and D -lactamases are serine-utilising hydrolases - class\ B enzymes utilise a catalytic zinc centre instead. The 3 classes of serine -lactamase are evolutionarily related and belong to a superfamily that\ also includes DD-peptidases and other penicillin-binding proteins [MEDLINE:88183346]. All\ these proteins contain an S-x-x-K motif, the Ser being the active site\ residue. Although clearly related, however, the sequences of the 3 classes\ of serine -lactamases vary considerably outside the active site.

\ \ \N \N \N 20178 IPR001464 The annexins are a family of proteins that bind to phospholipids in a calcium-dependent manner [MEDLINE:91266960]. The binding is specific\ for calcium and for acidic phospholipids. Annexins have been claimed to be\ involved in cytoskeletal interactions, phospholipase inhibition, intracellular\ signalling, anticoagulation, and membrane fusion.\ \ \

There are eleven distinct classes of annexin, each\ of which has an amino acid sequence consisting of an N-terminal 'arm' \ followed by either four or eight copies of a conserved domain of 61 residues (only one\ of these residues, an arginine, is conserved between all copies). The\ calcium binding sites are found within the repeated domains PUB00005502. Individual\ repeats (sometimes known as endonexin folds) consist of five -helices\ wound into a right-handed superhelix. Each annexin class is thought to have\ a specific function, although for some the precise role is unclear. It has\ been suggested that the N-terminal residues confer the functional\ specificity that differentiates each class.

\ \ calcium-dependent phospholipid binding activity ; GO:0005544 \N \N 20176 IPR001462 This domain is at the C-terminus of hepadnavirus P proteins and represents a functional domain that controls the RNase H activities of the protein. The domain is always associated with IPR000201.\ ribonuclease H activity ; GO:0004523 \N \N 20177 IPR001463

Sodium symporters can be divided by sequence and functional similarityinto various groups. One such group is the sodium/alanine symporter family,\ the members of which transport alanine in association with sodium ions.

\ \

These transporters are believed to possess 8 transmembrane (TM) helices\ [MEDLINE:93078621], [MEDLINE:93016116], forming a channel or pore through the cytoplasmic membrane, the\ interior face being hydrophilic to allow the passage of alanine molecules\ and sodium ions [MEDLINE:93078621]. This family is restricted to the bacteria and archaea, examples are the alanine carrier protein from the Thermophilic bacterium\ PS-3; the D-alanine/glycine permease from Alteromonas haloplanktis; and the\ hypothetical protein yaaJ from Escherichai coli.

\ \ sodium:amino acid transporter activity ; GO:0005283 membrane ; GO:0016020 sodium ion transport ; GO:0006814 20174 IPR001460

Penicillin binding proteins are responsible for the final stages of peptidoglycan biosynthesis for cell wall formation. The proteins synthesise cross-linked peptidoglycan from lipid intermediates, and contain a penicillin-sensitive transpeptidase carboxy-terminal domain. The active site serine (residue 337 in P14677).

\ penicillin binding activity ; GO:0008658 \N cell wall biosynthesis (sensu Bacteria) ; GO:0009273 20175 IPR001461

\ \

This family does not include the retroviral nor retrotransposon \ proteases which are much smaller and appear to \ be homologous to the single domain aspartic proteases.

\ \ pepsin A activity ; GO:0004194 \N proteolysis and peptidolysis ; GO:0006508 20170 IPR001455

A family of uncharacterized bacterial proteins (73 to 81 amino-acid residues in length) that contain a well conserved region in their N-terminal region belong to this group.

\ \ molecular_function unknown ; GO:0005554 \N \N 20171 IPR001456

\ \

The helper component-proteinase is required for aphid transmission.

\ \ cysteine-type endopeptidase activity ; GO:0004197 \N proteolysis and peptidolysis ; GO:0006508 20172 IPR001457 Bacterial proton-translocating NADH-quinone oxidoreductase (NDH-1) is composed of 14 different subunits. The chain belonging to this family is a subunit that constitutes the membrane sector of the complex. It reduces ubiquinone to ubiquinol utilising NADH.

\ Plant chloroplastic NADH-plastoquinone oxidoreductase reduces plastoquinone to plastoquinol. Mitochondrial NADH-ubiquinone oxidoreductase from a variety of sources reduces ubiquinone to ubiquinol.

\ \ NADH dehydrogenase (ubiquinone) activity ; GO:0008137 \N oxidative phosphorylation, NADH to ubiquinone ; GO:0006120 20173 IPR001458

At least eight sub-types of metabotropic receptor (MGR1-8) have been\ identified in cloning studies. The sub-types differ in their agonist\ pharmacology and signal transduction pathways PUB00005885.

mRNA for MGR2 is widespread in the brain, with a unique distribution; it is found in high\ levels in neurons in olfactory bulb, cerebral cortex, cerebellum Golgi\ cells, and dendate gyrus granule cells . MGR2 inhibits adenylyl cyclase\ through a pertussis-toxin-sensitive G-protein, probably of the Gi/Go class;\ the receptor has also been reported to cause a weak stimulation of\ phosphoinositide metabolism PUB00005885.

\ \ metabotropic glutamate, GABA-B-like receptor activity ; GO:0008067 membrane ; GO:0016020 \N 20169 IPR001453 Eukaryotic and prokaryotic molybdoenzymes require a molybdopterin cofactor (MoCF) for their activity. The biosynthesis of this cofactor involves a\ complex multistep enzymatic pathway. One of the eukaryotic proteins involved\ in this pathway is the Drosophila protein cinnamon [MEDLINE:94374679] which is highly similar\ to gephyrin, a rat microtubule-associated protein which was thought to anchor\ the glycine receptor to subsynaptic microtubules.

Cinnamon and gephyrin are\ evolutionary related, in their N-terminal half, to the Escherichia coli MoCF\ biosynthesis proteins mog/chlG and moaB/chlA2 and, in their C-terminal half,\ to Escherichia coli moeA/chlE.

\ \ \N \N Mo-molybdopterin cofactor biosynthesis ; GO:0006777 20166 IPR001450

Ferredoxins are iron-sulphur proteins that mediate electron transfer in a range of metabolic reactions; they fall into several subgroups\ according to the nature of their iron-sulphur cluster(s) [MEDLINE:86037262], [MEDLINE:89382659]. One group,\ originally found in bacteria, has been termed "bacterial-type", in which\ the active centre is a 4Fe-4S cluster. 4Fe-4S ferredoxins may in\ turn be subdivided into further groups, based on their sequence properties. Most contain at least one conserved domain, including four Cys residues\ that bind to a 4Fe-4S centre.

During the evolution of bacterial-type ferredoxins, intrasequence gene\ duplication, transposition and fusion events occured, resulting in the\ appearance of proteins with multiple iron-sulphur centres: e.g. dicluster-\ type (2[4Fe-4S]) and polyferredoxins, iron-sulphur subunits of bacterial\ succinate dehydrogenase/fumarate reductase, formate hydrogenlyase and\ formate dehydrogenase complexes, pyruvate-flavodoxin oxidoreductase,\ NADH:ubiquinone reductase and others. In some bacterial ferredoxins, one\ of the duplicated domains has lost one or more of the four conserved Cys\ residues. These domains have either lost their iron-sulphur binding\ property, or bind to a 3Fe-4S centre instead of a 4Fe-4S centre. \ 3D structures are now known both for a number of monocluster-type [MEDLINE:90096160] and\ dicluster-type [MEDLINE:95055710] 4Fe-4S ferredoxins.

\ \ electron transporter activity ; GO:0005489 \N electron transport ; GO:0006118 20167 IPR001451 A variety of bacterial transferases contain a repeat structure composed of tandem repeats of a [LIV]-G-X(4) hexapeptide which, in the tertiary structure\ of lpxA [MEDLINE:96069822], has been shown to form a left-handed parallel

helix.\ \ \N \N \N 20168 IPR001452 SH3 (src Homology-3) domains are small protein modules containing approximately 50 amino acid residues PUB00001025, PUB00001025. They are found in a \ great variety of intracellular or\ membrane-associated proteins [MEDLINE:92347554], PUB00005506, PUB00005506. They are found in a variety of\ of proteins with enzymatic activity, in adaptor\ proteins that lack catalytic sequences and in cytoskeletal\ proteins, such as fodrin and yeast actin binding protein ABP-1. \

The SH3 domain has a characteristic fold which consists of five or six -strands arranged as two tightly packed anti-parallel sheets. The linker\ regions may contain short helices PUB00001083. The surface of the SH2-domain bears a flat, hydrophobic ligand-binding pocket which consists of three shallow grooves defined by conservative aromatic residues in which the ligand adopts an extended left-handed helical arrangement. The ligand binds with low affinity but this may be enhanced by multiple interactions.\ The region bound by the SH3 domain is in all cases proline-rich and contains PXXP as a core-conserved binding motif. The function of the SH3 domain is not well understood but they may mediate many diverse processes such as increasing local concentration of proteins, altering their subcellular location and mediating the assembly of large multiprotein complexes PUB00001083

\ \ \N \N \N 20165 IPR001449

Phosphoenolpyruvate carboxylase (PEPCase), an enzyme found in all multicellular plants, catalyses the formation of oxaloacetate from phosphoenolpyruvate (PEP) and a hydrocarbonate ion [MEDLINE:93081735]. This reaction is harnessed by C4 plants to capture and concentrate carbon dioxide into the photosynthetic bundle sheath cells. It also plays a key role in the nitrogen\ fixation pathway in legume root nodules: here it functions in concert with\ glutamine, glutamate and asparagine synthetases and aspartate amido transferase, to synthesise aspartate and asparagine, the major nitrogen transport compounds in various amine-transporting plant species [MEDLINE:93043034].

PEPCase\ also plays an antipleurotic role in bacteria and plant cells, supplying\ oxaloacetate to the TCA cycle, which requires continuous input of C4\ molecules in order to replenish the intermediates removed for amino acid\ biosynthesis [MEDLINE:89384460].\ The C-terminus of the enzyme contains the active site that includes a\ conserved lysine residue, involved in substrate binding, and other conserved\ residues important for the catalytic mechanism [MEDLINE:92374996].

\ \ phosphoenolpyruvate carboxylase activity ; GO:0008964 \N tricarboxylic acid cycle ; GO:0006099 20164 IPR001448

Small, acid-soluble spore proteins (SASP or ASSP) are proteins bound to the spore DNA of bacteria of the genera Bacillus, Thermoactynomycetes, and Clostridium\ \ \ \ [MEDLINE:89075754], [MEDLINE:92234927]. They are double-stranded DNA-binding\ proteins that cause DNA to change to an A-like conformation. They protect the\ DNA backbone from chemical and enzymatic cleavage and are thus involved in\ dormant spore's high resistance to UV light. SASP are degraded in the first\ minutes of spore germination and provide amino acids for both new protein\ synthesis and metabolism.

There are two distinct families of SASP: the / type and the gamma-\ type. Alpha/ SASP are small proteins of about sixty to seventy amino acid\ residues that are generally coded by a multigene family. The N-terminus of / SASP contains the site which is cleaved by a SASP-\ specific protease that acts during germination while the C-terminus and is probably involved in DNA-binding.

\ \ double-stranded DNA binding activity ; GO:0003690 \N DNA topological change ; GO:0006265 20162 IPR001446

5-lipoxygenase-activating protein (FLAP) is an integral membrane protein found in cells that produce leukotrienes, the\ biologically active metabolites of arachidonic acid that have been\ implicated in a variety of inflammatory responses, including asthma,\ arthritis and psoriasis [MEDLINE:91060597].

FLAP appears to activatate 5-lipoxygenase (5LOX) by facilitating its\ binding to membranes [MEDLINE:94065561]. It binds arachidonic acid, and may play a role\ in its transfer to 5LOX. The protein has been shown to bind to MK-886, a\ compound that blocks leukotriene biosynthesis [MEDLINE:91060597], [MEDLINE:90136904].

\ \ enzyme activator activity ; GO:0008047 integral to membrane ; GO:0016021 leukotriene metabolism ; GO:0006691 20163 IPR001447

Arylamine N-acetyltransferase (NAT) is a cytosolic enzyme of approximately 30 kDa. It facilitates the transfer of an acetyl group from acetyl coenzyme A on to a wide range of arylamine, N-hydroxyarylamines and hydrazines. Acetylation of\ these compounds generally results in inactivation. NAT is found in many species from Mycobacteria (Mycobacterium tuberculosis, Mycobacterium\ smegmatis etc) to Homo sapiens. It was the first enzyme to be observed to have polymorphic activity amongst human individuals.\ NAT is responsible for the inactivation of Isoniazid (a drug used to treat tuberculosis) in humans. The NAT protein has\ also been shown to be involved in the breakdown of folic acid. NAT catalyses the reaction:

                \
Acetyl-coA + arylamine = coA + N-acetylarylamine\

\ \

NAT is the target of a common genetic polymorphism of clinical relevance in\ humans. The N-acetylation polymorphism is determined by low or high NAT\ activity in liver. NAT has been implicated in the action and toxicity \ of amine-containing drugs, and in the susceptibility to cancer and\ systematic lupus erythematosus. Two highly similar human genes for NAT, \ termed NAT1 and NAT2, encode genetically invariant and variant NAT proteins,\ respectively.

\ \ acetyltransferase activity ; GO:0016407 \N metabolism ; GO:0008152 20161 IPR001445

Group B carboxylesterases constitute a family of enzymes that includes proteins that catalyse the conversion of an acylcholine to a choline and a weak acid:\

\
Acylcholine + H₂O -> Choline + COO^-\

\ and those that catalyse the hydrolysis of acetylcholine to choline and acetate (acetylcholinesterases):\

\
Acetylcholine + H₂O -> Choline + Acetate\

\ \ Acetylcholinesterase also acts on a \ variety of acetic esters and catalyses transacetylations. It is found in, or attached to, cellular or \ basement membranes of presynaptic cholinergic neurons and postsynaptic cholinoceptive cells. To prevent \ continuous firing of nerve impulses, acetylcholinesterase has a high K(cat) (~14000/s), to ensure that \ acetylcholine is broken down quickly. Cholinesterases themselves constitute a family of enzymes that fall \ into two main types, depending on their substrate preference; enzymes that preferentially hydrolyse \ acetyl esters are termed acetylcholinesterase (AChE) (EC: 3.1.1.7); and those that prefer other types of \ ester, such as butyrylcholine are termed butyrylcholinesterase (BChE) \ (EC: 3.1.1.8). The 3D structure of \ acetylcholinesterase from Torpedo californica (Pacific Electric Ray) has been determined [MEDLINE:91343928]. The fold belongs to the

class, \ with a 3-layer

sandwich architecture.

\ \

Insect acetylcholinesterase\ is often targeted by insecticides,\ especially in the effort to eradicate mosquitos from certain\ areas of the world [MEDLINE:98119513].

\ \ acetylcholinesterase activity ; GO:0003990 \N acetylcholine breakdown in the synaptic cleft ; GO:0001507 20157 IPR001441

Synonym(s): Di-trans-poly-cis-undecaprenyl-diphosphate synthase, Undecaprenyl pyrophosphate synthetase, Undecaprenyl pyrophosphate synthase, UPP synthetase

Di-trans-poly-cis-decaprenylcistransferase (EC: 2.5.1.31) (UPP synthetase) \ generates undecaprenyl pyrophosphate (UPP) from isopentenyl pyrophosphate\ (IPP) [MEDLINE:99102211]. This bacterial enzyme is also found in archaebacteria and in a number of uncharacterized proteins including some from yeasts.

\ \ transferase activity ; GO:0016740 \N metabolism ; GO:0008152 20158 IPR001442

This duplicated domain is present at the C-terminal of type 4 collagen, the major structural component of glomerular basement membranes (GMB) forming a 'chicken-wire' meshwork together with laminins, proteoglycans and entactin/nidogen. Mutations in -5 collagen IV are associated with X-linked Alport syndrome.

\ \ extracellular matrix structural constituent ; GO:0005201 collagen ; GO:0005581 \N 20159 IPR001443 Staphylocoagulase is an extracellular protein produced by several strains of Staphylococcus aureus and which specifically forms a complex with\ prothrombin [MEDLINE:88139269], [MEDLINE:90067866]. This complex named staphylothrombin can clot fibrinogen without\ any proteolytic cleavage of prothrombin.\ The C terminus of staphylocoagulase contains the tandem repeat which does not seem to be \ required for the procoagulant activity.\ \ \N \N \N 20160 IPR001444

Many bacterial species swim actively by means of flagella. The flagella organelle is made of three parts: the basal body, the hook and the filament.\ The basal body consists of four rings (L,P,S, and M) mounted on a central rod [MEDLINE:90172414].

In Salmonella typhimurium and related organisms the rod has been shown to\ consist of four different, yet evolutionary related proteins: in the distal\ portion of the rod there are about 26 subunits of protein flgG and in the\ proximal portion there are about six subunits each of proteins flgB, flgC, and\ flgF.\ These four proteins contain a highly conserved\ asparagine-rich domain at their N terminus.

\ \ structural molecule activity ; GO:0005198 flagellum (sensu Bacteria) ; GO:0009288 ciliary/flagellar motility ; GO:0001539 20156 IPR001440 The tetratricopeptide repeat of typically 34 amino acids was first described in the yeast cell cycle regulator Cdc23p and later found to occur\ in a large number of proteins [MEDLINE:95397415], [MEDLINE:98151343], [MEDLINE:91352828]. A function for this repeat seems \ to be protein-protein interaction, but common features in the interaction\ partners have not been defined. It has been proposed that TPR proteins\ preferably interact with WD-40 repeat proteins, but in many instances\ several TPR-proteins seem to aggregate to multi-protein complexes.\ Prominent examples of TPR-proteins include, Cdc16p, Cdc23p and Cdc27p components of the cyclosome/APC, \ the Pex5p/Pas10p receptor for peroxisomal targeting signals,\ the Tom70p co-receptor for mitochondrial targeting signals,\ Ser/Thr phosphatase 5C and the p110 subunit of O-GlcNAc transferase.\ \ \N \N \N 20155 IPR001439

Family 56 (CAZY:GH_56)\ that includes venom hyaluronidases and mammalian sperm surface proteins\ (PH-20).

PH-20 is required for sperm adhesion to the egg zona pellucida; it is\ located on both the sperm plasma membrane and acrosomal membrane [MEDLINE:91100409]. During fertilisation, sperm must first penetrate a layer of cumulus cells\ that surrounds the egg, before reaching the zona pellucida. The cumulus\ cells are embedded in a matrix containing hyaluronic acid, which is formed\ prior to ovulation. PH-20 facilitates penetration of the cumulus cell layer\ by digesting hyaluronic acid.

The amino acid sequence of the mature protein contains 468 amino acids, and\ includes six potential N-linked glycosylation sites and twelve cysteines,\ eight of which are tightly clustered near the C-terminus [MEDLINE:91100409].

\ \ hyaluronoglucosaminidase activity ; GO:0004415 \N binding/fusion of sperm to egg plasma membrane ; GO:0007342 20152 IPR001437 Bacterial proteins greA and greB are necessary for efficient RNA polymerase transcription elongation past template-encoded arresting sites.\ Arresting sites in DNA have the property of trapping a certain fraction of\ elongating RNA polymerases that pass through, resulting in locked DNA/RNA/\ polymerase ternary complexes. Cleavage of the nascent transcript by cleavage\ factors, such as greA or greB, allows the resumption of elongation from the\ new 3'terminus [MEDLINE:93161419], [MEDLINE:95157641], .

GreA induces cleavage two or three nucleotides behind the terminus\ while greB releases longer sequences up to nine nucleotides in length.

\ \ transcriptional elongation regulator activity ; GO:0003711 \N regulation of transcription, DNA-dependent ; GO:0006355 20153 IPR001437 Bacterial proteins greA and greB are necessary for efficient RNA polymerase transcription elongation past template-encoded arresting sites.\ Arresting sites in DNA have the property of trapping a certain fraction of\ elongating RNA polymerases that pass through, resulting in locked DNA/RNA/\ polymerase ternary complexes. Cleavage of the nascent transcript by cleavage\ factors, such as greA or greB, allows the resumption of elongation from the\ new 3'terminus [MEDLINE:93161419], [MEDLINE:95157641], .

GreA induces cleavage two or three nucleotides behind the terminus\ while greB releases longer sequences up to nine nucleotides in length.

\ \ transcriptional elongation regulator activity ; GO:0003711 \N regulation of transcription, DNA-dependent ; GO:0006355 20154 IPR001438 EGF-like repeats occur in coagulation factors, notch and xotch proteins, protein Z, urokinases, plasminogen factors and the lin-12 protein [MEDLINE:90321281], [MEDLINE:86079539], [MEDLINE:86079540], [MEDLINE:88328994].\ The repeat pattern is EGF-like in the sense that it does not share the \ exact Cys spacings of the type I EGF motif. The primary \ structures of many of the superfamily members contain regions that are \ dominated by multiple EGF-like repeats: these have been linked to some \ physiological role, though the precise nature of this role is as yet\ unclear.\

The type II EGF-like signature is found in a variety of proteins having different functions and from a variety of sources.

\ \ \N \N \N 20151 IPR001436

\ \ \N \N \N 20150 IPR001435

In addition to their role in energy metabolism, purines (especially\ adenosine and adenine nucleotides) produce a wide range of pharmacological\ effects mediated by activation of cell surface receptors PUB00005868. Distinct\ receptors exist for adenosine. In the periphery, the main effects of\ adenosine include vasodilation, bronchoconstriction, immunosuppresion,\ inhibition of platelet aggregation, cardiac depression, stimulation of\ nociceptive afferents, inhibition of neurotransmitter release and\ inhibition of the release of other factors, e.g. hormones . In the CNS,\ adenosine exerts a pre- and post-synaptic depressant action, reducing motor\ activity, depressing respiration, inducing sleep and relieving anxiety. The\ physiological role of adenosine is thought to be to adjust energy demands\ in line with oxygen supply. Many of the clinical actions of methylxanthines\ are thought to be mediated through antagonism of adenosine receptors. Four\ subtypes of receptor have been identified, designated A1, A2A, A2B and A3.

\ \

A2B receptors are widespread in the human brain relative to A2A receptors.\ By contrast, however, in the rat its mRNA is found only in low levels in\ the brain and it has a unique distribution in the periphery, high levels\ occurring in the intestine and bladder PUB00005868. The receptor stimulates cAMP\ through Gs.

\ \ A2B adenosine receptor activity, G-protein coupled ; GO:0001612 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20149 IPR001434

This group of sequences is represented by a conserved region of about 53 amino acids shared between regions, usually repeated, of proteins from a small number of\ phylogenetically distant prokaryotes. Examples include a 132-residue region found\ repeated in three of the five longest proteins of Bacillus anthracis, a 131-residue\ repeat in a cell wall-anchored protein of Enterococcus faecalis, and a 120-residue\ repeat in Methanobacterium thermoautotrophicum. A similar region is found in some\ Chlamydia trachomatis outer membrane proteins.

In Chlamydia trachomatis three cysteine-rich proteins (also believed to be lipoproteins), MOMP, OMP6 and OMP3, make up the\ extracellular matrix of the outer membrane [MEDLINE:91141306]. They are involved \ in the essential structural integrity of both the elementary body (EB) and \ recticulate body (RB) phase. They are thought to be involved in porin formation and as these bacteria lack the peptidoglycan layer\ common to most Gram-negative microbes, such proteins are highly important \ in the pathogenicity of the organism.

\ \ molecular_function unknown ; GO:0005554 extrachromosomal circular DNA ; GO:0005727 \N 20148 IPR001433

Bacterial ferredoxin-NADP⁺ reductase may be bound to the thylakoid membrane or anchored to the thylakoid-bound phycobilisomes.Chloroplast ferredoxin-NADP⁺ reductase (EC: 1.18.1.2) may play a key role in regulating the relative amounts of cyclic and non-cyclic electron flow to meet the demands of the plant for ATP and reducing power. It is involved in the final step in the linear photosynthetic electron transport chain and has also been implicated in cyclic electron flow around photosystem I where its role would be to return electrons from ferredoxin to the cytochrome B-F complex.

\ \

This domain is present in a variety of proteins that include, bacterial flavohemoprotein, mammalian NADH-cytochrome b5 reductase, eukaryotic NADPH-cytochrome P450 reductase, nitrate reductase from plants, nitric-oxide synthase, bacterial vanillate demethylase and others.

\ \ oxidoreductase activity ; GO:0016491 \N electron transport ; GO:0006118 20146 IPR001431

A number of proteases dependent on divalent cations for their activity havebeen shown [MEDLINE:91222131], [MEDLINE:95334815] to belong to a single family, peptidase M16.

Included are insulinase, mitochondrial processing protease, pitrlysin, nardilysin and a number of bacterial proteins

These proteins do not share many regions of sequence similarity; the most noticeable is in the N-terminal section. This region includes a conserved histidine followed, two residues later by a glutamate and another histidine. In pitrilysin, it has been shown [MEDLINE:95082912] that this H-x-x-E-H motif is involved in enzymatic activity; the two histidines bind zinc and the glutamate is necessary for catalytic activity. Non active members of this family have lost from one to three of these active site residues.

\ \ metalloendopeptidase activity ; GO:0004222 \N proteolysis and peptidolysis ; GO:0006508 20147 IPR001432

The M4 receptor is found in high levels in neuronal cells of the CNS; its distribution\ largely overlaps with that of M1 and M3 subtypes. It is also found in cell lines. No\ selective agonist has been described PUB00005867.

\ \ muscarinic acetylcholine receptor activity ; GO:0004981 membrane ; GO:0016020 \N 20145 IPR001430 The uptake of protein by the nucleus is extremely selective and nuclear proteins must therefore contain within their final structure a signal that\ specifies selective accumulation in the nucleus [MEDLINE:87157268], [MEDLINE:91167535]. Studies on some nuclear\ proteins, such as the large T antigen of SV40, have indicated which part of\ the sequence is required for nuclear translocation.

The known nuclear\ targeting sequences are generally basic, but there seems to be no clear\ sequence similarity. Although some consensus\ sequence patterns have been proposed [MEDLINE:88112185], the current best\ strategy to detect a nuclear targeting sequence is based on the following\ definition of what is called a 'bipartite nuclear targeting sequence':\ (1) Two adjacent basic amino acids (Arg or Lys).\ (2) A spacer region of ten residues.\ (3) At least three basic residues (Arg or Lys) in the five positions\ after the spacer region [MEDLINE:92142226].

Note: No protein matches are shown due to the low specificity of this rule.

\ \ \N \N \N 20143 IPR001427 Pancreatic ribonucleases (RNAse) are pyrimidine-specific endonucleases found in high quantity in the pancreas of certain mammals and of\ some reptiles [MEDLINE:86082373]. Specifically, the enzymes are involved in endonucleolytic\ cleavage of 3'-phosphomononucleotides and 3'-phosphooligonucleotides ending\ in C-P or U-P with 2',3'-cyclic phosphate intermediates. Ribonuclease can\ unwind the DNA helix by complexing with single-stranded DNA; the complex\ arises by an extended multi-site cation-anion interaction between lysine\ and arginine residues of the enzyme and phosphate groups of the nucleotides.\ Other proteins belonging to the pancreatic RNAse family include: bovine\ seminal vesicle and brain ribonucleases; kidney non-secretory ribonucleases\ [MEDLINE:89282792]; liver-type ribonucleases [MEDLINE:90122868]; angiogenin, which induces vascularisation\ of normal and malignant tissues; eosinophil cationic protein [MEDLINE:89310354], a\ cytotoxin and helminthotoxin with ribonuclease activity; and frog liver\ ribonuclease and frog sialic acid-binding lectin.\ The sequence of pancreatic RNases contains four conserved disulphide bonds and\ three amino acid residues involved in the catalytic activity.\ \ pancreatic ribonuclease activity ; GO:0004522 \N \N 20144 IPR001429

\ \

\ \ ATP binding activity ; GO:0005524 membrane ; GO:0016020 ion transport ; GO:0006811 20140 IPR001424

Superoxide dismutases are ubiquitous metalloproteins that prevent damage by oxygen-mediated free radicals by catalysing the dismutation of superoxide\ into molecular oxygen and hydrogen peroxide [MEDLINE:89321563]. Superoxide is a normal \ by-product of aerobic respiration and is produced by a number of reactions, \ including oxidative phosphorylation and photosynthesis . The dismutase\ enzymes have a very high catalytic efficiency due to the attraction of\ superoxide to the ions bound at the active site [MEDLINE:92335247], [MEDLINE:85231234].

There are three forms of superoxide dismutase, depending on the metal cofactor: \ Cu/Zn (which binds both copper and zinc), Fe and Mn types. The Fe and Mn\ forms are similar in their primary, secondary and tertiary structures, but \ are distinct from the Cu/Zn form [MEDLINE:91088619]. Prokaryotes and protists contain Mn,\ Fe or both types, while most eukaryotic organisms utilise the Cu/Zn type.

\ \ heavy metal binding activity ; GO:0005505 \N superoxide metabolism ; GO:0006801 20141 IPR001425 The bacterial opsins are retinal-binding proteins that provide light- dependent ion transport and sensory functions to a family of halophilic \ bacteria [MEDLINE:89203927], [MEDLINE:90076116] ]. They are integral membrane proteins believed to contain\ seven transmembrane (TM) domains, the last of which contains the attachment\ point for retinal (a conserved lysine).

There are several classes of these\ bacterial proteins: they include bacteriorhodopsin and archaerhodopsin,\ which are light-driven proton pumps; halorhodopsin, a light-driven \ chloride pump; and sensory rhodopsin, which mediates both photoattractant\ (in the red) and photophobic (in the UV) responses.

\ \ ion channel activity ; GO:0005216 membrane ; GO:0016020 ion transport ; GO:0006811 20142 IPR001426 A number of growth factors stimulate mitogenesis by interacting with a family of cell surface receptors which possess an intrinsic, ligand-sensitive,\ protein tyrosine kinase activity [MEDLINE:89024579]. These receptor tyrosine kinases (RTK)\ all share the same topology: an extracellular ligand-binding domain, a single\ transmembrane region and a cytoplasmic kinase domain and have been\ classified into at least five groups on the basis of sequence similarities.\

The extracellular domain of class V RTK's has 16 conserved cysteine residues that are probably involved in\ disulfide bonds; this region is followed by two copies of a fibronectin type\ III domain. The ligands for these receptors are proteins known as ephrins. The EPHA subtype receptors bind to GPI-anchored ephrins while the EPHB subtype\ receptors bind to type-I membrane ephrins.

\ \ ATP binding activity ; GO:0005524 membrane ; GO:0016020 transmembrane receptor protein tyrosine kinase signaling pathway ; GO:0007169 20137 IPR001421 Adenosine triphosphate (ATP) synthase contains a rotary motor involved in biological energy conversion. Its membrane-embedded F0 sector has a rotation generator fueled by the proton-motive force, which provides the energy required for the synthesis of ATP by the F1 domain [MEDLINE:20044992]. Subunit 8 is one of the chains of the nonenzymatic component (F0) of the mitochondrial ATPase complex.\ hydrogen-transporting two-sector ATPase activity ; GO:0003936 membrane ; GO:0016020 proton transport ; GO:0015992 20138 IPR001422 Neuromodulin is a component of the motile growth cones. It is membrane protein whose expression is\ widely correlated with successful axon elongation [MEDLINE:90166498]. It is a crucial\ component of an effective regeneration response in the nervous system [MEDLINE:90380372].\ Although its function is uncertain, the N-terminal region is well\ conserved and contains both a calmodulin binding domain, and sites for\ acylation, membrane attachment and protein kinase C phosphorylation .\ Structure predictions suggest that the C-\ terminus may exist as an extended, negatively-charged rod with some\ similarity to the side arms of neurofilaments, indicating that the\ biological role of neuromodulin may depend on its ability to form a\ dynamic membrane-cytoplasm-calmodulin complex [MEDLINE:90380372].\ \ \N \N \N 20139 IPR001423 A number of prokaryotic and eukaryotic proteins belong to this family. \ These proteins are of variable size and share a glycine-rich domain of about 200\ residues that is located at the C-terminus of the eukaryotic members\ of this family.\ \ molecular_function unknown ; GO:0005554 \N \N 20135 IPR001419

Gluten is the protein component of wheat flour. It consists of numerous proteins, which are of two different types responsible for different physical\ properties of dough: the glutenins, which are primarily responsible for\ the elasticity, and the gliadins, which contribute to the extensibility.

The glutenins are of two different types, termed low (LMW) and high \ molecular weight (HMW) subunits [MEDLINE:86041882]. The glutenin high molecular weight subunits are classified as\ elastomeric proteins, because the glutenin network can withstand significant deformations without breaking, and return to the\ original conformation when the stress is removed. Elastomeric proteins differ considerably in amino acid sequence, but they are all\ polymers whose subunits consist of elastomeric domains, composed of repeated motifs, and non-elastic domains that mediate\ cross-linking between the subunits. The elastomeric domain motifs are all rich in glycine residues in addition to other hydrophobic\ residues. High molecular weight glutenin subunits have an extensive central elastomeric domain, flanked by two terminal non-elastic\ domains that form disulphide cross-links. The central elastomeric domain is characterised by the following three repeated motifs:\ PGQGQQ, GYYPTS[P/L]QQ, GQQ. It possesses overlapping -turns within and between the repeated motifs, and assumes a\ regular helical secondary structure with a diameter of approx. 1.9 nm and a pitch of approx. 1.5 nm [MEDLINE:20538698].

\ \ nutrient reservoir activity ; GO:0045735 \N \N 20136 IPR001420

The term opioid refers to a class of substance that produces its effects\ via the major classes of opioid receptor, termed mu, delta and kappa PUB00005896.\ The receptors are found in the CNS and certain smooth muscles: mu-opioid\ receptors are believed to mediate analgesia, hypothermia, respiratory\ depression, miosis, bradycardia, nausea, euphoria and physical dependence, -endorphin being the most potent endogenous ligand; delta-receptors\ mediate analgesia; and kappa-opioid receptors are believed to mediate\ analgesia, sedation, miosis and diuresis, dynorphin being the most potent\ endogenous ligand.

The X-receptor is closely related to opioid receptors, on grounds of both\ sequence and function, although it is not a typical opioid receptor PUB00005896.\ X-receptors are found in many regions of the brain and spinal cord,\ particularly limbic and hypothalamic structures. They are believed to\ represent a new class of opioid receptors, with a potential role in\ modulating various brain functions, including instinctive behaviours and\ emotions [MEDLINE:94185768].

\ \ X-opioid receptor activity ; GO:0015051 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20134 IPR001418

A human placental protein that binds opioid ligands with moderate affinity\ has been provisionally classified as an opioid receptor PUB00005896. However, it is\ not selective for kappa-ligands and is 93% similar to the human NK3\ tachykinin receptor, although it doesn't bind tachykinins.

\ \ \ opioid receptor activity ; GO:0004985 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20133 IPR001416

\ Several 7TM receptors have been cloned but their endogenous ligands are unknown;\ these have been termed orphan receptors. Canine RDC1 receptors were first\ characterised by Libert et al. as belonging to a new subfamily of receptors with a short\ non-glycosylated (extracellular) N-terminal extension [MEDLINE:89242119]. The human homologue of RDC1\ was originally believed to code for a VIP receptor [MEDLINE:91271317], but this is no longer thought to be\ correct PUB00005897.\ \ G-protein coupled receptor activity, unknown ligand ; GO:0016526 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20132 IPR001415 Parathyroid hormone (PTH) is a polypeptidic hormone that elevates calcium level by dissolving the salts in bone and preventing their renal excretion.\ \ The 'parathyroid hormone-related\ protein' (PTH-rP) is structurally related to PTH [MEDLINE:90048075] and seems to play a physiological role in lactation,\ possibly as a hormone for the mobilization and/or transfer of calcium to the\ milk. PTH and\ PTH-rP bind to the same G-protein coupled receptor.\ \ hormone activity ; GO:0005179 extracellular ; GO:0005576 \N 20131 IPR001414 Ocular albinism type 1 (OA1) is an X-linked disorder characterised by severe impairment of visual acuity, retinal hypopigmentation and the presence of\ macromelanosomes . A novel transcript from the OA1\ critical region is expressed in high levels in RNA samples from\ retina and from melanoma and encodes a potential integral membrane\ protein [MEDLINE:95375777]. This protein is of unknown function but is known to bind heterotrimeric G proteins.\ \ molecular_function unknown ; GO:0005554 membrane ; GO:0016020 \N 20128 IPR001411 The Tet protein confers resistance to tetracycline by active tetracycline efflux, by functioning as a metal-tetracycline/H+ antiporter. This is an\ energy-dependent process that decreases the accumulation of the antibiotic\ in whole cells. Tet is an integral membrane protein with twelve potential\ transmembrane domains [MEDLINE:86031344], [MEDLINE:87226167].\ \ tetracycline:hydrogen antiporter activity ; GO:0015520 integral to membrane ; GO:0016021 tetracycline transport ; GO:0015904 20129 IPR001412

\ \

\ \ ATP binding activity ; GO:0005524 \N amino acid activation ; GO:0006418 20130 IPR001413

D1 receptors are found in greatest abundance in the caudate-putamen,\ nucleus accumbens and olfactory tubercle, with lower levels in the frontal\ cortex, habenula, amygdala, hypothalamus and thalamus . In the periphery,\ binding sites are found in the kidney, heart, liver and parathyroid gland\ . The receptors stimulate adenylyl cyclase through Gs; they may also\ be able to stimulate phosphoinositide metabolism PUB00005878.

\ \ dopamine receptor activity ; GO:0004952 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20127 IPR001410

A number of eukaryotic and prokaryotic proteins involved in ATP-dependent, nucleic-acid unwinding have been characterized [MEDLINE:92203994], [MEDLINE:89097246], [MEDLINE:91125473] on the basis\ of their structural similarity. All these proteins share a number of conserved sequence motifs.\ Some of them are specific to this family while others are shared by other ATP-binding proteins or\ by proteins belonging to the helicases 'superfamily' PUB00004025.

\ \

Proteins containing this domain include the DEAD and DEAH box helicases. The DExH/D-box proteins are a large family of ATPases that have been proposed to mediate RNA structural\ rearrangements in a variety of cellular processes, including nuclear pre-mRNA splicing, ribosome assembly,\ protein synthesis, nuclear transport, and RNA degradation PUB00004025, [MEDLINE:99257316].

\ \ ATP dependent helicase activity ; GO:0008026 \N \N 20122 IPR001405 RadC is a DNA repair protein found in many bacteria. They share a region of similarity at the C-terminus that contains two perfectly conserved histidine residues.\ \ \N \N DNA repair ; GO:0006281 20123 IPR001406 Transfer RNA-pseudouridine synthetase contains one atom of zinc essential for its native conformation and tRNA recognition [MEDLINE:98254513] and has a strictly conserved aspartic acid that is likely to be involved in catalysis. \ It is involved in the formation of pseudouridine at positions 38, 39 and 40 in the anticodon stem\ and loop of transfer-RNAs.\ Pseudouridine is the most abundant modified nucleoside found in \ all cellular RNAs.\ \ \N \N \N 20124 IPR001407 Influenza RNA-dependent RNA polymerase is composed of three subunit;P1 (or PB1), P2 (or PA), and P3 (or PB2).\ There are two separate domains in the influenza\ virus PB1 protein involved in the interaction with the PB2\ and PA subunits [MEDLINE:98006317], [MEDLINE:97105887]. PB1 has two GTP binding sites.\ \ RNA-directed RNA polymerase activity ; GO:0003968 \N transcription ; GO:0006350 20125 IPR001408 The G protein

subunit binds guanyl nucleotide and is a weak GTPase. Seventeen distinct types of

subunit have been identified in mammals. These fall\ into four main groups on the basis of both sequence similarity and function:

-s,

-q,

-i and

-12 [MEDLINE:91227903].\ \

The G-protein -I (G -I) class can be divided into -I-like, -O-like, -T-like and -Z-like. The -I-like proteins were\ originally identified as the proteins responsible for receptor-mediated\ inhibition of adenylyl cyclase, hence 'I' for inhibitory. Alpha-O is an\ extremely abundant G-protein that is expressed predominantly in the brain,\ where it is known to couple receptors such as the M2 acetylcholine receptor\ to neuronal potassium and calcium channels, and has been implicated in\ membrane trafficking.\ Alpha-T, transducin, is the G protein responsible for transducing the light\ response in vertebrate retinae. It is activated by rhodopsin or cone opsin,\ and in turn activates the effector enzyme cyclic guanine monophosphate\ phosphodiesterase (cGMP-PDE). The resultant lowering of GDP levels causes\ cGMP-gated sodium channels to close, and the subsequent hyperpolarisation\ of the cell membrane leads to the generation of a nervous impulse. Alpha-Z\ is a relatively unknown protein showing significant divergence by comparison\ with conserved regions of other subunits.

\ \ \ GTP binding activity ; GO:0005525 \N G-protein coupled receptor protein signaling pathway ; GO:0007186 20126 IPR001409 Steroid or nuclear hormone receptors (NRs) constitute an important super- family of transcription regulators that are involved in widely diverse \ physiological functions, including control of embryonic development, cell\ differentiation and homeostasis. Members of the superfamily include the\ steroid hormone receptors and receptors for thyroid hormone, retinoids, \ 1,25-dihydroxy-vitamin D3 and a variety of other ligands. The proteins \ function as dimeric molecules in nuclei to regulate the transcription of \ target genes in a ligand-responsive manner [MEDLINE:95206940], [MEDLINE:94218237]. In addition to C-terminal\ ligand-binding domains, these nuclear receptors contain a highly-conserved,\ N-terminal zinc-finger that mediates specific binding to target DNA \ sequences, termed ligand-responsive elements. In the absence of ligand,\ steroid hormone receptors are thought to be weakly associated with nuclear\ components; hormone binding greatly increases receptor affinity.\ \

NRs are extremely important in medical research, a large number of them\ being implicated in diseases such as cancer, diabetes, hormone resistance\ syndromes, etc. While several NRs act as ligand-inducible transcription\ factors, many do not yet have a defined ligand and are accordingly termed \ "orphan" receptors. During the last decade, more than 300 NRs have been\ described, many of which are orphans, which cannot easily be named due to \ current nomenclature confusions in the literature. However, a new system \ has recently been introduced in an attempt to rationalise the increasingly \ complex set of names used to describe superfamily members.

\ The glucocorticoid receptor consists of 3 functional and structural\ domains: an N-terminal (modulatory) domain; a DNA binding domain that\ mediates specific binding to target DNA sequences (ligand-responsive\ elements); and a hormone binding domain. The N-terminal domain is unique\ to the glucocorticoid receptors; it spans the first 440 residues, and is\ primarily responsible for transcriptional activation. The smaller (around\ 65 residues), highly-conserved central portion of the protein is the DNA \ binding domain, which plays a role in DNA binding specificity, homo-\ dimerisation and in interactions with other proteins. The hormone binding \ domain comprises approximately 250 residues at the C-terminus of the\ receptor. This domain mediates receptor activity via interaction with heat\ shock proteins and cyclophilins, or with hormone. For more information, see\ the GRR resource [http://biochem1.basic-sci.georgetown.edu/GRR/GRR.html].

\ \ steroid binding activity ; GO:0005496 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 20120 IPR001403 The parvovirus coat protein VP2 together with VP1 forms a capsomer. Both of these proteins are formed from the same transcript using alternative \ splicing. As a result, VP1 and VP2 differ only in the N-terminus region.\ VP2 is involved in packaging the viral DNA [MEDLINE:97275906]. The mature viron contains three caaspid proteins \ VP1, VP2, and VP3 and a noncapsid protein NS-1.\ \ structural molecule activity ; GO:0005198 viral capsid ; GO:0019028 \N 20121 IPR001404

Prokaryotes and eukaryotes respond to heat shock and other forms of environmental stress by inducing synthesis of heat-shock proteins (hsp) [MEDLINE:89192244]. The hsp90 proteins are a group of hsps with an average molecular weight of \ 90 Kd.

The precise function of hsp90 is unclear. In higher eukaryotes, the protein\ has been found associated with steroid hormone receptors, tyrosine kinase\ oncogene products of various retroviruses, eIF2alpha kinase, and with actin\ and tubulin. They are probable chaperonins with ATPase activity [MEDLINE:93123274], [MEDLINE:94324075] ]. The\ sequences of hsp90s show a distinctive domain structure, with a highly-conserved N-terminal domain separated from a conserved, acidic C-terminal\ domain by a highly-acidic, flexible linker region.

\ \ chaperone activity ; GO:0003754 \N \N 20118 IPR001401 Dynamin is a microtubule-associated, force-producing protein involved in the production of microtubule bundles [MEDLINE:90328765]. It is structurally related to\ yeast vacuolar sorting protein [MEDLINE:90275602], yeast MGM1 protein [MEDLINE:92192451] and interferon-\ induced Mx proteins [MEDLINE:90111289]. These proteins all hydrolyse GTP, each containing\ motifs common to all GTP-binding proteins towards their N-termini.\ \ GTP binding activity ; GO:0005525 \N \N 20119 IPR001402

Hypothalamic peptide hormones regulate secretion of anterior pituitary hormones, such as growth hormone, follicle stimulating hormone, luteinising\ hormone and thyrotropin. A novel bioactive peptide has been identified from bovine hypothalamus and found to increase prolactin secretion from the \ anterior pituitary [MEDLINE:98268781]. This peptide - prolactin-releasing peptide (PrRP) - is a member of the structurally related RF-amide family, which includes neuropeptide FF [MEDLINE:20485331]. The peptide exists in two forms: a 31-amino acid form and a truncated 20-amino acid form [MEDLINE:98268781]. PrRP has been found in the medulla oblongata, hypothalamus and pituitary, as well as in a number of other tissues. This distribution suggests the peptide may have other roles in addition to prolactin release [MEDLINE:99426652].

The receptor for PrRP was identified to be an orphan receptor, previously known as GPR10 [MEDLINE:98268781]. This receptor is expressed in the central nervous system with highest levels in the pituitary. Expression has also been detected in the cerebellum, brainstem, hypothalamus, thalamus and spinal cord in rat [MEDLINE:99426652]. Binding of PrRP to the receptor results in activation of extracellular signal-related kinase (ERK) in a mainly pertussis toxin sensitive manner, suggesting coupling to Gi/o proteins [MEDLINE:20485331]. PrRP can also cause increases in intracellular calcium and activation of c-Jun N-terminal protein kinase (JNK) in a pertussis toxin insensitive manner, indicating that the receptor can also couple to Gq proteins, depending on the cell type in which it is expressed [MEDLINE:20485331].

\ \ \ \ \ neuropeptide Y receptor activity ; GO:0004983 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20115 IPR001398

Macrophage migration inhibitory factor (MIF) seems to play an important role in host inflammatory responses where it is involved in the host response to endotoxic shock probably serving as a\ pituitary "stress" hormone that regulates systemic inflammatory responses [MEDLINE:95255867]. MIF\ is a secreted protein that is not processed from a larger\ precursor.

D-dopachrome tautomerase, related to MIF, is a mammalian cytoplasmic enzyme involved in\ melanin biosynthesis that tautomerizes D-dopachrome with concomitant\ decarboxylation to give 5,6-dihydroxyindole (DHI) [MEDLINE:94092139].

\ \ \N \N \N 20116 IPR001399

Bluetongue virus VP6 protein binds ATP and exhibits an RNA-dependent ATPase function and a helicase activity that\ catalyses the unwinding of double-stranded RNA substrates [MEDLINE:97456481]. VP6 from five United States\ prototype bluetongue virus (BTV) serotypes contain unusually high concentrations of glycine, \ few aromatic amino acids, but a high concentration of charged amino acids,\ a characteristic of hydrophilic proteins [MEDLINE:93033709].

\ \

VP6 is an inner capsid protein that surrounds the genomic DS-RNA. Its\ hydrophilic nature coupled with a capability to bind ss- and ds-RNA,\ suggests that it interacts directly with the BTV genomic RNA.

\ \ structural molecule activity ; GO:0005198 viral capsid ; GO:0019028 \N 20117 IPR001400 Somatotropin is a hormone that plays an important role in growth control. It belongs to a family that includes choriomammotropin (lactogen), its placental analogue; \ prolactin, which promotes lactation in the mammary gland, and placental\ prolactin-related proteins; proliferin and proliferin related protein; and\ somatolactin from various fish PUB00003394, PUB00003394, [MEDLINE:91129219], [MEDLINE:90001249].\ The 3D structure of bovine somatotropin has been predicted using a \ combination of heuristics and energy minimisation [MEDLINE:91214979].\ \ hormone activity ; GO:0005179 extracellular ; GO:0005576 \N 20114 IPR001397

The 5HT5 receptor has a similar pharmacology to the 5HT1D receptor. In\ the CNS, its mRNA is found in the cerebral cortex, hippocampus, habenula,\ olfactory bulb and granular layer of the cerebellum . There are no\ selective agonists, and the receptor does not appear to be linked to the\ adenylyl cyclase or phosphoinositide pathways PUB00005889.

\ \ \N integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20113 IPR001396

\ \

Echinoidea (sea urchin, family 4) MTs are 64-67 residue proteins. Members of this family are recognised by the sequence pattern P-D-x-K-C-[V,F]-C-C-x(5)-C-x-C-x(4)-C-C-x(4)-C-C-x(4,6)-C-C located near the N terminus. \ The taxonomic range of the members extends to sea urchins (echinodea). \ The protein sequence is divided into two structural domains, each containing 9 and 11 Cys residues binding 3 and 4 bivalent metal ions, respectively.\ Family 4 includes subfamilies: e1, e2, they are separate phylogenetic groups.

\ \ heavy metal binding activity ; GO:0005505 \N \N 20112 IPR001395 The aldo-keto reductase family includes a number of related monomeric NADPH-dependent oxidoreductases, such as aldehyde reductase, aldose\ reductase, prostaglandin F synthase, xylose reductase, rho crystallin, and\ many others [MEDLINE:89255461]. All possess a similar structure, with a

fold \ characteristic of nucleotide binding proteins [MEDLINE:90154035].\ The fold comprises a parallel

-8/

-8-barrel, which contains a \ novel NADP-binding motif. The binding site is located in a large,\ deep, elliptical pocket in the C-terminal end of the

sheet, the \ substrate being bound in an extended conformation. The hydrophobic\ nature of the pocket favours aromatic and apolar substrates over highly\ polar ones [MEDLINE:92320300].

Binding of the NADPH coenzyme causes a massive\ conformational change, reorienting a loop, effectively locking the\ coenzyme in place. This binding is more similar to FAD- than to\ NAD(P)-binding oxidoreductases [MEDLINE:93077587].

\ \ \N \N \N 20111 IPR001394

Synonym(s): Ubiquitin carboxy-terminal esterase, Ubiquitin carboxy-terminal hydrolase

Ubiquitin thiolesterases (EC: 3.1.2.15) (UCH) (deubiquitinating\ enzymes) are thiol proteases that recognize and hydrolyze the peptide\ bond at the C-terminal glycine of ubiquitin [MEDLINE:91274342], [MEDLINE:99043406]. These enzymes are involved in the\ processing of poly-ubiquitin precursors as well as that of ubiquinated\ proteins.

There are two distinct families of UCH. The second family consist of large\ proteins (800 to 2000 residues) that share two regions of similarity, a region that contains\ a conserved cysteine which is probably implicated in the catalytic mechanism and a \ region that contains two conserved histidines residues, one of which is\ also probably implicated in the catalytic mechanism.

\ \ ubiquitin C-terminal hydrolase activity ; GO:0004221 \N ubiquitin-dependent protein catabolism ; GO:0006511 20110 IPR001393 Calsequestrin is the principal calcium-binding protein present in the sarcoplasmic reticulum of cardiac and skeletal muscle [MEDLINE:88243763]. It is a highly \ acidic protein that is able to bind over 40 calcium ions and acts as an internal\ calcium store in muscle. Sequence analysis has suggested that calcium is\ not bound in distinct pockets via EF-hand motifs, but rather via \ presentation of a charged protein surface.

Two forms of calsequestrin\ have been identified. The cardiac form is present in cardiac and slow\ skeletal muscle and the fast skeletal form is found in fast skeletal muscle.\ The release of calsequestrin-bound calcium (through a a calcium\ release channel) triggers muscle contraction.\ The active protein is not highly structured, more than 50% of\ it adopting a random coil conformation [MEDLINE:88107564]. When calcium binds there is a structural change whereby\ the -helical content of the protein increases from 3 to 11% [MEDLINE:88107564].\ Both forms of calsequestrin are phosphorylated by casein kinase II, but\ the cardiac form is phosphorylated more rapidly and to a higher degree [MEDLINE:91093153].

\ \ calcium ion storage activity ; GO:0005514 \N \N 20108 IPR001391

Opsins are the photoreceptors of animal retinas PUB00005667: vertebrate rhodopsinis found in rod cells and mediates scotopic vision; red, green and blue\ opsins are found in cone cells and mediate photopic vision. The opsins from\ the lateral eyes and median ocelli of the horseshoe crab, Limulus polyphemus,\ are likely to be the visible-wavelength rhodopsins in this animal PUB00005667. In\ the lateral eye, expression of the opsin gene is restricted to the photoreceptor cells of the ommatidia [MEDLINE:93317641]. Limulus opsins, and closely-related\ crayfish, mantid and honeybee rhodopsins, are most similar to the opsin\ from the R1-6 photoreceptors of flies.

\ \ rhodopsin-like receptor activity ; GO:0001584 integral to membrane ; GO:0016021 phototransduction ; GO:0007602 20109 IPR001392 Clathrin-coated pits and vesicles originate from the plasma membrane and the trans-Golgi, and mediate the trafficking of proteins to and from the\ membranes [MEDLINE:94116859]. The different vesicle types transport different proteins.\ Plasma membrane vesicles are involved in the endocytosis of membrane\ proteins, such as LDL and EGF receptors and trans-Golgi vesicles are\ involved in protein sorting and regulated secretion.

The main components\ of the pits are clathrin, and the clathrin-associated protein complex, AP,\ (also known as assembly or adaptor proteins) [MEDLINE:91113395]. Both trans-Golgi\ adaptor proteins, AP-1, and plasma membrane adaptor proteins, AP-2, are\ heterotetramers that consist of two large chains (' and gamma in AP-1,\ and and in AP-2); a medium chain (AP47 in AP-1, and AP50 in\ AP-2); and a small chain (AP19 in AP-1, and AP17 in AP-2).\

The adaptor complexes are believed to couple clathrin lattices with \ particular membrane proteins by interacting with their cytoplasmic tails,\ leading to their selection and concentration: the medium chains regulate\ this process by self-phosphorylation via a mechanism that is still unclear\ [MEDLINE:92104180]. The medium chains possess a highly conserved N-terminal domain of\ around 230 amino acids, which may be the region of interaction with other\ AP proteins; a linker region of between 10 and 42 amino acids; and a less\ well-conserved C-terminal domain of around 190 amino acids, which may be\ the site of specific interaction with the protein being transported\ in the vesicle [MEDLINE:92104180] .

\ \ \N clathrin vesicle coat ; GO:0030125 intracellular protein transport ; GO:0006886 20104 IPR001387 This is large family of DNA binding helix-turn helix proteins that include, a bacterial plasmid copy control protein, bacterial methylases, various bacteriophage transcription control proteins and a vegetative specific protein from slime mold.\ \ DNA binding activity ; GO:0003677 \N \N 20105 IPR001388 Synaptobrevin is an intrinsic membrane protein of small synaptic vesicles [MEDLINE:90180466], specialised secretory organelles of neurons that actively accumulate neurotransmitters and participate in their calcium-\ dependent release by exocytosis. Vesicle function is mediated by \ proteins in their membranes, although the precise nature of the protein-\ protein interactions underlying this are still uncertain [MEDLINE:91009161]. Synaptobrevin may play a role in the molecular events underlying neurotransmitter release and\ vesicle recycling and may be involved in the regulation of\ membrane flow in the nerve terminal, a process mediated by interaction\ with low molecular weight GTP-binding proteins [MEDLINE:94010306]. Synaptic vesicle-associated membrane proteins (VAMPs) from electric ray and SNC1 from yeast are related to synaptobrevin.\ \ \N \N \N 20106 IPR001389 Yeast flocculation protein may be directly involved in the flocculation process [MEDLINE:96076625] . The extensively O-glycosylated protein is probably attached to the membrane by a GPI-anchor.\ \N \N flocculation ; GO:0000128 20107 IPR001390

\ \

Alpha subunits\ largely determine benzodiazepine binding properties [MEDLINE:91193728]. Mutagenesis and agonist/antagonist binding studies have suggested a close functional and structural association of -subunits with the agonist/antagonist binding site, and involvement of N-terminal portions of the extracellular domains of all subunits in the gating of the channel [MEDLINE:92289664].

\ \ \ ion channel activity ; GO:0005216 membrane ; GO:0016020 ion transport ; GO:0006811 20103 IPR001385 Rotaviruses consist of three concentric protein shells. The intermediate (middle) protein layer contains VP6, the major internal structural protein. VP6 is the most \ abundant protein in the virion and is involved in virion assembly,\ VP6 possesses the ability to interact with VP2, VP4 and VP7 [MEDLINE:97410278], [MEDLINE:94335112].\ \ structural molecule activity ; GO:0005198 viral capsid ; GO:0019028 \N 20102 IPR001384

Metalloproteases can be split into five clans, and futher sub-divided into families, on the basis of their metal binding residues.

Deuterolysin is a microbial zinc-containing metalloprotease that shows\ some similarity to thermolysin [MEDLINE:91360097]. The protein is expressed with a\ possible 19-residue signal sequence, a 155-residue propeptide, and an\ active peptide of 177 residues [MEDLINE:94325364]. The latter contains an HEXXH motif\ towards the C-terminus, but the other zinc ligands are as yet undetermined\ [MEDLINE:91360097], [MEDLINE:94325364].

\ \ metalloendopeptidase activity ; GO:0004222 \N proteolysis and peptidolysis ; GO:0006508 20100 IPR001382

Glycoside hydrolase family 47 CAZY:GH_47).

Alpha-mannosidase is involved in the maturation of Asn-linked oligo-saccharides [MEDLINE:94193679]. The enzyme hydrolyses terminal 1,2-linked -D-mannose\ residues in the oligo-mannose oligosaccharide man(9)(glcnac)(2) in a\ calcium-dependent manner. The mannose residues are trimmed away to produce,\ first, man(8)glcnac(2), then a man(5)(glcnac)(2) structure.

\ \ calcium ion binding activity ; GO:0005509 membrane ; GO:0016020 N-linked glycosylation ; GO:0006487 20101 IPR001383

\ \ \

The ribosomal L28 protein family include proteins from bacteria\ and chloroplasts. The L24 protein from yeast, found in the large subunit of the mitochodrial ribosome, contains a region similar to the bacterial L28 protein.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 20096 IPR001378 This domain had been observed is a number of proteins of archaea and bacterial origin. The function of this domain is unknown.\ molecular_function unknown ; GO:0005554 \N \N 20097 IPR001379 Egg lysin is a fertilization protein that dissolves the egg vitelline layer nonenzymatically during fertilization. This creates a hole in the envelope of the egg thereby allowing the sperm to pass through the envelope and fuse with the egg [MEDLINE:95386571], [MEDLINE:94090312].\ \ lysin activity ; GO:0015465 \N fertilization (sensu Animalia) ; GO:0007338 20098 IPR001380

\ \ \

The ribosomal protein L13e is widely found in vertebrates [MEDLINE:94256964], Drosophila melanogaster, plants, yeast and others.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 20095 IPR001377

\ \ \

A number of eukaryotic and archaebacterial ribosomal proteins have been grouped\ on the basis of sequence similarities. \ Ribosomal protein S6 is the major substrate of protein kinases in eukaryotic ribosomes [MEDLINE:93179470] and\ may play an important role in controlling cell growth and proliferation\ through the selective translation of particular classes of mRNA.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 20099 IPR001381

3-dehydroquinate dehydratase (EC: 4.2.1.10), or dehydroquinase, catalyzes the conversion of 3-dehydroquinate into 3-dehydroshikimate. It is the third step\ in the shikimate pathway for the biosynthesis of aromatic amino acids from\ chorismate. Two classes of dehydroquinases exist, known as types I and II.

The\ best studied type I enzyme is from Escherichia coli (gene aroD) and related\ bacteria where it is a homodimeric protein.\ In fungi, dehydroquinase is part of a multifunctional enzyme which catalyzes\ five consecutive steps in the shikimate pathway. A histidine [MEDLINE:93054505] is involved in the catalytic mechanism.

\ \ \ 3-dehydroquinate dehydratase activity ; GO:0003855\ \N \N aromatic amino acid family biosynthesis ; GO:0009073 20091 IPR001373 The cullins are hydrophilic proteins involved in cell division control in yeasts\ \ \ [MEDLINE:97098640] and probably in various processes in the cell cycle of other organisms [MEDLINE:96279828]. Mammalian vasopressin-activated calcium-mobilizing receptor (VACM-1), a\ kidney-specific protein thought to form a cell surface receptor but\ which does not have any structural hallmarks of a receptor [MEDLINE:95335865] and \ Drosophila lin19 belong to this family of proteins.\ \ \N \N cell cycle ; GO:0007049 20092 IPR001374

The R3H motif: a domain that binds single-stranded nucleic acids.

The most prominent feature of the R3H motif is the presence of an invariant arginine residue and a highly conserved histidine residue that are separated by three residues. The motif also displays a conserved pattern of hydrophobic residues, prolines and glycines. The R3H motif is present in proteins from a diverse range of organisms that includes Eubacteria, green plants, fungi and various groups of metazoans. Intriguingly, it has not yet been identified in Archaea and Escherichia coli.

\ \

The sequences that contain the R3H domain, many of which are hypothetical proteins predicted from genome sequencing projects, can be grouped into eight families on the basis of similarities outside the R3H region. Three of the families contain ATPase domains either upstream (families II and VII) or downstream of the R3H domain (family VIII). The N-terminal part of members of family VII contains an SF1 helicase domain5. The C-terminal part of family VIII contains an SF2 DEAH helicase domain5. The ATPase domain in the members of family II is similar to the stage-III sporulation protein AA (S3AA_BACSU), the proteasome ATPase, bacterial transcription-termination factor r and the mitochondrial F1-ATPase b subunit (the F5 helicase family5). Family VI contains Cys-rich repeats6, as well as a ring-type zinc finger upstream of the R3H domain. JAG bacterial proteins (family I) contain a KH domain N-terminal to the R3H domain. The functions of other domains in R3H proteins support the notion that the R3H domain might be involved in interactions with single-stranded nucleic acids [MEDLINE:99003905].

\ \ nucleic acid binding activity ; GO:0003676 \N \N 20093 IPR001375

The prolyl oligopeptidase family [MEDLINE:92062013], [MEDLINE:92384936], [MEDLINE:92384937] consist of a number of evolutionary\ related peptidases whose catalytic activity seems to be provided by a charge\ relay system similar to that of the trypsin family of serine proteases, but\ which evolved by independent convergent evolution.

\ \

These proteins belong to families S9A/S9B/S9C in the classification of peptidases.

\ \ serine-type peptidase activity ; GO:0008236 \N proteolysis and peptidolysis ; GO:0006508 20090 IPR001372

Dynein is composed of a number of\ ATP-binding large subunits (see IPR004273), intermediate size subunits and small subunits.\ Among the small subunits, there is a family of highly conserved proteins which make up this family [MEDLINE:95263466], [MEDLINE:96189078].\

\ \ microtubule motor activity ; GO:0003777 microtubule associated complex ; GO:0005875 microtubule-based process ; GO:0007017 20094 IPR001376

Gluten is the protein component of Triticum aestivum (wheat) flour. It consists of numerous proteins, which are of 2 different types responsible for different physical properties of dough: the glutenins, which are primarily responsible for the elasticity, and the gliadins, which contribute to the extensibility. The glutenins themselves are of 2 different types, termed low and high [MEDLINE:86041882] molecular weight subunits. The latter have unusual structures: a central region contains multiple tandem repeats of blocks of amino acids, forming a loose helix based on reverse turns, and is flanked by globular regions, which can be cross-linked by disulphide bonds. The result is an elastic network in which the elasticity may derive from the cross-linking, the helical structure, or a combination of these [MEDLINE:89098419].

Gliadins are a complex mixture of proteins that contain at least 40 different components in a single variety of wheat. The / gliadins can be divided into five homology classes. Sequence divergence between the classes is due to single base substitutions and to duplications or deletions within or near direct repeats [MEDLINE:85234522].

\ \ nutrient reservoir activity ; GO:0045735 \N \N 20087 IPR001369

Phosphorylases that belong to the same family include, purine nucleoside phosphorylase (EC: 2.4.2.1) (PNP) from mammals as well as from some bacteria (gene deoD) (\ catalyzes the cleavage of guanosine or inosine to respective bases and sugar-1-phosphate \ molecules) [MEDLINE:90110256], 5'-methylthioadenosine\ phosphorylase (EC: 2.4.2.28) (MTA phosphorylase) from eukaryotes\ \ \ \ [MEDLINE:96268710] and xanthosine phosphorylase \ (EC: 2.4.2.-) from Escherichia coli (gene xapA) (degrades all purine nucleosides \ except adenosine and deoxyadenosine )[MEDLINE:96032385].\ Most bacterial PNP and archaebacterial MTA phosphorylases belong to a different group of \ phosphorylases IPR000845. A number of uncharacterized proteins also belong to this \ group.

\ \ phosphorylase activity ; GO:0004645 \N \N 20089 IPR001371

Family 14 (EC: 3.2.1.2, CAZY:GH_14) encompasses the -amylase enzymes.\ Beta-amylases, which are found in plants and bacteria, hydrolyse 1,4--glucosidic linkages in starch-type polysaccharide substrates, removing\ successive maltose units from the non-reducing ends of the chains PUB00004513. In\ potato plants, the enzyme has been found to work optimally at 40 degrees C,\ becoming unstable above this temperature PUB00004513. On the basis of sequence\ comparisons, plant and bacterial -amylases can be readily distinguished\ from each other.

\ \ beta-amylase activity ; GO:0016161 \N polysaccharide catabolism ; GO:0000272 20088 IPR001370 The baculovirus inhibitor of apoptosis protein repeat (BIR) is a domain of tandem repeatsseparated by a variable length linker that seems to confer cell death-preventing activity\ [MEDLINE:94187094], [MEDLINE:96149249]. It is found in proteins \ belonging to the IAP (inhibitor of apoptosis proteins) family. Members of this family (with \ the exception of NAIP)\ contain two or three BIR repeats and a RING finger IPR001841 in their C-terminus .\ \ apoptosis inhibitor activity ; GO:0008189 intracellular ; GO:0005622 anti-apoptosis ; GO:0006916 20085 IPR001367 The diphtheria toxin repressor protein (DTXR) is a member of this group [MEDLINE:96003876]. In Corynebacterium diphtheriae where it has been studied in some detail this protein acts\ as an iron-binding repressor of dipheteria toxin gene expression and may serve as a \ global regulator of gene expression. The N-terminus may be involved in iron binding and\ may associate with the Tox operator. Binding of DTXR to Tox operator requires a divalent\ metal ion such as cobalt, ferric, manganese and nickel whereas zinc shows weak \ activation [MEDLINE:95261708].\ \ iron ion binding activity ; GO:0005506 \N regulation of transcription, DNA-dependent ; GO:0006355 20086 IPR001368

A number of proteins, some of which are known to be receptors for growth factors have been found to contain a cysteine-rich domain at the N-terminal region that can be \ subdivided into four (or in some cases, three) repeats containing six conserved\ cysteines all of which are involved in intrachain disulfide bonds [MEDLINE:93258809].

\ \

CD27 (also called S152 or T14) mediates a co-stimulatory signal for T and B cell activation and is involved in murine T cell development. Tyrosine-phosphorylation of ZAP-70 following CD27 ligation of T cells has been reported [MEDLINE:95081590], but not confirmed independently. CD30 was originally identified as Ki-1, an antigen expressed on Reed-Sternberg cells in Hodgkin's\ lymphomas and other non-Hodgkin's lymphomas, particularly diffuse large-cell lymphoma and immunoblastic lymphoma. CD30 has pleiotropic effects on CD30-positive lymphoma cell lines ranging from cell proliferation to cell death. It is thought to be involved in negative selection of T-cells in the thymus and is involved in TCR-mediated cell death. CD30 is a member of the TNFR family of molecules, activate NFkB through interaction with TRAF2 and TRAF5. CD40 (Bp50) plays a central role in the regulation of cell-mediated immunity as well as antibody mediated immunity. It is central to T cell dependent (TD)-responses and may influence survival of B cell lymphomas.

CD95 (also called APO-1, fas antigen, Fas tumor necrosis factor receptor superfamily, member 6, TNFRSF6 or apoptosis antigen 1, APT1) is expressed, typically at high levels, on activated T and B cells. It is involved in the mediation of apoptosis-inducing signals.

\ \

Other proteins known to belong to this family [MEDLINE:91362790], [MEDLINE:91068289], \ PUB00001018, PUB00001018 are, tumor Necrosis Factor type I and type II receptors (TNFR), shope \ fibroma virus soluble TNF receptor (protein T2), lymphotoxin / receptor, \ low-affinity nerve growth factor receptor (LA-NGFR) (p75), T-cell antigen OX40,\ Wsl-1, a receptor (for a yet undefined ligand) that mediates apoptosis and Vaccinia virus \ protein A53 (SalF19R).

\ \

CD molecules are leucocyte antigens on cell surfaces. CD antigens nomenclature is updated at http://www.ncbi.nlm.nih.gov/PROW/guide/45277084.htm \

\ \ \ receptor activity ; GO:0004872 \N \N 20084 IPR001367 The diphtheria toxin repressor protein (DTXR) is a member of this group [MEDLINE:96003876]. In Corynebacterium diphtheriae where it has been studied in some detail this protein acts\ as an iron-binding repressor of dipheteria toxin gene expression and may serve as a \ global regulator of gene expression. The N-terminus may be involved in iron binding and\ may associate with the Tox operator. Binding of DTXR to Tox operator requires a divalent\ metal ion such as cobalt, ferric, manganese and nickel whereas zinc shows weak \ activation [MEDLINE:95261708].\ \ iron ion binding activity ; GO:0005506 \N regulation of transcription, DNA-dependent ; GO:0006355 20083 IPR001366 Proteins that transport heavy metals in micro-organisms and mammals share similarities in their sequences and structures. Some of these proteins are involved in bacterial resistance to toxic metals, such as lead and cadmium, \ while others are involved in inherited human syndromes, such as Wilson and Menkes diseases [MEDLINE:94378325].\

Cadmium-transporting ATPase is an integral membrane protein present only in prokaryotes that contains\ a single copy of the HMA domain and is predicted to contain 4 transmembrane\ (TM) domains. The protein, which functions as an electroneutral antiporter,\ ejecting one Cd²⁺ and accumulating two protons via an energy-dependent\ efflux mechanism, catalyses the reaction:

\ \

ATP + H₂O = ADP + orthophosphate

\ \ ATP binding activity ; GO:0005524 membrane ; GO:0016020 cation transport ; GO:0006812 20081 IPR001364 The haemagglutinin (HA) glycoprotein of influenza is a trimer containing three structurally distinct regions: a globular head of anti-parallel

-sheet, which contains the receptor binding site and the variable\ antigenic determinants (antigenic variation in haemagglutinin is\ associated with recurrent epidemics of respiratory diseases in man); a\ triple-stranded, coiled-coil,

-helical stalk; and a globular foot of\ anti-parallel

-sheet [MEDLINE:88232903], [MEDLINE:85012744], [MEDLINE:81123029], [MEDLINE:81123030]. \

The structural domains of haemagglutinin are arranged broadly as follows:\ a large globular, hydrophilic, carbohydrate-containing domain resides on \ the external suface of the membrane; a small, uncharged hydrophobic peptide\ spans the membrane; and a smaller globular, hydrophilic domain resides on\ the inside of the membrane.

Each monomer in the structure comprises two\ disulphide-linked chains, HA1 and HA2. The N-terminus of HA1 provides a \ central strand in the 5-stranded globular foot, the chain then making its\ way to the globular head, where it forms an 8-stranded Swiss-roll. HA2\ provides two -helices, which form part of the fibrous structure\ (three helices, one from each monomer, pack together as the triple-stranded\ coiled-coil that stablises the trimer), its C-terminus providing the\ remaining strands of the 5-stranded globular foot.

\ \ \N \N \N 20082 IPR001365

\ \ deaminase activity ; GO:0019239 \N purine ribonucleoside monophosphate biosynthesis ; GO:0009168 20080 IPR001363

The fetuins are known to consist of three domains: two tandemly arranged N-terminal cystatin\ domains (D1 and D2) and an unrelated domain (D3) located in the C-terminal region [MEDLINE:92209519], [MEDLINE:92223088]. When compared with the other members of this\ family, D3, especially its N-terminal half, varies greatly due to deletions, insertions or substitutions. Sequence comparisons suggests that the conformation of the human alpha2HS\ glycoprotein differs greatly from that of other members of this family. Human fetuin is a heterodimer of chains A and B, \ which are derived by cleavage of a connecting peptide from a common precursor. It is \ synthesized in the liver and selectively concentrated in bone matrix. It has a wide functional \ diversity having been \ shown to be involved in immune response, bone formation and resorption.

\ \

Mammalian fetuin also called -2-HS-glycoprotein, bone sialic acid-containing protein \ (BSP), countertrypin or PP63, is expressed in a tissue- and development-specific pattern \ which seems to be significantly different between species [MEDLINE:91190111], [MEDLINE:97279057].

\ \ \ \ \N \N \N 20079 IPR001362

Glycoside hydrolase family 32 CAZY:GH_32).

\ \ hydrolase activity, hydrolyzing O-glycosyl compounds ; GO:0004553 \N carbohydrate metabolism ; GO:0005975 20078 IPR001361 Equine infectious anemia (EIAV) belongs to the family retroviridae. EIAV gp90 is hypervariable in the carboxyl-end region and more stable in the amino-end region. This \ variability is a pathogenicity factor that allows the evasion of the host's immune \ response [MEDLINE:91303680].\ \ structural molecule activity ; GO:0005198 viral capsid ; GO:0019028 \N 20077 IPR001360

Glycoside hydrolase family 1 CAZY:GH_1).

\ \ hydrolase activity, hydrolyzing O-glycosyl compounds ; GO:0004553 \N carbohydrate metabolism ; GO:0005975 20076 IPR001359 Synapsins are neuronal phosphoproteins that coat synaptic vesicles, bind to several elements of the cytoskeleton (including actin filaments), and are believed to function in \ the regulation of neurotransmitter release [MEDLINE:90351456], [MEDLINE:20047107]. The synapsin family currently \ includes the highly related synapsin I and II. Both synapsins exist in two alternatively \ spliced variants, IA and IB and IIA and IIB, that only differ at the C-terminus. \ It also includes synapsin III.\ \ \N synaptic vesicle ; GO:0008021 neurotransmitter secretion ; GO:0007269 20075 IPR001359 Synapsins are neuronal phosphoproteins that coat synaptic vesicles, bind to several elements of the cytoskeleton (including actin filaments), and are believed to function in \ the regulation of neurotransmitter release [MEDLINE:90351456], [MEDLINE:20047107]. The synapsin family currently \ includes the highly related synapsin I and II. Both synapsins exist in two alternatively \ spliced variants, IA and IB and IIA and IIB, that only differ at the C-terminus. \ It also includes synapsin III.\ \ \N synaptic vesicle ; GO:0008021 neurotransmitter secretion ; GO:0007269 20072 IPR001356 The homeobox domain was first identified in a number of drosophila homeotic and segmentation proteins, but is now known to be well-conserved in many other animals, \ including vertebrates [MEDLINE:89323170], [MEDLINE:93032126], PUB00005540. Hox genes encode homeodomain-containing transcriptional regulators that operate differential genetic programs along the anterior-posterior axis of animal bodies PUB00005540. The domain binds DNA through a \ helix-turn-helix (HTH) structure. The HTH motif is characterised by two

-helices, \ which make intimate contacts with the DNA and are joined by a short turn. The second \ helix binds to DNA via a number of hydrogen bonds and hydrophobic interactions, which \ occur between specific side chains and the exposed bases and thymine methyl groups within \ the major groove of the DNA PUB00005540. The first helix helps to stabilise the \ structure.

\ \ transcription factor activity ; GO:0003700 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 20073 IPR001357

The BRCT domain (after the C_terminal domain of a breast cancer susceptibility protein) is found predominantly in proteins involved in cell cycle checkpoint functions responsive to DNA damage [MEDLINE:97186552]. The carboxyterminal BRCT domain corresponds precisely to the\ recently identified minimal transcription activation domain of the breast cancer protein BRCA1, indicating one such\ function.

A chitin biosynthesis protein from \ yeast also seems to belong to this group.

\ \ \N intracellular ; GO:0005622 \N 20074 IPR001358

Neuropeptide Y (NPY) is one of the most abundant peptides in mammalian\ brain, inducing a variety of behavioural effects (e.g., stimulation of food\ intake, anxiety, facilitation of learning and memory, and regulation of the\ cardiovascular and neuroendocrine systems) . In the periphery, NPY\ stimulates vascular smooth muscle contraction and modulates hormone\ secretion. NPY has been implicated in the pathophysiology of hypertension,\ congestive heart failure, affective disorders and appetite regulation PUB00005893.

Several pharmacologically distinct neuropeptide Y receptors have been\ characterised, designated NPY Y1-Y6. High densities of Y2 receptors are\ present in rat hippocampus and are also found in high levels in superficial\ layers of cortex, certain thalamic nuclei, lateral septum, and anterior\ olfactory nuclei; lower levels are found in striatum . The receptors are\ found in high levels in smooth muscle (e.g., vas deferens and intestine),\ kidney proximal tubules and in cell lines . They are believed to have a\ predominantly presynaptic location, and are involved in inhibition of\ adenylyl cyclase and voltage dependent calcium channels via a pertussis-toxin-sensitive G-protein, probably of the G0/Gi class PUB00005893.

\ \ neuropeptide Y receptor activity ; GO:0004983 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20070 IPR001354

Mandelate racemase (EC: 5.1.2.2) (MR) and muconate lactonizing enzyme (EC: 5.5.1.1) (MLE) are two bacterial enzymes involved in aromatic acid catabolism. They catalyze \ mechanistically distinct reactions yet they are related at the level of their primary, \ quaternary (homooctamer) and tertiary structures [MEDLINE:91015392], [MEDLINE:94078330].\ A number of other proteins also seem to be evolutionary related to these two\ enzymes. These include, various plasmid-encoded chloromuconate cycloisomerases \ (EC: 5.5.1.7), Escherichia coli protein rspA [MEDLINE:94310441], Escherichia coli bifunctional DGOA protein, Escherichia coli \ hypothetical proteins ycjG, yfaW and yidU and a hypothetical protein from Streptomyces \ ambofaciens\ \ \ \ [MEDLINE:94103730].

\ \ enzyme activity ; GO:0003824 \N metabolism ; GO:0008152 20069 IPR001354

\ \ enzyme activity ; GO:0003824 \N metabolism ; GO:0008152 20071 IPR001355

Interleukin-8 (IL8) is a pro-inflammatory cytokine involved in the cellular\ response to inflammation, being a powerful chemoattractant for neutrophils\ [MEDLINE:91368199]. There are 2 similar cell surface receptors for IL8: type 1 (IL-8RA) is\ a high affinity receptor for IL8 alone; while type 2 (IL-8RB) is a high\ affinity receptor for IL8, growth related gene (GRO) and neutrophil-activating protein-2 (NAP-2). The affinity of type 1 receptors for IL8 is\ higher than that of type 2 receptors [MEDLINE:91368199], [MEDLINE:93252387]. The receptors are coupled to\ Bordetella pertussis toxin-sensitive GTP-binding proteins [MEDLINE:92347562]. Signal\ transduction depends on the activation of a phospholipase C specific for\ phosphatidylinositol-4,5-bisphosphate, producing 2 second messengers:\ inositol triphosphate and diacylglycerol [MEDLINE:92347562]. Inositol triphosphate induces\ a rise in the levels of cytosolic free calcium, while diacylglycerol\ activates protein kinase C, leading to activation of neutrophils [MEDLINE:92347562].

IL8RA receptors are found in high density in neutrophils, monocytes,\ basophils, and melanoma cells, and in lower density in T-cells . IL8\ has been reported to stimulate the phosphoinositide pathway through an\ uncharacterised G-protein; pertussis toxin also inhibits several of its\ actions PUB00005876. The IL8RA receptor shares around 80% similarity with the\ IL8RB receptor.

\ \ interleukin-8 receptor activity ; GO:0004918 integral to membrane ; GO:0016021 chemotaxis ; GO:0006935 20066 IPR001351

\ \ \

Ribosomal protein S3 is one of the proteins from the small ribosomal subunit. In \ Escherichia coli, S3 is known to be involved in the binding of initiator Met-tRNA. This family of ribosomal proteins includes S3 from bacteria, algae and \ plant chloroplast, cyanelle, archaebacteria, plant mitochondria, vertebrates, insects,\ Caenorhabditis elegans and yeast [MEDLINE:94310455].

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 20065 IPR001351

\ \ \

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 20067 IPR001352 Ribonuclease HII is involved in the degradation of the ribonucleotide moiety on RNA-DNAhybrid molecules carrying out endonucleolytic cleavage to 5'-phospo-monoester. Proteins\ which belong to this family have been found in bacteria, archaea, and yeasts. This family also includes Ribonuclease HIII\ \ ribonuclease H activity ; GO:0004523 \N \N 20068 IPR001353 The proteasome (or macropain) (EC: 3.4.25.1) [MEDLINE:93228587], [MEDLINE:89104406], [MEDLINE:92278429], [MEDLINE:95211199], [MEDLINE:97036935] is a ubiquitous multicatalytic proteinase complex that seems to be involved inan ATP/ubiquitin-dependent nonlysosomal proteolytic pathway. In eukaryotes the\ proteasome is composed of about 28 distinct subunits which form a highly\ ordered ring-shaped structure (20S ring) of about 700 Kd.\ Most proteasome subunits can be classified, on the basis on sequence\ similarities into two groups, A and B.\ \ \ 20S core proteasome complex ; GO:0005839\ proteasome endopeptidase activity ; GO:0004299 \N ubiquitin-dependent protein catabolism ; GO:0006511 20061 IPR001347 The SIS (Sugar ISomerase) domain is a phosphosugar-binding domain [MEDLINE:99221848] found in many phosphosugar isomerases and phosphosugar binding proteins. SIS domains are also found\ in proteins that regulate the expression of genes involved in synthesis of phosphosugars\ possibly by binding to the end-product of the pathway.\ \ sugar binding activity ; GO:0005529 \N carbohydrate metabolism ; GO:0005975 20062 IPR001348

ATP phosphoribosyltransferase (EC: 2.4.2.17) is the enzyme that catalyzes the first step in the biosynthesis of histidine in bacteria, fungi and plants.

\ \ ATP phosphoribosyltransferase activity ; GO:0003879 \N histidine biosynthesis ; GO:0000105 20063 IPR001349

In eukaryotes, in addition to the \ three large subunits, I, II and III, that form the catalytic center of the enzyme complex, there are \ a variable number of small polypeptidic subunits. One of these subunits is known as VIa \ in vertebrates and fungi. Mammals have two tissue-specific isoforms of VIa, a liver and a \ heart form. Only one form is found in fish\ \ \ \ [MEDLINE:97261360].

\ \ cytochrome c oxidase activity ; GO:0004129 mitochondrial membrane ; GO:0005740 electron transport ; GO:0006118 20064 IPR001350

Several 7TM receptors have been cloned but their endogenous ligands are\ unknown; these have been termed orphan receptors. G10d was isolated from a\ rat genomic library and a liver cDNA library PUB00005897, PUB00005897. It is widely distributed,\ being found in high levels in the lung, liver and adrenal gland, and also\ in the kidney, aorta, heart, spinal cord, gut and testis PUB00005897, PUB00005897.

\ \ G-protein coupled receptor activity, unknown ligand ; GO:0016526 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 20060 IPR001346 The expression of type I interferon genes (interferons

and

) is induced by many agents, including viral attack [MEDLINE:88311092]. Induction is mediated by the binding of \ interferon regulatory factor 1 (IRF-1) to a region known as the interferon consensus \ sequence (ICS), located upstream of the interferon genes [MEDLINE:93094284]. Other factors may \ also bind to the ICS, including IRF-2, which does not function as an activator, but \ rather suppresses the function of IRF-1 under certain circumstances [MEDLINE:89354547]. \ IRF proteins contain a conserved N-terminal region of about 120 amino acids, which folds \ into a structure that binds specifically to the ICS; the remaining parts of the\ sequences vary depending on the precise function of the protein [MEDLINE:93094284].\ \ transcription factor activity ; GO:0003700 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 20059 IPR001345

Phosphoglycerate mutase(EC: 5.4.2.1) (PGAM) and bisphosphoglycerate mutase (EC: 5.4.2.4) (BPGM) are structurally related enzymes which catalyze reactions involving the transfer \ of phospho groups between the three carbon atoms of phosphoglycerate [MEDLINE:89050120], [MEDLINE:88152269]. Both enzymes can catalyze three \ different reactions with different specificities, the isomerization of 2-phosphoglycerate\ (2-PGA) to 3-phosphoglycerate (3-PGA) with 2,3-diphosphoglycerate (2,3-DPG) as the primer \ of the reaction, the synthesis of 2,3-DPG from 1,3-DPG with 3-PGA as a primer and the \ degradation of 2,3-DPG to 3-PGA (phosphatase EC: 3.1.3.13 activity).

In mammals, PGAM is a dimeric protein with two isoforms, the M (muscle) and B (brain) \ forms. In yeast, PGAM is a tetrameric protein.

BPGM is a dimeric protein and is found \ mainly in erythrocytes where it plays a major role in regulating hemoglobin oxygen \ affinity as a consequence of controlling 2,3-DPG concentration. The catalytic mechanism \ of both PGAM and BPGM involves the formation of a phosphohistidine intermediate [MEDLINE:83088106].

A number of other proteins including, the bifunctional \ enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase [MEDLINE:90099320] that catalyzes both the synthesis and \ the degradation of fructose-2,6-bisphosphate and bacterial -ribazole-5'-phosphate \ phosphatase that is involved in cobalamin biosynthesis belong to this family.\ [MEDLINE:95014494].

\ \ enzyme activity ; GO:0003824 \N metabolism ; GO:0008152 20053 IPR001339 The mRNA capping enzyme in yeasts is composed of two separate chains,

a mRNAguanyltransferase and

Aspartate kinase (EC: 2.7.2.4) (AK) catalyzes the phosphorylation of aspartate. The product \ of this reaction can then be used in the biosynthesis of lysine or in the pathway \ leading to homoserine, which participates in the biosynthesis of threonine, isoleucine \ and methionine [MEDLINE:88115350].

In bacteria there are three different isozymes which differ in sensitivity to repression \ and inhibition by Lys, Met and Thr. AK1 and AK2 are bifunctional enzymes which both \ consist of an N-terminal AK domain and a C-terminal homoserine dehydrogenase domain. \ AK1 is involved in threonine biosynthesis and AK2, in that of methionine. The third\ isozyme, AK3 is monofunctional and involved in lysine synthesis.

In archaea and plants \ there may be a single isozyme of AK which in plants is multifunctional.

\ \ aspartate kinase activity ; GO:0004072 \N amino acid biosynthesis ; GO:0008652 20056 IPR001342

Homoserine dehydrogenase (EC: 1.1.1.3) (HDh) catalyzes NAD-dependent reduction of aspartate -semialdehyde into homoserine [MEDLINE:93272973], [MEDLINE:93372178]. This reaction is the third step in\ a pathway leading from aspartate to homoserine. The latter participates in the \ biosynthesis of threonine and then isoleucine as well as in that of methionine.

HDh is found either as a single chain protein as in some bacteria and yeast,\ or as a bifunctional enzyme consisting of an N-terminal aspartokinase domain\ and a C-terminal HDh domain as in bacteria such as Escherichia coli and in plants.

\ \ homoserine dehydrogenase activity ; GO:0004412 \N amino acid biosynthesis ; GO:0008652 20057 IPR001343 Gram-negative bacteria produce a number of proteins that are secreted into the growth medium by a mechanism that does not require a cleaved N-terminal signal sequence. These \ proteins, while having different functions, seem to share two properties: they bind \ calcium and they contain a multiple tandem repeat of a nonapeptide [MEDLINE:90151607]. The \ nonapeptide is found in a group of bacterial exported proteins that includes haemolysin, \ cyclolysin, leukotoxin and two proteases.

\ \ calcium ion binding activity ; GO:0005509 \N \N 20058 IPR001344 The light-harvesting complex (LHC) consists of chlorophylls A and B and thechlorophyll A-B binding protein. LHC functions as a light receptor that captures and\ delivers excitation energy to photosystems with which it is closely associated.

The\ N-terminus of the chlorophyll A-B binding protein extends into the stroma where it is\ involved with adhesion of granal membranes and photoregulated by reversible\ phosphorylation of its threonine residues. Both these processes are believed to mediate \ the distribution of excitation energy between photosystems I and II.

\ \ \N \N photosynthesis light harvesting ; GO:0009765 20052 IPR001339 The mRNA capping enzyme in yeasts is composed of two separate chains,

a mRNAguanyltransferase and

an RNA 5'-triphosphate. X-ray crystallography reveals a large \ conformational change during guanyl transfer by mRNA capping enzymes [MEDLINE:97304383].\ Binding of the enzyme to nucleotides is specific to the GMP moiety of GTP. The viral \ mRNA capping enzyme is a monomer that transfers a GMP cap onto the end of mRNA that \ terminates with a 5'-diphosphate tail.\ \ mRNA guanylyltransferase activity ; GO:0004484 \N mRNA processing ; GO:0006397 20049 IPR001336 Epidermal growth factors and transforming growth factors belong to a general class of proteins that share a repeat pattern involving a number of conserved Cys residues. Growth \ factors are involved in cell recognition and division [MEDLINE:90321281]. The repeating \ pattern, especially of cysteines (the so-called EGF repeat), is thought to be important \ to the 3D structure of the proteins, and hence its recognition by receptors and other \ molecules. The type 1 EGF signature includes six conserved cysteines believed to be \ involved in disulphide bond formation. The EGF motif is found frequently in nature, \ particularly in extracellular proteins.\ \ \N \N \N 20050 IPR001337 This family contains coat proteins from tobamoviruses. Tobamoviruses are ssRNA positive-strand viruses with no DNA stage.

In order to establish infections, viruses must be delivered to the cells of potential hosts and must then engage in activities that enable their genomes to be expressed and replicated. With most viruses, the events that precede the onset of production of progeny virus particles are referred to as the early events and, in the case of positive-strand RNA viruses, they include the initial\ interaction with and entry of host cells and the release (uncoating) of the genome from the virus particles. The uncoating process in tobacco mosaic virus may involve the bidirectional release of coat protein subunits from the viral RNA which may be mediated by cotranslational and coreplicational disassembly mechanisms [MEDLINE:99229410].

The tobacco mosaic virus particle is assembled from its constituent coat protein and RNA by a complex process. The protein forms an obligatory intermediate (a cylindrical disk composed of two layers of protein units), which recognizes a specific RNA hairpin sequence. This mechanism simultaneously fulfils the physical requirement for nucleating the growth of the helical particle and the biological requirement for specific recognition of the viral DNA [MEDLINE:99229402].

\ \ structural molecule activity ; GO:0005198 viral capsid ; GO:0019028 \N 20051 IPR001338 The surface of many fungal spores is covered by a hydrophobic sheath, the rodlet layer whose main component is a protein known as the rodlet protein [MEDLINE:91293577], [MEDLINE:93093471]. The \ rodlet proteins of Neurospora crassa (gene eas) and Emericella nidulans (gene rodA) are \ evolutionary related to proteins found in the cell wall of fruiting bodies of the \ mushroom Schizophyllum commune\ \ \ \ [MEDLINE:90382666].\ Collectively, these low-molecular-weight, cysteine-rich (eight conserved cysteines), \ hydrophobic proteins, are known as hydrophobins.\ \ structural constituent of cell wall ; GO:0005199 cell wall ; GO:0005618 \N 20048 IPR001334

The papillomavirus E6 oncoproteins are small zinc-binding proteins that share a conserved zinc-binding CXXC motif and do not have identified intrinsic enzymatic activity. E6 proteins are thought to act as adapter proteins, thereby altering the function of E6-associated cellular proteins. This model for E6 function is best supported by observations of human papillomavirus type 16 (HPV-16) E6 (16E6), which can alter the metabolism of the p53 tumor suppressor through association with a cellular E3 ubiquitin ligase called E6AP. HPV-16 E6 interacts with an 18-amino-acid sequence in E6AP, and in an as yet ill-defined fashion the E6AP-16E6 complex binds to p53, inducing the ubiquitin-dependent degradation of the trimolecular complex. 16E6 apparently functions as an adapter protein in the complex with p53, since E6AP does not interact with p53 in the absence of E6 and since the degradation of p53 requires both E6 and E6AP.

Despite the similarity in structure of the E6 oncoproteins, studies have indicated surprising biochemical diversity among E6 oncoproteins of different papillomavirus types. E6 from the cancer-associated human papillomaviruses (HPVs) complex with a cellular protein termed E6-AP and together with E6-AP bind to the p53 tumor suppressor protein thereby degrading p53 through ubiquitin-mediated proteolysis. E6 from the non-cancer-associated HPV types do not bind E6-AP or degrade p53. Bovine papilloma virus E6 (BE6) binds E6-AP but fails either to complex with p53 or to degrade associated proteins, implying that BE6 might transform cells through a mechanism different from that of the HPVs. In addition to targeting p53, E6 of both cancer-associated HPVs and BPV-1 have been shown to associate with a cellular-calcium-binding protein localized to the endoplasmic reticulum [MEDLINE:20091336], [MEDLINE:97296304].

\ \ DNA binding activity ; GO:0003677 host cell nucleus ; GO:0042025 \N 20045 IPR001331 Ras proteins are membrane-associated molecular switches that bind GTP and GDP and slowly hydrolyze GTP to GDP [MEDLINE:91095015]. The balance \ between the GTP bound (active) and GDP bound (inactive) states is regulated by the \ opposite action of proteins activating the GTPase activity and that of proteins which \ promote the loss of bound GDP and the uptake of fresh GTP [MEDLINE:94081948], PUB00001017. The latter proteins\ are known as guanine-nucleotide dissociation stimulators (GDSs) or also as\ guanine-nucleotide releasing (or exchange) factors (GRFs). Proteins that act as GDS can \ be classified into at least two families. One of these families is currently known to \ group the CDC24 family of proteins.\ \ guanyl-nucleotide exchange factor activity ; GO:0005085 \N intracellular signaling cascade ; GO:0007242 20046 IPR001332 Arteriviruses encode four envelope proteins, Gl, Gs, M and N. Gl envelope glycoproteinis heterogenously glycosylated with N-acetyllactosamine in a cell-type-specific manner. \ The Gl glycoprotein expresses the neutralization determinants [MEDLINE:96130216].\ \ \N viral envelope ; GO:0019031 \N 20047 IPR001333

Metalloproteases can be split into five clans, and futher sub-divided into families, on the basis of their metal binding residues.

Carboxypeptidase Taq is a zinc-containing thermostable metallopeptidase that\ belongs to the M32 family. It does not share any significant sequence\ similarity with other carboypeptidases or metalloproteases, so has not been\ assigned to a clan. It was originally discovered and purified from Thermus\ aquaticus; optimal enzymatic activity occurs at 80 celcius. Although very\ little is known about this enzyme, it is thought either to be associated\ with a membrane or to be particle bound PUB00005937.

\ \ metallocarboxypeptidase activity ; GO:0004181 \N proteolysis and peptidolysis ; GO:0006508 20044 IPR001330

The subunit of the farnesyltransferases is responsible for peptide binding.Squalene-hopene cyclase is a bacterial enzyme that catalyzes the cyclization of \ squalene into hopene, a key step in hopanoid (triterpenoid) metabolism [MEDLINE:97442532]. \ Lanosterol synthase (EC: 5.4.99.7) (oxidosqualene-lanosterol cyclase) catalyzes the \ cyclization of (S)-2,3-epoxysqualene to lanosterol, the initial precursor of cholesterol, \ steroid hormones and vitamin D in vertebrates and of ergosterol in fungi [MEDLINE:94287446]. \ Cycloartenol synthase (EC: 5.4.99.8) (2,3-epoxysqualene-cycloartenol cyclase) is a plant \ enzyme that catalyzes the cyclization of (S)-2,3-epoxysqualene to cycloartenol.

\ \ enzyme activity ; GO:0003824 \N \N 20043 IPR001329

Family 56 (CAZY:GH_56)\ that includes venom hyaluronidases [MEDLINE:93234539] and mammalian sperm surface proteins (PH-20).

\ \

Allergies are hypersensitivity reactions of the immune system to specific substances called allergens (such as pollen, stings, drugs, or food) that, in most people, result in no symptoms. A nomenclature system has been established for antigens (allergens) that cause IgE-mediated atopic allergies in humans [WHO/IUIS Allergen Nomenclature Subcommittee\ King T.P., Hoffmann D., Loewenstein H., Marsh D.G., Platts-Mills T.A.E.,\ Thomas W. Bull. World Health Organ. 72:797-806(1994)]. This nomenclature system is defined by a designation that is composed of\ the first three letters of the genus; a space; the first letter of the\ species name; a space and an arabic number. In the event that two species\ names have identical designations, they are discriminated from one another\ by adding one or more letters (as necessary) to each species designation.

The allergens in this family include allergens with the following designations: Api m 2, Dol m 2 and Ves v 2.

The venom of honeybees contains several biologically-active peptides and\ two enzymes, one of which is a hyaluronidase [MEDLINE:93234539]. The amino acid sequence of bee venom hyaluronidase contains 349 amino acids, and includes four\ cysteines and a number of potential glycosylation sites [MEDLINE:93234539]. The sequence shows a high degree of similarity to PH-20, a membrane protein of mammalian\ sperm involved in sperm-egg adhesion, supporting the view that hyaluronidases play a role in fertilisation [MEDLINE:93234539].

\ \ hyaluronoglucosaminidase activity ; GO:0004415 \N defense response ; GO:0006952 20042 IPR001328

Peptidyl-tRNA hydrolase (EC: 3.1.1.29) (PTH) is a bacterial enzyme that cleavespeptidyl-tRNA or N-acyl-aminoacyl-tRNA to yield free peptides or N-acyl-amino acids and \ tRNA. The natural substrate for this enzyme may be peptidyl-tRNA which drop off the \ ribosome during protein synthesis [MEDLINE:92007806],\ [MEDLINE:96186910]. Bacterial PTH has been found to be \ evolutionary related to a yeast protein [MEDLINE:96155066].

\ \ aminoacyl-tRNA hydrolase activity ; GO:0004045 \N protein biosynthesis ; GO:0006412 20040 IPR001326 Eukaryotic elongation factor 1 (EF-1) is responsible for the GTP-dependent binding of aminoacyl-tRNAs to the ribosomes [MEDLINE:91118231]. \ EF-1 is composed of four subunits: the

chain which binds GTP and aminoacyl-tRNAs,\ the gamma chain that probably plays a role in anchoring the complex to other cellular\ components and the

and delta (or

') chains. The

and delta chains are highly \ similar proteins that both stimulate the exchange of GDP bound to the

chain for \ GTP [MEDLINE:91002651]. The

and \ delta chains are hydrophilic proteins. Their C-terminus seems to be \ important for the nucleotide exchange activity, while the N-termius is probably involved \ in the interaction with the gamma chain.\ \ translation elongation factor activity ; GO:0003746 eukaryotic translation elongation factor 1 complex ; GO:0005853 translational elongation ; GO:0006414 20041 IPR001327 This family includes both class I and class II oxidoreductases. FAD flavoproteins belonging to the family of pyridine nucleotide-disulphide \ oxidoreductases (glutathione reductase, trypanothione reductase, lipoamide dehydrogenase, \ mercuric reductase, thioredoxin reductase, alkyl hydroperoxide reductase) share sequence \ similarity with a number of other flavoprotein oxidoreductases, in particular with \ ferredoxin-NAD+ reductases involved in oxidative metabolism of a variety of hydrocarbons \ (rubredoxin reductase, putidaredoxin reductase, terpredoxin reductase, ferredoxin-NAD+ \ reductase components of benzene 1,2-dioxygenase, toluene 1,2-dioxygenase, chlorobenzene \ dioxygenase, biphenyl dioxygenase), NADH oxidase and NADH peroxidase [MEDLINE:90204534], \ [MEDLINE:93021109], [MEDLINE:91296031]. Comparison of the crystal structures of human glutathione \ reductase and Escherichia coli thioredoxin reductase reveals different locations of their active \ sites, suggesting that the enzymes diverged from an ancestral FAD/NAD(P)H reductase and \ acquired their disulphide reductase activities independently [MEDLINE:91296031]. \

\ Despite functional similarities, oxidoreductases of this family show no sequence \ similarity with adrenodoxin reductases [MEDLINE:89170752] and flavoprotein pyridine nucleotide\ cytochrome reductases (FPNCR) [MEDLINE:92084635]. Assuming that disulphide reductase activity \ emerged later, during divergent evolution, the family can be referred to as FAD-dependent \ pyridine nucleotide reductases, FADPNR.

To date, 3D structures of glutathione reductase [MEDLINE:88011277], thioredoxin reductase \ [MEDLINE:91296031], mercuric reductase [MEDLINE:91296030], lipoamide dehydrogenase [MEDLINE:91350192], \ trypanothione reductase [MEDLINE:92020931] and NADH peroxidase [MEDLINE:92046067] have been solved. \ The enzymes share similar tertiary structures based on a doubly-wound / fold, \ but the relative orientations of their FAD- and NAD(P)H-binding domains may vary \ significantly. By contrast with the FPNCR family, the folds of the FAD- and \ NAD(P)H-binding domains are similar, suggesting that the domains evolved by gene \ duplication [MEDLINE:81009573].\

\ \ disulfide oxidoreductase activity ; GO:0015036 \N electron transport ; GO:0006118 20038 IPR001323 Erythropoietin, a plasma glycoprotein, is the primary physiological mediator of erythropoiesis [MEDLINE:87039105]. It is involved in the regulation of the level of peripheral \ erythrocytes by stimulating the differentiation of erythroid progenitor cells, found in \ the spleen and bone marrow, into mature erythrocytes [MEDLINE:88153657]. It is primarily \ produced in adult kidneys and foetal liver, acting by attachment to specific binding \ sites on erythroid progenitor cells, stimulating their differentiation [MEDLINE:87055236]. \ Severe kidney dysfunction causes reduction in the plasma levels of erythropoietin,\ resulting in chronic anaemia - injection of purified erythropoietin into the blood stream \ can help to relieve this type of anaemia. Levels of erythropoietin in plasma fluctuate \ with varying oxygen tension of the blood, but androgens and prostaglandins also modulate \ the levels to some extent [MEDLINE:87055236]. Erythropoietin glycoprotein sequences are well \ conserved, a consequence of which is that the hormones are cross-reactive among mammals,\ i.e. that from one species, say human, can stimulate erythropoiesis in\ other species, say mouse or rat [MEDLINE:93042015]. \ \

Thrombopoeitin (TPO), a glycoprotein, is the mammalian0 hormone which functions as a \ megakaryocytic lineage specific growth and differentiation factor affecting the \ proliferation and maturation from their committed progenitor cells acting at a late \ stage of megakaryocyte development. It acts as a circulating regulator of platelet \ numbers.

\ \ hormone activity ; GO:0005179 extracellular ; GO:0005576 \N 20039 IPR001325 Interleukin-4 (IL-4) is a cytokine that plays a central role in the control and regulation of the immune and inflammatory system [MEDLINE:88212466], [MEDLINE:90262670]. \ IL-4 is a participant in several B-cell activation processes. It also stimulates other\ cell types such as T cells or mast cells. IL-4 is a glycoprotein that contains three \ disulfide bonds [MEDLINE:91129220].\ \

Interleukin-13 (IL-13) is a pleiotropic cytokine which may be important in the regulation \ of the inflammatory and immune responses [MEDLINE:93211479].

The sequences of IL-4 and IL-13 are distantly related.

\ \ hematopoietin/interferon-class (D200-domain) cytokine receptor ligand activity ; GO:0005126 extracellular ; GO:0005576 immune response ; GO:0006955 20037 IPR001322

Intermediate filaments (IF) are primordial components of the cytoskeleton and the nuclear envelope [MEDLINE:96367075]. They generally form filamentous structures 8 to 14 nm \ wide. IF proteins are members of a very large multigene family of proteins which has been \ subdivided in five major subgroups, type I: acidic cytokeratins, type II: basic \ cytokeratins, type III: vimentin, desmin, glial fibrillary acidic protein (GFAP),\ peripherin, and plasticin, type IV: neurofilaments L, H and M, -internexin and \ nestin, and type V: nuclear lamins A, B1, B2 and C. The lamins are components of the\ nuclear lamina, a fibrous layer on the nucleoplasmic side of the inner nuclear membrane\ that may provide a framework for the nuclear envelope and may interact with chromatin.

All IF proteins are structurally similar in that they consist of a central rod domain \ arranged in coiled-coil -helices, with at least two short characteristic \ interruptions; a N-terminal non-helical domain (head) of variable length; and a C-terminal\ domain (tail) which is also non-helical, and which shows extreme length variation between \ different IF proteins. The C-terminal domain has been charcterised for the lamins.

\ \ \N \N \N 20036 IPR001321 Hypoxia inducible factor 1

(HIF-1alpha) is a basic-helix-loop-helix-PAS (bHLH-PAS) protein. It is an obligatory component of hypoxia-inducible factor 1 (HIF-1), which \ exists as a heterodimer of HIF-1alpha and another bHLH-PAS protein, the arylhydrocarbon \ receptor nuclear translocator (HIF-1beta, ARNT) [MEDLINE:98325000], [MEDLINE:95296340]. HIF-1 acts \ to regulate the response to hypoxia, both at the cellular and system (body) level. On \ binding to DNA, it increases the expression of genes that encode glycolytic enzymes, \ certain glucose transporters, erythropoietin, and vascular endothelial growth factor\ (VEGF). Thus it acts at the cellular level to promote glycolysis, and at the organ and \ body level to promote red blood cell production, and formation of new blood vessels. \ Besides being stimulated by low oxygen conditions, HIF-1 activity has also been found to \ be stimulated by insulin and insulin-like growth factor-1; however, the mechanism(s) \ whereby any of these agents can promote its activity remains unclear [MEDLINE:98393549].\

HIF-1 induction has also been implicated in the vascularisation of tumours, which depend \ for their survival on the recruitment of new blood microvessels, in part through \ angiogenic factors such as VEGF and molecular studies of cancer have suggested that \ HIF-1alpha may have a role in regulating hypoxic control of cell growth and apoptosis, \ suggesting there may be an interplay between it and tumour supressors such as p53, and \ other apoptotic regulators, including p21 and Bcl-2 [MEDLINE:98361237], [MEDLINE:99198474].

\ \ transcription factor activity ; GO:0003700 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 20034 IPR001319 Nuclear transition protein 1 (TP1) is one of the spermatid-specific proteins [MEDLINE:91249791]. TP1 is a basic protein well \ conserved in mammalian species. In mammals, the second stage of spermatogenesis is \ characterized by the conversion of nucleosomal chromatin to the compact, nonnucleosomal \ and transcriptionally inactive form found in the sperm nucleus. This condensation is \ associated with a double-protein transition. The first transition corresponds to the \ replacement of histones by several spermatid-specific proteins (also called transition \ proteins) which are themselves replaced by protamines during the second transition.\ \ DNA binding activity ; GO:0003677 nucleus ; GO:0005634 spermatogenesis ; GO:0007283 20035 IPR001320 The ability of synapses to modify their synaptic strength in response to activity is a fundamental property of the nervous system and may be an essential component of learning and memory. There are three classes of ionotropic glutamate receptor, namely NMDA (N-methyl-D-aspartate), AMPA (

-amino-3-hydroxy-5-methyl-4-isoxazole-4-propionicacid) and kainate receptors. They are believed to play critical roles in synaptic plasticity. At many synapses in the brain, transient activation of NMDA receptors leads to a persistent modification in the strength of synaptic transmission mediated by AMPA receptors and kainate receptors can act as the induction trigger for long-term changes in synaptic transmission [MEDLINE:20046446].\ \ glutamate-gated ion channel activity ; GO:0005234 membrane ; GO:0016020 \N 20033 IPR001318

Inhibin has two isoforms, A and B, with the same subunit but different subunits. Inhibin A is a dimer of and A subunits, inhibin B is a dimer of and B subunits.

Activin A is a dimer of A subunits, activin AB is a dimer of A and B chains.

Genes coding for mouse activin C and E are closely linked and exhibit a liver-specific expression pattern in adult tissues.

\ \ hormone activity ; GO:0005179 extracellular ; GO:0005576 cell growth and/or maintenance ; GO:0008151 20032 IPR001317 The conversion of glutamine to glutamate is the initial step in the pyrimidine biosynthetic pathway. In the reaction, glutamine amidotransferase\ transfers the amide nitrogen of glutamine to a second enzyme, carbamoyl-\ phosphate synthase (CPSase), which then synthesises carbamoyl phosphate.\ This function has been detected in some other enzymes, including p-amino- \ benzoate and anthranilate synthase component II, all of which show sequence\ similarity in the area thought to contain the glutamine amidotransferase \ (GATase) activity. The active site contains a conserved Cys residue, which \ is necessary for catalytic activity, and several conserved residues in the \ areas surrounding this Cys have also been found to be important.\

Carbamoyl phosphate synthetase is\ isolated from Escherichia coli as a heterodimeric protein. The smaller of the two subunits\ catalyzes the hydrolysis of glutamine to glutamate and ammonia. The larger subunit catalyzes the\ formation of carbamoyl phosphate using 2 mol of ATP, bicarbonate, and ammonia. Kinetic\ investigations have led to a proposed chemical mechanism for this enzyme that requires carboxy\ phosphate, ammonia, and carbamate as kinetically competent reaction intermediates. The\ three-dimensional X-ray crystal structure of CPS has localized the positions of three active sites [MEDLINE:99315161].

\ \ \ \N \N \N 20030 IPR001315 The CARD domain was first described as a homology region in the N-terminus of the death adaptor protein RAIDD and the caspases ced-3 and ICH1 [MEDLINE:97318595]. Recently, it was \ shown that this domain is widespread among apoptotic signaling molecules and a possible function \ in caspase-recruitment has been proposed. The apoptotic signal coming from ligand-induced \ oligomerization of death receptors is mediated by a number of adaptor proteins \ containing specialized interaction domains. Besides the caspase recruitment domain (CARD),\ this group is formed by the death domain and the death effector domain. The CARD domain typically associates with other CARD-containing proteins, forming either dimers or \ trimers [MEDLINE:97138227], [MEDLINE:97318595], [MEDLINE:97429944], [MEDLINE:97263500]. It has been predicted that \ the CARD is related in structure and sequence to both DD and DED domains, which work in\ similar pathways and show similar interaction properties.\ \ apoptosis regulator activity ; GO:0016329 intracellular ; GO:0005622 apoptosis ; GO:0006915 20031 IPR001316

Alpha-lytic endopeptidases belong to the chymotrypisin (SA) clan, within\ which they have been assigned to subfamily A of the S2 family (S2A) [MEDLINE:93176119].\ Since the original classification, the S2 family has been split into three\ subfamilies on the basis of sequence similarity . S2 proteases\ are only known to be expressed in bacteria, from which they are secreted to\ act externally [MEDLINE:95147689]. These proteases have endopeptidase activity, which is\ specific for basic, hydrophobic or alanine P1 residues. The -lytic\ endopeptidase family also contains members that can cleave glutamyl\ bonds [MEDLINE:95147689].

\ \ \ serine-type endopeptidase activity ; GO:0004252 \N proteolysis and peptidolysis ; GO:0006508 20029 IPR001314

Proteolytic enzymes that exploit serine in their catalytic activity areubiquitous, being found in viruses, bacteria and eukaryotes [MEDLINE:95147689]. They\ include a wide range of peptidase activity, including exopeptidase, endopeptidase,\ oligopeptidase and omega-peptidase activity. Over 20 families\ (denoted S1 - S27) of serine protease have been identified, these being\ grouped into 6 clans (SA, SB, SC, SE, SF and SG) on the basis of structural\ similarity and other functional evidence [MEDLINE:95147689]. Structures are known for four\ of the clans (SA, SB, SC and SE): these appear to be totally unrelated,\ suggesting at least four evolutionary origins of serine peptidases and\ possibly many more [MEDLINE:95147689].

\ \

Notwithstanding their different evolutionary origins, there are similarities\ in the reaction mechanisms of several peptidases. Chymotrypsin, subtilisin\ and carboxypeptidase C clans have a catalytic triad of serine, aspartate and\ histidine in common: serine acts as a nucleophile, aspartate as an\ electrophile, and histidine as a base [MEDLINE:95147689]. The geometric orientations of\ the catalytic residues are similar between families, despite different\ protein folds [MEDLINE:95147689]. The linear arrangements of the catalytic residues\ commonly reflect clan relationships. For example the catalytic triad in\ the chymotrypsin clan (SA) is ordered HDS, but is ordered DHS in the\ subtilisin clan (SB) and SDH in the carboxypeptidase clan (SC) [MEDLINE:95147689], [MEDLINE:93176119].

\ \ \

Members of the chymotrypsin family may occasionally function intracellularly\ (for example, the intracellular digestion of bacteria in neutrophils), but\ most function extracellularly, for example in roles such as food digestion, \ fibrinolysis and complement activation [MEDLINE:95147689].\ The essential catalytic unit of the chymotrypsin family is around 220 \ amino acids in length, although the protein may be extended at the\ N-terminus with unrelated sequences, often containing modules. They are\ rarely extended at the C-terminus: exceptions include acrosin, complement \ component C2, and coagulation factor X, which has a 16 residue extension\ that is removed upon activation [MEDLINE:95147689].

\ \ \ chymotrypsin activity ; GO:0004263 \N proteolysis and peptidolysis ; GO:0006508 20025 IPR001311 Proteins with this domain are found in both prokaryotes and eukaryotes. In bacteria theyare involved in active transport of solutes across the cytoplasmic membrane. The protein \ components of these traffic systems include one or two transmembrane protein components, \ one or two membrane-associated ATP-binding proteins and a high affinity periplasmic \ solute-binding protein. The solute-binding proteins are thought to bind the substrate in \ the vicinity of the inner membrane, and to transfer it to a complex of inner membrane \ proteins for concentration into the cytoplasm. In eukaryotes, proteins with this domain are mostly glutamate receptors which mediate neuronal functions in glutamate\ neurotransmission.\ \ transporter activity ; GO:0005215 \N transport ; GO:0006810 20026 IPR001312 Hexokinase is an important enzyme that catalyses the ATP-dependent conversion of aldo- and keto-hexose sugars to the hexose-6-phosphate. The enzyme can catalyse this reaction \ on glucose, fructose, sorbitol and glucosamine, and as such is the first step in a \ number of metabolic pathways [MEDLINE:89211944], [MEDLINE:92147096].

The enzyme is widely distributed\ in eukaryotes. There are three isozymes of hexokinase in yeast (PI, PII and glucokinase):\ isozymes PI and PII phosphorylate both aldo- and keto-sugars; glucokinase is specific for \ aldo-hexoses. All three isozymes contain a single copy of the hexokinase domain \ [MEDLINE:89211944], [MEDLINE:92147096]. Structural studies of yeast hexokinase reveal a well-defined catalytic\ pocket that binds ATP and hexose, allowing easy transfer of the phosphate from ATP to the \ sugar [MEDLINE:81049625]. Vertebrates contain four hexokinase isozymes (designated I to IV: \ types I to III contain two repeats of the hexokinase domain, and are thought to be derived \ by gene duplication of a yeast hexokinase that is insensitve to product inhibition [MEDLINE:92344570]. The N-terminus of types I to III is the regulatory- and the C-terminus\ is the catalytic-region. Type IV hexokinase contains only one hexokinase domain, and is \ sometimes incorrectly referred to as glucokinase.

\ \ ATP binding activity ; GO:0005524 \N glycolysis ; GO:0006096 20027 IPR001312 Hexokinase is an important enzyme that catalyses the ATP-dependent conversion of aldo- and keto-hexose sugars to the hexose-6-phosphate. The enzyme can catalyse this reaction \ on glucose, fructose, sorbitol and glucosamine, and as such is the first step in a \ number of metabolic pathways [MEDLINE:89211944], [MEDLINE:92147096].

\ \ ATP binding activity ; GO:0005524 \N glycolysis ; GO:0006096 20028 IPR001313 The Drosophila pumilio gene codes for an unusual protein that binds through the Pufdomain that usually occurs as a tandem repeat of eight domains. The FBF-2 protein of\ Caenorhabditis elegans also has a Puf domain. Both proteins function as translational \ repressors in early embryonic development by binding sequences in the 3' UTR of target \ mRNAs [MEDLINE:98054147], [MEDLINE:98067397]. The same type of repetitive domain has been found in\ in a number of other proteins from all eukaryotic kingdoms. The yeast suppressor protein, MPT5, is required for growth at high temperature\ and is needed for recovery from mating pheromone-induced G1 arrest.\ \ RNA binding activity ; GO:0003723 \N \N 20022 IPR001308 The electron transfer flavoprotein (ETF) serves as a specific electron acceptor for various mitochondrial dehydrogenases. ETF transfers electrons to the main respiratory \ chain via ETF-ubiquinone oxidoreductase. ETF is an heterodimer that consists of an

and a

subunit which binds one molecule of FAD per dimer [MEDLINE:90222268], [MEDLINE:96099680]. A similar system also exists in some bacteria.\

\ The subunit of ETF is structurally related to the bacterial nitrogen fixation \ protein fixB which could play a role in a redox process and feed electrons to ferredoxin.

\ \ electron transporter activity ; GO:0005489 \N electron transport ; GO:0006118 20023 IPR001309

Synonym(s): Interleukin 1- converting enzyme (ICE)

Caspase-1 (EC: 3.4.22.36) is responsible for the \ cleavage of the IL-1 precursor at an Asp-Ala bond to generate the mature,\ biologically active cytokine. ICE is a thiol protease composed of two subunits of 10 kDa (p10) \ and 20 kDa (p20), both derived by the autocleavage of a 45 kDa precursor (p45) \ [MEDLINE:94309732]. Two residues are implicated in the catalytic mechanism: a cysteine and \ a histidine [MEDLINE:95291179], [MEDLINE:95334823]. ICE belongs to a family of peptidases which is \ implicated in programmed cell death (apoptosis) and which has been termed 'caspase' for \ cysteine aspase [MEDLINE:97416345].\ ICE is known as Caspase-1 and the other caspases range from Caspase-2 to Caspase-12\ [MEDLINE:97015072].

\ \ caspase activity ; GO:0004199 \N proteolysis and peptidolysis ; GO:0006508 20024 IPR001310 The Histidine Triad (HIT) motif, His-phi-His-phi-His-phi-phi (phi, ahydrophobic amino acid) was identified as being highly conserved in a\ variety of organisms [MEDLINE:93112998]. Crystal structure of rabbit Hint, purified as an adenosine and AMP-binding protein, showed that proteins in the HIT\ superfamily are conserved as nucleotide-binding proteins and that Hint\ homologs, which are found in all forms of life, are structurally related to\ Fhit homologs and GalT-related enzymes, which have more restricted\ phylogenetic profiles [MEDLINE:97307258]. Hint homologs including rabbit Hint and yeast\ Hnt1 hydrolyze adenosine 5' monophosphoramide substrates such as AMP-NH2 and\ AMP-lysine to AMP plus the amine product and function as positive regulators\ of Cdk7/Kin28 in vivo [MEDLINE:21909585]. Fhit homologs are diadenosine polyphosphate\ hydrolases [MEDLINE:96387192] and function as tumor suppressors in human and mouse [MEDLINE:20243766]\ though the tumor suppressing function of Fhit does not depend on ApppA\ hydrolysis [MEDLINE:98245105]. The third branch of the HIT superfamily, which includes\ GalT homologs, contains a related His-X-His-X-Gln motif and transfers\ nucleoside monophosphate moeities to phosphorylated second substrates rather\ than hydrolyzing them [MEDLINE:22114327].\ \ \ \ \N \N \N 20019 IPR001304

Animal lectins display a wide variety of architectures.They are classified according to the carbohydrate-recognition\ domain (CRD) of which there are two main types, S-type and C-type.

C-type lectins display a wide range of specificities.\ They require Ca²⁺ for their activity\ They are found predominantly but not exclusively in vertebrates.

They can be classified into a number of subgroups based on their function and structure:\

Endocytic lectins - \ Membrane-bound receptors that mediate endocytosis \ of glycoproteins

Collectins -\ Represented by the soluble mannose-binding proteins of \ mammalian serum and liver

Selectins - \ Membrane-bound proteins involved in inflammation

CD22 (also called BL-CAM or Lyb8) are adhesion and signaling molecules. Targeted disruption of CD22 in mice results in a reduced level of surface IgM on peripheral B cells, enhanced Ca⁺⁺ flux in response to Ig signaling, variable proliferative responses to surface Ig crosslinking. Several studies observed a reduced response to thymus independent antigens. The CD22-knockout data support a role for CD22 in limiting antigen receptor signaling although a positive role in certain B cell response cannot be excluded.

\ \

CD molecules are leucocyte antigens on cell surfaces. CD antigens nomenclature is updated at http://www.ncbi.nlm.nih.gov/PROW/guide/45277084.htm \

\ \ \ sugar binding activity ; GO:0005529 \N \N 20020 IPR001305 The prokaryotic heat shock protein dnaJ interacts with the chaperone hsp70-like dnaK protein [MEDLINE:94287451]. Structurally, the dnaJ protein consists of an N-terminal conserved \ domain(called 'J' domain), a glycine-rich region ('G' domain'), a central domain.\ The J- and CRR-domains are found either together or separately in many prokaryotic and \ eukaryotic proteins [MEDLINE:92263470]. Those \ containing both J- and CRR-domains include yeast proteins MAS5/YDJ1, MDJ1, SCJ1, XDJ1 and\ YNL077w, plant dnaJ homologues from leek and cucumber, and human HDJ2. Those with only the J-domain include R.fredii nolC, E.coli cbpA, yeast proteins SEC63/NPL1, SIS1, CAJ1, \ YFR041c, YIR004w and YJL162c, P.falciparum ring-infected erythrocyte surface antigen, \ human HDJ1 and HSJ1, and Drosophila cysteine-string protein.\ \ chaperone activity ; GO:0003754 \N \N 20021 IPR001307

Synonym(s): Rhodanese

Thiosulfate sulfurtransferase (EC: 2.8.1.1) is an enzyme which catalyzes \ the transfer of the sulfane atom of thiosulfate to cyanide, to form sulfite and \ thiocyanate. In vertebrates, rhodanese is a mitochondrial enzyme that is involved in \ forming iron-sulfur complexes and cyanide detoxification. A cysteine residue takes part \ in the catalytic mechanism [MEDLINE:82124319], [MEDLINE:91207296]. Some bacterial proteins may also express sulfotransferase \ activity. These include, sseA from Mycobacterium leprae and E. coli, Azotobacter \ vinelandii rhdA, Saccharopolyspora erythraea cysA [MEDLINE:90094240] and Synechococcus strain PCC 7942 rhdA [MEDLINE:91210163].

\ \ thiosulfate sulfurtransferase activity ; GO:0004792 \N sulfate transport ; GO:0008272 20016 IPR001301 Geminiviruses are characterised by a genome of circular single-stranded DNA encapsidated in twinned (geminate) quasi-isometric particles, from which the group derives its name \ PUB00001145. Most geminiviruses can be divided into two subgroups on the basis of host \ range and/or insect vector: i.e.those that infect dicotyledenous plants and are transmitted \ by the same whitefly species, and those that infect monocotyledenous plants and are\ transmitted by different leafhopper vectors. The genomes of the whitefly-transmitted \ cassava latent (CLV), tomato golden mosaic (TGMV) and bean golden mosaic (BGMV) viruses \ possess a bipartite genome. By contrast, only a single DNA component has been identified \ for the leafhopper-transmitted maize streak (MSV) and wheat dwarf (WDV) viruses \ PUB00001145, [MEDLINE:88124198]. Beet curly top (BCTV), bean summer death and tobacco yellow \ dwarf viruses belong to a third possible subgroup. Like MSV and WDV, BCTV is transmitted \ by a specific leafhopper species, yet like the whitefly-transmitted geminiviruses it has a \ host range confined to dicotyledenous plants.\ \

Sequence comparison of the whitefly-transmitted squash leaf curl\ and tomato yellow leaf curl viruses with the genomic components of\ TGMV and BGMV reveals a close evolutionary relationship [MEDLINE:92107660], [MEDLINE:91082449], \ [MEDLINE:92024070]. Amino acid sequence alignments of potato yellow mosaic viral (PYMV) \ proteins with those encoded by other geminiviruses show that PYMV is closely related \ to geminiviruses isolated from the New World, especially in the putative \ coat protein gene regions [MEDLINE:92024070].

\ \ \ structural molecule activity ; GO:0005198 viral capsid ; GO:0019028 \N 20017 IPR001302 PsaI has a crucial role in aiding normal structural organization of PsaL within the photosystem I complex and the absence of PsaI alters PsaL organization, leading to a small, but physiologically significant, defect in photosystem I function [MEDLINE:95332332].PsaL encodes a subunit of photosystem I and is necessary for trimerization of photosystem I. PsaL may constitute the trimer-forming domain in the structure of photosystem I [MEDLINE:94085633].\ \ \N photosystem I ; GO:0009522 photosynthesis ; GO:0015979 20018 IPR001303 This family includes L-fuculose phosphate aldolase (EC: 4.1.2.17) [MEDLINE:93294819], [MEDLINE:96256522] that is involved in the third step in fucose metabolism, L-ribulose- 5-phosphate 4-epimerase (EC: 5.1.3.4)\ involved in the third step of L-arabinose catabolism, a probable sugar isomerase SGBE,\ adducins which have not been ascribed any enzymatic function but which play a role in\ cell membrane cytoskeleton organisation and the hypothetical protein from MER2-BNA1\ intergenic region in the yeast genome.\ \ \N \N \N 20015 IPR001300

\ \

Calpain is an intracellular protease involved in many important cellular\ functions that are regulated by calcium [MEDLINE:89197947]. The protein is a complex of 2\ polypeptide chains (light and heavy), with three known forms in mammals\ [MEDLINE:95147707], [MEDLINE:90062125]: a highly calcium-sensitive (i.e., micro-molar range) form known as\ mu-calpain, mu-CANP or calpain I; a form sensitive to calcium in the\ milli-molar range, known as m-calpain, m-CANP or calpain II; and a third\ form, known as p94, which is found in skeletal muscle only [MEDLINE:90062125].

\ \

All three forms have identical light but different heavy chains [MEDLINE:95147707], [MEDLINE:89197947].\ The heavy chain comprises four domains: domain 2 contains the catalytic\ region; domain 4 binds calcium and regulates activity [MEDLINE:95147707]. Domain 2 shows\ low levels of sequence similarity to papain; although the catalytic His has\ not been located by biochemical means, it is likely that calpain and papain\ are related [MEDLINE:95147707]. Domain 4 has four EF hand calcium-binding regions and is\ simmilar to sorcin and the Ca²⁺-binding region of calpain light chain [MEDLINE:95147707]. Ca²⁺-binding causes a rearrangement of the protein backbone, the net effect of which is that a Trp\ side chain, which acts as a wedge between catalytci domains 2a\ and 2b in the apo state, moves away from the active site cleft\ allowing for the proper formation of the catalytic triad [MEDLINE:21912435].

\ \

Calpain shows preferential cleavage for Tyr-with leucine or valine as the P2 residue.\ The product of the Drosophila\ gene sol has also been shown to be similar to calpain [MEDLINE:95147707].

\ \ calpain activity ; GO:0004198 intracellular ; GO:0005622 proteolysis and peptidolysis ; GO:0006508 20012 IPR001298

The many different actin cross-linking proteins share a common architecture, consisting of a globular actin-binding domain and an extended rod. Whereas their actin-binding domains consist of two calponin homology domains (see IPR001715), their rods fall into three families.

The rod domain of the family including the Dictyostelium discoideum gelation factor (ABP120) and human filamin (ABP280) is constructed from tandem repeats of a 100-residue motif that is glycine and proline rich [MEDLINE:97307257]. The gelation factor's rod contains 6 copies of the repeat, whereas filamin has a rod constructed from 24 repeats. The resolution of the 3D structure of rod repeats from the gelation factor has shown that they consist of a -sandwich, formed by two -sheets arranged in an immunoglobulin-like fold [MEDLINE:97307257], [MEDLINE:99396737]. Because conserved residues that form the core of the repeats are preserved in filamin, the repeat structure should be common to the members of the gelation factor/filamin family.

\ \

The head to tail homodimerisation is crucial to the function of the ABP120 and ABP280 proteins. This interaction involves a small portion at the distal end of the rod domains. For the gelation factor it has been shown that the carboxy-terminal repeat 6 dimerises through a double edge-to-edge extension of the -sheet and that repeat 5 contributes to dimerisation to some extent [MEDLINE:98080557], [MEDLINE:99396737], [MEDLINE:89340643].

\ \ \N \N \N 20013 IPR001299 Ependymins are secretory proteins found predominantly in the cerebrospinal fluid of teleost fish\ \ \ \ [MEDLINE:91353972], [MEDLINE:93353529]. A bound form of the glycoproteins is associated \ with the extracellular matrix, probably with collagen fibrils, that may be the functional \ form of ependymins [MEDLINE:94273927]. The proteins bind calcium via N-linked sialic acid \ residues. The molecular function of ependymins appear to be related to cell contact\ phenomena involving the extracellular matrix [MEDLINE:94273927].\ \ calcium ion binding activity ; GO:0005509 extracellular ; GO:0005576 cell-matrix adhesion ; GO:0007160 20014 IPR001300

\ \

Calpain shows preferential cleavage for Tyr-with leucine or valine as the P2 residue.\ The product of the Drosophila\ gene sol has also been shown to be similar to calpain [MEDLINE:95147707].

\ \ calpain activity ; GO:0004198 intracellular ; GO:0005622 proteolysis and peptidolysis ; GO:0006508 20009 IPR001295

Dihydroorotate dehydrogenase (EC: 1.3.3.1) (DHOdehase) catalyzes the fourth step in the de novo biosynthesis of pyrimidine, the conversion of dihydroorotate into orotate. \ DHOdehase is a ubiquitous FAD flavoprotein. In bacteria (gene pyrD), DHOdease is \ located on the inner side of the cytosolic membrane. In some yeasts, such as in \ Saccharomyces cerevisiae (gene URA1), it is a cytosolic protein while in other \ eukaryotes it is found in the mitochondria [MEDLINE:93028386].

\ \ dihydroorotate dehydrogenase activity ; GO:0004152 \N 'de novo' pyrimidine base biosynthesis ; GO:0006207 20010 IPR001296

Proteins containign this domain transfer UDP, ADP, GDP or CMP linked sugars to a variety of \ substrates, including glycogen, fructose-6-phosphate and lipopolysaccharides. The \ bacterial enzymes are involved in various biosynthetic processes that include\ exopolysaccharide biosynthesis, lipopolysaccharide core biosynthesis and the biosynthesis\ of the slime polysaccaride colanic acid. Mutations in this domain of the human\ N-acetylglucosaminyl-phosphatidylinositol biosynthetic protein are the cause of \ paroxysmal nocturnal hemoglobinuria (PNH), an acquired hemolytic blood disorder\ characterized by venous thrombosis, erythrocyte hemolysis, infections and defective \ hematopoiesis.

\ \ \N \N biosynthesis ; GO:0009058 20011 IPR001297 The phycobilisome linker polypeptide determines the state of aggregation and the location of the disc-shaped phycobiliprotein units within the phycobilisome and modulates their\ spectroscopic properties in order to mediate a directed and optimal energy transfer.\ The phycobilisome is a hemidiscoidal structure that is composed of two distinct\ substructures, a core complex (that contains the phycobiliproteins) and a number of\ rods radiating from the core. The linker polypeptide is also found in the chloroplast of\ some eukaryotes where it is required for attachment of phycocyanin to allophycocyanin\ in the core of the phycobilisome.\ \ \N phycobilisome ; GO:0030089 photosynthesis ; GO:0015979 20006 IPR001292 Steroid or nuclear hormone receptors (NRs) constitute an important superfamily of transcription regulators that are involved in widely diverse physiological functions, including control of embryonic development, cell\ differentiation and homeostasis. Members of the superfamily include the\ steroid hormone receptors and receptors for thyroid hormone, retinoids, \ 1,25-dihydroxy-vitamin D3 and a variety of other ligands. The proteins \ function as dimeric molecules in nuclei to regulate the transcription of \ target genes in a ligand-responsive manner [MEDLINE:95206940], [MEDLINE:94218237]. In addition to C-terminal\ ligand-binding domains, these nuclear receptors contain a highly-conserved,\ N-terminal zinc-finger (IPR001628) that mediates specific binding to target DNA \ sequences, termed ligand-responsive elements. In the absence of ligand,\ steroid hormone receptors are thought to be weakly associated with nuclear\ components; hormone binding greatly increases receptor affinity.\ \

The oestrogen receptor consists of 3 functional and structural domains:\ an N-terminal (modulatory) domain; a DNA binding domain that mediates\ specific binding to target DNA sequences, termed ligand-responsive\ elements; and a hormone binding domain. The N-terminal domain is unique to\ the oestrogen receptors and spans approximately the first 180 residues; the\ highly-conserved DNA-binding domain is smaller (around 65 residues) and\ occupies the central portion of the protein; and the hormone binding\ domain lies at the receptor C-terminus.

\ \

The oestrogen receptor [MEDLINE:92191989] stimulates transcription via 2 distinct\ transcriptional activation domains: TAF-1 in the N-terminal domain, and\ TAF-2 in the hormone-binding domain. TAF-2 activity requires a region in\ the C-terminus of the hormone-binding domain (between residues 538-552 in\ the mouse oestrogen receptor) that is conserved in many nuclear hormone\ receptors. It is therefore suggested that this region may be essential\ for ligand-dependent transcriptional activation by other members of the\ nuclear receptor family [MEDLINE:94218237].

\ \ steroid binding activity ; GO:0005496 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 20007 IPR001293 Some of the proteins that have this domain are mammalian signal transducers associated with the cytoplasmic domain of the 75 kDa tumor necrosis factor receptor. A heterocomplex, homodimer or heterodimer of TRAF1 and\ TRAF2, binds to the N-terminal of the inhibitor of apoptosis proteins 1 and 2 (IAPS) and recruits them to the tumor\ necrosis factor receptor 2. Other proteins, F45G2.6 protein from C. elegans and DG17 protein from slime mold also\ have this domain.\ \ zinc ion binding activity ; GO:0008270 \N \N 20008 IPR001294 Phytochrome belongs to a family of plant photoreceptors that mediate physiological and developmental responses to changes in red and far-red light conditions [MEDLINE:92255261].\ The protein undergoes reversible photochemical conversion between a biologically-inactive \ red light-absorbing form and the active far-red light-absorbing form. Phytochrome is a \ dimer of identical 124Kd subunits, each of which contains a linear tetrapyrrole \ chromophore, covalently-attached via a Cys residue.\

In Arabidopsis, there are genes for at least five phytochrome proteins [MEDLINE:90108670].\ These photoreceptors control such responses as germination, stem elongation, flowering, \ gene expression, and chloroplast and leaf development. It is not yet known which red \ light responses are controlled by which phytochrome species, or whether the different \ phytochromes have overlapping functions [MEDLINE:93200802]. Synechocystis strain PCC 6803 \ hypothetical protein slr0473 contains a domain similar to that of plants phytochrome and \ seems also to bind a chromophore.\

\ \ G-protein coupled photoreceptor activity ; GO:0008020 \N regulation of transcription, DNA-dependent ; GO:0006355 20003 IPR001288

Initiation factor 3 (IF-3) (gene infC) is one of the three factors required for the initiation of protein biosynthesis in bacteria. IF-3 is thought to function as a \ fidelity factor during the assembly of the ternary initiation complex which consist of \ the 30S ribosomal subunit, the initiator tRNA and the messenger RNA. IF-3 is a basic\ protein that binds to the 30S ribosomal subunit [MEDLINE:94010248]. The chloroplast initiation factor IF-3(chl) is a protein that \ enhances the poly(A,U,G)-dependent binding of the initiator tRNA to chloroplast ribosomal\ 30s subunits in which the central section is evolutionary related to the sequence of \ bacterial IF-3 [MEDLINE:94193615].

\ \ translation initiation factor activity ; GO:0003743 \N translational initiation ; GO:0006413 20004 IPR001289 The CCAAT-binding factor (CBFB/NF-YA) is a mammalian transcription factor that binds to a CCAAT motif in the promoters of a wide variety of genes, including type I collagen and \ albumin [MEDLINE:91093096]. The factor is a heteromeric complex of A and B subunits, both of \ which are required for DNA-binding [MEDLINE:92195809]. The subunits can \ interact in the absence of DNA-binding, conserved regions in each being important in \ mediating this interaction.

The B subunit contains a region of similarity with the yeast \ protein HAP2 [MEDLINE:91156727]. For the B subunit it has been suggested that the N-terminal \ portion of the conserved region is involved in subunit interaction and the C-terminal\ region involved in DNA-binding [MEDLINE:92235046].

\ \ transcription factor activity ; GO:0003700 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 20005 IPR001290 Poly(ADP-ribose) polymerase (PARP) modifies various nuclear proteins by poly(ADP-rybosyl)ation. The modification is dependent on DNA and is involved in the \ regulation of various important cellular processes such as differentiation,\ proliferation and tumor transformation and also in the regulation of the molecular\ events involved in the recovery of the cell from DNA damage [MEDLINE:93293867], [MEDLINE:96353841]. \ Poly(ADP-ribose) polymerase catalyses the covalent attachment of ADP-ribose units from NAD+ to itself and to a limited number of other DNA binding proteins, which decreases \ their affinity for DNA. The C-terminal catalytic domain of the polymerase is almost always associated with the N-terminal regulatory domain (see IPR004102).\ \ NAD+ ADP-ribosyltransferase activity ; GO:0003950 nucleus ; GO:0005634 protein amino acid ADP-ribosylation ; GO:0006471 20001 IPR001287 These enzymes are involved in nitrate assimilation in the denitrification pathway.The 3D structure of the copper-containing nitrite reductase (NIR) from Achromobacter \ cycloclastes has been determined to 2.3A resolution [MEDLINE:91320115]. The enzyme is a \ trimer, each monomer of which contains two Greek key

-barrel domains (similar to \ that of plastocyanin) and houses two copper sites. The two copper atoms in the monomer \ comprise a type I copper site (Cu-I: two His, one Cys and one Met ligand) that plays a \ crucial role for electron transfer from pseudoazurin to the type II copper site (Cu-II: three His and one solvent ligand), the catalytic centre of NIR for the reduction of\ nitrite. The Cu-II site lies at the bottom of a 12A deep solvent channel and is the \ site to which the substrate (NO2-) binds [MEDLINE:91320115].\ \ nitrite reductase activity ; GO:0016666 \N nitrogen metabolism ; GO:0006807 20002 IPR001288

\ \ translation initiation factor activity ; GO:0003743 \N translational initiation ; GO:0006413 19991 IPR001275 This domain was first discovered in the doublesex proteins of Drosophila melanogaster and is also seen in proteins from C. elegans\ \ \ [MEDLINE:98140704]. In Drosophila the \ doublesex gene controls somatic sexual differentiation by producing alternatively spliced mRNAs encoding related sex-specific polypeptides [MEDLINE:97132599]. These proteins are believed to function as transcription factors on downstream sex-determination genes, especially on neuroblast differentiation and yolk protein genes transcription [MEDLINE:91330881], [MEDLINE:88327846]. The DM domain binds DNA as a dimer, allowing the recognition of pseudopalindromic sequences [MEDLINE:97132599], [MEDLINE:99128178], [MEDLINE:20357108]. The NMR analysis of the DSX DM domain [MEDLINE:20357108] revealed a novel zinc module containing 'intertwined' CCHC and HCCC \ zinc-binding sites. The recognition of the DNA requires the carboxy-terminal basic\ tail which contacts the minor groove of the target sequence.\ \ transcription factor activity ; GO:0003700 nucleus ; GO:0005634 sex differentiation ; GO:0007548 19992 IPR001277

Several 7TM receptors have been cloned but their endogenous ligands are\ unknown; these have been termed orphan receptors. LCR1 was isolated from a locus coeruleus library and its mRNA is also present in cerebellum, pons, dorsal raphe, thalamus and substantia nigra PUB00005876, [MEDLINE:92100053]. It was originally thought to encode a neuropeptide Y receptor (NPY3-R) [MEDLINE:92100053], but this has been shown to be incorrect [MEDLINE:94052833], and it is now thought to be a type 4 C-X-C chemokine receptor.

\ \ C-X-C chemokine receptor activity ; GO:0016494 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19993 IPR001278

\ \

Arginyl-tRNA synthetase (EC: 6.1.1.19) has been crystallized and preliminary X-ray crystallographic analysis of yeast\ arginyl-tRNA synthetase-yeast tRNAArg complexes is available [MEDLINE:20207129].

\ \ ATP binding activity ; GO:0005524 \N arginyl-tRNA aminoacylation ; GO:0006420 19994 IPR001279 Apart from the

-lactamases a number of other proteins contain this domain [MEDLINE:96067120]. These proteins include thiolesterases, members of the glyoxalase II family,\ that catalyse the hydrolysis of S-D-lactoyl-glutathione to form glutathione and \ D-lactic acid and a competence protein that is essential for natural transformation in \ Neisseria gonorrhoeae and could be a transporter involved in DNA uptake. Except for the \ competence protein these proteins bind two zinc ions per molecule as cofactor.\ \ \N \N \N 19995 IPR001280 Photosystem I, a membrane complex found in the chloroplasts of plants and cyanobacteria uses light energy to transfer electrons from plastocyanin to ferredoxin PUB00003191. \ The electron transfer components of the photosystem include the primary electron donor \ chlorophyll P-700 and 5 electron acceptors: chlorophyll (A0), phylloquinone (A1) and \ three 4Fe-4S iron-sulphur centres, designated Fx, Fa and Fb.\ \

The proteins psaA and psaB are similar and form a dimer in the membrane, the complex \ being involved in binding the electron transfer components PUB00003191.

\ \ \N membrane ; GO:0016020 photosynthesis ; GO:0015979 19996 IPR001282

Glucose-6-phosphate dehydrogenase (EC: 1.1.1.49) (G6PDH) is a ubiquitous protein, presentin bacteria and all eukaryotic cell types [MEDLINE:88255872]. The enzyme catalyses the\ the first step in the pentose pathway, i.e. the conversion of glucose-6-phosphate to \ gluconolactone 6-phosphate in the presence of NADP, producing NADPH. The ubiquitous \ expression of the enzyme gives it a major role in the production of NADPH for the many \ NADPH-mediated reductive processes in all cells [MEDLINE:88276919]. Deficiency of G6PDH is \ a common genetic abnormality affecting millions of people worldwide. Many sequence variants, most caused by single point mutations, are known, exhibiting a wide variety of \ phenotypes [MEDLINE:88276919].

\ \ glucose-6-phosphate 1-dehydrogenase activity ; GO:0004345 \N glucose metabolism ; GO:0006006 19997 IPR001282

\ \ glucose-6-phosphate 1-dehydrogenase activity ; GO:0004345 \N glucose metabolism ; GO:0006006 19998 IPR001283

A number of eukaryotic extracellular proteins have been shown to be evolutionarily related. The family includes rodent sperm-coating glycoprotein (or acidic epididymal \ glycoprotein), which is thought to be involved in sperm maturation [MEDLINE:93246016]; \ mammalian testis-specific protein (Tpx-1) [MEDLINE:90129048]; glioma \ pathogenesis-related protein; lizard helothermine, a toxin that blocks ryanodine \ receptors; venom allergen 5 from vespid wasps and venom allergen 3 from fire ants, \ which are potent allergens that mediate allergic reactions to stings insects of \ the Hymenoptera family [MEDLINE:93203603]; plant pathogenesis proteins of the PR-1 family \ [MEDLINE:91224081], which are synthesised during pathogen infection or other stress-related \ responses; proteins Sc7 and Sc14 from the basidiomycete fungus Schizophyllum commune, \ which are loosely associated with fruiting body hyphal walls [MEDLINE:94065639]; ancylostoma \ secreted protein from dog hookworm; and yeast hypothetical proteins YJL078c, YJL079c\ and YKR013w. The precise functions of these proteins is still unclear.

\ \ \ \N extracellular ; GO:0005576 \N 19999 IPR001285 Synaptophysin and synaptoporin are related glycoproteins: they are the major integral membrane proteins of a certain class of small neurosecretory vesicles, although they may \ also be found in vesicles of various non-endocrine cells [MEDLINE:88111510], [MEDLINE:89093117]. \ The polypeptide chain spans the membrane four times and possibly acts as an ion or \ solute channel.\ \ transporter activity ; GO:0005215 membrane ; GO:0016020 transport ; GO:0006810 20000 IPR001286

Glycoside hydrolase family 59 CAZY:GH_59).

\ \

Globoid cell leukodystrophy (Krabbe disease) is a severe, autosomal\ recessive disorder that results from deficiency of galactocerebrosidase\ (GALC) activity [MEDLINE:96299640], [MEDLINE:95324938], [MEDLINE:98094242]. GALC is responsible for the lysosomal catabolism of\ certain galactolipids, including galactosylceramide and psychosine [MEDLINE:96299640].

\ \ galactosylceramidase activity ; GO:0004336 \N galactosylceramide catabolism ; GO:0006683 19984 IPR001267

Thymidine kinase (TK) (EC: 2.7.1.21) is an ubiquitous enzyme that catalyzes theATP-dependent phosphorylation of thymidine. Two different families of TK have \ been identified [MEDLINE:87122176], [MEDLINE:90357780] and are included in this family; one family groups\ together TK from herpesviruses as well as cellular thymidylate kinases and the \ second family groups TK from various sources that include, vertebrates, bacteria, the \ bacteriophage T4, poxviruses, african swine fever virus (ASF) and fish lymphocystis \ disease virus (FLDV). The major capsid protein of insect iridescent viruses also\ belongs to this family. The Prosite pattern recognises only the cellular type of thymidine kinases.

\ \ ATP binding activity ; GO:0005524 \N \N 19985 IPR001268

Synonym(s): Ubiquinone reductase, Type I dehydrogenase, Complex I dehydrogenase

NADH dehydrogenase (ubiquinone) (EC: 1.6.5.3) is an oligomeric enzymatic complex located in the \ inner mitochondrial membrane, in the chloroplast or in cyanobacteria (as a \ NADH-plastoquinone oxidoreductase). The 30 kDa subunit is one of the 25 to 30 polypeptide \ subunits of this bioenergetic enzyme complex. In mammals and in Neurospora crassa it is\ nuclear encoded as a precursor form with a transit peptide, in paramecium (protein P1)\ and in the slime mold it is mitochondrial encoded and it is chloroplast encoded in various higher plants. It is also present in bacteria.

\ \ NADH dehydrogenase (ubiquinone) activity ; GO:0008137 \N oxidative phosphorylation, NADH to ubiquinone ; GO:0006120 19986 IPR001269 A number of uncharacterized proteins share this region. Rhodobacter capsulatus nifR3 was believed to be a transcriptional regulatory protein [MEDLINE:93360820], but it may be that these proteins constitute\ a family of enzymes whose active site could include a conserved cysteine.\ \ molecular_function unknown ; GO:0005554 \N \N 19987 IPR001270 A group of ATP-binding proteins that includes the regulatory subunit of the ATP-dependent protease clpA; heat shock proteins clpB, 104 and 78; and chloroplast\ proteins CD4a and CD4b belong to this family [MEDLINE:91375541], [MEDLINE:90239044]. The proteins are thought to protect \ cells from stress by controlling the aggregation and denaturation of vital cellular \ structures. They vary in size, but share a domain\ which contains an ATP-binding site.\ \ \N \N \N 19988 IPR001272 Phosphoenolpyruvate carboxykinase (ATP) (EC: 4.1.1.49) (PEPCK) catalyzes the formation of phosphoenolpyruvate by decarboxylation of oxaloacetate while hydrolyzing ATP, a rate \ limiting step in gluconeogenesis (the biosynthesis of glucose) [MEDLINE:91072271], [MEDLINE:96190956], \ [MEDLINE:96185447]. It is involved in the glyoxylate bypass, an alternative to the \ tricarboxylic acid cycle in bacteria, fungi and plants.\ \ ATP binding activity ; GO:0005524 \N gluconeogenesis ; GO:0006094 19982 IPR001265 The formins are a set of protein isoforms encoded by the alternatively spliced transcripts arising from the murine limb deformity (ld) locus [MEDLINE:92112033], [MEDLINE:90363291].\ Mutations in this locus disrupt formation of the anteroposterior axis of the embryonic \ limb. In the developing limb bud, the protein is expressed in the apical ectodermal \ ridge and mesenchymal compartment, predominantly in the posterior region [MEDLINE:92112031].\ During kidney morphogenesis, early expression is restricted to the epithelial compartment \ of the pronephros and mesonephros [MEDLINE:92112031].\ \ \N nucleus ; GO:0005634 development ; GO:0007275 19983 IPR001266

\ \ \

This family includes a number of eukaryotic and archaebacterial ribosomal proteins;\ mammalian S19, Drosophila S19, Ascaris lumbricoides S19g (ALEP-1) and S19s, yeast YS16 \ (RP55A and RP55B), Aspergillus S16 and Haloarcula marismortui HS12.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 19990 IPR001274

The accumulation of phagocytic cells at the site of injury or infection is\ regulated by substances that stimulate chemotaxis, granule secretion,\ superoxide generation and upregulation of cell surface adhesion molecules\ in cells of the immune system . The chemoattractant substances include\ C5a, N-formylmethionyl-containing peptides, interleukin 8, leukotriene B4\ and platelet activating factor, many of which participate in anaphylactoid\ and septic shock PUB00005873. The C5a receptor is found on cells of the immune\ system (e.g., neutrophils, macrophages, mast cells and related cell lines),\ and is also present in smooth muscle. The amino acid sequence of the\ receptor contains several N-terminal acidic residues, which may be\ involved in binding the basic C5a peptide.

\ \ \ C5a anaphylatoxin receptor activity ; GO:0004944 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19989 IPR001273

Phenylalanine, tyrosine and tryptophan hydroxylases constitute a family of tetrahydrobiopterin-dependent aromatic amino acid hydroxylases, all of which are \ rate-limiting catalysts for important metabolic pathways [MEDLINE:87289638]. The proteins \ are structurally and functionally related, each containing iron, and catalysing ring \ hydroxylation of aromatic amino acids, using tetra-hydrobiopterin (BH4) as a substrate. \ All are regulated by phosphorylation at serines in their N-termini. It has been suggested \ that the proteins each contain a conserved C-terminal catalytic (C) domain and an unrelated N-terminal regulatory (R) domain. It is possible that the R domains arose from \ genes that were recruited from different sources to combine with the common gene for the \ catalytic core. Thus, by combining with the same C domain, the proteins acquired\ the unique regulatory properties of the separate R domains.

\ \

A variety of enzymes belong to this family that includes, phenylalanine-4-hydroxylase from Chromobacterium violaceum where it is copper-dependent; it is \ iron-dependent in Pseudomonas aeruginosa, phenylalanine-4-hydroxylase catalyzes the conversion of phenylalanine to tyrosine. \ In humans, deficiencies are the cause of phenylketonuria, the most common inborn error \ of amino acid metabolism [MEDLINE:98069646], tryptophan 5-hydroxylase catalyzes the rate-limiting step in serotonin biosynthesis: \ the conversion of tryptophan to 3-hydroxy-anthranilate and tyrosine 3-hydroxylase catalyzes the rate limiting step in catecholamine biosynthesis: \ the conversion of tyrosine to 3,4-dihydroxy-L-phenylalanine.

\ \ iron ion binding activity ; GO:0005506 \N aromatic amino acid family metabolism ; GO:0009072 19976 IPR001259 Calpain inhibitor specifically inhibits calpain (calcium-dependent cysteine protease) andplays a key role in postmortem tenderization of meat. It may be involved in muscle\ protein degradation in living tissue.\ \ \N \N \N 19977 IPR001260 Coprogen oxidase (i.e. coproporphyrin III oxidase or coproporphyrinogenase) catalyses the oxidative decarboxylation of coproporphyrinogen III to proto-porhyrinogen IX in the \ haem and chlorophyll biosynthetic pathways [MEDLINE:94012692], [MEDLINE:94033295]. The protein is a \ homodimer containing two internally bound iron atoms per molecule of native protein \ [MEDLINE:86192489]. The enzyme is active in the presence of molecular oxygen that acts\ as an electron acceptor). The enzyme is widely distributed having been found in a variety of eukaryotic and \ prokaryotic sources.\ \ coproporphyrinogen oxidase activity ; GO:0004109 \N porphyrin biosynthesis ; GO:0006779 19978 IPR001261

This domain is present in a variety of proteins from different sources that hydrolyse peptidic bonds in substrates that share a common structure and are dependent on cobalt \ or zinc for their activity. These proteins include, glutamate acetyltransferase\ (EC: 2.3.1.35), acetylornithine deacetylase (EC: 3.5.1.16), leucoanthocyanidin dioxygenase,\ succinyldiaminopimelate desuccinylase (EC: 3.5.1.18), aminoacylase-1, carboxypeptidase G2 \ (EC: 3.4.17.11), vacuolar carboxypeptidase S (EC: 3.4.17.4), peptidase T (EC: 3.4.11.-) \ and Xaa-His dipeptidase (EC: 3.4.13.3).

\ \ metallopeptidase activity ; GO:0008237 \N proteolysis and peptidolysis ; GO:0006508 19979 IPR001262

Arthropods express a family of neuropeptides which include, hyperglycemichormone (CHH), molt-inhibiting hormone (MIH), gonad-inhibiting hormone (GIH) and \ mandibular organ-inhibiting hormone (MOIH) from crustaceans and ion transport peptide (ITP) from\ locust\ \ \ \ [MEDLINE:96135434].

Members of this family are the molt-inhibiting-like hormone, the mandibular \ organ-inhibiting hormone and gonad-inhibiting hormone of crustaceans. They belong to\ the larger family of hyperglycemic-like hormones.

\ \ neuropeptide hormone activity ; GO:0005184 extracellular ; GO:0005576 \N 19980 IPR001263

Phosphatidylinositol 3-kinase (PI3-kinase) (EC: 2.7.1.137) is an enzyme that phosphorylates phosphoinositides on the 3-hydroxyl group of the inositol\ ring. The role of the accessory domain of phosphoinositide 3-kinase (PI3-kinase) \ is unclear. It may be involved in substrate presentation \ [MEDLINE:94069320].

\ \ inositol/phosphatidylinositol kinase activity ; GO:0004428 \N \N 19981 IPR001264

Glycosyltransferase family 51 CAZY:GT_51 comprises enzymes with only one known activity; murein polymerases (EC: 2.4.-.-"/). These enzymes utilise MurNAc-GlcNAc-P-P-lipid II as the sugar donor.

\ \ \

The family includes the bifunctional penicillin-binding proteins that have a \ transglycosylase (N-terminus) and transpeptidase (C-terminus) domain PUB00007032 and \ the monofunctional biosynthetic peptidoglycan transglycosylases [MEDLINE:96228711].

\ \ enzyme activity ; GO:0003824 cell wall (sensu Bacteria) ; GO:0009274 peptidoglycan biosynthesis ; GO:0009252 19967 IPR001251 This family defines various retinaldehyde/retinal-binding proteins that may befunctional components of the visual cycle. Cellular retinaldehyde-binding protein (CRALBP) carries 11-cis-retinol or 11-cis-retinaldehyde as endogenous ligands and may function as a substrate carrier protein that modulates interaction of these retinoids with visual cycle enzymes [MEDLINE:91358461]. \ The multidomain protein Trio binds the LAR transmembrane tyrosine phosphatase, contains a protein kinase domain, and has separate rac-specific and rho-specific guanine nucleotide exchange factor domains [MEDLINE:96224308]. Trio is a multifunctional protein that integrates and amplifies signals involved in coordinating actin remodeling, which is necessary for cell migration and growth.\

Other members of the family are \ transfer proteins that include, guanine nucleotide exchange factor that may \ function as an effector of RAC1, phosphatidylinositol/phosphatidylcholine transfer \ protein that is required for the transport of secretory proteins from the golgi\ complex and -tocopherol transfer protein that enhances the transfer of the \ ligand between separate membranes.

\ \ \N \N \N 19968 IPR001251 This family defines various retinaldehyde/retinal-binding proteins that may befunctional components of the visual cycle. Cellular retinaldehyde-binding protein (CRALBP) carries 11-cis-retinol or 11-cis-retinaldehyde as endogenous ligands and may function as a substrate carrier protein that modulates interaction of these retinoids with visual cycle enzymes [MEDLINE:91358461]. \ The multidomain protein Trio binds the LAR transmembrane tyrosine phosphatase, contains a protein kinase domain, and has separate rac-specific and rho-specific guanine nucleotide exchange factor domains [MEDLINE:96224308]. Trio is a multifunctional protein that integrates and amplifies signals involved in coordinating actin remodeling, which is necessary for cell migration and growth.\

\ \ \N \N \N 19969 IPR001252 The malate dehydrogenase family is widely distributed in prokaryotes andeukaryotes. In eukaryotes there are two forms, chloroplastic and mitochondrial.\ The chloroplastic form is NADP-dependent and is essential for the photosynthetic\ C4 cycle that allows plants to circumvent the problem of photorespiration.\ \ malate dehydrogenase activity ; GO:0016615 \N tricarboxylic acid cycle ; GO:0006099 19970 IPR001253 Eukaryotic translation initiation factor A (eIF-1A) (formerly known as eiF-4C) is a protein that seems to be required for maximal rate of protein biosynthesis. It enhances \ ribosome dissociation into subunits and stabilizes the binding of the initiator Met-tRNA \ to 40S ribosomal subunits [MEDLINE:96032702].\ AArchaebacteria also seem to possess an eIF-1A homolog.\ \ translation initiation factor activity ; GO:0003743 \N translational initiation ; GO:0006413 19971 IPR001254

The trypsin family is almost totally confined to animals, although trypsin-like\ enzymes are found in actinomycetes of the genera Streptomyces and\ Saccharopolyspora, and in the fungus Fusarium oxysporum\ \ \ \ [MEDLINE:95147689]. The enzymes\ are inherently secreted, being synthesised with a signal peptide that\ targets them to the secretory pathway. Animal enzymes are either secreted\ directly, packaged into vesicles for regulated secretion, or are retained\ in leukocyte granules [MEDLINE:95147689].

\ \ trypsin activity ; GO:0004295 \N proteolysis and peptidolysis ; GO:0006508 19975 IPR001258 The NHL (NCL-1, HT2A and LIN-41) repeat is found in a variety of enzymes of the copper type II, ascorbate-dependent monooxygenase family which catalyse the C-terminus

-amidation of biological peptides [MEDLINE:91373306]. The repeat also occurs in a human \ zinc finger protein that specifically interacts with the activation domain of \ lentiviral Tat proteins [MEDLINE:95297135]. The repeat domain that is often associated \ with RING finger and B-box motifs [MEDLINE:99085260].\ \ \N \N \N 19974 IPR001257 Parvoviruses encode two noncapsid/non-structural proteins, NS1 and NS2. NS1 is essentialfor viral DNA replication [MEDLINE:93383389]. These proteins include the ATP/GTP-binding site \ motif A (P-loop) IPR001687.\ \ \N \N \N 19973 IPR001256

At least eight sub-types of metabotropic receptor (MGR1-8) have been\ identified in cloning studies. The sub-types differ in their agonist\ pharmacology and signal transduction pathways PUB00005885.

mRNA for MGR1 is widespread in the brain and is abundant in neuronal cells in hippocampal\ dentate gyrus and CA2-3 regions, cerebellum Purkinje cells, olfactory bulb\ and thalamic nuclei . MGR1 activates the phophoinositide pathway,\ probably via a G-protein of the Gq/G11 class; pertussis toxin partially\ inhibits the response to MGR1, but not to MGR5 PUB00005885.

\ \ \ metabotropic glutamate, GABA-B-like receptor activity ; GO:0008067 membrane ; GO:0016020 \N 19972 IPR001255 Beta-amyloid protein (

-APP) is a 40-residue peptide implicated in the pathogenesis of Alzheimers disease (AD) and aged Down's Syndrome (which is promoted by the acquisition \ of an additional copy of chromosome 21) [MEDLINE:93145954], [MEDLINE:93133829], [MEDLINE:93250996]. The peptide is a proteolytic product of the much \ larger amyloid precursor protein (APP) encoded by a gene on chromosome 21. \ The protein comprises a large extracellular N-terminal domain, and a short hydrophobic \ membrane-spanning domain, followed by a short C-terminal region. Beta-APP both precedes \ and forms part of the transmembrane region. \

In AD, pathologically the brain is characterised by extracellular amyloid plaques, \ intraneuronal neurofibrillary tangles, and vascular and neuronal damage. The major\ protein found within these deposits is a small, highly aggregating peptide (-APP), \ which is thought to be derived from aberrant catabolism of its precursor.\

\ \ \N membrane ; GO:0016020 \N 19959 IPR001245 Protein kinases comprise a large family of enzymes that mediate the response of eukaryotic cells to external stimuli by phosphorylation of hydroxyamino acids. The \ enzymes fall into two broad classes, characterised with respect to substrate specificity: \ serine/threonine specific and tyrosine specific [MEDLINE:88264399]. \ \

Tyrosine phosphorylating activity was originally detected in two viral transforming \ proteins PUB00005923, but many retroviral transforming \ proteins and their cellular counterparts have since been shown to possess such activity. \ The growth factor receptors, which are activated by ligand binding, and the\ insulin-related peptide receptor, are also family members.

\ \ \ ATP binding activity ; GO:0005524 \N protein amino acid phosphorylation ; GO:0006468 19960 IPR001246

\ \ \

Plant lipoxygenases (EC: 1.13.11.12\ \ \ \ IPR001246). Plants express a variety of cytosolic\ isozymes as well as what seems to be a chloroplast isozyme [MEDLINE:94148883] .

Mammalian arachidonate 5-lipoxygenase (EC: 1.13.11.34\ \ \ \ IPR001246/>).

Mammalian arachidonate 12-lipoxygenase (EC: 1.13.11.31\ \ \ \ IPR001885).

Mammalian erythroid cell-specific 15-lipoxygenase (EC: 1.13.11.33\ \ \ \ IPR001885/>).

\ \ \

\ \ lipoxygenase activity ; GO:0016165 \N electron transport ; GO:0006118 19961 IPR001247 This family includes the 3'-5' exoribonucleases, ribonuclease PH that contains a single copy of this domain, and removes nucleotide residues following the -CCA terminus of \ tRNA and polyribonucleotide nucleotidyltransferase (PNPase) that contains two tandem \ copies of the domain and is involved in mRNA degradation in a 3'-5' direction. PNPase\ is involved in the RNA degradosome, a multi-enzyme complex important in RNA processing \ and messenger RNA degradation. In yeast these proteins are components of the exosome \ 3'-5' exoribonuclease complex that is required for 3' processing of the 5.8S rRNA\ [MEDLINE:98050921].\ \ \ 3'-5' exoribonuclease activity ; GO:0000175\ RNA binding activity ; GO:0003723 \N RNA processing ; GO:0006396 19962 IPR001247 This family includes the 3'-5' exoribonucleases, ribonuclease PH that contains a single copy of this domain, and removes nucleotide residues following the -CCA terminus of \ tRNA and polyribonucleotide nucleotidyltransferase (PNPase) that contains two tandem \ copies of the domain and is involved in mRNA degradation in a 3'-5' direction. PNPase\ is involved in the RNA degradosome, a multi-enzyme complex important in RNA processing \ and messenger RNA degradation. In yeast these proteins are components of the exosome \ 3'-5' exoribonuclease complex that is required for 3' processing of the 5.8S rRNA\ [MEDLINE:98050921].\ \ \ 3'-5' exoribonuclease activity ; GO:0000175\ RNA binding activity ; GO:0003723 \N RNA processing ; GO:0006396 19963 IPR001247 This family includes the 3'-5' exoribonucleases, ribonuclease PH that contains a single copy of this domain, and removes nucleotide residues following the -CCA terminus of \ tRNA and polyribonucleotide nucleotidyltransferase (PNPase) that contains two tandem \ copies of the domain and is involved in mRNA degradation in a 3'-5' direction. PNPase\ is involved in the RNA degradosome, a multi-enzyme complex important in RNA processing \ and messenger RNA degradation. In yeast these proteins are components of the exosome \ 3'-5' exoribonuclease complex that is required for 3' processing of the 5.8S rRNA\ [MEDLINE:98050921].\ \ \ 3'-5' exoribonuclease activity ; GO:0000175\ RNA binding activity ; GO:0003723 \N RNA processing ; GO:0006396 19964 IPR001248

The Nucleobase Cation Symporter-1 (NCS1) family consists of bacterial and yeast transporters for nucleobases including purines and pyrimidines. Members of this family possess twelve putative transmembrane a-helical spanners (TMSs). At least some of them have been shown to function in uptake by substrate:H+ symport mechanism.

\ nucleobase transporter activity ; GO:0015205 membrane ; GO:0016020 nucleobase, nucleoside, nucleotide and nucleic acid transport ; GO:0015931 19965 IPR001249 The proteins in this family are a component of the acetyl coenzyme A carboxylase complex(EC: 6.4.1.2) and are involved in the first step in long-chain fatty acid synthesis. In\ plants this is usually located in the chloroplast. In the first step, biotin carboxylase \ catalyses the carboxylation of the carrier protein to form an intermediate. Next, the \ transcarboxylase complex transfers the carboxyl group from the intermediate to \ acetyl-CoA forming malonyl-CoA.\ \ acetyl-CoA carboxylase activity ; GO:0003989 acetyl-CoA carboxylase complex ; GO:0009317 fatty acid biosynthesis ; GO:0006633 19966 IPR001250

Type I includes eukaryotic PMI and the enzyme encoded \ by the manA gene in enterobacteria. PMI has a bound zinc ion, which is essential for \ activity.\ \

A crystal structure of PMI from Candida albicans shows that the enzyme has three distinct domains [MEDLINE:96196885]. The active site lies in the central domain, contains a single essential zinc atom, and forms a deep, open cavity of suitable dimensions to contain M6P or F6P The central domain is flanked by a helical domain on one side and a jelly-roll like domain on the other.

\ \ zinc ion binding activity ; GO:0008270 \N carbohydrate metabolism ; GO:0005975 19955 IPR001241

\ \

Eukaryotic topoisomerase II exists as a homodimer; in bacteriophage T4 it \ consists of three heterologous subunits; in prokaryotes it exists as a tetramer\ of two subunits (two each of gyrA and gyrB); and in E.coli, a second type II\ topoisomerase, involved in chromosome segregation (topoisomerase IV),\ consists of two subunits (parC and parE). GyrB, parE, and the product of \ bacteriophage T4 gene 39, are all similar to the eukaryotic proteins.

\ \ ATP binding activity ; GO:0005524 \N DNA topological change ; GO:0006265 19956 IPR001242 This domain is found in many multi-domain enzymes which synthesize peptide antibiotics. This domain catalyses a condensation reaction to form peptide bonds in non-ribosomal peptide biosynthesis. It is usually found to the carboxy\ side of a phosphopantetheine binding domain (pp-binding). It has been shown that mutations in the HHXXXDG motif\ abolish activity suggesting this is part of the active site [MEDLINE:98380507]. \ \ molecular_function unknown ; GO:0005554 \N \N 19957 IPR001243 Rusticyanin from Thiobacillus ferrooxidans is an electron carrier from cytochrome c-552 to the a-type oxidase. This protein belong to the family of type I blue copper proteins that \ are found in methylothropic bacteria, where they appear to function as the electron \ acceptor to methylamine dehydrogenase IPR000923. The NMR structure indicates the\ fold to be a compact

-barrel or

-sandwich, which contains a hydrophobic core \ rich in aromatic residues [MEDLINE:95082008]. Its \ sequence is highly diverged from related copper-blue proteins, but it has a similar \ active site, containing conserved His and Cys residues responsible for binding\ copper.\ \ copper ion binding activity ; GO:0005507 \N electron transport ; GO:0006118 19958 IPR001244

\ \ prostaglandin receptor activity ; GO:0004955 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19953 IPR001239

\ \ serine protease inhibitor activity ; GO:0004867 \N \N 19954 IPR001240 Indole-3-glycerol phosphate synthase (EC: 4.1.1.48) (IGPS) (see IPR001468).

Phosphoribosylanthranilate isomerase (PRAI) is monomeric and labile in most mesophilic microorganisms, but dimeric and stable in the hyperthermophile Thermotoga maritima (tPRAI) [MEDLINE:20211862]. The comparison to the known 2.0 A structure of PRAI from Escherichia coli (ePRAI) shows that tPRAI has the complete TIM- or ( )8-barrel fold, whereas helix alpha5 in ePRAI is replaced by a loop. The subunits of tPRAI associate via the N-terminal faces of their central -barrels. Two long, symmetry-related loops that protrude reciprocally into cavities of the other subunit provide for multiple hydrophobic interactions. Moreover, the side chains of the N-terminal methionines and the C-terminal leucines of both subunits are immobilized in a hydrophobic cluster, and the number of salt bridges is increased in tPRAI. These features appear to be mainly responsible for the high thermostability of tPRAI [MEDLINE:97309356].

\ \ phosphoribosylanthranilate isomerase activity ; GO:0004640 \N tryptophan metabolism ; GO:0006568 19945 IPR001232 SKP1 (together with SKP2) was identified as an essential component of the cyclin A-CDK2 S phase kinase complex [MEDLINE:99221829]. It was found to bind several \ F-box containing proteins (e.g., Cdc4, Skp2, cyclin F) and to be involved in the \ ubiquitin protein degradation pathway. A yeast homologue of SKP1 (P52286) was \ identified in the centromere bound kinetochore complex [MEDLINE:96312958] and is also \ involved in the ubiquitin pathway [MEDLINE:98050924] ]. In the slime mold FP21 \ was shown to be glycosylated in the cytosol and has homology to SKP1 [MEDLINE:95155385].\ \ \N \N \N 19946 IPR001233 A number of uncharacterized proteins including Escherichia coli rtcB, Mycobacterium tuberculosis MtCY441.01., Caenorhabditis elegans F16A11.2 and Methanococcus jannaschii \ MJ0682 belong to this family.\ \ molecular_function unknown ; GO:0005554 \N \N 19947 IPR001234

At least eight sub-types of metabotropic receptor (MGR1-8) have been\ identified in cloning studies. The sub-types differ in their agonist\ pharmacology and signal transduction pathways PUB00005885.

MGR3 is brain-specific, and is expressed in neurones in the cerebral cortex, caudate-putamen,\ thalamus and cerebellum PUB00005885. MGR3 inhibits adenylyl cyclase through a\ pertussis-toxin-sensitive G-protein, probably of the Gi/Go class PUB00005885.

\ \ metabotropic glutamate, GABA-B-like receptor activity ; GO:0008067 membrane ; GO:0016020 \N 19948 IPR001235 Blue (type 1) copper proteins are small proteins which bind a singlecopper atom and which are characterized by an intense electronic absorption\ band near 600 nm [MEDLINE:94309118], [MEDLINE:93164266]. The most well known members of this \ class of proteins are the plant chloroplastic plastocyanins, which exchange electrons \ with cytochrome c6, and the distantly related bacterial azurins, which exchange\ electrons with cytochrome c551. \ \

Several subclasses of the blue copper proteins, such as the amicyanins, azurins, \ lastocyanins and rusticyanins, have been identified. Although there is an appreciable\ amount of divergence in the sequences of these proteins, the copper ligand sites are \ conserved.

\ \ copper ion binding activity ; GO:0005507 \N electron transport ; GO:0006118 19949 IPR001236 L-lactate dehydrogenases are metabolic enzymes which catalyse the conversion of L-lactate to pyruvate, the last step in anaerobic glycolysis. L-lactate dehydrogenase \ is also found as a lens crystallin in bird and crocodile eyes. L-2-hydroxyisocaproate \ dehydrogenases are also members of the family. \ \ Malate dehydrogenases catalyse the interconversion of malate to oxaloacetate. The \ enzyme participates in the citric acid cycle.\ \ oxidoreductase activity ; GO:0016491 \N \N 19950 IPR001236 L-lactate dehydrogenases are metabolic enzymes which catalyse the conversion of L-lactate to pyruvate, the last step in anaerobic glycolysis. L-lactate dehydrogenase \ is also found as a lens crystallin in bird and crocodile eyes. L-2-hydroxyisocaproate \ dehydrogenases are also members of the family. \ \ Malate dehydrogenases catalyse the interconversion of malate to oxaloacetate. The \ enzyme participates in the citric acid cycle.\ \ oxidoreductase activity ; GO:0016491 \N \N 19943 IPR001231 CD44 is a polymorphic cell-surface glycoprotein synthesised in a varietyof cells. The protein interacts with actin-based cytoskeletons, and co-\ localises with ERM proteins (ezrin, radixin and moesin) at actin filament-\ plasma membrane interaction sites. CD44 may be involved in cell migration, \ adhesion and differentiation in normal cells, as well as in metastasis in cancer \ cells. It is a receptor for extracellular materials, such as soluble or cell-bound \ hyaluronic acid, collagen, fibronectin and serglycin. The protein has a single \ membrane-spanning domain and has a heavily glycosylated extracellular domain; its \ cytoplasmic domain is reportedly associated with an ankyrin-like protein [MEDLINE:97200562].\

\ \ cell adhesion receptor activity ; GO:0004895 membrane ; GO:0016020 cell adhesion ; GO:0007155 19944 IPR001232 SKP1 (together with SKP2) was identified as an essential component of the cyclin A-CDK2 S phase kinase complex [MEDLINE:99221829]. It was found to bind several \ F-box containing proteins (e.g., Cdc4, Skp2, cyclin F) and to be involved in the \ ubiquitin protein degradation pathway. A yeast homologue of SKP1 (P52286) was \ identified in the centromere bound kinetochore complex [MEDLINE:96312958] and is also \ involved in the ubiquitin pathway [MEDLINE:98050924] ]. In the slime mold FP21 \ was shown to be glycosylated in the cytosol and has homology to SKP1 [MEDLINE:95155385].\ \ \N \N \N 19952 IPR001238

All proteins in this family, including recF, for which functions are known are DNA binding proteins that assist the filamentation of RecA onto DNA for the initiation of recombination or recombinational repair. RecF is involved in DNA metabolism and is required for recombinational DNA repair and for induction of the SOS response [MEDLINE:95206242], [MEDLINE:92178981].

\ \ \ ATP binding activity ; GO:0005524 \N DNA repair ; GO:0006281 19951 IPR001237 The 43kDa postsynaptic protein is a peripheral membrane protein thought to be involved in the anchoring or stabilisation of the nicotinic acetylcholine receptor at synaptic \ sites [MEDLINE:89289985], PUB00005537. It may link the receptor to the postsynaptic \ cytoskeleton through direct association with actin or spectrin. The 43 kDa protein is \ highly conserved across species. Two highly conserved regions, one encompassing the \ N-terminus and the other near the C-terminus, may be important for interaction of the \ protein with other components of the postsynaptic membrane.\ \ \N \N \N 19938 IPR001226 Flavodoxins are electron-transfer proteins that function in various electron transport systems. Flavodoxins bind one FMN molecule, which serves as a\ redox-active prosthetic group [MEDLINE:90088453] and are functionally interchangeable\ with ferredoxins.. They have been isolated from prokaryotes, cyanobacteria, and\ some eukaryotic algae.\ \ \N \N electron transport ; GO:0006118 19939 IPR001227 Enzymes like bacterial malonyl CoA-acly carrier protein transacylase (EC: 2.3.1.39) and eukaryotic fatty acid synthase (EC: 2.3.1.85) that are involved in fatty acid\ biosynthesis belong to this group. Also included are the polyketide synthases \ 6-methylsalicylic acid synthase (EC: 2.3.1.-), a multifunctional enzyme that involved\ in the biosynthesis of patulin and conidial green pigment synthase (EC: 2.3.1.-).\ \ transferase activity ; GO:0016740 \N metabolism ; GO:0008152 19940 IPR001228 The bacterial ispD protein catalyzes the third step of the deoxyxylulose-5-phosphate pathway (DXP) of isoprenoid biosynthesis; the formation of 4-diphosphocytidyl-2C-methyl-D-erythritol from CTP and 2C-methyl-D-erythritol 4-phosphate.\ \ \ 4-diphosphocytidyl-2C-methyl-D-erythritol synthase activity ; GO:0008699\ \N \N isoprenoid biosynthesis ; GO:0008299 19941 IPR001229 Jacalin, from the seed of the jackfruit is specific for galactose.A variety of proteins belong to this group including lectins that stimulate distinct\ T- and B- cell functions. The salt-stress induced protein from rice and an animal \ prostatic spermine-binding protein also belong to this group.\ \ \N \N \N 19942 IPR001230

A number of eukaryotic proteins undergo post-translational modification by the attachment of either a farnesyl or a geranyl-geranyl group to a cysteine residue at the C terminus. A diverse list of proteins are\ known or strongly presumed to be the target of this modification including ras \ and ras-like proteins, nuclear lamins, and gamma G-proteins, cyclic nucleotide \ phosphodiesterases, a number of fungal mating factors, Rhodopsin kinase (EC: 2.7.1.125)\ and some dnaJ-like proteins.

Three distinct protein prenyl transferases, one protein farnesyl transferase (FTase) and two protein geranylgeranyl transferases (GGTase), catalyze prenylation of cellular proteins. One group of protein substrates contains a C-terminal CAAX motif (C is Cys, A is aliphatic, and X is a variety of amino acids) in which the single cysteine residue is modified with either farnesyl or geranylgeranyl (GG) by FTase or GGTase type-I (GGTase-I), respectively. Rab proteins constitute a second group of substrates that contain a C-terminal double-cysteine motif (such as XXCC in Rab1a) in which both cysteines are geranylgeranylated by Rab GG transferase (RabGGTase). Previous characterization of CAAX prenyl transferases showed that the enzymes form stable complexes with their prenyl pyrophosphate substrates, acting as prenyl carriers. RabGGTase has been shown to have a prenyl carrier function similar to the CAAX prenyl transferases. Chromatographic analysis of prenylated products revealed that Rab is mono-geranylgeranylated. All three protein prenyl transferases contain a single prenyl-binding site and suggests that RabGGTase transfers two GG groups to Rabs in independent and consecutive reactions [MEDLINE:98445360].

\ \ \ \N \N \N 19937 IPR001224

Vasopressin and oxytocin are members of the neurohypophyseal hormone family\ found in all mammalian species . They are present in high levels in the\ posterior pituitary. Vasopressin has an essential role in the control of\ the water content of the body, acting in the kidney to increase water and\ sodium absorption . In higher concentrations, vasopressin stimulates\ contraction of vascular smooth muscle, stimulates glycogen breakdown in the\ liver, induces platelet activation, and evokes release of corticotrophin\ from the anterior pituitary PUB00005908. Vasopressin and its analogues are used\ clinically to treat diabetes insipidus .

In the periphery, the V1A receptor is found in high levels in vascular\ smooth muscle, myometrium and the bladder where it mediates contraction .\ In the CNS, V1 sites are distributed widely and are found in lateral septal\ nucleus, hippocampus, superior collicular, substantia nigra and central\ grey matter . The receptors activate phosphoinositide metabolism through\ a pertussis-toxin-insensitive G-protein, probably of the Gq/G11 class PUB00005908.

\ \ vasopressin receptor activity ; GO:0005000 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19935 IPR001222 Transcription factor S-II (TFIIS) is a eukaryotic protein necessary forefficient RNA polymerase II transcription elongation, past template-encoded\ pause sites. TFIIS shows DNA-binding activity only in the presence of RNA\ polymerase II [MEDLINE:88153686]. It \ is widely distributed being found in mammals, Drosophila, yeast and in the \ archaebacteria Sulfolobus acidocaldarius\ \ \ \ [MEDLINE:93275759]. S-II proteins have a relatively conserved C-terminal region but variable N-terminal\ region , and some members of this family are expressed in a tissue-specific manner [MEDLINE:92011448], [MEDLINE:96144291]. \

Some viral proteins also contain the TFIIS zinc ribbon C-terminal domain. The vaccinia virus protein, unlike its eucaryotic homolog, is an integral RNA polymerase subunit rather than a readily separable transcription factor [MEDLINE:90377234].

\ \ transcription factor activity ; GO:0003700 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 19936 IPR001223

Some members of this family, CAZY:GH_18, belong to the chitinase class II group which includes chitinase, chitodextrinase and the killer toxin of Kluyveromyces lactis. The chitinases hydrolyse chitin oligosaccharides. The family also includes various glycoproteins from mammals; cartilage\ glycoprotein and the oviduct-specific glycoproteins are two examples.

\ \ \ hydrolase activity ; GO:0016787 \N metabolism ; GO:0008152 19934 IPR001221

Phenol hydroxylase [MEDLINE:91072230], benzoate-1,2-dioxygenase [MEDLINE:91358314],toluate-1,2-dioxygenase [MEDLINE:92041666], xylene monooxygenase [MEDLINE:91154124] and \ methane monooxygenase [MEDLINE:90382694] contain an oxidoreductase FAD/NAD(P)-binding domain. They are the electron transfer components of a number \ of bacterial multi-component aromatic-ring and alkyl-group oxygenases.

\ \ \N \N electron transport ; GO:0006118 19930 IPR001217

The STAT protein (Signal Transducers and Activators of Transcription) family containstranscription factors that are specifically activated to regulate gene transcription\ when cells encounter cytokines and growth factors [MEDLINE:22035350]. In mammals, STATs comprise a family of seven structurally and functionally related proteins: Stat1, Stat2, Stat3, Stat4, Stat5a\ and Stat5b, Stat6. STATs are activated by phosphorylation by members of the JAK family of protein kinases. Once activated, STAT then play a critical role in regulating innate and acquired host immune responses.\ Dysregulation of at least two STAT signaling cascades (i.e. Stat3 and Stat5) is associated with cellular transformation.

Signaling through the JAK/STAT pathway is initiated when a cytokine binds to its corresponding receptor. This leads to conformational changes in the\ cytoplasmic portion of the receptor, initiating activation of receptor associated members of the JAK family of kinases. The JAKs, in turn, mediate phosphorylation at\ the specific receptor tyrosine residues, which then serve as docking sites for STATs and other signaling molecules. Once recruited to the receptor, STATs also\ become phosphorylated by JAKs, on a single tyrosine residue. Activated STATs dissociate from the receptor, dimerize, translocate to the nucleus and bind to\ members of the GAS (gamma activated site) family of enhancers.

The seven STAT proteins identified in mammals range in size from 750 and 850 amino acids. The chromosomal distribution of these STATs, as well as the\ identification of STATs in more primitive eukaryotes, suggest that this family arose from a single primordial gene. STATs share structurally and\ functionally conserved domains including the amino-terminal domain, the coiled-coiled domain, the DNA binding domain, the\ linker domain and the SH2/tyrosine activation domain IPR000980. In contrast, the carboxy-terminal transcriptional activation domain (TAD) is quite divergent and contributes to\ STAT specificity. The crystal structure of the N-terminus of Stat4 reveals a dimer. The\ interface of this dimer is formed by a ring-shaped element consisting of five short helices. Several studies suggest that this N-terminal dimerization promotes\ cooperativity of binding to tandem GAS elements and with the transcriptional coactivator CBP/p300. The DNA binding domain is a -barrel with an immunoglobulin fold and lies carboxy-terminal to the coiled-coil domain.

\ \ signal transducer activity ; GO:0004871 nucleus ; GO:0005634 signal transduction ; GO:0007165 19931 IPR001218 The coronavirus nucleocapsid protein.Sequence comparison of the N genes of five strains of the\ coronavirus mouse hepatitis virus suggests a three domain structure\ for the nucleocapsid protein [MEDLINE:91021052]. There seems to be a specific interaction between the\ coronavirus mouse hepatitis virus A59 nucleocapsid protein\ and packaging signal [MEDLINE:98087828].\ \ \N viral nucleocapsid ; GO:0019013 \N 19932 IPR001219 A variety of scorpion and plant toxins have been identified as belonging to this familyof toxins. The peptide scorpion toxins exert their effect by binding to sodium or\ potassium channels, inhibiting inactivation of activated channels and hence blocking\ neuronal transmission [MEDLINE:78191225], [MEDLINE:89073189]. Another class of toxin includes plant proteins that\ are toxic to animal cells. Again, their effect is exerted at the level of the cell\ membrane, although the precise mechanism is unknown [MEDLINE:92322947].\ \ toxin activity ; GO:0015070 \N \N 19933 IPR001220 Legume lectins are one of the largest lectin families with more than 70 lectinsreported. Leguminous plant lectins resemble each other in their physicochemical properties although they differ in their carbohydrate specificities. They consist of two or four subunits with relative molecular mass of 30 kDa and each subunit has one carbohydrate-binding site. The interaction with sugars requires tightly bound calcium and manganese ions. The structural similarities of these lectins are reported by the primary structural analyses and X-ray crystallographic studies. X-ray studies have shown that the folding of the polypeptide chains in the region of the carbohydrate-binding sites is also similar, despite differences in the primary sequences. The carbohydrate-binding sites of these lectins consist of two conserved amino acids on

pleated sheets. One of these loops contains transition metals, calcium and manganese,\ which keep the amino acid residues of the sugar-binding site at the required\ positions. Amino acid sequences of this loop play an important role in the\ carbohydrate-binding specificities of these lectins. These lectins bind either glucose/mannose or galactose.\

The exact function of legume lectins \ is not known but they may be involved in the attachment of nitrogen-fixing bacteria to legumes and \ in the protection against pathogens.

Some legume lectins are proteolytically processed to produce two chains, (which corresponds to \ the N-terminal) and (C-terminal)(IPR000985). The lectin concanavalin A (conA) from jack bean is exceptional \ in that the two chains are transposed and ligated (by formation of a new peptide bond). The N-terminus \ of mature conA thus corresponds to that of the chain and the C-terminus to the chain.

\ \ \N \N \N 19929 IPR001217

\ \ signal transducer activity ; GO:0004871 nucleus ; GO:0005634 signal transduction ; GO:0007165 19927 IPR001216

Cysteine synthase (EC: 4.2.99.8) (CSase) is the enzyme responsible for the formation ofcysteine from O-acetyl-serine and hydrogen sulfide with the concomitant release of\ acetic acid [MEDLINE:93345669]. In bacteria such two forms\ of the enzyme are known (genes cysK and cysM). In plants there are also two forms, one\ located in the cytoplasm and the other in chloroplasts.

\ \

Cystathionine -synthase (EC: 4.2.1.22) that catalyzes the first irreversible\ step in homocysteine transulfuration; the conjugation of homocysteine and\ serine forming cystathionine also belongs to this family [MEDLINE:92283859]. Both synthases are pyridoxal-phosphate dependent.

\ \ \N \N cysteine biosynthesis from serine ; GO:0006535 19928 IPR001217

\ \ signal transducer activity ; GO:0004871 nucleus ; GO:0005634 signal transduction ; GO:0007165 19925 IPR001214

Synonym(s): Suvar3-9, Enhancer-of-zeste, Trithorax

Proteins bearing the widely distributed SET domain (~130 amino acid) have been shown to contribute to epigenetic mechanisms of gene regulation by methylation of lysine residues in histones and other proteins. The SET domain genes are widely represented in the eukaryotic genomes, and proteins were initially distributed into four families, SU(VAR)3-9, E(Z), ASH1 and TRITHORAX based on the homology of their SET domains. Additional proteins have now been identified which do not fit into this classification [MEDLINE:22035351].

The SET domain appears generally as one part of a larger multidomain protein, and recently there were described three structures of very different proteins with distinct domain compositions: Neurospora DIM-5, a member of the Su(var) family of HKMTs which methylate histone H3 on lysine 9,human SET7 (also called SET9), which methylates H3 on lysine 4 and garden pea Rubisco LSMT, an enzyme that does not modify histones, but instead methylates lysine 14 in the flexible tail of the large subunit of the enzyme Rubisco. The SET domain itself turned out to be an uncommon structure. Although in all three studies, electron density maps revealed the location of the AdoMet or AdoHcy cofactor, the SET domain bears no similarity at all to the canonical/AdoMet-dependent methyltransferase fold. Strictly conserved in the C-terminal motif of the SET domain tyrosine could be involved in abstracting a proton from the protonated amino group of the substrate lysine, promoting its nucleophilic attack on the sulfonium methyl group of the AdoMet cofactor. In contrast to the AdoMet-dependent protein methyltranferases of the classical type, which tend to bind their polypeptide substrates on top of the cofactor, it is noted from the Rubisco LSMT structure that the AdoMet seems to bind in a separate cleft, suggesting how a polypeptide substrate could be subjected to multiple rounds of methylation without having to be released from the enzyme. In contrast, SET7/9 is able to add only a single methyl group to its substrate. It has been demonstrated that association of SET domain and myotubularin-related proteins modulates growth control [MEDLINE:98196760]. The SET domain-containing Drosophila protein, enhancer of zeste, has a function in segment determination and the mammalian homologue may be involved in the regulation of gene transcription and chromatin structure.

It seems likely that the varied domains that occur together with the SET domain will be involved in recognizing protein substrates and ''reading'' histone tails in order to dictate which (if any) of their multiple lysine residues should get methylated [MEDLINE:22259591].

\ \ \ \N \N \N 19926 IPR001215

Ryanodine receptors are involved in communication between transverse-tubules\ and the sarcoplamic reticulum of cardiac and skeletal muscle. The proteins\ function as a Ca²⁺-release channels following depolarisation of transverse-tubules [MEDLINE:91250425]. The function is modulated by Ca²⁺, Mg2+, ATP and calmodulin.\ Deficiency in the ryanodine receptor may be the cause of malignant\ hyperthermia (MH) and of central core disease of muscle (CCD) [MEDLINE:95130087]. MH is\ an autosomal dominant disorder of skeletal muscle and is a principal\ cause of death due to anaesthesia.

Calcium release activity of the receptors resides in the C-terminal region\ of the protein, the remaining part of the molecule forming a 'foot'\ structure that spans the junctional gap between the sarcoplamic reticulum\ and the transverse-tubule. The foot structure may interact with the\ cytoplasmic region of the dihydropyridine receptor.

Analysis of the sequence reveals 10 potential transmembrane (TM) regions\ in the C-terminal fifth of the molecule and 2 further potential TM regions\ nearer to the centre [MEDLINE:90130482]. These may contribute to the formation of the Ca²⁺\ conducting pore. The rest of the sequence is hydrophilic, and presumably\ constitutes the cytoplasmic domain of the protein.

\ \ \ calcium channel activity ; GO:0005262 membrane ; GO:0016020 calcium ion transport ; GO:0006816 19922 IPR001211

Phospholipase A2 (EC: 3.1.1.4) (PLA2) is a small lipolytic enzyme that releases fattyacids from the second carbon group of glycerol. It is involved in a number\ of physiologically important cellular processes, such as the liberation of arachidonic\ acid from membrane phospholipids [MEDLINE:95393214]. It plays a pivotal role in the biosynthesis of prostaglandin and other\ mediators of inflammation. PLA2 has four to seven disulphide bonds and binds a calcium\ ion that is essential for activity. Within the active enzyme, the amino group is\ involved in a conserved hydrogen-bonding network linking the N-terminal region to\ the active site. The side chains of two conserved residues, His and Asp, participate in\ the catalytic network.

\ \

Many PLA2's are widely distributed in snakes, lizards, bees and mammals. In mammals\ there are at least four forms: pancreatic, membrane-associated as well as two less\ well characterized forms. The venom of most snakes contains multiple forms of PLA2.\ Some of them are presynaptic neurotoxins which inhibit neuromuscular transmission by\ blocking acetylcholine release from the nerve termini.

The allergens in this family include allergens with the following designations: Api m 1.

\ \ calcium ion binding activity ; GO:0005509 \N lipid catabolism ; GO:0016042 19920 IPR001209

\ \ \

S14 is one of the proteins from the small ribosomal subunit.\ In Escherichia coli, S14 is known to be required for the assembly of 30S particles\ and may also be responsible for determining the conformation of 16S rRNA at the A site.\ It belongs to a family of ribosomal proteins [MEDLINE:93181260], PUB00005070 that\ include, bacterial, algal and plant chloroplast, yeast mitochondrial, cyanelle and\ archaebacterial Methanococcus vannielii S14's as well as yeast mitochondrial MRP2,\ yeast YS29A/B and mammalian S29.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 19923 IPR001212 Somatomedin B, a serum factor of unknown function, is a small cysteine-rich peptide,derived proteolytically from the N-terminus of the cell-substrate adhesion protein\ vitronectin [MEDLINE:88107592]. Cys-rich\ somatomedin B-like domains are found in a number of proteins [MEDLINE:91248172], including plasma-cell membrane glycoprotein (which\ has nucleotide pyrophosphate and alkaline phosphodiesterase I activities) [MEDLINE:91271356] and placental protein 11 (which appears\ to possess amidolytic activity).\ \ \N \N \N 19924 IPR001213 The mouse mammary tumor virus (MMTV) is a milk-transmitted type B retrovirus. Thesuperantigen (SAg) is encoded in the long terminal repeat [MEDLINE:95336687].\ \ \N \N \N 19919 IPR001208

The MCM domain is found in DNA-dependent ATPases required for the initiation ofeukaryotic DNA replication [MEDLINE:93087163], [MEDLINE:94089373], PUB00005507. In eukaryotes there is a family of six proteins that contain this\ domain, MCM2 to MCM7. They were first identified in yeast where most of them have a\ direct role in the initiation of chromosomal DNA replication by interacting directly\ with autonomously replicating sequences (ARS). They were thus called minichromosome\ maintenance proteins, MCM proteins PUB00005507.

\ \

This family is also present in the archebacteria in 1 to 4 copies. Methanococcus jannaschii has four members, MJ0363, MJ0961, MJ1489 and MJECL13.

\ \

The "MCM motif" contains Walker-A and Walker-B type nucleotide binding motifs.\ The diagnostic sequence defining the MCMs is IDEFDKM. Only Mcm2 (aka Cdc19 or\ Nda1) has been subjected to mutational analysis in this region, and most\ mutations abolish its activity [MEDLINE:98043398]. The presence of a putative ATP-binding domain implies that these proteins may\ be involved in an ATP-consuming step in the initiation of DNA replication in\ eukaryotes.

\ \

The MCM proteins bind together in a large complex [MEDLINE:98031880].\ Within this complex, individual subunits associate\ with different affinities, and there is a tightly associated core of\ Mcm4 (Cdc21), Mcm6 (Mis5) and Mcm7 [MEDLINE:98324928]. This core complex\ in human MCMs has been associated with helicase activity in vitro [MEDLINE:97450981],\ leading to the suggestion that the MCM proteins are the eukaryotic replicative helicase.

\ \

Fission yeast (Schizosaccharomyces pombe) MCMs, like those in metazoans, are found in the nucleus\ throughout the cell cycle. This is in contrast to the budding yeast (Saccharomyces cerevisiae)\ in which MCM proteins move in and out of the nucleus during each cell\ cycle. The assembly of the MCM complex in fission yeast is required\ for MCM localization, ensuring that only intact MCM complexes remain\ in the nucleus [MEDLINE:20056089].

\ \ DNA dependent ATPase activity ; GO:0008094 \N DNA replication initiation ; GO:0006270 19921 IPR001210

\ \ \

A number of eukaryotic and archaebacterial ribosomal proteins can be grouped\ in this family of ribosomal proteins, S17e. They include, vertebrate, Drosophila and\ Neurospora crassa (crp-3) S17's as well as yeast S17a (RP51A) and S17b (RP51B) and\ archaebacterial S17e [MEDLINE:89196902], [MEDLINE:90006758], [MEDLINE:85036340].

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 19917 IPR001206 Diacylglycerol kinase (DGK, EC: 2.7.1.107) phosphorylates diacylglycerol (DAG) to yield phosphatidic acid. This enzyme initiates resynthesis of phosphoinositides consumed by phospholipase C during cellular signal transduction. Mammalian DGK consists of nine isozymes encoded by separate genes [MEDLINE:21979573]. In addition to\ PKC-like zinc fingers and catalytic regions commonly conserved in all DGKs, these isozymes contain a variety of regulatory\ domains of known and/or predicted functions. The mammalian isozymes are named according to the order of their cDNA\ cloning and are subdivided into five groups based on their characteristic structural features. Each DGK isozyme is a critical downstream component of a\ DAG-dependent signaling system. \

This domain is usually associated with an accessory domain (see IPR000756).

\ \ diacylglycerol kinase activity ; GO:0004143 \N protein kinase C activation ; GO:0007205 19918 IPR001207 Autonomous mobile genetic elements such as transposon or insertion sequences (IS)encode an enzyme, transposase, that is required for excising and inserting\ the mobile element. Transposases have been grouped into various families [MEDLINE:94316508], [MEDLINE:92149305], [MEDLINE:92039004]. The mutator\ family of transposases consists of a number of elements that include, mutator from maize,\ IsT2 from Thiobacillus ferrooxidans, Is256 from Staphylococcus aureus, Is1201 from\ Lactobacillus helveticus, Is1081 from Mycobacterium bovis, IsRm3 from Rhizobium meliloti\ and others.\ \ \N \N \N 19913 IPR001203

Enzymes of the aldehyde ferredoxin oxidoreductase (AOR) family [MEDLINE:97386817] contain a tungsten cofactor and an 4Fe4S cluster and catalyse the interconversion of aldehydes to carboxylates [MEDLINE:96228741]. This family includes AOR, formaldehydeferredoxin oxidoreductase (FOR), glyceraldehyde-3-phosphate ferredoxin oxidoreductase (GAPOR), all isolated from\ hyperthermophilic archea [MEDLINE:97386817]; carboxylic acid reductase found in clostridia [MEDLINE:89377874]; and hydroxycarboxylate viologen\ oxidoreductase from Proteus vulgaris, the sole member of the AOR family containing molybdenum [MEDLINE:94298804]. GAPOR may be involved in glycolysis [MEDLINE:95238315], but the functions of the other proteins are not yet clear. AOR has been proposed to be the\ primary enzyme responsible for oxidising the aldehydes that are produced by the 2-keto acid oxidoreductases [MEDLINE:97420728].

\ \ oxidoreductase activity, acting on iron-sulfur proteins as donors ; GO:0016730 \N electron transport ; GO:0006118 19914 IPR001203

\ \ oxidoreductase activity, acting on iron-sulfur proteins as donors ; GO:0016730 \N electron transport ; GO:0006118 19915 IPR001204 The PHO-4 family of transporters includes the phosphate-repressible phosphate permease(PHO-4) from Neurospora crassa which is probably a sodium-phosphate symporter [MEDLINE:95249577]. This family also includes\ the human leukemia virus receptor.\ \ inorganic phosphate transporter activity ; GO:0005315 membrane ; GO:0016020 phosphate transport ; GO:0006817 19916 IPR001205 RNA-directed RNA polymerase, P3D (EC: 2.7.7.48) is part of the genome polyprotein thatalso contains, coat proteins VP1 to VP4, core proteins P2A to P2C and P3A, genome-linked\ protein VPG and picornain 3C (EC: 3.4.22.28) (protease 3C) (P3C). RNA-directed RNA\ polymerase catalyses RNA-template-directed extension of the 3'-end of an RNA strand by\ one nucleotide at a time. Can initiate a chain de novo.\ \ RNA-directed RNA polymerase activity ; GO:0003968 \N transcription ; GO:0006350 19909 IPR001199 Cytochromes b5 are ubiquitous electron transport proteins found in animals, plants andyeasts\ \ \ \ [MEDLINE:89323209]. The microsomal and mitochondrial variants are membrane-bound, \ while those from erythrocytes and other animal tissues are water-soluble [MEDLINE:85289161], [MEDLINE:93176833].

The 3D structure of bovine cyt b5 is known, the\ fold belonging to the + class, with 5 strands and 5 short helices\ forming a framework for supporting a central haem group [MEDLINE:75095526]. The cytochrome b5 domain is similar to that of a number\ of oxidoreductases, such as plant and fungal nitrate reductases, sulphite oxidase, yeast\ flavocytochrome b2 (L-lactate dehydrogenase) and plant cyt b5/acyl lipid desaturase\ fusion protein.

\ \ \N \N \N 19910 IPR001200 The outer and inner segments of vertebrate rod photoreceptor cells contain phosducin,a soluble phosphoprotein that complexes with the

/gamma-subunits of the GTP-binding\ protein, transducin. Light-induced changes in cyclic nucleotide levels modulate the\ phosphorylation of phosducin by protein kinase A [MEDLINE:90368806]. The protein is thought to participate in the regulation of\ visual phototransduction or in the integration of photo-receptor metabolism. Similar\ proteins have been isolated from the pineal gland and it is believed that the functional\ role of the protein is the same in both retina and pineal gland [MEDLINE:91007277].\ \ \N \N phototransduction ; GO:0007602 19911 IPR001201 The polyA-related domain is found in a number of proteins that include,poly(A) polymerase (EC: 2.7.7.19)(PAP), 2-5A synthetase (EC: 2.7.7.-) and\ topoisomerase 1. The polymerase creates the 3' poly(A) tail of mRNA's, the\ 2-5A synthetase binds double-stranded RNA and polymerizes ATP into PPP(A2'P5'A)N\ oligomers that activate the latent RNase that cleaves single-stranded RNA's.\ Yeast topoisomerase 1 is essential for proper nuclear division on mitosis.\ \ nucleic acid binding activity ; GO:0003676 \N \N 19912 IPR001202

Synonym(s): Rsp5 or WWP domain

The WW domain is a short conserved region in a number of\ unrelated proteins, which folds as a stable, triple stranded -sheet.\ This short domain of approximately 40 amino acids, may be repeated up to four times in some proteins [MEDLINE:95149368], [MEDLINE:95100946], [MEDLINE:95129701],\ [MEDLINE:95369475]. The name WW or WWP derives from the presence of two signature tryptophan residues that are spaced 20-23 amino acids apart and are present in most WW domains known to date, as well as that of a\ conserved Pro. The WW domain binds to proteins with\ particular proline-motifs, [AP]-P-P-[AP]-Y, and/or phosphoserine- phosphothreonine-containing motifs [MEDLINE:95372370], [MEDLINE:21909371]. It is frequently associated with other domains typical for proteins in\ signal transduction processes.

\ \

A large variety of proteins containing the WW domain are known. These include; dystrophin,\ a multidomain cytoskeletal protein; utrophin, a dystrophin-like protein of unknown\ function; vertebrate YAP protein, substrate of an unknown serine kinase; mouse NEDD-4, \ involved in the embryonic development and differentiation of the central nervous system;\ yeast RSP5, similar to NEDD-4 in its molecular organization; rat FE65, a \ transcription-factor activator expressed preferentially in liver; tobacco DB10 protein\ and others.

\ \ \N \N \N 19908 IPR001197

\ \ \

A variety of eukaryotic and plant ribosomal L10E proteins can be grouped.\ This family consists of vertebrate L10 (QM) [MEDLINE:96374425], plant L10, Caenorhabditis elegans L10, yeast L10 (QSR1) and\ Methanococcus jannaschii MJ0543.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 19904 IPR001194 The human serine- and leucine-rich DENN protein possesses a RGD cellular adhesion motif and a leucine-zipper-like motif associated with protein dimerization, and shows partial homology to the receptor binding domain of tumor necrosis factor

. DENN is virtually identical to MADD, a human MAP kinase-activating death domain protein that interacts with type I tumor necrosis factor receptor. DENN displays significant homology to Rab3 GEP, a rat GDP/GTP exchange protein specific for Rab3 small G proteins implicated in intracellular vesicle trafficking. DENN also exhibits strong similarity to Caenorhabditis elegans AEX-3, which interacts with Rab3 to regulate synaptic vesicle release [MEDLINE:99012195].\ \N \N \N 19905 IPR001195

Proteins in this group are responsible for the molecular basis of the blood group antigens, surface markers on the outside of the red blood cell membrane. Most of these markers are proteins, but some are carbohydrates attached to lipids or proteins [Reid M.E., Lomas-Francis C. The Blood Group Antigen FactsBook Academic Press, London / San Diego, (1997)]. Glycophorin A (PAS-2) and glycophorin B (PAS-3) belong to the MNS blood group system and are associated with antigens that include M/N, S/s, U, He, Mi(a), M(c), Vw, Mur, M(g), Vr, M(e), Mt(a), St(a), Ri(a), Cl(a), Ny(a), Hut, Hil, M(v), Far, Mit, Dantu, Hop, Nob, En(a), ENKT, and others.

Glycophorin A is the major sialoglycoprotein of the erythrocyte membrane [MEDLINE:90105533]. Structurally, glycophorin A consists of\ an N-terminal extracellular domain, heavily glycosylated on serine and threonine residues,\ followed by a transmembrane region and a C-terminal cytoplasmic domain. \

\ \ \N membrane ; GO:0016020 \N 19906 IPR001196

\ \ \

L15 is one of the proteins from the large ribosomal subunit.\ In Escherichia coli, L15 is known to bind the 23S rRNA. Ribosomal protein, L15 from\ bacteria and plant chloroplasts (nuclear-encoded) belong to this family. Vertebrate L27a, Tetrahymena thermophila L29 and fungal L27a (L29, CRP-1, CYH2)\ also are members of this group PUB00005071.

Ribosomal L18E protein from a number of archebacteria show homology to both the eukaryotic L18 and eubacterial ribosomal protein L15, an observation which has been seen to substantiate the belief that archaea represent an evolutionary stage between bacteria and eukaryotes PUB00005071.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 19903 IPR001193

Metalloproteases can be split into five clans, and futher sub-divided into families, on the basis of their metal binding residues.

Members of the M50 metallopeptidase family include mammalian sterol-regulatory element binding protein (SREBP) site 2 proteases and various hypothetical\ bacterial homologues . SREBPs are membrane-bound transcription factors\ that regulate cholesterol and fatty acid synthesis in mammalian cells. In\ order to be activated, the N-terminal domain must be released from the\ membrane into the nucleus by proteolytic cleavage at two sites: the first\ site is located within the lumen of the endoplasmic reticulum, and second\ site within the transmembrane (TM) region. SREBP site 2 proteases act at\ this second, TM, site. In humans, the protease is encoded by the S2P gene. Once the SREBP has been released into the nucleus, it acts to stimulate\ transcription of genes involved in lipid metabolism. The site 2 protease has\ been shown to act on SREBP at the Leu522-Ser523 bond [MEDLINE:97284760].

\ \ metalloendopeptidase activity ; GO:0004222 membrane ; GO:0016020 proteolysis and peptidolysis ; GO:0006508 19907 IPR001196

\ \ \

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 19899 IPR001189 Superoxide dismutases (SODs) (EC: 1.15.1.1) catalyse the conversion of superoxide radicalsto molecular oxygen. Their function is to destroy the radicals which are normally\ produced within cells and are toxic to biological systems. Three evolutionarily distinct\ families of SODs are known, of which the Mn/Fe-binding family is one [MEDLINE:88054040], [MEDLINE:88152268], [MEDLINE:92211732].\ \ heavy metal binding activity ; GO:0005505 \N superoxide metabolism ; GO:0006801 19900 IPR001190

The egg peptide speract receptor is a transmembrane glycoprotein [MEDLINE:94188934]. Other members of this family include the macrophagescavenger receptor type I (a membrane glycoprotein implicated in the pathologic\ deposition of cholesterol in arterial walls during artherogenesis), an enteropeptidase\ and T-cell surface glycoprotein CD5 (may act as a receptor in regulating T-cell\ proliferation).

\ \ scavenger receptor activity ; GO:0005044 membrane ; GO:0016020 \N 19901 IPR001191 Geminiviruses are characterised by a genome of circular single-stranded DNA encapsidatedin twinned (geminate) quasi-isometric particles, from which the group derives its name\ PUB00001145. Most geminiviruses can be divided\ into 2 subgroups on the basis of host range and/or insect vector: i.e. those that infect\ dicotyledenous plants and are transmitted by the same whitefly species, and\ those that infect monocotyledenous plants and are transmitted by different leafhopper\ vectors. The genomes of the whitefly-transmitted cassava latent (CLV),\ tomato golden mosaic (TGMV) and bean golden mosaic (BGMV) viruses possess a bipartite\ genome. By contrast, only a single DNA component has been identified for the leafhopper-transmitted \ maize streak (MSV) and wheat dwarf (WDV) viruses PUB00001145, [MEDLINE:88124198].\ Beet curly top (BCTV), bean summer death and tobacco yellow dwarf viruses belong to a\ third possible subgroup. BCTV is transmitted by a specific leafhopper species, yet like\ the whitefly-transmitted geminiviruses it has a host range confined to dicotyledenous\ plants.\ \ structural molecule activity ; GO:0005198 viral capsid ; GO:0019028 \N 19902 IPR001192 Phosphoinositide-specific phospholipase C (PLC) mediates the cellular actions of avariety of hormones, neurotransmitters and growth factors PUB00005667. \ Agonist-dependent activation of PLC causes hydrolysis of membrane phosphatidylinositol\ 4,5-bisphosphate (PIP2), generating the second messengers inositol 1,4,5-trisphosphate\ (IP3) and diacylglycerol (DAG). IP3 binds specific intracellular receptors to trigger\ Ca²⁺ mobilisation, while DAG mediates activation of a family of protein kinase C isozymes.\ Based on molecular size, immunoreactivity and amino acid sequence, several\ subtypes have been classified. Overall, sequence identity between sub-types is low,\ yet all isoforms share two conserved domains, \ designated X IPR000909.\ \

In PLC- subtypes, X and Y domains are separated by a stretch of 70-120 amino acids\ rich in Ser, Thr and acidic residues. Their C terminus is rich in basic residues. In \ PLC-gammas, there is an insert of more than 400 residues containing an SH3 and two SH2 \ domains. PLCs show little similarity in the 300-residue N-terminal region preceding the \ X-domain.

\ \ \ 1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase activity ; GO:0004435\ \N \N intracellular signaling cascade ; GO:0007242 19896 IPR001187 Tissue factor (TF) is an integral membrane glycoprotein that initiates blood coagulationby forming a complex with circulating factor VII or VIIa. The complex then activates\ factors IX or X by specific limited proteolysis [MEDLINE:89152269], [MEDLINE:91200676]. TF plays a role in\ normal hemostasis by initiating the cell-surface assembly and propagation of the\ coagulation protease cascade.\ \ \N integral to membrane ; GO:0016021 blood coagulation ; GO:0007596 19897 IPR001188

The bacterial periplasmic spermidine/putrescine-binding proteins are involved in\ the polyamine transport system. They are required for the activity of the bacterial\ periplasmic transport system of putrescine and spermidine [MEDLINE:92041956], [MEDLINE:93106992].

\ \ transporter activity ; GO:0005215 periplasmic space (sensu Gram-negative Bacteria) ; GO:0030288 transport ; GO:0006810 19898 IPR001189 Superoxide dismutases (SODs) (EC: 1.15.1.1) catalyse the conversion of superoxide radicalsto molecular oxygen. Their function is to destroy the radicals which are normally\ produced within cells and are toxic to biological systems. Three evolutionarily distinct\ families of SODs are known, of which the Mn/Fe-binding family is one [MEDLINE:88054040], [MEDLINE:88152268], [MEDLINE:92211732].\ \ heavy metal binding activity ; GO:0005505 \N superoxide metabolism ; GO:0006801 19892 IPR001183

The M3 receptor is found in high levels in neuronal cells of the CNS ;\ its distribution largely overlaps with that of M1 and M4 subtypes. It is\ also found in peripheral ganglia, exocrine glands, smooth muscle, vascular\ endothelium, and in cell lines. No selective agonist has been described PUB00005867.

\ \ muscarinic acetylcholine receptor activity ; GO:0004981 membrane ; GO:0016020 \N 19893 IPR001184

\ \ somatostatin receptor activity ; GO:0004994 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19891 IPR001182 A number of prokaryotic integral membrane proteins involved in cell cycle processeshave been found to be structurally related [MEDLINE:90036736], [MEDLINE:90286928]. These proteins include, the\ Escherichia coli and related bacteria cell division protein ftsW and the rod\ shape-determining protein rodA (or mrdB), the Bacillus subtilis stage V sporulation\ protein E (spoVE), the Bacillus subtilis hypothetical proteins ywcF and ylaO and the\ Cyanophora paradoxa cyanelle ftsW homolog.\ \ \N \N \N 19894 IPR001185 Mechanosensitive ion channels (MscL) play a critical role in transducing physical stressesat the cell membrane into an electrochemical response. MscL is a protein which forms a\ channel organized as a homopentamer, with each subunit containing two transmembrane\ regions [MEDLINE:99074367]. Prokaryotes harbor a\ large-conductance mechanosensitive channel (gene mscL) that opens in response to stretch\ forces in the membrane lipid bilayer and may participate in the regulation of osmotic\ pressure changes within the cell [MEDLINE:98294049].\ \ ion channel activity ; GO:0005216 membrane ; GO:0016020 transport ; GO:0006810 19895 IPR001186

Bradykinins (BKs) are a family of short, structurally similar peptides that\ activate sensory fibres, contract venous smooth muscle, stimulate release\ of cytokines, induce connective tissue proliferation and mediate endothelium-dependent vasodilation PUB00005872. BK antagonists are of potential use\ in the treatment of inflammation, asthma, mild pain and endotoxic shock.\ BK receptors are widespread in peripheral tissues, and at least 3 different\ receptor subtypes have been proposed, designated B1, B2 and B3.\ B2 is the predominant bradykinin subtype. The B1 receptor has limited\ distribution in the periphery, but has not been described in the CNS.\ It stimulates contraction of rabbit aorta and rat duodenum, and mediates\ relaxation of rabbit mesenteric and coeliac arteries . In rabbit\ vascular smooth muscle, the expression of B1 receptors is increased\ following various pathological insults, in vitro or in vivo . In the\ majority of tissues, bradykinin induces activation of phosphoinositide\ metabolism via a pertussis-toxin-insensitive G-protein, probably of the\ Gq/G11 class PUB00005872. It has also been reported to inhibit adenylyl cyclase\ through a persussis-toxin-insensitive G-protein, and to raise levels of\ cGMP and open ion channels. It also stimulates PLA2, possibly by direct\ activation of a G-protein.

\ \ bradykinin receptor activity ; GO:0004947 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19885 IPR001177 Papillomavirus helicase E1 protein is an ATP-dependent DNA helicase required forinitiation of viral NA replication. It forms a complex with the viral E2 protein.\ The E1-E2 complex binds to the replication origin which contains binding sites for\ both proteins.\ \ ATP binding activity ; GO:0005524 \N DNA replication ; GO:0006260 19886 IPR001177 Papillomavirus helicase E1 protein is an ATP-dependent DNA helicase required forinitiation of viral NA replication. It forms a complex with the viral E2 protein.\ The E1-E2 complex binds to the replication origin which contains binding sites for\ both proteins.\ \ ATP binding activity ; GO:0005524 \N DNA replication ; GO:0006260 19887 IPR001178 This family contains insecticidal toxins produced by Bacillus species of bacteria.During spore formation the bacteria produce crystals of this protein. When an insect\ ingests these proteins they are activated by proteolytic cleavage. The N terminus is\ cleaved in all of the proteins and a C-terminal extension is cleaved in some members.\ Once activated the endotoxin binds to the gut epithelium and causes cell lysis leading\ to death. This activated region of the delta endotoxin is composed of three structural\ domains. The N-terminal helical domain is involved in membrane insertion and pore\ formation. The second and third domains are involved in receptor binding.\ \ toxin activity ; GO:0015070 \N defense response ; GO:0006952 19888 IPR001179

Synonym(s): Peptidylprolyl cis-trans isomerase

\ FKBP-type peptidylprolyl isomerases (EC: 5.2.1.8) in vertebrates, are receptors for the\ two immunosuppressants, FK506 and rapamycin. The drugs inhibit T cell proliferation\ by arresting two distinct cytoplasmic signal transmission pathways. Peptidylprolyl isomerases accelerate protein folding by\ catalyzing the cis-trans isomerization of proline imidic peptide bonds in oligopeptides.\ These proteins are found in a variety of organisms.\ \ \N \N protein folding ; GO:0006457 19889 IPR001180

Based on sequence similarities a domain of homology has been identified in the following proteins [MEDLINE:99321922]:

Citron and Citron kinase. These two proteins interact with the GTP-bound forms of the small GTPases Rho and Rac but not with Cdc42.
Myotonic dystrophy kinase-related Cdc42-binding kinase (MRCKalpha). This serine/threonine kinase interacts with the GTP-bound form of the small GTPase Cdc42 and to a lesser extent with that of Rac.
NCK Interacting Kinase (NIK), a serine/threonine protein kinase.
ROM-1 and ROM-2, from yeast. These proteins are GDP/GTP exchange proteins (GEPs) for the small GTP binding protein Rho1.

This domain, called the citron homology domain, is often found after cysteine rich and pleckstrin homology (PH) domains at the C-terminal end of the proteins [MEDLINE:99321922]. It acts as a regulatory domain and could be involved in macromolecular interactions [MEDLINE:99321922], [MEDLINE:97280817].

\ \ small GTPase regulatory/interacting protein activity ; GO:0005083 \N \N 19890 IPR001181

Interleukin-7 (IL7) is a hematopoietic growth factor produced by bone marrowstromal cells. It promotes growth of B-cell precursors, and functions with IL2 in\ the activation of mature T-cells [MEDLINE:89098903], [MEDLINE:88232938]. Interleukin-7 and\ Interleukin-9 belong to the same larger family.

\ \ growth factor activity ; GO:0008083 extracellular ; GO:0005576 immune response ; GO:0006955 19882 IPR001173

\ This is a diverse family of a variety of glycosyl transferases that transfer the sugar\ from UDP-glucose, UDP-N-acetyl-galactosamine, GDP-mannose or CDP-abequose, to a range\ of substrates including cellulose, dolichol phosphate and teichoic acids.\ \ \ \N \N \N 19883 IPR001174

Galactokinase (EC: 2.7.1.6), homoserine kinase (EC: 2.7.1.39), mevalonate kinase (EC: 2.7.1.36) and related kinases are grouped in this family.

\ kinase activity ; GO:0016301 \N metabolism ; GO:0008152 19884 IPR001176

1-aminocyclopropane-1-carboxylate (ACC) synthase (EC: 4.4.1.14), a Class I aminotransferase,is the key regulatory enzyme in the biosynthetic pathway of the plant hormone ethylene.\ It catalyses the formation of 1-aminocyclopropane-1-carboxylate, a direct precursor of\ ethylene in higher plants. The enzyme functions as a homodimer and requires\ pyridoxal-5'-phosphate as a cofactor [MEDLINE:92106351].

\ \ \ 1-aminocyclopropane-1-carboxylate synthase activity ; GO:0016847\ \N \N biosynthesis ; GO:0009058 19879 IPR001170 Natriuretic peptides are hormones involved in the regulation of fluid andelectrolyte homeostasis. These hormones stimulate the intracellular production of\ cyclic GMP as a second messenger. They belong to a family that includes extracellular\ ligand binding domains of a wide range of receptors IPR001828. Three peptide receptors\ are known, two of which express quanylate cyclase activity (GC-A or ANP-A and GC-B or\ ANP-B), while the third (ANP-C) is probably responsible for the clearance of atrial\ natriuretic peptide (ANP) from the circulation and does not play a role in signal\ transduction [MEDLINE:91056089], [MEDLINE:89306276].\ \

GC-A and GC-B are plasma membrane-bound proteins that share the following\ topology: an N-terminal extracellular domain which acts as the ligand binding\ region, then a transmembrane domain followed by a large cytoplasmic C-terminal region that can be subdivided into two domains: a protein kinase-like\ domain IPR001828/> that appears important for proper signalling and a\ guanylate cyclase catalytic domain IPR001054. The topology of ANP-C is\ different: like GC-A and -B it possesses an extracellular ligand-binding\ region and a transmembrane domain, but its cytoplasmic domain is very short.

\ \ peptide receptor activity, G-protein coupled ; GO:0008528 membrane ; GO:0016020 \N 19880 IPR001171 The two fungal enzymes, C-14 sterol reductase (gene ERG24 in budding yeast and erg3 inNeurospora Crassa) and C-24(28) sterol reductase (gene ERG4 in budding yeast and sts1\ in fission yeast), are involved in ergosterol biosynthesis. They act by reducing\ double bonds in precursors of ergosterol [MEDLINE:94171077].\ These proteins are highly hydrophobic and seem to contain seven or eight transmembrane\ regions. Chicken lamin B receptor that is thought to anchor the lamina to the inner\ nuclear membrane belongs to this family.\ \ \N membrane ; GO:0016020 \N 19881 IPR001172 The flagellar motor switch in E.coli and S.typhimurium regulates the direction offlagellar rotation and hence controls swimming behaviour. The switch is a complex\ apparatus that responds to signals transduced by the chemotaxis sensory signalling\ system during chemotactic behaviour [MEDLINE:94040782]. The\ switch complex comprises at least three proteins - FliG, FliM and FliN. It has been\ shown that FliG interacts with FliM, FliM interacts with itself, and FliM interacts with\ FliN [MEDLINE:96200097]. The proteins\ are not particularly hydrophobic and may be peripheral to the membrane, possibly mounted\ on the basal body M ring [MEDLINE:89255090], [MEDLINE:92335286].\ \ motor activity ; GO:0003774 flagellar basal body (sensu Bacteria) ; GO:0009425 chemotaxis ; GO:0006935 19878 IPR001169

\ Some receptors share a common

chain while\ having different

chains [MEDLINE:87131067], \ [MEDLINE:90337122]. A number of different

chains,

-1 to

-8\ are known in higher eukaryotes.\ \ cell adhesion receptor activity ; GO:0004895 integrin complex ; GO:0008305 cell-matrix adhesion ; GO:0007160 19874 IPR001164

The Rev protein of human immunodeficiency virus type 1 (HIV-1) facilitates nuclear export of unspliced and partly-spliced viral RNAs [MEDLINE:95364930]. Rev contains\ an RNA-binding domain and an effector domain; the latter is believed to \ interact with a cellular cofactor required for the Rev response and hence\ HIV-1 replication. Human Rev interacting protein (hRIP) specifically\ interacts with the Rev effector. The amino acid sequence of hRIP is \ characterised by an N-terminal, C-4 class zinc finger motif.

\ \

All proteins in this family for which functions are known are DNA helicases that function in the nucleotide excision repair and are endonucleases that make the 3' incision next to\ DNA damage. They are part of a pathway requiring UvrA, UvrB, UvrC, and UvrD\ homologs.

\ \ DNA binding activity ; GO:0003677 nucleus ; GO:0005634 \N 19875 IPR001165

Glycoside hydrolase family 24 CAZY:GH_24). This family includes lambda phage lysozyme.

\ \

T4 lysozyme helps to release mature phage particles from the cell wall by\ breaking down the peptidoglycan. The enzyme hydrolyses the 1,4- linkages between N-acetyl-D-glucosamine and N-acetylmuramic acid in\ peptidoglycan heteropolymers of prokaryotic cell walls.

The T4 lysozyme structure contains 2 domains, the interface between which\ forms the active-site cleft. The N-terminus of the 2 domains undergoes a\ 'hinge-bending' motion about an axis passing through the molecular waist\ [MEDLINE:91043097]. This mobility is thought to be important in allowing access of\ substrates to the enzyme active site.

\ \ \ lysozyme activity ; GO:0003796 \N cell wall catabolism ; GO:0016998 19876 IPR001166

Hyperglycemic hormone, which controls blood sugar levels, is an abundant\ peptide in the sinus glands of isopods and decapods\ \ \ \ [MEDLINE:93170291]. The peptide is a potent secretagogue, releasing digestive enzymes\ from the hepatopancreas. It may act as a stress hormone. American lobster molt-inhibiting\ hormone also shows hyper-glycemic hormone activity [MEDLINE:90386659].

\ \ neuropeptide hormone activity ; GO:0005184 extracellular ; GO:0005576 \N 19869 IPR001159 The DsRBD domain is found in a variety of RNA-binding proteins with differentstructures and exhibiting a diversity of functions [MEDLINE:94310455].\ It is involved in localization of at least five different mRNAs in the early Drosophila embryo and by interferon-induced protein kinase in humans, which is part of the cellular response to dsRNA.\ \ double-stranded RNA binding activity ; GO:0003725 intracellular ; GO:0005622 \N 19870 IPR001160

Metalloproteases can be split into five clans, and futher sub-divided into families, on the basis of their metal binding residues.

X-His dipeptidases are zinc-containing metallopeptidases that belong to the\ M20C protease family, which forms part of the MH clan [MEDLINE:95405261], see Protease database http://merops.sanger.ac.uk/merops.htm]. These \ cytoplasmic endopeptidases cleave Xaa+His dipeptides (where Xaa is any\ hydrophobic residue). The zinc ligands of the M20 clan are His/Asp, Asp, Glu,\ Asp/Glu and His [MEDLINE:95405261], [MEDLINE:90330577].

\ \

The amino acid sequence deduced from Escherichia coli reveals that peptidase D is a\ slightly hydrophilic protein of 485 residues that contains no extended\ domains of marked hydrophobicity [MEDLINE:90330577].

\ \ Xaa-His dipeptidase activity ; GO:0008769 \N proteolysis and peptidolysis ; GO:0006508 19877 IPR001168

Adrenocorticotrophin (ACTH), melanocyte-stimulating hormones and -endorphin are peptide products of pituitary pro-opiomelanocortin. ACTH\ regulates synthesis and release of glucocorticoids and aldosterone in\ the adrenal cortex; it also has a trophic action on these cells PUB00005891.\ ACTH and -endorphin are synthesised and released in response to\ corticotrophin-releasing factor at times of stress (heat, cold, infections,\ etc.) - their release leads to increased metabolism and analgesia res..\ The ACTH receptor is found in high levels in the adrenal cortex - binding\ sites are present in lower levels in the CNS.

\ \ adrenocorticotropin receptor activity ; GO:0004978 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19871 IPR001161 Defects in DNA repair proteins can give rise, in humans, to the autosomalrecessive disorders xeroderma pigmentosum (XP) and Cockayne's syndrome [MEDLINE:94212451]. XP is characterised by a high\ incidence of sunlight-induced skin cancer, the effect of skin-cell hypersensitivity\ to UV resulting from defects in the nucleotide excision pathway. Seven XP complementation\ groups have been identified: XP-A to XP-G. XP group B (XP-B) give rise to both XP and\ Cockayne syndrome [MEDLINE:94136478]. The DNA/RNA helicase domain IPR001650 is also present in this group of proteins.\ \ ATP binding activity ; GO:0005524 nucleus ; GO:0005634 nucleotide-excision repair ; GO:0006289 19872 IPR001162

During the process of Escherichia coli nucleotide excision repair, DNA damage recognition and processing are achieved by the action of the uvrA, uvrB, and uvrC gene products [MEDLINE:22030824]. The UvrC proteins contain 4 conserved regions: a central region which interacts with UvrB (Uvr domain), a Helix hairpin Helix (HhH) domain important for 5 prime incision of damage DNA and the homology regions 1 and 2 of unknown function. UvrC homology region 2 is specific for UvrC proteins, whereas UvrC homology region 1 is also shared by few other nucleases.

Proteins that contain the UvrC homology region 1, IPR000305, are listed below:

\ \

Prokaryotic UvrC proteins.

Bacteriophage T4 END2 protein. Small subunit of ribonucleotide reductase\ enzyme.

Bacteriophage T4 TEV1 protein. Endonuclease specific to the thymidylate\ synthase (td) gene splice junction.

Found in putative intron-homing endonucleases encoded by group I introns of fungi and phage.

Mycobacterium hypothetical protein Y002. Exonuclease by similarity.

Bacillus subtilis hypothetical protein YURQ.

\ \ nuclease activity ; GO:0004518 \N nucleotide-excision repair ; GO:0006289 19873 IPR001163 The U1, U2, U4/U6, and U5 small nuclear ribonucleoprotein particles (snRNPs) involvedin pre-mRNA splicing contain seven Sm proteins (B/B', D1, D2, D3, E, F and G) in common,\ which assemble around the Sm site present in four of the major spliceosomal small\ nuclear RNAs [MEDLINE:95262647]. The Sm proteins are essential\ for pre-mRNA splicing and are implicated in the formation of stable, biologically\ active snRNP structures.\ \ pre-mRNA splicing factor activity ; GO:0008248 small nucleolar ribonucleoprotein complex ; GO:0005732 mRNA splicing ; GO:0006371 19865 IPR001155 The NADH:flavin oxidoreductase/NADH oxidases that belong to this family are mostly of bacterial or yeast origin and reduce a range of alternative electron acceptors. Most use FAD/FMN as a cofactor. Members of this family have TIM barrel structure.\ oxidoreductase activity ; GO:0016491 \N electron transport ; GO:0006118 19866 IPR001156 Transferrins are eukaryotic iron-binding glycoproteins that control thelevel of free iron in biological fluids [MEDLINE:87190419]. The proteins have arisen by duplication of a\ domain, each duplicated domain binding one iron atom. Members of the family include\ blood serotransferrin (siderophilin); milk lactotransferrin (lactoferrin); egg white\ ovotransferrin (conalbumin); and membrane-associated melanotransferrin.\ \ ferric iron binding activity ; GO:0008199 extracellular ; GO:0005576 iron ion homeostasis ; GO:0006879 19867 IPR001157 The flavivirus genome polypepetide contains the capsid protein C (core protein),the matrix protein (envelope protein M), the major envelope protein E, a number\ of small non structural proteins (NS1, NS2A, NS2B, NS4A and NS4B), helicase and\ RNA-directed polymerase (NS5) [MEDLINE:98037676].\ \ \N \N \N 19868 IPR001158 Dishevelled (Dsh) protein is an important component of the Wnt signal-transduction pathway. It has three relatively conserved domains: DIX, PDZ and DEP. The DIX domain of Dvl-1 (a mammalian Dishevelled homolog) shares 37% identity with the C-terminal region of Axin. Dsh can interact with the Axin/APC/GSK3/

-catenin complex, and may thus modulate its activity [MEDLINE:99263012].

The Wnt signaling pathway is conserved in various species from worms to\ mammals, and plays important roles in development, cellular proliferation,\ and differentiation. The molecular mechanisms by which the Wnt signal\ regulates cellular functions are becoming increasingly well understood. Wnt\ stabilizes cytoplasmic -catenin, which stimulates the expression of genes\ including c-myc, c-jun, fra-1, and cyclin D1. Axin and its homolog Axil are components of the Wnt signaling pathway that negatively regulate this pathway. Other components of the Wnt signaling pathway, including Dvl, glycogen synthase kinase-3beta (GSK-3beta), -catenin, and adenomatous polyposis coli (APC), interact with Axin, and the phosphorylation and stability of -catenin are regulated in the Axin complex. Axil has similar functions to Axin. Thus, Axin and Axil act as scaffold proteins in the Wnt signaling pathway, thereby modulating the Wnt-dependent cellular functions [MEDLINE:20112306].

\ \ signal transducer activity ; GO:0004871 intracellular ; GO:0005622 development ; GO:0007275 19861 IPR001151

Several 7TM receptors have been cloned but their endogenous ligands are\ unknown; these have been termed orphan receptors. A new GPCR, GPR12, was\ isolated from a rat pituitary library, and is found in discrete regions\ of the brain, pituitary and testis, but is absent in other tissues [MEDLINE:92070499], [MEDLINE:96015070].\ Three human homologues (GPR12, GPR6 and GPR3) have also been isolated [MEDLINE:96015070].\ The 3 genes have been localised to human chromosomal regions 13q12, 6q21\ and 1p34.3-p36.1 respectively.

\ \ G-protein coupled receptor activity, unknown ligand ; GO:0016526 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19862 IPR001152 Thymosin

-4 is a small polypeptide whose exact physiological role is notyet known [MEDLINE:86117855]. It was first\ isolated as a thymic hormone that induces terminal deoxynucleotidyltransferase. It is\ found in high quantity in thymus and spleen but is widely distributed in many tissues.\ It has also been shown to bind to actin monomers and thus to inhibit actin\ polymerization PUB00001015.\ \ \ \

A number of peptides closely related to thymosin -4 belong to this family. They\ include, thymosin -9 (and -8) in Bos taurus and Sus scrofa (pig), thymosin -10 \ in man and Rattus norvegicus (rat), thymosin -11 and -12 in Oncorhynchus mykiss (Rainbow Trout) and human Nb thymosin .

\ \ \N \N \N 19863 IPR001153 Barwin is a basic protein isolated from aqueous extracts of barley seeds. It is125 amino acids in length, and contains six cysteine residues that combine to form\ three disulphide bridges [MEDLINE:93003009],\ [MEDLINE:93003010]. Comparative analysis\ shows the sequence to be highly similar to a 122 amino acid stretch in the C-terminal\ of the products of two wound-induced genes (win1 and win2) from potato, the\ product of the hevein gene of rubber trees, and pathogenesis-related protein 4 from\ tobacco. The high levels of similarity to these proteins, and their ability to bind\ saccharides, suggest that the barwin domain may be involved in a common defense\ mechanism in plants.\ \ \N \N \N 19864 IPR001154

\ \

Eukaryotic topoisomerase II exists as a homodimer; in bacteriophage T4 it \ consists of three heterologous subunits; in prokaryotes it exists as a tetramer\ of two subunits (two each of gyrA and gyrB); and in E.coli, a second type II topoisomerase, involved in chromosome segregation (topoisomerase IV), consists of two subunits (parC and parE). GyrB, parE, and the product of bacteriophage T4 gene 39, are all similar to the eukaryotic proteins.

\ \

Human cells express two distinct type II topoisomerase isozymes, designated\ topoisomerase II (170kDa form) and topoisomerase II (180kDa form) [MEDLINE:93087165]. The predicted topoisomerase II protein sequence shares a high level of similarity (72% identical residues) to that of the human isozyme, and is similar to topoisomerase II from Drosophila, yeast and bacteria. Regions of greatest sequence divergence lie at the extreme N-terminus and over a C-terminal domain comprising approximately 25% of the total protein [MEDLINE:93087165].

\ \

The crystal structure of a fragment of yeast topoisomerase II reveals a\ heart-shaped dimeric protein with a large central cavity [MEDLINE:96138378]. It provides a molecular model of the enzyme as an ATP-modulated clamp, with two sets of jaws at opposite ends, connected by multiple joints. An enzyme with bound DNA can admit a second DNA duplex through one set of jaws, transport it through the cleaved first duplex, and expel it through the other set of jaws [MEDLINE:96138378].

\ \ ATP binding activity ; GO:0005524 \N DNA topological change ; GO:0006265 19856 IPR001144

E.coli heat-labile enterotoxin is a bacterial protein toxin with an AB5 multimer structure, in which the B pentamer (IPR001835.

\ \ toxin activity ; GO:0015070 extracellular ; GO:0005576 pathogenesis ; GO:0009405 19857 IPR001146 Geminiviruses are characterised by a genome of circular single-strandedDNA encapsidated in twinned (geminate) quasi-isometric particles, from\ which the group derives its name. Most geminiviruses can be divided\ into two subgroups on the basis of host range and/or insect vector: i.e.\ those that infect dicotyledenous plants and are transmitted by the same\ whitefly species, and those that infect monocotyledenous plants and are\ transmitted by different leafhopper vectors. The genomes of the whitefly-transmitted \ cassava latent (CLV), tomato golden mosaic (TGMV) and bean\ golden mosaic (BGMV) viruses possess a bipartite genome. By contrast, only\ a single DNA component has been identified for the leafhopper-transmitted\ maize streak (MSV) and wheat dwarf (WDV) viruses \ [MEDLINE:85126910], [MEDLINE:88124198].\ \ \ \N \N \N 19858 IPR001147

\ \ \

L21E family contains proteins from a number of eukaryotic\ and archaebacterial organisms which include; mammalian L2, Entamoeba histolytica L21,\ C. elegans L21 (C14B9.7), yeast L21E (URP1) and Halobacterium marismortui HL31.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 19859 IPR001148

Synonym(s): Carbonic dehydratase, Carbonic anhydrase

\ Carbonate dehydratase (EC: 4.2.1.1) (CA) are zinc metalloenzymes which catalyze the\ reversible hydration of carbon dioxide. Eight enzymatic and evolutionary related forms\ of carbonic anhydrase are currently known to exist in vertebrates: three cytosolic\ isozymes (CA-I, CA-II and CA-III); two membrane-bound forms (CA-IV and CA-VII); a\ mitochondrial form (CA-V); a secreted salivary form (CA-VI); and a yet uncharacterized\ isozyme.\ \ zinc ion binding activity ; GO:0008270 \N one-carbon compound metabolism ; GO:0006730 19860 IPR001150

Synonym(s):Pyruvate formate-lyase

Escherichia coli Formate C-acetyltransferase (EC: 2.3.1.54) (genes pflB and pflD) is\ a key enzyme of anaerobic glucose metabolism, it converts pyruvate and CoA\ into acetyl-CoA and pyruvate. This enzyme is posttranslationally interconverted,\ under anaerobic conditions, from an inactive to an active form that carries a stable\ radical localized to a specific glycine at the C-terminus \ [MEDLINE:92141244]. \ Such a glycine radical seems\ [MEDLINE:93133831] also to be present\ in Escherichia coli (gene nrdD) and bacteriophage T4 (gene nrdD or sunY) anaerobic\ ribonucleoside-triphosphate reductase (EC: 1.17.4.2).

\ \ enzyme activity ; GO:0003824 \N metabolism ; GO:0008152 19853 IPR001140

A variety of ATP-binding transport proteins have a six transmembrane\ helical region. They are all integral membrane proteins\ involved in a variety of transport systems. Members of this family include; the\ cystic fibrosis transmembrane conductance regulator (CFTR), bacterial leukotoxin\ secretion ATP-binding protein, multidrug resistance proteins, the yeast leptomycin B\ resistance protein, the mammalian sulfonylurea receptor and antigen peptide\ transporter 2. Many of these proteins have two such regions.

\ \ ATP binding activity ; GO:0005524 membrane ; GO:0016020 transport ; GO:0006810 19854 IPR001141

\ \ \

Ribosomal protein, L27 is found in fungi, plants and algae and vertebrates\ [MEDLINE:94198298], [MEDLINE:94336771].\ The family has a specific signature at the C terminus.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 19850 IPR001137

Glycoside hydrolase family 11 CAZY:GH_11\ comprises enzymes with only one known activity; xylanase (EC: 3.2.1.8). These enzymes were formerly known as cellulase family G.

\ \ hydrolase activity, hydrolyzing O-glycosyl compounds ; GO:0004553 \N carbohydrate metabolism ; GO:0005975 19851 IPR001138 The N-terminal region of a number of fungal transcriptional regulatoryproteins contains a Cys-rich motif that is involved in zinc-dependent\ binding of DNA. The region forms a binuclear Zn cluster, in which two Zn\ atoms are bound by six Cys residues \ [MEDLINE:90192750], [MEDLINE:92212455].\ A wide range of proteins are known to contain this domain. These include the\ proteins involved in arginine, proline, pyrimidine, quinate, maltose and galactose\ metabolism; amide and GABA catabolism; leucine biosynthesis and others.\ \ zinc ion binding activity ; GO:0008270 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 19852 IPR001139

Glycoside hydrolase family 30 CAZY:GH_30\ comprises enzymes with only one known activity; glucosylceramidase (EC: 3.2.1.45).

\ \

Family 30 encompasses the mammalian glucosylceramidases. Human acid -glucosidase (D-glucosyl-N-acylsphingosine glucohydrolase),\ cleaves the glucosidic bonds of glucosylceramide and synthetic -glucosides [MEDLINE:86149363]. Any one of over 50 different mutations in the gene of glucocerebrosidase have been found to affect activity of this hydrolase, producing variants of Gaucher disease, the most prevalent lysosomal storage disease [MEDLINE:86149363], [MEDLINE:97462015].

\ \ glucosylceramidase activity ; GO:0004348 lysosome ; GO:0005764 lysosome organization and biogenesis ; GO:0007040 19855 IPR001142 A number of uncharacterised integral membrane proteins from yeast contain an internal duplication due to duplicated genes. Duplicated copies of genes may be classified in two types of cluster organization. The first type includes genes sharing a significant level of identity in the amino acid sequences of their predicted protein product. They are recovered on two different chromosomes, transcribed in the same orientation and the distance between them is conserved. The second type of cluster is based on one gene unit tandemly repeated. This duplication is itself repeated elsewhere in the genome. The basic gene unit is recovered many times in the genome and is a component of a multigene family of unknown function. These organizations in clusters of genes suggest a 'Lego organization' of the yeast chromosomes [MEDLINE:97377993]. The proteins belonging to this family are of unknown function.\ molecular_function unknown ; GO:0005554 \N \N 19846 IPR001133 NADH-ubiquinone oxidoreductase, chain 4L (EC: 1.6.5.3) catalyses the reductionof ubiquinone to ubiquinol. It is present in either mitochondria or chloroplasts as\ part of the respiratory-chain NADH dehydrogenase (also known as complex I or\ NADH-ubiquinone oxidoreductase), an oligomeric enzymatic complex.\ \ \ NADH dehydrogenase (ubiquinone) activity ; GO:0008137 \N oxidative phosphorylation, NADH to ubiquinone ; GO:0006120 19847 IPR001134 Netrins are extracellular proteins that control the guidance of CNS commissuralaxons at the midline and peripheral motor axons. This domain is present in a\ number of other proteins. The UNC-6 protein from C. elegans that guides\ dorsoventral migrations on the epidermus and that is required for the guidance\ of pioneering axons and migrating cells along the body wall has this domain.\ The domain is also found in cobra venom factor and in complement factors C3, C4 and C5.\ \ \N \N \N 19848 IPR001135 NADH-ubiquinone oxidoreductase, chain 49kDa (EC: 1.6.5.3) is the third largestsubunit of complex I and is a component of the iron-sulfur (IP) fragment of the\ enzyme. The respiratory-chain NADH dehydrogenase (also known as complex I or\ NADH-ubiquinone oxidoreductase) is an oligomeric enzymatic complex located in the\ inner mitochondrial membrane and which also seems to exist in the chloroplast and\ in cyanobacteria (as a NADH-plastoquinone oxidoreductase). NADH-ubiquinone\ oxidoreductase, 49Kd chain is one of the 25 to 30 polypeptide subunits of this\ bioenergetic enzyme complex.\ \

A number of bacterial enzymes also belong to this family. They include;\ NADH-ubiquinone oxidoreductase, subunit D (gene nuoD), formate hydrogenlyase,\ subunit 5 (gene hycE) and hydrogenase-4, subunit G (gene hyfG) all from E. coli and\ subunit NQO4 of NADH-ubiquinone oxidoreductase from Paracoccus denitrificans\ \ \ \ [MEDLINE:93075828], [MEDLINE:93389724].

\ \ electron transporter activity ; GO:0005489 \N electron transport ; GO:0006118 19849 IPR001136 The merozoite surface antigen 2 (MSA-2) may play a role in the merozoite\ attachment to the erythrocyte. It is thought to be attached to the membrane\ by a GPI-anchor.\ \ \ cell adhesion molecule activity ; GO:0005194 \N cell adhesion ; GO:0007155 19841 IPR001128

\ \

\ \ \N \N electron transport ; GO:0006118 19842 IPR001129 This family describes a widespread superfamily of membrane-associated proteins withhighly divergent functions in eicosanoid and glutathione metabolism (MAPEG)\ [MEDLINE:99190093]. Included are\ the 5-lipoxygenase activating protein (gene FLAP) that seems to be required for the activation of 5-lipoxygenase,\ leukotriene C4 synthase (EC: 2.5.1.37) that catalyzes the production of LTC4 from LTA4\ and microsomal glutathione S-transferase II (EC: 2.5.1.18) (GST-II) that also produces LTC4 from LTA4.\ \ \N \N \N 19843 IPR001130 This family of proteins are related to a large superfamily of metalloenzymes [MEDLINE:97290007]. TatD, a member of this family has been shown experimentally to be a DNase enzyme [MEDLINE:20287539]. Allantoinase (EC: 3.5.2.5), \ N-isopropylammelide isopropyl amidohydrolase (EC: 3.5.1.-) and \ the SCN1 protein from fission yeast belong to this family.\ \ \N \N \N 19844 IPR001131

Synonym(s): X-Pro dipeptidase, Proline dipeptidase, X-Pro aminopeptidase, Proline aminopeptidase, Aminopeptidase P

A number of different enzymes from various sources have the proline dipeptidase\ domain. All belong to the larger M24 family of metallopeptidases. Enzymes know to have this domain include the Xaa-Pro dipeptidase (EC: 3.4.13.9)\ (prolidase) and the Xaa-Pro aminopeptidase (EC: 3.4.11.9).

\ \

Xaa-Pro dipeptidase (EC: 3.4.13.9) (prolidase) splits dipeptides with a prolyl\ residue in the carboxyl terminal position. Xaa-Pro aminopeptidase (EC: 3.4.11.9) is the\ enzyme responsible for the release of any N-terminal amino acid adjacent to a\ proline residue.

\ \ metalloexopeptidase activity ; GO:0008235 \N proteolysis and peptidolysis ; GO:0006508 19845 IPR001132 This family of proteins was first identified in C. elegans. Mammalian dwarfins arephosphorylated in response to transforming growth factor

and are implicated\ in control of cell growth \ [MEDLINE:96392344]. \ The dwarfin family also includes the Drosophila protein MAD\ that is required for the function of decapentaplegic (DPP) and may play a role in\ DPP signaling. Drosophila Mad binds to DNA and directly mediates activation\ of vestigial by Dpp [MEDLINE:97373960].\ \ \N intracellular ; GO:0005622 regulation of transcription, DNA-dependent ; GO:0006355 19838 IPR001125 Recoverin, a retinal calcium-binding protein, belongs to the larger family ofproteins which have an EF-hand calcium-binding domain IPR002048. Recoverin\ participates in the recovery phase of visual excitation and in adaption to light.\ The Ca²⁺-bound form of recoverin prolongs the photoresponse, presumably by blocking\ phosphorylation of photoexcited rhodopsin. Recoverin contains a covalently-attached\ myristoyl group, or acyl group, at its N-terminus, and two Ca²⁺-binding sites \ [MEDLINE:95356838].\ \

A number of other proteins including visinin, hippocalcin, neurocalcin,\ S-modulin, visinin-like protein, and frequenin belong to this family. All of the\ family memebers have the aromatic residues that contribute to the myristoyl-binding\ pocket.

\ \ calcium ion binding activity ; GO:0005509 \N \N 19839 IPR001126

In Escherichia coli, UV and many chemicals appear to cause mutagenesis by aprocess of translesion synthesis that requires DNA polymerase III and the\ SOS-regulated proteins UmuD, UmuC and RecA. This machinery allows the\ replication to continue through DNA lesion, and therefore avoid lethal\ interruption of DNA replication after DNA damage [MEDLINE:98240724].\ The UmuC is a well conserved protein in prokaryotes, with a homologue in yeast.

\ \

Proteins currently known to belong to this family are listed below:

\ \

Escherichia coli MucB protein. Plasmid-born analog of the UmuC protein.

Yeast Rev1 protein. Homologue of UmuC also required for normal induction of\ mutations by physical and chemical agents.

Salmonella typhimurium ImpB protein. Plasmid-born analog of the UmuC\ protein.

Bacterial UmuC protein.

Escherichia coli DNA-damage-inducible protein P (DinP).

Salmonella typhimurium SamB homologue of UmuC plasmid associated.

\ \ \ \N \N DNA repair ; GO:0006281 19840 IPR001127

The sugar-specific permease of the phosphoenolpyruvate-dependent sugarphosphotransferase system (PTS) consists of at least three structurally distinct\ domains (IIA, IIB, and IIC) which can either be fused together in a single\ polypeptide chain or exist as two or three interactive chains [MEDLINE:92165716]. \ The IIA domain, carries the first permease-specific phosphorylation site, an histidine which is\ phosphorylated by phospho-HPr. The second domain (IIB) is phosphorylated by\ phospho-IIA on a cysteinyl or histidyl residue, depending on the permease. Finally,\ the phosphoryl group is transferred from the IIB domain to the sugar substrate in a\ process catalyzed by the IIC domain; this process is coupled to the transmembrane\ transport of the sugar.

\ \

The PTS, a major carbohydrate transport system in bacteria, catalyzes the\ phosphorylation of incoming sugar substrates concomitant with their translocation\ across the cell membrane [MEDLINE:90328751], [MEDLINE:94066914]. \ The general mechanism of\ the PTS is the following: a phosphoryl group from phosphoenolpyruvate (PEP) is\ transferred to enzyme-I (EI) of PTS which in turn transfers it to a phosphoryl carrier\ protein (HPr). Phospho-HPr then transfers the phosphoryl group to the sugar-specific\ permease.

\ \ sugar porter activity ; GO:0005351 membrane ; GO:0016020 phosphoenolpyruvate-dependent sugar phosphotransferase system ; GO:0009401 19833 IPR001120 A number of bacteria express filamentous adhesins known as pili. The pili arepolar flexible filaments of about 5.4 nm diameter and 2500 nm average length;\ they consist of a single polypeptide chain (called pilin or fimbrial protein)\ arranged in a helical configuration of five subunits per turn in the assembled\ pilus. Gram-negative bacteria produce pilin which are characterized by the\ presence of a very short leader peptide followed by a\ methylated N-terminal phenylalanine residue and by a highly conserved sequence\ of hydrophobic residues. This class of pilin is often referred to as\ NMePhe or type-4 pili [MEDLINE:88250000], [MEDLINE:88036063]. A number of bacterial proteins\ have been sequenced which share the N-terminal conserved region characteristics\ with type-4 pili [MEDLINE:95020523].\ \ \N \N \N 19834 IPR001122 The flavivirus genome polypeptide contains the caspid protein C (core protein),the matrix protein (envelope protein M), the major envelope protein E, a number\ of small nonstructural proteins, helicase and RNA-directed polymerase (NS5).\ The virion of these viruses is a nucleocapsid covered by a lipoprotein envelope.\ The nucleocapsid is a complex of capsid protein C and mRMA.\ \ structural molecule activity ; GO:0005198 viral capsid ; GO:0019028 \N 19835 IPR001123 Lysine exporter protein is involved in the efflux of excess L-lysine as acontrol for intracellular levels of L-lysine. A number of proteins belong\ to this family. These include the chemotactic transduction protein from\ Pseudomonas aeruginosa, the threonine efflux protein and a number of\ uncharacterised proteins from a variety of sources.\ \ lysine permease activity ; GO:0005293 membrane ; GO:0016020 amino acid transport ; GO:0006865 19836 IPR001124 A number of mammalian lipid-binding serum glycoproteins belong to this family.They include; the lipopolysaccharide-binding protein (LBP), the bactericidal\ permeability-increasing protein (BPI), the cholesteryl ester transfer protein\ (CETP) and the phospholipid transfer protein (PLTP) \ [MEDLINE:89255455], [MEDLINE:94179366], PUB00005128.\ \ lipid binding activity ; GO:0008289 \N \N 19837 IPR001124 A number of mammalian lipid-binding serum glycoproteins belong to this family.They include; the lipopolysaccharide-binding protein (LBP), the bactericidal\ permeability-increasing protein (BPI), the cholesteryl ester transfer protein\ (CETP) and the phospholipid transfer protein (PLTP) \ [MEDLINE:89255455], [MEDLINE:94179366], PUB00005128.\ \ lipid binding activity ; GO:0008289 \N \N 19831 IPR001118

\ \

NHE3, which shares around 40% amino acid identity with NHE1, appears not to\ be glycosylated, and is found preferentially in the gastrointestinal tract\ and the kidney. It is not readily inhibited by the diuretic amiloride, and\ immunological studies have localised it to the apical membranes of the renal\ proximal tubule and intestinal epithelia, implicating this isoform in Na⁺\ absorption.

\ \ ion channel activity ; GO:0005216 membrane ; GO:0016020 sodium ion transport ; GO:0006814 19832 IPR001119 S-layers are paracrystalline mono-layered assemblies of (glyco)proteins whichcoat the surface of bacteria. Several S-layer proteins and some other cell\ wall proteins contain one or more copies of a domain of about 50-60 residues,\ which has been called SLH (for S-layer homology). There is strong evidence\ that this domain serves as an anchor to the peptidoglycan [MEDLINE:94156823], [MEDLINE:95247680].\ The SLH domain is present in a variety of S-layer proteins from different sources,\ outer membrane protein Omp-

from Thermotoga maritima, cellulosome anchoring\ protein (gene ancA) from Clostridium thermocellum, amylopullulanases, xylanase A\ (gene xynA) from Thermoanaerobacter saccharolyticum and many others.\ \ \N \N \N 19830 IPR001117 Multicopper oxidases are enzymes that possess three spectroscopically differentcopper centers [MEDLINE:90126844], [MEDLINE:91138766]. The enzymes that belong to\ this family include laccase (EC: 1.10.3.2) that in fungi and plants oxidizes many\ different types of phenols and diamines, ascorbate oxidase (EC: 1.10.3.3), a higher plant\ enzyme and ceruloplasmin (EC: 1.16.3.1), a protein found in the serum of mammals and\ birds that oxidizes a great variety of inorganic and organic substances.\ \

The multicopper oxidase, type 1 family domain is also present in proteins that have lost the ability\ to bind copper. Proteins which belong to this group are copper resistance protein A\ (copA) from a plasmid in Pseudomonas syringae, blood coagulation factors V (Fa V) and\ VIII (Fa VIII) [E1] and yeast FET3 which is required for ferrous iron uptake and others.

\ \ copper ion binding activity ; GO:0005507 \N \N 19828 IPR001115

Alpha-1B receptor mRNA is distributed widely, high levels occurring in\ the CNS (e.g., cerebral cortex and brainstem) and in peripheral tissues\ (e.g., the kidney and lung). The receptor is coupled to the phosphoinositide\ pathway through a pertussis-toxin-insensitive G-protein, probably of the\ Gq/G11 class PUB00005869.

\ \ alpha1-adrenergic receptor activity ; GO:0004937 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19827 IPR001114 Adenylosuccinate synthetase (EC: 6.3.4.4) plays an important role in purinebiosynthesis, by catalyzing the GTP-dependent conversion of IMP and aspartic\ acid to AMP. Adenylosuccinate synthetase has been characterized from various\ sources ranging from Escherichia coli (gene purA) to vertebrate tissues. In\ vertebrates, two isozymes are present - one involved in purine biosynthesis\ and the other in the purine nucleotide cycle.\

The crystal structure of adenylosuccinate synthetase from Escherichia coli reveals that the dominant structural element of each monomer of the homodimer is a central -sheet of 10 strands. The first nine strands of the sheet are mutually parallel with right-handed crossover connections between the strands. The 10th strand is antiparallel with respect to the first nine strands. In addition, the enzyme has two antiparallel -sheets, comprised of two strands and three strands each, 11 -helices and two short 3/10-helices. Further, it has been suggested that the similarities in the GTP-binding domains of the synthetase and the p21ras protein are an example of convergent evolution of two distinct families of GTP-binding proteins [MEDLINE:94064593]. Structures of adenylosuccinate synthetase from Triticum aestivum and Arabidopsis thaliana when compared with the known structures from E. coli reveals that the overall fold is very similar to that of the E. coli protein [MEDLINE:20135989].

\ \ GTP binding activity ; GO:0005525 \N purine nucleotide biosynthesis ; GO:0006164 19829 IPR001116

High levels of mRNA for human SS1 receptors have been found in the jejunum\ and stomach, with lower levels in the pancreas, colon and kidney - mRNA is\ absent in the brain. Conversely, in rodent tissue, high levels of mRNA\ are found in the brain, but are absent in peripheral tissues . The\ binding of agonists to recombinant receptor expressed in CHO cells is not\ regulated by GTP and is unaffected by pertussis toxin PUB00005902.

\ \ \ somatostatin receptor activity ; GO:0004994 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19825 IPR001111 The transforming growth factor

, N-terminus (TGFb) domain is present in avariety of proteins which include the transforming growth factor

,\ decapentaplegic proteins and bone morphogenetic proteins. Transforming growth\ factor

is a multifunctional peptide that controls proliferation,\ differentiation and other functions in many cell types. The decapentaplegic\ protein acts as an extracellular morphogen responsible for the proper\ development of the embryonic dorsal hypoderm, for viability of larvae and\ for cell viability of the epithelial cells in the imaginal disks. Bone\ morphogenetic protein induces cartilage and bone formation and may be responsible\ for epithelial osteogenesis in some organisms.\ \ \N \N \N 19826 IPR001112

The ETB receptors are thought to play a significant role in endothelium-dependent vasodilation and a lesser role in vasoconstriction. In the CNS,\ the receptor has been found in the cerebral cortex, hippocampus, cerebellum\ and astrocytes. ETB receptors activate the phosphoinositide pathway through\ a pertussis-toxin-insensitive G-protein, though some actions are pertussis-sensitive PUB00005879.

\ \ endothelin receptor activity ; GO:0004962 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19818 IPR001104

Synonym(s): Steroid 5--reductase

3-oxo-5--steroid 4-dehydrogenases, EC: 1.3.99.5 catalyse the conversion of 3-oxo-5--steroid + acceptor to 3-oxo-delta(4)-steroid + reduced acceptor. The steroid 5--reductase enzyme is responsible for the formation of dihydrotestosterone, this hormone promotes the differentiation of male external genitalia and the prostate during fetal development [MEDLINE:92147107]. In humans mutations in this enzyme can cause a form of male pseudohermaphorditism in which the external genitalia and prostate fail to develop normally. A related\ enzyme is also found in plants is DET2, a steroid reductase from Arabidopsis. Mutations in this enzyme cause defects in light-regulated development [MEDLINE:96185496]. This domain is present in both type 1 and type 2 forms.

\ \ \N \N \N 19819 IPR001105

Prostanoids (prostaglandins (PG) and thromboxanes (TX)) mediate a wide\ variety of actions and play important physiological roles in the cardiovascular and immune systems, and in pain sensation in peripheral systems\ . PGI2 and TXA2 have opposing actions, involving regulation of the\ interaction of platelets with the vascular endothelium. To date, evidence\ for at least 5 classes of prostanoid receptor has been obtained. However,\ identification of subtypes and their distribution is hampered by expression\ of more than one receptor within a tissue, coupled with poor selectivity of\ available agonists and antagonists. Moreover, many endogenous prostanoids\ undergo rapid metabolism, especially TXA2 PUB00005901.

\ \ thromboxane receptor activity ; GO:0004960 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19820 IPR001106 Phenylalanine ammonia-lyase (EC: 4.3.1.5) (PAL) is a key enzyme of plant andfungi phenylpropanoid metabolism, involved in the biosynthesis of a wide\ variety of secondary metabolites such as flavanoids, furanocoumarin phytoalexins\ and cell wall components. These compounds are important for normal growth and in\ responses to environmental stress.\ \

The family also includes histidine ammonia-lyase (EC: 4.3.1.3) (histidase) that catalyzes the first step in\ histidine degradation, the removal of an ammonia group from histidine to produce\ urocanic acid.

\ \ ammonia ligase activity ; GO:0016211 \N biosynthesis ; GO:0009058 19821 IPR001107 The band 7 protein is an integral membrane protein which is thought to regulatecation conductance. A variety of proteins belong to this family. These include the\ prohibitins, cytoplasmic anti-proliferative proteins and stomatin, an erythrocyte membrane protein. Bacterial HflC protein also belongs\ to this family.\ \ \N \N \N 19822 IPR001108 Presenilins are polytopic transmembrane (TM) proteins, mutations in whichare associated with the occurrence of early-onset familial Alzheimer's\ disease, a rare form of the disease that results from a single-gene\ mutation \ [MEDLINE:99007742], [MEDLINE:98180715]. \ The physiological functions of\ presenilins are unknown, but they may be related to developmental signalling,\ apoptotic signal transduction, or processing of selected proteins, such as the

-amyloid precursor protein(

-APP). There are a number of subtypes which\ belong to this presenilin family. That presenilin homologues have been\ identified in species that do not have an Alzhemier's disease correlate suggests\ that they may have functions unrelated to the disease, homologues having been\ identified in mouse, Drosophila and C.elegans\ \ \ \ [MEDLINE:96032531].\ \ \N membrane ; GO:0016020 intracellular signaling cascade ; GO:0007242 19823 IPR001109 The hydrogenase expression/formation proteins (HUPF/HYPC) form a family of small\ proteins which are one of a number of gene products which are required by the\ bacterial membrane-bound nickel-dependent hydrogenases for their expression\ and/or synthesis [MEDLINE:93268090].\ \ \ \N \N \N 19824 IPR001110 A group of uncharacterized proteins share this well-conserved region centered on a cysteine residue. These proteins are a subset of the carbon-nitrogen hydrolase family indicating that these as yet uncharacterised proteins may be related to members of this family [MEDLINE:95078742].\ molecular_function unknown ; GO:0005554 \N \N 19817 IPR001103

Steroid or nuclear hormone receptors (NRs) constitute an important super-family of transcription regulators that are involved in diverse physiological functions, including control of embryonic development, cell\ differentiation and homeostasis. Members include the\ steroid hormone receptors and receptors for thyroid hormone, retinoids and \ 1,25-dihydroxy-vitamin D3. The proteins \ function as dimeric molecules in the nucleus to regulate the transcription of \ target genes in a ligand-responsive manner [MEDLINE:95206940], [MEDLINE:94218237].

\ \

NRs are extremely important in medical research, a large number of them\ being implicated in diseases such as cancer, diabetes and hormone resistance\ syndromes. Many do not yet have a defined ligand and are accordingly termed \ "orphan" receptors. More than 300 NRs have been\ described to date and a new system \ has recently been introduced in an attempt to rationalise the increasingly \ complex set of names used to describe superfamily members.

\ The androgen receptor (AR) consists of 3 functional and structural domains:\ an N-terminal (modulatory) domain; a DNA binding domain (IPR001628) that mediates\ specific binding to target DNA sequences (ligand-responsive elements);\ and a hormone binding domain. The N-terminal domain (NTD) is unique to the \ androgen receptors and spans approximately the first 530 residues; the\ highly-conserved DNA-binding domain is smaller (around 65 residues) and\ occupies the central portion of the protein; and the hormone ligand binding\ domain (LBD) lies at the receptor C-terminus. . In the absence of ligand,\ steroid hormone receptors are thought to be weakly associated with nuclear\ components; hormone binding greatly increases receptor affinity.

\ \

The LBDs of steroid hormone\ receptors fold into 12 helices that form a ligand-binding pocket. When an agonist is bound, helix 12 folds over\ the pocket to enclose the ligand [MEDLINE:22084013]. When an antagonist is unbound, helix 12 is positioned away from the pocket in a way that interferes with the binding of\ coactivators to a groove in the hormone-binding domain formed after ligand binding. In AR, ligand binding that induces folding of helix 12 to overlie the\ pocket discloses a groove that binds a region of the NTD. Coactivator molecules can also bind to this groove, but the predominant site for coactivator binding\ to AR is in the NTD. AR ligand resides in a pocket and primarily contacts helices 4, 5, and 10. The DNA-binding region includes eight\ cysteine residues that form two coordination complexes, each composed of four cysteines and a Zn²⁺ ion. These two zinc fingers form the structure that binds\ to the major groove of DNA. The second zinc finger stabilizes the binding complex by hydrophobic interactions with the first finger and contributes to specificity of receptor DNA binding.\ It is also necessary for receptor dimerization that occurs during DNA binding

Defects in the androgen receptor cause testicular feminisation syndrome,\ androgen insensibility syndrome (AIS) [MEDLINE:93338440], [MEDLINE:92235226]. AIS may be complete (CAIS),\ where external genitalia are phenotypically female; partial (PAIS), where\ genitalia are substantively ambiguous; or mild (MAIS), where external\ genitalia are normal male, or nearly so. Defects in the receptor also cause\ X-linked spinal and bulbar muscular atrophy (also known as Kennedy's disease).\

\ \ \ steroid binding activity ; GO:0005496 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 19814 IPR001101 Plectin may have a role in cross-linking intermediate filaments, in inter-linking\ intermediate filaments with microtubules and microfilaments and in anchoring\ intermediate filaments to the plasma and nuclear membranes. The plectin repeat\ is also seen in the cell adhesion junction plaque proteins, desmoplakin and bullous\ pemphigoid antigen.\ \ \ \N \N \N 19815 IPR001102 Synonym(s): Transglutaminase, Fibrinoligase, TGase

Protein-glutamine gamma-glutamyltransferases (EC: 2.3.2.13) (TGase) are calcium-dependent enzymes that\ catalyze the cross-linking of proteins by promoting the formation of\ isopeptide bonds between the gamma-carboxyl group of a glutamine in one\ polypeptide chain and the epsilon-amino group of a lysine in a second\ polypeptide chain. TGases also catalyze the conjugation of polyamines to\ proteins [MEDLINE:92077334], [MEDLINE:90337934].

\ \

Transglutaminases are widely distributed in various organs, tissues and\ body fluids. The best known transglutaminase is blood coagulation factor XIII,\ a plasma tetrameric protein composed of two catalytic A subunits and two\ non-catalytic B subunits. Factor XIII is responsible for cross-linking fibrin chains,\ thus stabilizing the fibrin clot.

\ \ \N \N \N 19816 IPR001102 Synonym(s): Transglutaminase, Fibrinoligase, TGase

\ \

\ \ \N \N \N 19810 IPR001098 Synonym(s): DNA nucleotidyltransferase (DNA-directed)

DNA-directed DNA polymerases(EC: 2.7.7.7) are the key enzymes catalyzing the\ accurate replication of DNA. They require either a small RNA molecule or a\ protein as a primer for the de novo synthesis of a DNA chain. A number of\ polymerases belong to this family.

\ \ DNA-directed DNA polymerase activity ; GO:0003887 \N DNA replication ; GO:0006260 19811 IPR001099 Synonym(s): Chalcone synthase, Flavonone synthase, 6'-deoxychalcone synthase

Naringenin-chalcone synthases (EC: 2.3.1.74) and stilbene synthases (STS) \ (formerly known as resveratrol synthases) are related plant enzymes. CHS is an\ important enzyme in flavanoid biosynthesis and STS is a key enzyme in \ stilbene-type phyloalexin biosynthesis. Both enzymes catalyze the addition of three\ molecules of malonyl-CoA to a starter CoA ester (a typical example is\ 4-coumaroyl-CoA), producing either a chalcone (with CHS) or stilbene (with\ STS) PUB00005665.

\ \

These enzymes have a conserved cysteine residue, located in the central section\ of the protein sequence, which is essential for the catalytic activity of both\ enzymes and probably represents the binding site for the 4-coumaryl-CoA group\ PUB00005665.

\ \ acyltransferase activity ; GO:0008415 \N biosynthesis ; GO:0009058 19812 IPR001099 Synonym(s): Chalcone synthase, Flavonone synthase, 6'-deoxychalcone synthase

\ \

\ \ acyltransferase activity ; GO:0008415 \N biosynthesis ; GO:0009058 19813 IPR001100 The pyridine nucleotide-disulphide reductases (PNDR) use the isoalloxazine ring of FAD to shuttle reducing equivalents from NAD(P)H to a Cys residue\ that is usually a part of a redox-active disulphide bridge. In a second\ step, the reduced disulphide reduces the substrate. On the basis of \ sequence and structural similarities [MEDLINE:91296031], PNDR can be categorised into 2\ groups.\

Class I includes glutathione reductase, trypanothione reductase,\ lipoamide dehydrogenase and mercuric reductase. They cover a wide range of\ catalytic functions: glutathione reductase ensures that the cell has \ enough reduced glutathione to maintain protein thiol groups in the reduced\ state [MEDLINE:91053135]; trypanothione reductase carries out the analogous reaction in \ trypanosomal cells (trypanothione is an analogue of glutathione) [MEDLINE:86243316]; \ lipoamide dehydrogenase, the E3 component of -ketoacid dehydrogenase\ multienzyme complex, oxidises the dihydrolypoyl groups of lipoate \ acyltransferase, and so couples glycolysis to the tricarboxylic acid cycle \ [MEDLINE:89117136]; and mercuric reductase enables bacteria to detoxify the mercuric ion\ by reducing it to elemental mercury, which evaporates from the cell [MEDLINE:92159260].

\ \ oxidoreductase activity ; GO:0016491 \N electron transport ; GO:0006118 19807 IPR001094 Flavodoxins act in various electron-transport systems as functionalanalogues of ferredoxins [MEDLINE:95131791]. Although flavodoxins are found only\ in certain bacteria and algae [MEDLINE:90088453] the proteins share similarity\ with a number of protein domains of both prokaryotic and eukaryotic origin \ [MEDLINE:86216074].\ \ electron transporter activity ; GO:0005489 \N electron transport ; GO:0006118 19808 IPR001095 This protein is a subunit of the acetyl coenzyme A carboxylase complex (EC: 6.4.1.2).It catalyzes the first step in the synthesis of long-chain fatty acids which\ involves the carboxylation of acetyl-CoA to malonyl-CoA.\ The acetyl-CoA carboxylase complex (EC: 6.4.1.2) is a heterohexamer of biotin carboxyl\ carrier protein, biotin carboxylase and two non-identical carboxyl transferase subunits\ (

and

) in a 2:2 association [MEDLINE:92380982].\ The reaction involves two steps:\

 \
Biotin carrier protein + ATP + HCO₃^- -> Carboxybiotin carrier protein + ADP + P_i\

\ \ \ \

\
Carboxybiotin carrier protein + Acetyl-CoA -> Malonyl-CoA + Biotin carrier protein\

\ \ acetyl-CoA carboxylase activity ; GO:0003989 acetyl-CoA carboxylase complex ; GO:0009317 fatty acid biosynthesis ; GO:0006633 19804 IPR001091

Synonym(s): N-4 cytosine-specific DNA methylase, Modification methylase

Site-specific DNA-methyltransferase (cytosine-N4-specific) (EC: 2.1.1.113) are enzymes that\ specifically methylate the amino group at the C-4 position of cytosines in\ DNA. In prokaryotes, the major role of DNA methylation is to protect host\ DNA against degradation by restriction enzymes. There are two major classes\ of DNA methyltransferase that differ in the nature of the modifications\ they effect. The members of one class (C-MTases) methylate a ring carbon and\ form C5-methylcytosine and members of the second class (N-MTases) methylate\ exocyclic nitrogens and form either N4-methylcytosine (N4-MTases) or\ N6-methyladenine (N6-MTases). Both classes of MTase utilise the cofactor\ S-adenosyl-L-methionine (SAM) as the methyl donor and are active as monomeric enzymes\ [MEDLINE:95392155].

\ \ N-methyltransferase activity ; GO:0008170 \N DNA methylation ; GO:0006306 19805 IPR001092 Basic helix-loop-helix proteins (bHLH) are a group of eukaryotic transcription factors that exert a determinative influence in a variety of developmental pathways. These transcription factors are characterised by a highly evolutionary conserved bHLH domain that mediates specific dimerisation [MEDLINE:96057862]. They facilitate the conversion of inactive monomers to trans-activating dimers at appropriate stages of development [MEDLINE:92095937].

The bHLH proteins can be classified into discrete categories. One such subdivision according to dimerisation, DNA binding and expression characteristics defines seven groups [MEDLINE:94289469]. Class I proteins form dimers within the group or with class II proteins. Class II can only form heterodimers with class I factors. Class III factors are characterised by the presence of a leucine zipper (IPR002418).\

\ \ \N \N \N 19806 IPR001093 Synonym(s): Inosine-5'-monophosphate dehydrogenase, Inosinic acid dehydrogenase; Synonym(s): Guanosine 5'-monophosphate oxidoreductase \ \ \

This entry contains two related enzymes IMP dehydrogenase and GMP reducatase. These enzymes adopt a TIM barrel structure.

\ \

IMP dehydrogenase (EC: 1.1.1.205) (IMPDH) catalyzes the rate-limiting reaction of de novo GTP biosynthesis, the NAD-dependent reduction of IMP into XMP [MEDLINE:89008491].\ \

\
Inosine 5-phosphate + NAD⁺ + H₂O = xanthosine 5-phosphate + NADH\

\ \ IMP dehydrogenase is associated with cell proliferation and is a possible target for cancer chemotherapy. Mammalian and bacterial IMPDHs are tetramers of identical chains. There are two IMP dehydrogenase isozymes in humans [MEDLINE:90203022]. IMP dehydrogenase nearly always contains a long insertion that has two CBS domains within it.

\ \

GMP reductase (EC: 1.7.1.7) catalyzes the irreversible and NADPH-dependent reductive deamination of GMP into IMP [MEDLINE:89061679].\ \

\
NADPH + guanosine 5-phosphate = NADP⁺ + inosine 5-phosphate + NH₃ \

\ \ It converts nucleobase, nucleoside and nucleotide derivatives of G to A nucleotides, and maintains intracellular balance of A and G nucleotides.

\ \ enzyme activity ; GO:0003824 \N \N 19809 IPR001096 Synonym(s): Bean endopeptidase, Vicilin peptidohydrolase, Phaseolin, Asparaginyl endopeptidase, Hemoglobinase

Cysteine protease activity is dependent on an active dyad of cysteine and\ histidine, the order and spacing of these residues varying in the 20 or so\ known families. Families C1, C2 and C10 are loosely termed papain-like.\ Nearly half of all cysteine proteases are found exclusively in viruses [MEDLINE:95147707].

\ \

The blood fluke parasite Schistosoma mansoni has two cysteine proteases in\ its digestive tract, one a cathepsin B-like protease, the other termed\ hemoglobinase [MEDLINE:95147707], [MEDLINE:87308326]. The latter has been hard to purify, free of cathepsin\ B, and expressed forms in E.coli prove to be inactive, suggesting that\ hemoglobinase may act in association with cathepsin B [MEDLINE:95147707], [MEDLINE:93207533]. Plant vacuolar\ processing enzyme and legumain from legumes [MEDLINE:95147707] have been shown to have\ sequence and functional similarity to hemoglobinase. The catalytic residues\ of the family are currently unknown, but sequence alignments reveal one\ totally conserved cysteine and two totally conserved histidines.

\ \ cysteine-type endopeptidase activity ; GO:0004197 \N proteolysis and peptidolysis ; GO:0006508 19801 IPR001088

Glycoside hydrolase family 4 CAZY:GH_4\ comprises enzymes with several known activities; 6-phospho--glucosidase (EC: 3.2.1.86); 6-phospho--glucosidase (EC: 3.2.1.122); -galactosidase (EC: 3.2.1.22).

\ \ \

6-phospho--glucosidase requires both NAD(H) and divalent metal (Mn2+, Fe2+, Co2+, or Ni2+) for activity [MEDLINE:98438507].

\ \ hydrolase activity, hydrolyzing O-glycosyl compounds ; GO:0004553 \N carbohydrate metabolism ; GO:0005975 19803 IPR001090

Interactions between the Eph receptor tyrosine kinases and their \ membrane-bound ligands, ephrins are promiscuous, but largely fall \ into two groups: EphA receptors bind to GPI-anchored ephrin-A ligands, \ while EphB receptors bind to ephrin-B proteins that have a transmembrane \ and cytoplasmic domain [MEDLINE:99172312]. \ Remarkably, ephrin-B proteins transduce signals, such that bidirectional \ signaling can occur upon interaction with Eph receptor. An important\ role of Eph receptors and ephrins is to mediate cell-contact-dependent \ repulsion. Eph receptors and ephrins also act at boundaries to channel \ neuronal growth cones along specific pathways, restrict the migration \ of neural crest cells, and via bidirectional signaling prevent \ intermingling between hindbrain segments. \ Intriguingly, Eph receptors and ephrins can also trigger an adhesive\ response of endothelial cells and are required for the remodeling of\ blood vessels [MEDLINE:20194409].

\ Biochemical studies suggest that the extent of multimerization of\ Eph receptors modulates the cellular response and that the actin\ cytoskeleton is one major target of the intracellular pathways \ activated by Eph receptors [MEDLINE:99225451].\ Eph receptors and ephrins have thus emerged as key regulators of the\ repulsion and adhesion of cells that underlie the establishment,\ maintenance, and remodeling of patterns of cellular \ organization [MEDLINE:20194409].

\ \ ATP binding activity ; GO:0005524 membrane ; GO:0016020 \N 19802 IPR001089 Most members of this family of low-molecular weight proteins seem to havemitogenic, chemotactic or inflammatory activities. They are released by phagocytes,\ mesenchymal cells and a wide variety of tissue cells, upon exposure to inflammation\ [MEDLINE:92347562]. These small cytokines are also called intercrines or chemokines. They\ are cationic proteins of 70 to 100 amino acid residues that share four conserved\ cysteine residues involved in two disulfide bonds.\ \

\ \ chemokine activity ; GO:0008009 extracellular ; GO:0005576 immune response ; GO:0006955 19796 IPR001083 Some fungal transcription factors contains a N-terminal domain, the copper fist,which seems to be involved in copper-dependent DNA-binding [MEDLINE:94085378], [MEDLINE:93286085].\ This protein activates the transcription of the metallothionein gene in response to\ copper. Metallothionein maintains copper levels in yeast \ [MEDLINE:89028682], [MEDLINE:94085378]. \ The copper fist domain, which is similar in structure to metallothionein itself, undergoes\ a large conformational change on copper-binding that allows DNA-binding.\ \ transcription factor activity ; GO:0003700 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 19797 IPR001084 Microtubules consist of tubulins as well as a group of additional proteinscollectively known as the Microtubule Associated Proteins (MAP). MAP's have\ been classified into two classes: high molecular weight MAP's and Tau\ protein. The Tau proteins promote microtubule assembly and stabilize\ microtubules.\ \

The C-terminal region of these proteins contains three or four tandem repeats\ of a conserved domain of about thirty amino acid residues which is implicated\ in tubulin-binding and which seems to have a stiffening effect on microtubules.

\ \ \N \N \N 19798 IPR001085 Synonym(s): Serine hydroxymethyltransferase, Serine aldolase, Threonine aldolase

Glycine hydroxymethyltransferase (EC: 2.1.2.1) catalyzes the transfer\ of the hydroxymethyl group of serine to tetrahydrofolate to form \ 5,10-methylenetetrahydrofolate and glycine. Pyridoxal phosphate acts as the cofactor.\ The pyridoxal-P group is attached to a lysine residue around which the sequence\ is highly conserved in all forms of the enzyme [MEDLINE:94137764].

\ \

In vertebrates, glycine hydroxymethyltransferase exists in a cytoplasmic and a mitochondrial form whereas\ only one form is found in prokaryotes.

\ \ glycine hydroxymethyltransferase activity ; GO:0004372 \N one-carbon compound metabolism ; GO:0006730 19799 IPR001086

Prephenate dehydratase (EC: 4.2.1.51, PDT) catalyses the decarboxylation of prephenate to phenylpyruvate. In microorganisms it is part of the terminal pathway of phenylalanine biosynthesis. In some bacteria such as Escherichia coli PDT is part of a bifunctional enzyme (P-protein) that also catalyzes the transformation of chorismate into prephenate (chorismate mutase, IPR002701.

\ prephenate dehydratase activity ; GO:0004664 \N phenylalanine biosynthesis ; GO:0009094 19800 IPR001087 A variety of lipolytic enzymes with serine as part of the active site have beenidentified [MEDLINE:95334818]. Members of this family include; Aeromonas hydrophila lipase,\ Vibrio mimicus arylesterase, Vibrio parahaemolyticus thermolabile hemolysin,\ rabbit phospholipase (AdRab-B), and Brassica napus anter-specific proline-rich\ protein.\ \ enzyme activity ; GO:0003824 \N \N 19792 IPR001078 This domain is found in the lipoamide acyltransferase component of the branched-chain

-keto acid dehydrogenase complex (EC: 2.3.1.-), which catalyses the overall conversion of

-keto acids to acyl-CoA and carbon dioxide. It contains multiple copies of three enzymatic components: branched-chain

-keto acid decarboxylase (E1), lipoamideacyltransferase (E2) and lipoamide dehydrogenase (E3). The domain is also found in the dihydrolipoamide succinyltransferase component of the 2-oxoglutarate dehydrogenase complex (EC: 2.3.1.61).\ These proteins contain one to three copies of a lipoyl binding domain followed by the catalytic domain.\ \ acyltransferase activity ; GO:0008415 \N metabolism ; GO:0008152 19793 IPR001079 Animal lectins display a wide variety of architectures.They are classified according to the carbohydrate-recognition\ domain (CRD) of which there are two main types, S-type and C-type.\

Galectins (previously S-lectins) bind exclusively -galactosides like lactose. They do not require metal ions for activity.\ Galectins are found predominantly, but not exclusively in mammals [MEDLINE:94170361]. Their function is unclear. They are developmentally regulated and may be involved in differentiation, cellular regulation and tissue\ construction.

\ \ \N \N \N 19794 IPR001080 In a few bacterial P450-containing systems, the transfer of electrons fromflavoprotein reductase to P450 is mediated by 3Fe-4S ferredoxins [MEDLINE:94222824],\ [MEDLINE:93247481], [MEDLINE:93023839]. Despite functional similarity of such ferredoxins to\ the adrenodoxin family, they do not share sequence similarity but seem to be\ similar to some mono-[4Fe-4S] cluster ferredoxins but lack the fourth cysteine\ residue conserved in 4Fe-4S sequences [MEDLINE:91105127]. It has been shown\ experimentally that the 4Fe-4S cluster of related ferredoxins from archaebacteria\ easily converts to a 3Fe-4S cluster [MEDLINE:93075813].\ \ electron transporter activity ; GO:0005489 \N electron transport ; GO:0006118 19795 IPR001082 Pilin is a subunit of the pilus, a polar flexible filament, which consistsof a single polypeptide chain arranged in a helical configuration of five\ subunits per turn. Gram-negative bacteria produce pilin which is characterized\ by the presence of a very short leader peptide of 6 to 7 residues, followed by\ a methylated N-terminal phenylalanine residue and by a highly conserved sequence\ of about 24 hydrophobic residues the NMePhe type pilin IPR001120\ \ \ \ [MEDLINE:88250000], [MEDLINE:88036063].\ \ \N fimbria ; GO:0009289 cell adhesion ; GO:0007155 19790 IPR001075

\ \

In a number of organisms, for example Azotobacter vinelandii, NifU is a protein associated with the nif operon. It contains two domains, the N-terminal (IPR002871) and the C-terminal presented in this entry. These domains exist either together or on different polypeptides, both domains being found in organisms that do not fix nitrogen e.g. yeast, so they have a broader significance in the cell than nitrogen fixation. It has been proposed that they are specifically required for the formation and maturation of Fe-S clusters that in eukaryotes occurs in the mitochondrial matrix. In yeast, for example, deletion of the C-terminal domain does not markedly affect Fe-S biosynthesis but in combination with inactivation of ISU1 there is a defect in mitochondrial FE-S-protein maturation.

\ \ \ \N \N \N 19791 IPR001077

\ \

This family includes a range of O-methyltransferases some of which utilize S-adenosyl methionine as substrate [MEDLINE:93167811]. In prokaryotes, the major role of DNA methylation is to protect host DNA against degradation by restriction enzymes. In eukaryotes, DNA methylation has been implicated in the control of several cellular processes, including differentiation, gene regulation, and embryonic development. O-methyltransferases have a common catalytic domain structure, which might be universal among S-adenosyl-L-methionine (AdoMet)-dependent methyltransferases [MEDLINE:95292061].

Comparative analysis of the predicted amino acid sequences of a number of plant O-methyltransferase cDNA clones show that they share some 32-71% sequence identity, and can be grouped according to the different compounds they utilise as substrates [MEDLINE:98145451].

\ \ O-methyltransferase activity ; GO:0008171 \N \N 19786 IPR001070 This family includes the VP2 and VP3 internal coat proteinsfrom polyomavirusess. Polyomaviruses are small dsDNA tumor viruses.\ Their capsids contain 360 copies of the VP1 proteins IPR000662 arranged in 72 pentamers. This capsid\ encloses the internal proteins VP2 and VP3, as well as the viral\ DNA. A single copy of VP2 or VP3 associates with each VP1 pentamer. A\ crystal structure shows that the C terminal region of the VP2/VP3 protein\ interacts with the VP1 pentamer [MEDLINE:98292443].\ \ structural molecule activity ; GO:0005198 viral capsid ; GO:0019028 \N 19787 IPR001071 Alpha-tocopherol transport protein belongs to a large family of proteins whichcontain the CRAL_TRIO domain IPR001251. Alpha-tocopherol transport protein\ binds only

-tocopherol (and not the gamma form), and as such displays\ the same sort of stereo-selective binding as implicated with cellular\ retinaldehyde-binding protein (CRALBP) with which it is known to share sequence\ similarity [MEDLINE:93352574].\ \ \ transporter activity ; GO:0005215 intracellular ; GO:0005622 transport ; GO:0006810 19788 IPR001072 The uncharacterised protein MJ0414 from Methanococcus jannaschii belongsto a conserved family that includes proteins from other archaea and from the\ thermophilic bacterium Aquifex aeolicus\ \ \ \ [MEDLINE:96337999]. Nothing is known about\ the function of this conserved family.\ \ molecular_function unknown ; GO:0005554 \N \N 19789 IPR001073 C1q is a subunit of the C1 enzyme complex that activates the serum complement\ system. C1q comprises 6 A, 6 B and 6 C chains. These share the same topology, each\ possessing a small, globular N-terminal domain, a collagen-like Gly/Pro-rich central\ region, and a conserved C-terminal region, the C1q domain [MEDLINE:91174759]. The C1q\ protein is produced in collagen-producing cells and shows sequence and structural\ similarity to collagens VIII and X [MEDLINE:90076497], [MEDLINE:91210292].\ \ \ \N \N \N 19785 IPR001069

The 5HT2 receptor was originally classified according to its ability to\ display micromolar affinity for 5HT, to be labelled with [MEDLINE:90262152] spiperone,\ and by its susceptibility to 5HT antagonists PUB00005889. At least 3 members of\ the family exist (including the re-classified 5HT1C receptor), all of\ which share a high degree of sequence similarity and stimulate the\ phosphoinositide pathway.

\ \ \N integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19784 IPR001068

In addition to their role in energy metabolism, purines (especially\ adenosine and adenine nucleotides) produce a wide range of pharmacological\ effects mediated by activation of cell surface receptors . Distinct\ receptors exist for adenosine. In the periphery, the main effects of\ adenosine include vasodilation, bronchoconstriction, immunosuppresion,\ inhibition of platelet aggregation, cardiac depression, stimulation of\ nociceptive afferents, inhibition of neurotransmitter release and\ inhibition of the release of other factors, e.g. hormones PUB00005868. In the CNS,\ adenosine exerts a pre- and post-synaptic depressant action, reducing motor\ activity, depressing respiration, inducing sleep and relieving anxiety. The\ physiological role of adenosine is thought to be to adjust energy demands\ in line with oxygen supply. Many of the clinical actions of methylxanthines\ are thought to be mediated through antagonism of adenosine receptors. Four\ subtypes of receptor have been identified, designated A1, A2A, A2B and A3.

\ \

A1 receptors are distributed widely in peripheral tissues (e.g., heart,\ adipose tissue, kidney, stomach and pancreas), where they have a mainly\ inhibitory role, and are also found in peripheral nerves (e.g., in the\ intestine and vas deferens) PUB00005868. In the CNS, they are present in high\ levels, notably in the cerebral cortex, hippocampus, cerebellum, thalamus\ and striatum. The receptors inhibit adenylyl cyclase and voltage-dependent\ calcium channels, and activate potassium channels through a pertussis-toxin-sensitive G-protein, probably of the Gi/Go class.

\ \ A1 adenosine receptor activity, G-protein coupled ; GO:0001610 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19783 IPR001067 The Ah (dioxin) receptor nuclear translocator protein (Arnt) belongs to the basichelix-loop-helix (bHLH) family of transcription factors and is required for\ Ah receptor function. The Ah receptor binds, and mediates the carcinogenic\ effects of a variety of environmental pollutants, including \ 2,3,7,8-tetrachlorodibenzo-p-dioxin and polycyclic aromatic hydrocarbons. \ Arnt is a structural component of the\ XRE-binding form of the Ah receptor. These proteins are class VII members of the basic helix-loop-helix (bHLH) family. The bHLH domain may be responsible for interacting with both the XRE and the ligand-binding\ subunit [MEDLINE:94344118], [MEDLINE:92271249].\

The activated Ah receptor and Arnt protein bind DNA as a heterodimer. Both\ proteins contain PAS homology regions, which in Drosophila PER and SIM\ proteins function as dimerisation domains [MEDLINE:94344118].

\ \ transcription factor activity ; GO:0003700 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 19782 IPR001065

The M2 receptor is found in low levels in the CNS, where it has a limited\ distribution . By contrast, M2 receptors are expressed in high density\ in the heart, where they induce a decrease in inotropy and bradycardia .\ They are also found in smooth muscle. No selective agonist has been\ described PUB00005867.

\ \ muscarinic acetylcholine receptor activity ; GO:0004981 membrane ; GO:0016020 \N 19781 IPR001064 Crystallins are the dominant structural components of the eye lens. Among thedifferent type of crystallins, the

and gamma crystallins form a family of\ related proteins [MEDLINE:89024580], [MEDLINE:89113769]. Structurally,

and gamma crystallins\ are composed of two similar domains which, in turn, are each composed of two similar\ motifs with the two domains connected by a short connecting peptide. Each motif,\ which is about forty amino acid residues long, is folded in a distinctive \ 'Greek key' pattern.\ \ \N \N \N 19779 IPR001062 Bacterial transcription antitermination protein, nusG, is a component of thetranscription complex and interacts with the termination factor rho and RNA\ polymerase [MEDLINE:93138385], [MEDLINE:92210569]. NusG is a bacterial transcriptional\ elongation factor involved in transcription termination and anti-termination [MEDLINE:94093297].\ \ transcriptional elongation regulator activity ; GO:0003711 \N regulation of transcription, DNA-dependent ; GO:0006355 19780 IPR001063

\ \ \

Ribosomal protein L22 is one of the proteins from the large ribosomal subunit.\ In Escherichia coli, L22 is known to bind 23S rRNA. It belongs to a family of\ ribosomal proteins which includes: bacterial L22; algal and plant chloroplast L22\ (in legumes L22 is encoded in the nucleus instead of the chloroplast); cyanelle L22;\ archaebacterial L22; mammalian L17; plant L17 and yeast YL17.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 19776 IPR001059 Elongation factor P (EF-P) is a prokaryotic protein translation factor requiredfor efficient peptide bond synthesis on 70S ribosomes from fMet-tRNAfMet [MEDLINE:97338480].\ Probably functions indirectly by altering the affinity of the ribosome for aminoacyl-tRNA,\ thus increasing their reactivity as acceptors for peptidyl transferase.\ \ \ translation elongation factor activity ; GO:0003746 \N translational elongation ; GO:0006414 19777 IPR001060 This domain was first identified in cell division control protein 15 fromfission yeast where after the onset of mitosis, it forms a ring-like structure\ which co-localizes with the medial actin ring. It may mediate cytoskeletal\ rearrangements required for cytokinesis. \

Also occurs in protein-tyrosine kinases, where it may play a role\ in regulatory processes such as cell cycle control, and in human Rho-GAP\ hematopoietic protein C1, where it has an inhibitory effect on stress fiber\ organisation.

\ \ \N \N \N 19778 IPR001061 Transgelin (SM22-

) is a calponin which is expressed exclusivelyin smooth muscle-containing tissues of adult animals and is one of the earliest\ markers of differentiated smooth muscle cells [MEDLINE:95042787], [MEDLINE:95286641]. It is the product of a single gene that is conserved in yeast,\ Drosophila, molluscs and humans [MEDLINE:95042787], and is highly similar to several other\ proteins of unknown function (including mouse p27 and human WS3-10). The \ smaller domains of similarity shared between transgelin and other proteins, \ such as rat NP25, chicken calponins

and

, and Drosophila mp20,\ suggest that these proteins may be classified as members of a new transgelin\ multigene family [MEDLINE:95042787].\ \ \N \N muscle development ; GO:0007517 19773 IPR001056 This family consists of the 10 kDa photosystem II phosphoprotein PsbH. PsbH is phosphorylated in a light dependent reaction catalyzed by amembrane-bound kinase. Studies on photosystem II of Chlamydomonas reinhardtii suggest that a primary role of PSII-H may be to facilitate PSII assembly/stability through dimerization. PSII-H phosphorylation, which possibly occurs at two sites, may also be germane to its role in regulating PSII structure, stabilization, or activity [MEDLINE:97267150].\ \ protein stabilization activity ; GO:0017028 photosystem II ; GO:0009523 \N 19774 IPR001057 Synonym(s): Gamma-glutamyl kinase\

Glutamate 5-kinase (EC: 2.7.2.11) catalyses the first step\ in the biosynthesis of proline, the ATP-dependent phosphorylation of glutamate to\ glutamate 5-phosphate [MEDLINE:92283773], [MEDLINE:94364946]. \ It belongs to the larger family of aspartokinases.

\ \ \ glutamate 5-kinase activity ; GO:0004349 \N proline biosynthesis ; GO:0006561 19775 IPR001058

\ \ \N cytoplasm ; GO:0005737 \N 19772 IPR001055 Adrenodoxin, putidaredoxin and terpredoxin are soluble 2Fe-2S iron-sulphurproteins that act as single electron carriers. They are a subgroup of the ferredoxin\ family of iron-sulfur proteins.\ \

In mitochondrial monooxygenase systems, adrenodoxin transfers an electron from\ NADPH:adrenodoxin reductase to membrane-bound P450 PUB00003474. In bacteria, putidaredoxin\ and terpredoxin serve as electron carriers between corresponding NADH-dependent ferredoxin\ reductases and soluble P450 PUB00003474, [MEDLINE:92332528]. The exact functions of other members\ of this family are not known.

\ \ electron transporter activity ; GO:0005489 \N electron transport ; GO:0006118 19771 IPR001054 Guanylate cyclases (EC: 4.6.1.2) catalyze the formation of cyclic GMP(cGMP)from GTP. cGMP acts as an intracellular messenger, activating cGMP-dependent kinases \ and regulating CGMP-sensitive ion channels. The role of cGMP as a second messenger in \ vascular smooth muscle relaxation and retinal photo-transduction is well established. \ Guanylate cyclase is found both in the\ soluble and particular fraction of eukaryotic cells. The soluble and plasma\ membrane-bound forms differ in structure, regulation and other properties [MEDLINE:92246445],\ [MEDLINE:93008232], [MEDLINE:92008958], [MEDLINE:91208101]. \ Most currently known plasma membrane-bound\ forms are receptors for small polypeptides. The soluble forms of guanylate cyclase are\ cytoplasmic heterodimers having

and

subunits.\ \ guanylate cyclase activity ; GO:0004383 \N intracellular signaling cascade ; GO:0007242 19768 IPR001050 Syndecans are a family of transmembrane heparan sulfate proteoglycans which are\ implicated in the binding of extracellular matrix components and growth factors.\ Syndecans bind a variety of molecules via their heparan sulfate chains and can act\ as receptors or as co-receptors [MEDLINE:93119743], [MEDLINE:93380587].\ \ \ cytoskeletal protein binding activity ; GO:0008092 membrane ; GO:0016020 \N 19769 IPR001052

Rubredoxin is a low molecular weight iron-containing bacterial protein involved in electron transfer [MEDLINE:91058526], [MEDLINE:91124457], sometimes replacing ferredoxin as an electron carrier [MEDLINE:95243660].

The 3-D structures of a number of rubredoxins have been solved [MEDLINE:93271899], [MEDLINE:88155649]. The fold belongs to the + class, with 2 -helices and 2-3 -strands. Its active site contains an iron ion which is co-ordinated by the sulphurs of four conserved cysteine residues forming an almost regular tetrahedron [MEDLINE:88155649]. The conserved cysteines reside on two loops, which are the most conserved regions of the protein. In addition, a ring of acidic residues in the proximity of the [Fe(Cys)4] centre is also well-conserved [MEDLINE:88155649].

\ \ heavy metal binding activity ; GO:0005505 \N electron transport ; GO:0006118 19770 IPR001053

A novel C-X-C chemokine, named B cell-attracting chemokine 1 (BCA-1), was\ identified through screening of expressed sequence tag data PUB00005876. The chemokine was found to be expressed at highest levels in the liver, spleen, lymph nodes, appendix and stomach. Lower levels of BCA-1 were also found in the salivary and mammary glands. Expression appears to be constitutive in lymphoid tissues.

The receptor for BCA-1 was found to be a previously identified orphan receptor, expressed on B lymphocytes and Burkitt's lymphoma cells. This receptor, originally named BLR1 (Burkitt's lymphoma receptor 1), has now\ been renamed CXCR5 (C-X-C chemokine receptor type 5) [MEDLINE:98130629]. B lymphocytes expressing CXCR5 migrate in a concentration dependent manner in response to BCA-1. BCA-1 does not induce chemotaxis in T lymphocytes, monocytes or neutrophils. This selectivity for B lymphocytes is unique among the chemokines. BCA-l/CXCR5 may be important for the development of B cell areas of secondary lymphoid tissue; deletion of the CXCR5 gene in mice results in animals lacking inguinal lymph nodes and having defective formation of primary follicles and germinal centres of the spleen and Peyer's patches. Receptor-deficient B cells enter T cell areas but do not migrate into B cell areas. The expression of CXCR5 in Burkitt's lymphoma cells also suggests a role for the receptor in lymphomagenesis [MEDLINE:93049615].

\ \ C-X-C chemokine receptor activity ; GO:0016494 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19766 IPR001047

\ \ \

A number of eukaryotic and archebacterial ribosomal proteins have been grouped\ based on sequence similarities [MEDLINE:95391073]. One of these families, S8E, consists\ of a number of proteins with either about 220 amino acids (in eukaryotes) or about\ 125 amino acids (in archebacteria).

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 19767 IPR001048 This family contains proteins with various specificities and includes the aspartate, glutamate and uridylate kinase families. In prokaryotes and plants the synthesis of the essential amino acids lysine and threonine is predominantly regulated by feed-back inhibition of aspartate kinase (AK) and dihydrodipicolinate synthase (DHPS).In Escherichia coli, thrA, metLM, and lysC encode aspartokinase isozymes that show feedback inhibition by threonine, methionine, and lysine, respectively [MEDLINE:99237246]. The lysine-sensitive isoenzyme of aspartate kinase from spinach leaves has a subunit composition of 4 large and 4 small subunits [MEDLINE:98244392]. \

In plants although the control of carbon fixation and nitrogen assimilation has been studied in detail, relatively little is known about the regulation of carbon and nitrogen flow into amino acids. The metabolic regulation of expression of an Arabidopsis aspartate kinase/homoserine dehydrogenase (AK/HSD) gene, which encodes two linked key enzymes in the biosynthetic pathway of aspartate family amino acids has been studied PUB00006598. The conversion of aspartate into either the storage amino acid asparagine or aspartate family amino acids may be subject to a coordinated, reciprocal metabolic control, and this biochemical branch point is a part of a larger, coordinated regulatory mechanism of nitrogen and carbon storage and utilization.

\ \ \N \N amino acid biosynthesis ; GO:0008652 19763 IPR001044 Defects in DNA repair proteins can give rise, in humans, to the autosomalrecessive disorders xeroderma pigmentosum (XP) and Cockayne's syndrome [MEDLINE:93247645],\ [MEDLINE:94212451]. XP is characterised by a high incidence of sunlight-induced skin\ cancer, the effect of skin-cell hypersensitivity to UV resulting from defects in\ the nucleotide excision pathway. Seven XP complementation groups have\ been identified: XP-A to XP-G. XP-G is one of the most rare and phenotypically\ heterogeneous of XP, showing anything from slight to extreme dysfunction in DNA\ excision repair [MEDLINE:94266772], [MEDLINE:93219111].\ \

XPGC, an acidic protein that confers normal UV resistance in expressing cells, can\ correct XP-G. It is a magnesium-dependent, single-strand DNA endonuclease that\ makes structure-specific endonucleolytic incisions in a DNA substrate containing\ a duplex region and single-stranded arms. XPGC cleaves one strand of the duplex at the\ border with the single-stranded region [MEDLINE:94266772], [MEDLINE:94376899].

\ \ endonuclease activity ; GO:0004519 nucleus ; GO:0005634 nucleotide-excision repair ; GO:0006289 19764 IPR001045 Synonym(s): Spermidine aminopropyltransferase

A group of polyamine biosynthetic enzymes involved in the fifth (last) step in the\ biosynthesis of spermidine from arginine and methionine which includes; \ spermidine synthase (EC: 2.5.1.16), \ spermine synthase (EC: 2.5.1.22) and \ putrescine N-methyltransferase (EC: 2.1.1.53) [MEDLINE:98178071].

\ \ \ enzyme activity ; GO:0003824 \N \N 19765 IPR001046 The natural resistance-associated macrophage protein (NRAMP) family consists of Nramp1, Nramp2, and yeast proteins Smf1 and Smf2. The NRAMP family is a novel family of functionally related proteins defined by a conserved hydrophobic core of ten transmembrane domains [MEDLINE:96036029]. Nramp1 is an integral membrane protein expressed exclusively in cells of \ the immune system and is recruited to the membrane of a phagosome upon \ phagocytosis. Nramp2 is a multiple divalent cation transporter for Fe2+, Mn2+ and Zn2+\ amongst others. It is expressed at high levels in the intestine; and is \ major transferrin-independent iron uptake system in mammals [MEDLINE:98383996]. The yeast proteins Smf1 and Smf2 may also transport divalent cations [MEDLINE:98294035].\ \

The natural resistance of mice to infection with intracellular parasites is\ controlled by the Bcg locus, which modulates the cytostatic/cytocidal\ activity of phagocytes. Nramp1, the gene responsible, is expressed exclusively in\ macrophages and poly-morphonuclear leukocytes, and encodes a polypeptide\ (natural resistance-associated macrophage protein) with features typical of integral\ membrane proteins. Other transporter proteins from a variety of sources also belong\ to this family.

\ \ transporter activity ; GO:0005215 membrane ; GO:0016020 transport ; GO:0006810 19761 IPR001041 The ferredoxins are iron-sulfur proteins that transfer electrons in a widevariety of metabolic reactions. They have a cofactor which binds a 2FE-2S\ cluster. Ferredoxins can be divided into several subgroups depending upon the\ physiological nature of the iron-sulfur cluster(s) and according to sequence\ similarities.\ \ electron transporter activity ; GO:0005489 \N electron transport ; GO:0006118 19762 IPR001042 Ty are yeast transposons. A 5.7kb transcript codes for p3 a fusion protein ofTYA and TYB. The TYA protein is analogous to the gag protein of retroviruses.\ TYA is cleaved to form 46kd protein which can form mature virion like particles\ [MEDLINE:97404699].\ \ \N \N \N 19760 IPR001040 Eukaryotic translation initiation factor 4E (eIF-4E) [MEDLINE:92127580] is a protein thatbinds to the cap structure of eukaryotic cellular mRNAs. eIF-4E recognizes and binds\ the 7-methylguanosine-containing (m7Gppp) cap during an early step in the initiation\ of protein synthesis and facilitates ribosome binding to a mRNA by inducing the unwinding\ of its secondary structures. A tryptophan in the central part of the sequence of human\ eIF-4E seems to be implicated in cap-binding [MEDLINE:91192132].\ \ translation initiation factor activity ; GO:0003743 cytoplasm ; GO:0005737 translational initiation ; GO:0006413 19758 IPR001038 Equine herpesvirus glycoprotein 13 (EHV-1 gp13) has the characteristicfeatures of a membrane-spanning protein: an N-terminal signal sequence;\ a hydrophobic membrane anchor region; a charged C-terminal cytoplasmic tail;\ and an exterior domain with nine potential N-glycosylation sites [MEDLINE:88275055].\ EHV-1 gp13 is the structural homologue of the gC-like glycoproteins of Herpes\ simplex virus (gC-1 and gC-2), pseudorabies Herpesvirus (gIII) and Varicella-zoster\ virus (gp66).\ \ \N \N \N 19759 IPR001039

Major Histocompatibility Complex (MHC) superfamily molecules are hetero- dimeric cell surface receptors that function to present antigen peptide\ fragments to T cells responsible for cell-mediated immune responses. MHC\ molecules can be subdivided into two groups on the basis of structure and\ function: class I molecules present intracellular antigen peptide fragments \ (~10 amino acids) on the surface of the host cells to cytotoxic T cells; \ class II molecules present exogenously derived antigenic peptides (~15 amino\ acids) to helper T cells. MHC class I and II molecules are assembled and\ loaded with their peptide ligands via different mechanisms. However, both\ present T cells with antigen peptides for recognition and subsequent host\ cell degradation.

\ Class I molecules are expressed on the surface of all somatic nucleated\ cells, with the exception of neurons. Cytotoxic T cell receptors (TCR) are\ able to recognise peptides, but only when they are complexed with MHC I\ molecules on the surface of the host cell. Antigen peptide fragments are\ generated within the cytosol of the host cell by the proteosome. These\ peptides are then translocated from the cytoplasm to the rough endoplasmic\ reticulum (RER) by the transporter of antigenic peptide (TAP) protein.\ Inside the RER, some of these peptides bind to the MHC class I protein,\ resulting in a change in conformation [MEDLINE:98153185]. This allows for the association \ of -2 microglobulin, without which the MHC molecule would destabilise\ and not be expressed on the cell surface.

\ MHC class I molecules comprise two chains: the chain consists\ of three extracellular domains ( 1-3, -1 being closest to the \ N-terminus and -3 closest to the membrane), a transmembrane region \ and a C-terminal cytoplasmic tail; the soluble extracellular -2\ microglobulin chain associates primarily with the -3 domain and is\ necessary for MHC stability. A deep groove exists between the -1 and -2 domains, which binds peptides in order to display them to the TCR.

\ The crystal structure of human major histocompatibility complex class I B\ allele HLA B*3501 complexed with the 8-mer peptide epitope HIV1 Nef 75-82 \ (VPLRPMTY) has been determined to 2.0A resolution [MEDLINE:96209671]. The structure \ exhibits a novel conformation of the peptide within the binding groove.\ Comparison with crystal structures of closely related alleles reveals\ significant differences at both N- and C-termini, indicating a strong \ interdependence between the HLA class I molecule and the bound peptide [MEDLINE:99096952].

\ \ \N membrane ; GO:0016020 immune response ; GO:0006955 19757 IPR001037

Integrase comprises three domains capable of folding independently and whose three-dimensional structures are known. However, the manner in which the N-terminal, catalytic core, and C-terminal domains interact in the holoenzyme remains obscure. Numerous studies indicate that the enzyme functions as a multimer, minimally a dimer. The integrase proteins from HIV-1 and ASV have been studied most carefully with respect to the structural basis of catalysis. Although the active site of ASV integrase does not undergo significant conformational changes on binding the required metal cofactor, that of HIV-1 IN does. This active site-mediated conformational change in HIV-1 reorganizes the catalytic core and C-terminal domains and appears to promote an interaction that is favourable for catalysis [MEDLINE:99312236].

HIV integrase catalyses the incorporation of virally derived DNA into the human genome. This unique step in the virus life cycle provides a variety of points for intervention and hence is an attractive target for the development of new therapeutics for the treatment of AIDS [MEDLINE:97304688]. Substrate recognition by the retroviral integrase enzyme is critical for retroviral integration. To catalyze this recombination event, integrase must recognize and act on two types of substrates, viral DNA and host DNA, yet the necessary interactions exhibit markedly different degrees of specificity [MEDLINE:99312237].

\ \ integrase activity ; GO:0008907 \N \N 19755 IPR001035 Energy to power the rotation of bacterial flagella can be derived from the proton or sodium transmembrane potential.\ MotY protein, a component of the sodium-type flagellar motor, may play the role of\ a stator in the sodium flagellar motor, stabilising the force-generating unit through\ direct interaction with the cell wall [MEDLINE:94292449]. Although, until now, sequence\ analysis has failed to reveal significant similarity to known motility components, the\ MotY C terminus is similar to a number of outer membrane proteins known to interact with\ peptidoglycan, including OmpA and peptidoglycan-associated lipoproteins [MEDLINE:94292449].\ \ motor activity ; GO:0003774 flagellum (sensu Bacteria) ; GO:0009288 ciliary/flagellar motility ; GO:0001539 19756 IPR001036 The E.coli acrA and acrB genes encode a multi-drug efflux system that isbelieved to protect the bacterium against hydrophobic inhibitors [MEDLINE:94012493].\ Members of this family are integral membrane proteins some of which are involved in drug resistance.\

Proteins which belong to this family include the P.aeruginosa multidrug resistance\ protein mexB, A.eutrophus cation efflux system protein czcA, and various R.meliloti nodulation proteins.

\ \ \N \N \N 19753 IPR001033 Catenins associate with the cytoplasmic domains of a variety of cadherins [MEDLINE:92021009] producing a complex that links to the actin filament network. This\ association appears to be indispensable for tight cell-cell adhesion. Dysfunction of\ the complex causes dissociation of cancer cells from primary tumours, possibly\ contributing to cancer invasion and metastasis [MEDLINE:93312345].\

Three different forms of catenin (designated , and gamma) comprise the\ cytoplasmic domain of the cadherin cell-cell adhesion complex [MEDLINE:95032048].\ Alpha-catenins are evolutionarily related to vinculin IPR006077.

\ \ \N \N \N 19754 IPR001034 Many bacterial transcription regulatory proteins bind DNA via a helix-turn-helix (HTH) motif. These proteins are very diverse, but for convenience may be grouped into\ subfamilies on the basis of sequence similarity. The deoR family groups together a range of proteins, including lacR, deor, fucR and gutR. Within this family, the\ HTH motif is situated towards the N-terminus [MEDLINE:89231635], [MEDLINE:93015655], [MEDLINE:89315234].\ \ transcription factor activity ; GO:0003700 intracellular ; GO:0005622 regulation of transcription, DNA-dependent ; GO:0006355 19751 IPR001031 Thioesterase domains often occur integrated in or associated with peptide synthetaseswhich are involved in the non-ribosomal synthesis of peptide antibiotics [MEDLINE:98228193].\ Thioesterases are required for the addition of the last amino acid to the peptide\ antibiotic, thereby forming a cyclic antibiotic. Next to the operons encoding these\ enzymes, in almost all cases, are genes that encode proteins that have similarity to\ the type II fatty acid thioesterases of vertebrates.\ \ hydrolase activity, acting on ester bonds ; GO:0016788 \N biosynthesis ; GO:0009058 19752 IPR001032 Leghaemoglobins are haem-proteins, first identified in root nodules ofleguminous plants: their physiological role involves fixation of\ atmospheric nitrogen, formed symbiotically in the nodules by the bacteria\ Rhizobium where they provide oxygen to the bacteroids [MEDLINE:75118996]. Related globins have now been identified in the roots of\ non-leguminous plants, where they have a role in respiratory metabolism in the\ root cells [MEDLINE:88122571].\

The structure of leghaemoglobins is similar to that of haemoglobins and myoglobins,\ although there is little sequence conservation. The proteins are largely -helical, eight helices providing the scaffold for a well-defined haem-binding\ pocket. By contrast with the tetrameric mammalian globin assembly, the plant form\ is monomeric.

\ \ \N \N oxygen transport ; GO:0015671 19750 IPR001030 Synonym(s): Citrate hydro-lyase, Aconitase

Aconitase (aconitate hydratase) (EC: 4.2.1.3) is the enzyme from the\ tricarboxylic acid cycle that catalyzes the reversible, stereo-specific,\ isomerization of citrate to isocitrate via cis-aconitate in the tricarboxylic acid\ cycle, a non-redox active process [MEDLINE:90092136], [MEDLINE:97172692]. Aconitase, in\ its active form, contains a 4Fe-4S iron-sulfur cluster; three cysteine residues have\ been shown to be ligands of the 4Fe-4S cluster [MEDLINE:89264479]. Unlike the majority of\ iron-sulphur proteins that function as electron carriers, the Fe-S cluster of\ aconitase reacts directly with an enzyme substrate [MEDLINE:94202210].

In eukaryotes two isozymes of aconitase are known to exist: one found in the\ mitochondrial matrix and the other found in the cytoplasm. The aconitase family\ contains a variety of proteins which include: the iron-responsive element binding\ protein (IRE-BP)[MEDLINE:93349425]; -isopropylmalate isomerase, an enzyme catalysing\ the second step in the biosynthesis of leucine; and homoaconitase.

The aconitate hydratase, N-terminal domain is almost always found along with the aconitate hydratase, C-terminal domain IPR000573.

\ \ \N \N \N 19747 IPR001027 Human immunodeficiency virus (HIV) and equine infectious anemia virus (EIAV) are closely related lentiviruses that infect immune cells, but their pathogenesis differ. The coat polyprotein of equine infectious anemia virus (EIAV) contains gp90 and gp45 [MEDLINE:88306253].

A fluorescence polarization-based diagnostic assay for EIAV has been developed providing the basis of an improved commercial diagnostic assay for EIAV infection of horses. The most sensitive and specific peptide probe was a peptide corresponding to the immunodominant region of the EIAV transmembrane protein, gp45 [MEDLINE:20250997].

\ \ structural molecule activity ; GO:0005198 viral envelope ; GO:0019031 \N 19749 IPR001029 Flagellin is the subunit which polymerizes to form the filaments ofbacterial flagella. Two regions, one at the N terminus IPR001492 and the other,\ this one, at the C terminus seem always to occur \ together [MEDLINE:90272638].\ \ structural molecule activity ; GO:0005198 flagellum (sensu Bacteria) ; GO:0009288 ciliary/flagellar motility ; GO:0001539 19748 IPR001028 Phosphatidylinositol-glycan-specific phospholipase D is an extracellularamphiphilic glycoprotein [MEDLINE:92299002], [MEDLINE:91205309]. It hydrolyses the\ inositol phosphate linkage in proteins anchored by phosphatidylinositol glycans,\ releasing these proteins from the membrane.\ The enzyme catalyses the reaction: glycoprotein\

\
phosphatidylinositol + H₂O = phosphatidate + glycoprotein inositol\

\ \ glycoprotein phospholipase D activity ; GO:0004621 extracellular ; GO:0005576 \N 19745 IPR001025

The BAH (bromo-adjacent homology) family contains proteins such as eukaryotic DNA (cytosine-5) methyltransferases IPR001525.

\ \ DNA binding activity ; GO:0003677 \N \N 19746 IPR001026

The ENTH (Epsin N-terminal homology) domain is approximately 150 amino acids in length and is always found located at the N-termini of proteins. The domain forms a compact globular structure, composed of 9 -helices connected by loops of varying length. The general topology is determined by three helical hairpins that are stacked consecutively with a right hand twist. [MEDLINE:21909368]. An N-terminal helix folds back, forming a deep basic groove thatforms the binding pocket for the Ins(1,4,5)P3 ligand [MEDLINE:22239932]. The ligand is coordinated by residues from surrounding -helices and all three phosphates are multiply coordinated. The coordination of Ins(1,4,5)P3 suggests that ENTH is specific for particular head groups.

Proteins containing this domain have been found to bind PtdIns(4,5)P2 and PtdIns(1,4,5)P3 suggesting that the domain may be a membrane interacting module. The main function of proteins containing this domain appears to be to act as accessory clathrin adaptors in endocytosis, Epsin is able to recruit and promote clathrin polymerization on\ a lipid monolayer, but may have additional roles in signalling and actin regulation [MEDLINE:99156083]. Epsin causes a strong degree of membrane curvature and\ tubulation, even fragmentation of membranes with a high PtdIns(4,5)P2 content. Epsin binding to\ membranes facilitates their deformation by insertion of the N-terminal helix into the outer leaflet of the bilayer, pushing the head groups\ apart. This would reduce the energy needed to curve the membrane into a vesicle, making it easier for the clathrin cage to\ fix and stabilize the curved membrane. This points to a pioneering role for epsin in vesicle\ budding as it provides both a driving force and a link between membrane invagination and clathrin polymerization.

\ \ \N \N \N 19744 IPR001024 This domain, the PLAT (Polycystin-1, Lipoxygenase, Alpha-Toxin) domain or\ LH2 (Lipoxygenase homology) domain, is found in a variety of membrane or\ lipid associated proteins. It is present in lipogenases, enzymes involved at various steps in the biosynthesis of leukotrienes with iron as the cofactor. The known structure\ of pancreatic lipase shows this domain binds to procolipase\ that mediates membrane association.\ This domain may mediate membrane\ attachment via other protein binding partners. The\ structure of this domain is known for many members of the\ family and is composed of a

sandwich.\ \ \N \N \N 19741 IPR001021

\ \ \

The bacterial ribosomal protein L25 is an RNA binding protein. Ribosomal protein L25\ shows homology to general stress proteins and glutaminyl-tRNA synthetases [MEDLINE:99016057].

\ \ \ 5S RNA binding activity ; GO:0008097\ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 19739 IPR001019 Guanine nucleotide binding proteins (G-proteins) are a family of membrane-associated proteins that couple extracellularly-activated integral-membranereceptors to intracellular effectors, such as ion channels and enzymes that\ vary the concentration of second messenger molecules [MEDLINE:91354032], [MEDLINE:91227903].\ G-proteins are composed of 3 subunits (

and gamma) which, in the\ resting state, associate as a trimer at the inner face of the plasma membrane.\

This family consists of the G protein subunit which binds guanyl nucleotide\ and is a weak GTPase. Seventeen distinct types of subunit have been identified\ in mammals. These fall into four main groups on the basis of both sequence\ similarity and function: -s, -q, -i and -12 [MEDLINE:91227903].

\ \ signal transducer activity ; GO:0004871 \N G-protein coupled receptor protein signaling pathway ; GO:0007186 19742 IPR001022 The movement protein of tobamoviruses is necessary for the initial cell-to-cellmovement during the early stages of a viral infection. This movement is active,\ and involves the interaction of the movement protein with the plasmodesmata.\ The movement protein possesses the ability to bind to RNA to achieve its\ role [MEDLINE:92188524].\

The N terminus contains two particularly well-conserved regions, substitutions\ in one of these results in temperature-sensitive cell-to-cell movement. The C terminus contains three sub-regions characterised by the distributions of charged\ amino acid residues [MEDLINE:89073773].

\ \ nucleic acid binding activity ; GO:0003676 \N transport ; GO:0006810 19743 IPR001023 A family of heat shock proteins, the hsp70 proteins have an average molecular weight of 70 kDa [MEDLINE:90073608], [MEDLINE:87002476], [MEDLINE:88189333]. In most species,there are many proteins that belong to the hsp70 family. Some of these are only\ expressed under stress conditions (strictly inducible), while some are present in cells\ under normal growth conditions and are not heat-inducible (constitutive or cognate) [MEDLINE:90348961], [MEDLINE:88297155] . Hsp70 proteins can be found in different cellular compartments\ (nuclear, cytosolic, mitochondrial, endoplasmic reticulum, etc.).\

Little is known of the function of hsp70 proteins. Some evidence suggests that\ the constitutive members have a role in the disassembly of clathrin cages [MEDLINE:90348961], and\ may also participate in the post-translational transmembrane targetting of proteins to cellular\ organelles. No specific activities or associations have been found for the inducible members\ [MEDLINE:90348961], although it has been suggested that they may accept incoming precursor proteins,\ keep them unfolded, then pass them on to the hsp60/hsp10 (cpn60/cpn10) complex for folding and\ assembly.

\ \ \N \N \N 19740 IPR001020

HPr is a small cytoplasmic protein IPR000032.In some bacteria HPr is a domain in a larger protein that includes a EIII(Fru)\ (IIA) domain and in some cases also a EI domain IPR000032/>. HPr is a\ component of the phosphoenolpyruvate-dependent sugar phosphotransferase\ system (PTS) major carbohydrate transport system in bacteria [MEDLINE:94066914], [MEDLINE:90328751].

The conserved histidine in the N-terminus of HPr serves as an acceptor for\ the phosphoryl group of EI. In the central part of HPr there is a conserved serine\ IPR002114 only, is phosphorylated by an\ ATP-dependent protein kinase; a process which probably play a regulatory role in sugar\ transport.

\ \ sugar porter activity ; GO:0005351 \N phosphoenolpyruvate-dependent sugar phosphotransferase system ; GO:0009401 19736 IPR001016 Paramyxoviridae, like other non-segmented negative strand RNA viruses, have an RNA-dependent RNA polymerase composed of two subunits, a large protein L and a phosphoprotein P. The L protein confers the RNA polymerase activity on the complex while the P protein acts as a transcription factor [MEDLINE:97368161].\ RNA-directed RNA polymerase activity ; GO:0003968 \N transcription ; GO:0006350 19737 IPR001017 This family includes a number of dehydrogenases all of which use thiaminepyrophosphate as a cofactor and are members of a multienzyme complex.\ Pyruvate dehydrogenase (EC: 1.2.4.1), a component of the multienzyme\ pyruvate dehydrogenase complex; 2-oxoglutarate dehydrogenase (EC: 1.2.4.2),\ a component of the multienzyme 2-oxoglutarate dehydrogenase which contains\ multiple copies of three enzymatic components: 2-oxoglutarate dehydrogenase (E1),\ dihydrolipoamide succinyltransferase (E2) and lipoamide dehydrogenase (E3);\ and 2-oxoisovalerate dehydrogenase (EC: 1.2.4.4), a component of the multienzyme\ branched-chain

-keto dehydrogenase complex all belong to this family.\ \ oxidoreductase activity, acting on the aldehyde or oxo group of donors, disulfide as acceptor ; GO:0016624 \N metabolism ; GO:0008152 19738 IPR001018 Synonym(s): Penicillinase, Cephalosporinase \

Beta-lactamases (EC: 3.5.2.6) are enzymes which catalyze the hydrolysis\ of an amide bond in the -lactam ring of antibiotics belonging to the\ penicillin/cephalosporin family IPR001279. The class-B enzymes are zinc\ containing proteins whilst class -A, C and D enzymes are serine hydrolases.\ Class-B -lactamases have been described in several Gram-negative\ bacterial species; they seem to share the characteristic of being able to\ hydrolyze carbapenem compounds, new -lactam antibiotics of great\ therapeutic potential.

The conserved regions in the sequence of known class-B -lactamases are\ centered on residues known to be involved in binding the zinc ion essential\ for the enzyme's catalytic activity [MEDLINE:94190056], [MEDLINE:96434328].

\ \ beta-lactamase activity ; GO:0008800 \N antibiotic catabolism ; GO:0017001 19735 IPR001015 Synonym(s): Protoheme ferro-lyase, Iron chelatase, etc.

Ferrochelatase (EC: 4.99.1.1) catalyzes the last step in heme biosynthesis: the chelation of a ferrous ion to proto-porphyrin IX, to form protoheme [MEDLINE:90237021], [MEDLINE:91126092]. In eukaryotic cells, it binds to the mitochondrial inner membrane with its active site on the matrix side of the membrane.

The X-ray structure of Bacillus subtilis and human ferrochelatase have been solved [MEDLINE:98046098], [MEDLINE:21109797].\ The human enzyme exists as a homodimer. Each\ subunit contains one [Fe2S2] cluster. The monomer is folded into two\ similar domains, each with a four-stranded parallel -sheet flanked by an -helix in a -- motif that is\ reminiscent of the fold found in the periplasmic binding\ proteins. The topological similarity between the domains suggests that\ they have arisen from a gene duplication event. However,\ significant differences exist between the two domains, including an\ N-terminal section (residues 80-130) that forms part of the\ active site pocket, and a C-terminal extension (residues 390-423) that\ is involved in coordination of the [Fe2S2]cluster and in\ stabilization of the homodimer. The [Fe2S2] cluster ligands are Cys196,\ Cys403, Cys406 and Cys411. The experiments with\ Co(II) binding show that His230 and Asp383 are part of the enzyme active\ site [MEDLINE:21109797].

Ferrochelatase seems to have a structurally conserved core region that is common to the enzyme from bacteria, plants and mammals. Porphyrin binds in the identified cleft; this cleft also includes the metal-binding site of the enzyme. It is likely that the structure of the cleft region will have different conformations upon substrate binding and release [MEDLINE:98046098].

\ \ ferrochelatase activity ; GO:0004325 \N heme biosynthesis ; GO:0006783 19734 IPR001014

\ \ \

Ribosomal protein L23 is one of the proteins from the large ribosomal subunit that binds to a specific region on either the 23S or 26S rRNA. This family includes eukaryotic L25 and bacterial and eukaryotic L23.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 19733 IPR001013

NK3 receptors are distributed widely throughout the rat CNS, and are found\ in high levels in cerebral cortex, basal ganglia and dorsal horn of the\ spinal chord. They have limited distribution in peripheral tissues, and\ are found in ganglia (e.g., myenteric plexus), kidney, and in a limited\ number of smooth muscles (e.g., rat portal vein) . NK3 receptors\ activate the phosphoinositide pathway through a pertussis-toxin-insensitive\ G-protein, probably of the Gq/G11 class PUB00005903.

\ \ tachykinin receptor activity ; GO:0004995 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19729 IPR001009 Synonym(s): RNA nucleotidyltransferase (RNA-directed) \

The pattern describes the P2 subunit of influenza RNA polymerase (EC: 2.7.7.48),an enzyme which is composed of three subunits: P1 (or PB1), P2 (or PA), and P3 (or PB2). The P2 subunit in addition to the P1 subunit is required for viral RNA synthesis in replication of the influenza virus genome [MEDLINE:96323162].

\ \ RNA-directed RNA polymerase activity ; GO:0003968 \N transcription ; GO:0006350 19730 IPR001010 Thionins are small, basic plant proteins, 45 to 50 amino acids in length, which include three or four conserved disulphide linkages. The proteins are toxic to animal cells, presumably attacking the cell membrane and rendering it permeable: this results in the inhibition of sugar uptake and allows potassium and phosphate ions, proteins, and nucleotides to leak from cells [MEDLINE:85173323]. Thionins are mainly found in seeds where they may act as a defence against consumption by animals. A barley leaf thionin that is highly toxic to plant pathogens and is involved in the mechanism of plant defence against microbial infections has also been identified [MEDLINE:92322947]. The hydrophobic protein crambin from the Abyssinian cabbage (Crambe abyssinica) is also a member of the thionin family [MEDLINE:85173323].\ toxin activity ; GO:0015070 \N defense response ; GO:0006952 19731 IPR001011 Class A bacterial acid phosphatases (EC: 3.1.3.2) are a group of related proteins that catalyse the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate [MEDLINE:92041557], [MEDLINE:94362901]. This reaction is non-specific and occurs in the periplasm. The enzyme is found as a homotetramer in Proteus morganii\ \ \ [MEDLINE:92041557] and possibly as a homodimer in Salmonella typhimurium, where it is regulated by a 2-component regulatory system formed by the products of the phoP and phoQ genes [MEDLINE:94362901].\ \ acid phosphatase activity ; GO:0003993 periplasmic space (sensu Gram-negative Bacteria) ; GO:0030288 \N 19732 IPR001012 The UBX domain is found in ubiquitin-regulatory proteins, which are members of the ubiquitination pathway, as well as a number of other proteins including FAF-1 (FAS-associated factor 1), the human Rep-8 reproduction protein and several hypothetical proteins from yeast. The function of the UBX domain is not known although the fragment of avian FAF-1 containing the UBX domain causes apoptosis of transfected cells.\ \N \N \N 19728 IPR001008

\ \

Mollusc MTs are 64-75 residue proteins. They usually contain 18-23 Cys, at least 13 of them are totally conserved. The protein sequence is divided into two structural domains. The Cys residues are arranged in C-X-C groups, and a C-X-X-C grouping is also observed. In particular, the consensus pattern C-x-C-x(3)-C-T-G-x(3)-C-x-C-x(3)-C-x-C-K has been shown to be diagnostic of family 2 metallothioneins. MTs locate at the C terminus of the sequence. These proteins show more similarily to the vertebrate metallothioneins than to those from other invertebrate phyla [MEDLINE:89372898], and on this basis they are classified as class I metallothioneins. The protein is induced by cadmium and binds divalent cations of several transition elements, including cadmium, zinc and copper. Family 2 includes subfamilies: mo1, mo2, mog, mo, which hit the same entry, except the subfamily mog.

\ \ heavy metal binding activity ; GO:0005505 \N \N 19726 IPR001006 Synonym(s): Lysine hydroxylase, Lysyl hydroxylase, etc

Procollagen-lysine 5-dioxygenase (EC: 1.14.11.4) catalyzes the hydroxylation of lysine residues in X-Lys-Gly sequences in collagens. The resulting hydroxylysines serve as sites of attachment for carbohydrate units and are essential for the stability of the intermolecular collagen crosslinks. At least three isoforms are known in vertebrates.The enzyme requires iron, 2-oxoglutarate, oxygen and ascorbate for its activity.[MEDLINE:96199192]. Three residues, two histidine and an aspartate, are involved in the binding of the iron ion.

\ \ procollagen-lysine 5-dioxygenase activity ; GO:0008475 endoplasmic reticulum ; GO:0005783 \N 19727 IPR001007 The vWF domain is found in various plasma proteins:complement factors B, C2, CR3 and CR4; the integrins (I-domains); collagen \ types VI, VII, XII and XIV; and other extracellular proteins [MEDLINE:94018965], [MEDLINE:94194513], [MEDLINE:91323531]. Although the majority of VWA-containing proteins are extracellular, the most ancient ones present in all eukaryotes are all intracellular proteins involved in functions such as transcription, DNA repair, ribosomal and membrane transport and the proteasome. A common feature appears to be involvement in multiprotein complexes. Proteins\ that incorporate vWF domains participate in numerous biological events\ (e.g. cell adhesion, migration, homing, pattern formation, and signal\ transduction), involving interaction with a large array of ligands [MEDLINE:94018965]. A number of human diseases arise from mutations in VWA domains. Secondary structure prediction from 75 aligned vWF sequences has revealed a largely alternating sequence of

-helices and

-strands [MEDLINE:94194513].\ The domain is named after the von Willebrand factor (VWF) type C repeat which is found in multidomain protein/multifunctional proteins involved in maintaining homeostasis [MEDLINE:87213283], [MEDLINE:91323531]. For the von Willebrand factor the duplicated VWFC domain is thought to participate in oligomerization, but not in the initial dimerization step [MEDLINE:91177957]. The presence of this region in a number of other complex-forming proteins points to the possible involvment of the VWFC domain in complex formation.\ \ \N \N \N 19725 IPR001005 The retroviral oncogene v-myb, and its cellular counterpart c-myb, encode nuclear DNA-binding proteins. These belong to the SANT domain family that specifically recognize the sequence YAAC(G/T)G.[MEDLINE:89040179], [MEDLINE:97036933]. In myb, one of the most conserved regions consisting of three tandem repeats has been shown to be involved in DNA-binding [MEDLINE:88054969].\ DNA binding activity ; GO:0003677 nucleus ; GO:0005634 \N 19723 IPR001003 Describes the

-1 domain of the

chain of class II major histocompatibility complex (MHC) proteins. The major histocompatibility complex molecules are made of two chains. In class II PUB00002017, both the

and the

IPR000353 chains are composed of two extracellular domains: an Ig domain and this domain, a transmembrane region and a cytoplasmic tail.\ \N membrane ; GO:0016020 immune response ; GO:0006955 19724 IPR001004

The -1C receptor has not been detected in rat or bovine tissues by\ Northern analysis . Its expression is thus either very low, or highly\ specialised in tissue distribution . The receptor is coupled to the\ phosphoinositide pathway through a pertussis-toxin-insensitive G-protein,\ probably of the Gq/G11 class PUB00005869.

\ \ alpha1-adrenergic receptor activity ; GO:0004937 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19720 IPR001001 Describes the

chain of DNA polymerase III. This is a complex, multichain enzyme responsible for most of the replicative synthesis in bacteria. The

chain is required for initiation of replication from an RNA primer, nucleotide triphosphate (dNTP) residues being added to the 5'-end of the growing DNA chain.\ \ \ 3'-5' exonuclease activity ; GO:0008408\ DNA-directed DNA polymerase activity ; GO:0003887 \N DNA replication ; GO:0006260 19722 IPR001002 A number of plant and fungal proteins that bind N-acetylglucosamine (e.g. solanaceous lectins eg of tomato and potato; plant endochitinases; wound-induced proteins, hevein and win1/win2; and K.lactis killer toxin

subunit) contain this domain [MEDLINE:92099313]. The domain may occur singly or multiply and is thought to be involved in recognition or binding of chitin subunits [MEDLINE:91301161], [MEDLINE:92283806]. In chitinases, as well as in the potato wound-induced proteins, the 43-residue domain directly follows the signal sequence and is therefore at the N-terminus of the mature protein; in the killer toxin

subunit it is located in the central section of the protein.\ chitin binding activity ; GO:0008061 \N \N 19717 IPR000999 Prokaryotic ribonuclease III (EC: 3.1.26.3) (gene rnc) [MEDLINE:86039802] is an enzyme that digests double-stranded RNA. It is involved in the processing of ribosomal RNA precursors and of some mRNAs. \ RNase III is evolutionary related [MEDLINE:97439408] to the fission yeast pac1, a ribonuclease that probably\ inhibits mating and meiosis by degrading a specific mRNA required for sexual development; yeast \ ribonuclease III (gene RNT1), a dsRNA-specific nuclease that cleaves eukaryotic preribosomal RNA at \ various sites; Caenorhabditis elegans hypothetical protein F26E4.13; Paramecium bursaria chlorella virus \ 1 protein A464R; Synechocystis strain PCC 6803 hypothetical protein slr0346; fission yeast hypothetical \ protein SpAC8A4.08c, a protein with a N-terminal helicase domain and a C-terminal RNase III domain; and\ Caenorhabditis elegans hypothetical protein K12H4.8, a protein with the same structure as SpAC8A4.08c.\ \ ribonuclease III activity ; GO:0004525 \N RNA processing ; GO:0006396 19718 IPR001000

Glycoside hydrolase family 10 CAZY:GH_10\ comprises enzymes with a number of known activities; xylanase (EC: 3.2.1.8); endo-1,3--xylanase (EC: 3.2.1.32); cellobiohydrolase (EC: 3.2.1.91). These enzymes were formerly known as cellulase family F.

\ \

The microbial degradation of cellulose and xylans requires several types of\ enzymes such as endoglucanases (EC: 3.2.1.4), cellobiohydrolases (EC: 3.2.1.91)\ (exoglucanases), or xylanases (EC: 3.2.1.8) [MEDLINE:91069220], [MEDLINE:91359927]. Fungi and bacteria produces\ a spectrum of cellulolytic enzymes (cellulases) and xylanases which, on the\ basis of sequence similarities, can be classified into families. One of these\ families is known as the cellulase family F [MEDLINE:90034189] or as the glycosyl hydrolases\ family 10 [MEDLINE:92082464].

\ \ hydrolase activity, hydrolyzing O-glycosyl compounds ; GO:0004553 \N carbohydrate metabolism ; GO:0005975 19719 IPR001001 Describes the

chain of DNA polymerase III. This is a complex, multichain enzyme responsible for most of the replicative synthesis in bacteria. The

Group B carboxylesterases constitute a family of enzymes that includes proteins that catalyse the conversion of an acylcholine to a choline and a weak acid:\

\
Acylcholine + H₂O -> Choline + COO^-\

\ and those that catalyse the hydrolysis of acetylcholine to choline and acetate (acetylcholinesterases):\

\
Acetylcholine + H₂O -> Choline + Acetate\

class, \ with a 3-layer

sandwich architecture.

\ \ cholinesterase activity ; GO:0004104 \N \N 19716 IPR000998 A 170 amino acid domain, the so-called MAM domain, has been recognised in the extracellular region of functionally diverse proteins [MEDLINE:93255615]. These proteins have a modular, receptor-like architecture \ comprising a signal peptide, an N-terminal extracellular domain, a single transmembrane domain and an \ intracellular domain. Such proteins include meprin (a cell surface glycoprotein) [MEDLINE:92250517]; A5 \ antigen (a developmentally-regulated cell surface protein) [MEDLINE:91337458]; and receptor-like tyrosine \ protein phosphatase [MEDLINE:92008644]. The MAM domain is thought to have an adhesive function. It contains \ 4 conserved cysteine residues, which probably form disulphide bridges.\ \ \N membrane ; GO:0016020 \N 19714 IPR000996 Clathrin [MEDLINE:90328748], [MEDLINE:89072706] is the major coat-forming protein that encloses vesicles such as coated pits and forms cell surface patches involved in membrane traffic within eukaryotic cells. The \ clathrin coats (called triskelions) are composed of three heavy chains (180 kD) and three light chains \ (23 to 27 kD). The clathrin light chains [MEDLINE:91368356], which may help to properly orient the assembly\ and disassembly of the clathrin coats, bind non-covalently to the heavy chain, they also bind calcium \ and interact with the hsc70 uncoating ATPase. In higher eukaryotes two genes code for distinct but \ related light chains, LC(a) and LC(b). Each of the two genes can yield, by tissue-specific alternative \ splicing, two separate forms which differ by the insertion of a sequence of respectively thirty or \ eighteen residues. There is, in the N-terminal part of the clathrin light chains a domain of twenty one \ amino acid residues which is perfectly conserved in LC(a) and LC(b). In yeast there is a single light \ chain (gene CLC1) whose sequence is only distantly related to that of higher eukaryotes.\ \ \N \N \N 19712 IPR000994

Metalloproteases can be split into five clans, and futher sub-divided into families, on the basis of their metal binding residues.

Metalloprotease family M24 includes the enzymes, proline dipeptidase and methionine aminopeptidase.

\ \ \ metalloexopeptidase activity ; GO:0008235 \N proteolysis and peptidolysis ; GO:0006508 19713 IPR000995

\ \ \ muscarinic acetylcholine receptor activity ; GO:0004981 membrane ; GO:0016020 \N 19711 IPR000992 It has recently been shown [MEDLINE:93284106] that three yeast proteins, two of which are known to be induced by various stress conditions, are structurally related and are probably part of a larger family. These \ proteins include cold-shock inducible protein TIR1 (also known as serine-rich protein 1, SRP1), which is \ induced by glucose [MEDLINE:89011972] and cold shock [MEDLINE:95264920]; temperature-shock inducible protein 1 \ (SRP2) [MEDLINE:95264920]; seripauperins, which are closely related protein of about 13 kD (120 to 124 residues) \ and are generally encoded at the extremity of yeast chromosomes (eg. PAU1, PAU2, PAU3, PAU4, PAU5, PAU6, \ YBR301w, YGL261c, YGR294w, YHL046c, YIL176c, YIR041w and YKL224c) [MEDLINE:95011647]; and hypothetical proteins \ YIL011w, YJR150c and YJR151c. These proteins all seem to start with a putative signal sequence followed by \ a conserved domain of about 90 residues. In TIR1, TIR2, TIP1, YIL011w, YJR150c and YJR151c, this domain is \ followed by a repetitive serine and alanine rich region absent in the other members of this family.\ \ \N \N response to stress ; GO:0006950 19707 IPR000988

\ \ \

A number of eukaryotic and archaeabacterial ribosomal proteins can be grouped on the basis of sequence \ similarities. One of these families [MEDLINE:94324945] consists of mammalian ribosomal protein L24; yeast\ ribosomal protein L30A/B (Rp29) (YL21); Kluyveromyces lactis ribosomal protein L30; Arabidopsis thaliana \ ribosomal protein L24 homolog; Haloarcula marismortui ribosomal protein HL21/HL22; and Methanococcus jannaschii MJ1201. These proteins have 60 to 160 amino-acid residues.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 19708 IPR000989 Replication proteins (rep) are involved in plasmid replication. The Rep protein binds to the plasmid DNA and nicks it at the double strand origin (dso) of replication. The 3'-hydroxyl end created is \ extended by the host DNA replicase, and the 5' end is displaced during synthesis. At the end of one \ replication round, Rep introduces a second single stranded break at the dso and ligates the ssDNA\ extremities generating one double-stranded plasmid and one circular ssDNA form. Complementary strand \ synthesis of the circular ssDNA is usually initiated at the single-stranded origin by the host RNA\ polymerase [MEDLINE:98230329].\ \ DNA binding activity ; GO:0003677 extrachromosomal circular DNA ; GO:0005727 DNA replication ; GO:0006260 19709 IPR000990 Members of this family are integral membrane proteins which are involved in the formation of gap junctions [MEDLINE:98089040]. These proteins have been named the Innexins [MEDLINE:98441865]. This family includes \ the Drosophila proteins Ogre, which has prominent effects on the postembryonic development of the central \ nervous system, and shaking-B, which may be involved in the gustatory response; and the C. elegans \ proteins Unc-7 and Unc-9. Unc-7 is required for coordinated locomotion, and may be involved in the \ function of neuronal ion channels and in the nematodes response to anesthetics.\ \ \N \N \N 19710 IPR000991 Glutamine amidotransferase (GATase) (EC: 2.4.2.-) activity involves the removal of the ammonia group from a glutamate molecule and its subsequent transfer to a specific substrate, thus creating a new \ carbon-nitrogen group on the substrate. This activity is found in a range of biosynthetic enzymes, \ including glutamine amidotransferase, anthranilate synthase component II, p-aminobenzoate, and \ glutamine-dependent carbamoyl-transferase (CPSase). Glutamine amidotransferase (GATase) domains can occur \ either as single polypeptides, as in glutamine amidotransferases, or as domains in a much larger \ multifunctional synthase protein, such as CPSase. On the basis of sequence similarities two classes of \ GATase domains have been identified [MEDLINE:87250264], [MEDLINE:84264639], class-I (also known as trpG-type) and \ class-II (also known as purF-type). Class-I GATase domains have been found in the following enzymes, the \ second component of anthranilate synthase and 4-amino-4-deoxychorismate (ADC) synthase; CTP synthase; GMP \ synthase; glutamine-dependent carbamoyl-phosphate synthase; phosphoribosylformylglycinamidine synthase II; \ and the histidine amidotransferase hisH.\ \ enzyme activity ; GO:0003824 \N \N 19706 IPR000987

EDG-1 was the first member of the family to be cloned (from phorbol-ester\ differentiated human endothelial cells); its ligand, however, was unknown, so it was named endothelial differentiation gene (EDG) 1, reflecting its potential function [MEDLINE:90264425]. EDG-1 is expressed widely, with highest levels in the brain, heart, lung, liver and spleen. Moderate levels are also found in the thymus, kidney and muscle [MEDLINE:99132320]. Within these regions, EDG-1 is expressed in endothelial cells, vascular smooth muscle, fibroblasts, melanocytes and cells of epithelioid origin [MEDLINE:90264425]. Upon binding of S1P, the receptor can couple to Gi1, Gi2, Gi3, Go and Gz type G proteins, leading to inhibition of adenylyl cylase, phospholipase C activation and MAP kinase activation [MEDLINE:20583949], [MEDLINE:21164675].

\ \ lysosphingolipid and lysophosphatidic acid receptor activity ; GO:0001619 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19705 IPR000986

Neuropeptide Y (NPY) is one of the most abundant peptides in mammalian\ brain, inducing a variety of behavioural effects (e.g., stimulation of food\ intake, anxiety, facilitation of learning and memory, and regulation of the\ cardiovascular and neuroendocrine systems) . In the periphery, NPY\ stimulates vascular smooth muscle contraction and modulates hormone\ secretion. NPY has been implicated in the pathophysiology of hypertension,\ congestive heart failure, affective disorders and appetite regulation PUB00005893.

Several pharmacologically distinct neuropeptide Y receptors have been\ characterised, designated NPY Y1-Y6. NPY Y6 shares 60% sequence identity\ with the Y1 receptor. Its pharmacology resembles that of the Y1 receptor\ and is distinct from that described for Y2, Y3 and Y4 receptors PUB00005893. The\ receptor is expressed within discrete regions of the hypothalamus, including\ the suprachiasmatic nucleus, anterior hypothalamus, bed nucleus stria\ terminalis, and the ventromedial nucleus, with no localisation apparent\ elsewhere in the brain [MEDLINE:96279200].

\ \ neuropeptide Y receptor activity ; GO:0004983 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19704 IPR000985 Legume lectins are one of the largest lectin families with more than 70 lectinsreported. Leguminous plant lectins resemble each other in their physicochemical properties although they differ in their carbohydrate specificities. They consist of two or four subunits with relative molecular mass of 30 kDa and each subunit has one carbohydrate-binding site. The interaction with sugars requires tightly bound calcium and manganese ions. The structural similarities of these lectins are reported by the primary structural analyses and X-ray crystallographic studies. X-ray studies have shown that the folding of the polypeptide chains in the region of the carbohydrate-binding sites is also similar, despite differences in the primary sequences. The carbohydrate-binding sites of these lectins consist of two conserved amino acids on

The exact function of legume lectins \ is not known but they may be involved in the attachment of nitrogen-fixing bacteria to legumes and \ in the protection against pathogens.

Some legume lectins are proteolytically processed to produce two chains, (which corresponds to \ the N-terminal) (IPR001220 (jack bean) is exceptional \ in that the two chains are transposed and ligated (by formation of a new peptide bond). The N-terminus \ of mature conA thus corresponds to that of the chain and the C-terminus to the chain.

\ \ \N \N \N 19703 IPR000984

\ \ G-protein coupled receptor activity, unknown ligand ; GO:0016526 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19700 IPR000981 Oxytocin and vasopressin are nine-residue, structurally and functionally related neurohypophysial peptide hormones. Oxytocin mediates contraction of the smooth muscle of the uterus and mammary gland, while \ vasopressin has antidiuretic action on the kidney, and mediates vasoconstriction of the peripheral vessels \ [MEDLINE:89150313]. In common with most active peptides, both hormones are synthesised as larger protein \ precursors that are enzymatically converted to their mature forms. Members of this family are found in birds,\ fish, reptiles and amphibians (mesotocin, isotocin, valitocin, glumitocin, aspargtocin, vasotocin, seritocin, \ asvatocin, phasvatocin), in worms (annetocin), octopi (cephalotocin), locust (locupressin or neuropeptide\ F1/F2) and in molluscs (conopressins G and S) [MEDLINE:96059313].\ \ neurohypophyseal hormone activity ; GO:0005185 extracellular ; GO:0005576 \N 19701 IPR000982 The matrix protein plays a crucial role in virus assembly, and interacts with the RNP complex as wellas with the viral membrane. It is found in Morbillivirus and paramyxovirus, pneumovirus.\ \ structural molecule activity ; GO:0005198 \N viral assembly ; GO:0019068 19702 IPR000983 The general (type II) secretion pathway (GSP) within Gram-negative bacteria is a signal sequence-dependent process responsible for protein export [MEDLINE:93174466], [MEDLINE:95099573], [MEDLINE:92276315]. The process has two stages, \ exoproteins are first translocated across the inner membrane by the general signal-dependent export pathway \ (GEP), and then across the outer membrane by a species-specific accessory mechanism. Several proteins are \ involved in the GSP, one of these is termed general secretion pathway protein G (GSPG). This protein shares \ several sequence similarities with bacterial fimbrial protein, or pilin, the major structural protein of \ pili [MEDLINE:94012544], [MEDLINE:95204361]. Pili are polar flexible filamentous adhesions ~2500 nm in length, and \ diameter ~5.4 nm. Fimbrial and GSPG proteins share the following characteristics; a methylated, hydrophobic \ N-terminal residue; a hydrophobic leader peptide of 5-10 residues, terminating with glycine; glutamate as \ the fifth residue of the mature sequence; and a highly hydrophobic N-terminus.\ \ protein transporter activity ; GO:0008565 type II protein secretion system complex ; GO:0015627 type II protein (Sec) secretion system ; GO:0015628 19699 IPR000981 Oxytocin and vasopressin are nine-residue, structurally and functionally related neurohypophysial peptide hormones. Oxytocin mediates contraction of the smooth muscle of the uterus and mammary gland, while \ vasopressin has antidiuretic action on the kidney, and mediates vasoconstriction of the peripheral vessels \ [MEDLINE:89150313]. In common with most active peptides, both hormones are synthesised as larger protein \ precursors that are enzymatically converted to their mature forms. Members of this family are found in birds,\ fish, reptiles and amphibians (mesotocin, isotocin, valitocin, glumitocin, aspargtocin, vasotocin, seritocin, \ asvatocin, phasvatocin), in worms (annetocin), octopi (cephalotocin), locust (locupressin or neuropeptide\ F1/F2) and in molluscs (conopressins G and S) [MEDLINE:96059313].\ \ neurohypophyseal hormone activity ; GO:0005185 extracellular ; GO:0005576 \N 19697 IPR000979 The following uncharacterized proteins have been shown to share regions of similarities; Escherichia coli hypothetical protein yfcE; Bacillus subtilis hypothetical protein ysnB; Mycoplasma genitalium and pneumoniae \ hypothetical protein MG207; and Methanococcus jannaschii hypothetical proteins MJ0623 and MJ0936. These are \ hydrophilic proteins of about 20 kD.\ \ molecular_function unknown ; GO:0005554 \N \N 19698 IPR000980

The Src homology 2 (SH2) domain is a protein domain of about 100 amino-acid residues first identified as a conserved sequence region between the oncoproteins Src and Fps [MEDLINE:87089798]. Similar sequences were later \ found in many other intracellular signal-transducing proteins [MEDLINE:92316188]. SH2 domains function as \ regulatory modules of intracellular signalling cascades by interacting with high affinity to \ phosphotyrosine-containing target peptides in a sequence-specific, SH2 domains recognize between 3-6 residues C-terminal to the phosphorylated tyrosine in a fashion that differs from\ one SH2 domain to another, and strictly phosphorylation-dependent \ manner [MEDLINE:95189829], PUB00001025, PUB00001025, [MEDLINE:95157628]. They are found in a wide variety of protein \ contexts e.g., in association with catalytic domains of phospholipase Cy (PLCy) and the non-receptor protein \ tyrosine kinases; within structural proteins such as fodrin and tensin; and in a group of small adaptor \ molecules, i.e Crk and Nck. The domains are frequently found as repeats in a single protein \ sequence and will then often bind both mono- and di-phosphorylated substrates.

The structure of the SH2 domain belongs to the + class, its overall shape forming a \ compact flattened hemisphere. The core structural elements comprise a central hydrophobic anti-parallel -sheet, flanked by 2 short -helices. The loop between \ strands 2 and 3 provides many of the binding interactions with the phosphate group of its phosphopeptide \ ligand, and is hence designated the phosphate binding loop, the phosphorylated ligand binds perpendicular to the -sheet and typically interacts with the phosphate binding loop and a hydrophobic binding pocket that interacts with a pY+3 side chain. The N- and C-termini of the domain are close together in space and on the opposite face from the phosphopeptide binding surface and it has been speculated that this has facilitated their integration into surface-exposed regions of host proteins [MEDLINE:21909367].

\ \ \N \N intracellular signaling cascade ; GO:0007242 19696 IPR000978 Adenoviruses are responsible for diseases such as pneumonia, cystitis, conjunctivitis and diarrhoea, all of which can be fatal to patients who are immunocompromised [MEDLINE:95219386]. Viral infection commences with \ recognition of host cell receptors by means of specialised proteins on viral surfaces. Specific attachment \ of adenovirus is achieved through interactions between host-cell receptors and the adenovirus fiber protein \ and is mediated by the globular carboxy-terminal domain of the adenovirus fiber protein, termed the \ carboxy-terminal knob domain.\ \ \N \N cell recognition ; GO:0008037 19695 IPR000977

DNA ligase (polydeoxyribonucleotide synthase) is the enzyme that joins two DNA fragments by catalyzing the formation of an internucleotide ester bond between phosphate and deoxyribose. It is active during \ DNA replication, DNA repair and DNA recombination. There are two forms of DNA ligase, one requires ATP\ (EC: 6.5.1.1), the other NAD (EC: 6.5.1.2). Eukaryotic, archaebacterial, virus and phage DNA ligases are \ ATP-dependent. The first step in the ligation reaction is the formation of a covalent enzyme-AMP complex. The co-factor ATP is cleaved to pyrophosphate and AMP, with the AMP being covalently joined\ to a highly conserved lysine residue in the active site of the ligase. The activated AMP residue is then transferred to the 5'\ phosphate of the nick, before the nick is sealed by phosphodiester-bond formation and AMP elimination [MEDLINE:91110537],\ [MEDLINE:92359492].

\ \

Vertebrate cells encode three well-characterized DNA ligases - DNA ligases I, III and IV, all of which are related in structure and sequence. With the exception of the atypically small PBCV-1 viral enzyme,\ two regions of primary sequence are common to all members of the family. The catalytic region comprises six conserved\ sequence motifs (I, III, IIIa, IV, V-VI), motif I includes the lysine\ residue that is adenylated in the first step of the ligation reaction. The function of the second, less well conserved region is unknown. When folded, each protein comprises of two distinct sub-domains: a large amino-terminal sub-domain ('domain 1') and a\ smaller carboxy-terminal sub-domain ('domain 2'). The ATP-binding site of the enzyme lies in the cleft between the two\ sub-domains. Domain 1 consists of two antiparallel sheets flanked by helices, whereas domain 2 consists of a five-stranded barrel and a single helix which form the oligonucleotide binding fold [MEDLINE:93065206], PUB00010654.

\ \ ATP binding activity ; GO:0005524 \N DNA recombination ; GO:0006310 19694 IPR000977

\ \

\ \ ATP binding activity ; GO:0005524 \N DNA recombination ; GO:0006310 19688 IPR000972 The octamer-binding protein is a transcription factor that binds specifically to the octamer motif (ATTTGCAT) of immunoglobulin promoters and activates these genes. There are two Ig octamer-binding \ proteins, designated NF-A1 and NF-A2. NF-A1 is found in all cell types, while NF-A2 is found only in \ lymphoid cells. The sequences of these proteins contain a region that correponds closely to the \ DNA-binding homeobox domains and POU transcription factors.\ \ transcription factor activity ; GO:0003700 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 19689 IPR000973 The CD4 glycoprotein on the surface of T cells participates in the immune response and is the receptor for HIV infection. The structure of a soluble fragment of CD4 has been determined to 2.3 A and reveals \ that the molecule has two intimately-associated immunoglobulin-like domains connected by a continuous

strand. Residues implicated in HIV recognition reside in domain D1. Domain D2 is distinguished by \ a variation in the

-strand topologies of antibody domains that results in a truncated

-barrel\ with a non-standard intra-sheet disulphide bond [MEDLINE:91061882], [MEDLINE:91061881]. The binding sites for \ monoclonal antibodies, class II major histocompatibility complex molecules, and HIV gp120 can be mapped \ on the molecular surface.\ \ \N membrane ; GO:0016020 immune response ; GO:0006955 19690 IPR000974

Glycoside hydrolase family 22 CAZY:GH_22) and -lactalbumins. Asp and/or the carbonyl oxygen of the C-2 acetamido group \ of the substrate acts as the catalytic nucleophile/base.

Lysozyme is a muramidase that hydrolyses -1,4-links between N-acetyl-\ muramic acid and N-acetyl-D-glucosamine in the peptidoglycan of bacterial \ cell walls [MEDLINE:88320415], thus helping to fight invading bacteria. In this capacity,\ the enzyme is found in tears and saliva , but it has also been recruited\ for a digestive role in the true stomach (abomasum) of ruminants and \ colobine monkeys: here it probably degrades the cell walls of bacteria \ passing from the foregut, allowing the breakdown products to be digested by\ other stomach enzymes [MEDLINE:88065863], [MEDLINE:89291894]. The stomach form of lysozyme is endowed with \ special physiochemical properties that allow it to function in an acidic \ and protease-rich environment.

Lysozyme C is similar to -lactalbumin in terms of primary sequence and\ structure [MEDLINE:84185596], and both have probably evolved from a common ancestral \ protein. There is, however, no similarity in function, lactalbumin being \ involved in the formation of lactose and is essential for milk production. \ Another significant difference between the two enzymes is that while all \ lactalbumins have the ability to bind calcium, this property is restricted \ to only a few lysozymes [MEDLINE:88030086].

\ \ lysozyme activity ; GO:0003796 \N cell wall catabolism ; GO:0016998 19691 IPR000975 Interleukin-1 is a cytokine with a wide range of biological and physiological effects, including fever, prostaglandin synthesis (in e.g., fibroblasts, muscle and endothelial cells), T-lymphocyte activation, \ and interleukin 2 production PUB00002016. This family is a member of a superfamily that also contains\ the heparin binding growth factors (HBGF), the Kunitz-type soybean trypsin inhibitors (STI) and \ histactophilin. All have very similar structures, but although the interleukin-1 and HBGF families share \ some sequence similarity (about 25%), they show none at all to the STIs. \

The interleukin-1 family consists \ of 2 main classes, designated (IL1A) and (IL1B), as well as the more recently discovered \ interleukin 1 receptor antagonist (IL1RA). Sequence similarity is high within the IL1A and IL1B subfamilies \ (about 60-70%) but low between them (less than 30%). IL1As and IL1Bs are synthesised as larger precursors, \ which are processed to give mature carboxy fragments. IL1B requires this cleavage to become biologically \ active, but IL1A precursor is already active. Both IL1A and IL1B bind to the same IL1-specific receptor on \ the target cell, which is then internalised to initiate the relevant effects. IL1RA binds to the IL1 \ receptor, blocking the effects of IL1A and IL1B whilst eliciting no response of its own. From sequence \ comparisons it seems to have arisen by gene duplication before IL1 diverged into IL1A and IL1B PUB00002016. The crystal structures of IL1A and IL1B [MEDLINE:90099325] have been solved, \ they share the same 12-stranded -sheet structure as both the heparin binding growth factors \ and the Kunitz-type soybean trypsin inhibitors [MEDLINE:92148835]. The -sheets are arranged in 3 similar lobes \ around a central axis, 6 strands forming an anti-parallel -barrel. Several regions, especially the loop \ between strands 4 and 5, have been implicated in receptor binding.

\ \ interleukin-1 receptor ligand activity ; GO:0005149 extracellular ; GO:0005576 immune response ; GO:0006955 19687 IPR000971 Globins are heme-containing proteins involved in binding and/or transporting oxygen. They belong to a very large and well studied family which is widely distributed in many organisms. The major groups of globins are\ hemoglobins (Hb) and myoglobins (Mg) from vertebrates, invertebrate globins, leghemoglobins from plants,\ and flavohemoproteins from bacteria. Hb is the protein responsible for transporting oxygen from the lungs to \ other tissues, and is a tetramer of two

and two

chains. Most vertebrate species also express\ specific embryonic or fetal forms of hemoglobin where the

or the

chains are replaced by a chain \ with higher oxygen affinity, as for the gamma, delta, epsilon and zeta chains in mammals, for example.\ Mg is a monomeric protein responsible for oxygen storage in muscles. A wide variety of globins are found in\ invertebrates [MEDLINE:88333014]. Molluscs generally have one or two muscle globins which are either monomeric \ or dimeric, while insects, such as the midge Chironomus thummi, have a large set of extracellular globins. \ Nematodes and annelids have a variety of intracellular and extracellular globins, some of them are \ multi-domain polypeptides (from two up to nine-domain globins), and some produce large, disulfide-bonded \ aggregates. Leghemoglobins (Lg) from the root nodules of leguminous plants provides oxygen for bacteroids.\ Flavohemoproteins from bacteria (Escherichia coli hmpA) and fungi consist of two distinct domains, an \ N-terminal globin domain and a C-terminal FAD-containing reductase domain. In bacteria such as Vitreoscilla, \ the enzyme-associated globin is a single domain protein. All these globins seem to have evolved from a \ common ancestor.\ \ \N \N oxygen transport ; GO:0015671 19693 IPR000977

\ \

\ \ ATP binding activity ; GO:0005524 \N DNA recombination ; GO:0006310 19692 IPR000976 Wilm's tumour (WT) is an embryonal malignancy of the kidney, affecting around 1 in 10,000 infants. It occurs in both sporadic and hereditary forms. Inactivation of WT1 is one of the causes of Wilm's tumour. \ Defects in the WT1 gene are also associated with Denys-Drash Syndrome (DDS), which is characterised by \ typical nephropathy and genital abnormalities. The WT1 gene product shows similarity to the zinc fingers \ of the mammalian growth regulated EGR1 and EGR2 proteins [MEDLINE:93345769], [MEDLINE:91141522], [MEDLINE:90158822], [MEDLINE:92279213].\ \ transcription factor activity ; GO:0003700 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 19683 IPR000966

Metallothioneins (MT) are small proteins that bind heavy metals, such as zinc, copper, cadmium, and nickel. They have a high content of cysteine residues that bind the metal ions through clusters of thiolate bonds \ [MEDLINE:92140136], PUB00001490, PUB00001490 species, including sea urchins, fungi, insects and cyanobacteria. \ Class III MTs are atypical polypeptides composed of gamma-glutamylcysteinyl units. This original \ classification system has been found to be limited, in the sense that it does not allow clear differentiation \ of patterns of structural similarities, either between or within classes. Consequently, all class I and class \ I MTs (the proteinaceous sequences) have now been grouped into families of phylogenetically-related and thus \ alignable sequences.

Diptera (Drosophila, family 5) MTs are 40-43 residue proteins that contain 10 conserved \ cysteines arranged in five Cys-X-Cys groups. In particular, the consensus pattern \ C-G-x(2)-C-x-C-x(2)-Q-x(5)-C-x-C-x(2)-D-C-x-C has been found to be diagnostic of family 5 MTs. The protein \ is found primarily in the alimentary canal, and its induction is stimulated by ingestion of cadmium or copper \ [MEDLINE:85105016]. Mercury, silver and zinc induce the protein to a lesser extent. Family 5 includes subfamilies: d1, d2. Only one d2 is known until now. Subfamilies hit the same entry.

\ \ heavy metal binding activity ; GO:0005505 \N \N 19684 IPR000967 This domain is presumed to be a zinc binding domain. The following pattern describes the zinc finger:C-X(1-6)-H-X-C-X3-C(H/C)-X(3-4)-(H/C)-X(1-10)-C, where X can be any amino acid, and numbers in brackets\ indicate the number of residues. The two position can be either his or cys. This domain is found in the \ human transcriptional repressor NK-X1, a repressor of HLA-DRA transcription; the Drosophila shuttle craft \ protein, which plays an essential role during the late stages of embryonic neurogenesis; and a yeast \ hypothetical protein YNL023C.\ \ transcription factor activity ; GO:0003700 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 19685 IPR000968 Influenza virus belongs to the class of ssRNA negative-strand viruses. Nonstructural protein 2 (NS2) may play a role in promoting normal replication of the genomic RNAs by preventing the replication of\ short-length RNA species [MEDLINE:94157474]. NS1 and NS2 proteins are produced from the same gene by \ alternative splicing.\ \ \N \N \N 19686 IPR000969 Human structure-specific recognition protein, SSRP1, [MEDLINE:92196107] binds specifically to DNA modified withthe anti-cancer drug cisplatin. An 81 kD protein is predicted, containing several highly-charged domains \ and a stretch of 75 residues that share 47% identity with a portion of the high mobility group (HMG) protein \ HMG1. This HMG box probably constitutes the structure recognition element for cisplatin-modified DNA, the \ probable recognition motif being the local duplex unwinding and bending that occurs on formation of \ intra-strand cross-links [MEDLINE:92196107]. SSRP1 is the human homologue of a recently identified mouse protein \ that binds to recombination signal sequences [MEDLINE:91342655]. These sequences have been postulated to form \ stem-loop structures, further implicating local bends and unwinding in DNA as a recognition target for \ HMG-box proteins. A Drosophila melanogaster cDNA encoding an HMG-box-containing protein has also been \ isolated [MEDLINE:93342017], [MEDLINE:93241947]. This protein shares 50% sequence identity with human SSRP1. In vitro\ binding studies using Drosophila SSRP showed that the protein binds to single-stranded DNA and RNA, with \ highest affinity for nucleotides G and U. Comparison of the predicted amino acid sequences among SSRP family \ members reveals 48% identity, with structural conservation in the C-terminus of the HMG box, as well as \ domains of highly charged residues. The most highly conserved regions lie in the poorly understood N-terminus, \ suggesting that this portion of the protein is critical for its function [MEDLINE:93241947].\ \ DNA binding activity ; GO:0003677 nucleus ; GO:0005634 \N 19681 IPR000962 The dksA gene product suppresses the temperature-sensitive growth and filamentation of a dnaK deletion mutant of E. coli. Gene knockout [MEDLINE:90202727] and deletion [MEDLINE:94341577] experiments have shown the gene \ to be non-essential, mutations causing a mild sensitivity to UV light, but not affecting DNA recombination \ [MEDLINE:94341577]. The protein contains a C-terminal region thought to fold into a 4-cysteine zinc finger. \ Other proteins found to contain a similar domain include the traR gene product, present on the conjugative \ plasmid F\ \ \ \ [MEDLINE:94292442], and several hypothetical proteins from bacteria and bacteriophages.\ \ \N \N \N 19682 IPR000965 Gamma-glutamyl phosphate reductase (EC: 1.2.1.41) (GPR) is the enzyme that catalyzes the second step in the biosynthesis of proline from glutamate, the NADP-dependent reduction of L-glutamate 5-phosphate into \ L-glutamate 5-semialdehyde and phosphate. In eubacteria (gene proA) and yeast [MEDLINE:97051589] (gene PRO2), \ GPR is a monofunctional protein, while in plants and mammals, it is a bifunctional enzyme (P5CS) \ [MEDLINE:93028463] that consists of two domains, an N-terminal glutamate 5-kinase domain (EC: 2.7.2.11) and a \ C-terminal GPR domain.\ \ glutamate-5-semialdehyde dehydrogenase activity ; GO:0004350 \N proline biosynthesis ; GO:0006561 19679 IPR000960 Flavin-containing monooxygenases (FMOs) constitute a family of xenobiotic-metabolising enzymes [MEDLINE:94145088]. Using an NADPH cofactor and FAD prosthetic group, these microsomal proteins catalyse the oxygenation of \ nucleophilic nitrogen, sulphur, phosphorous and selenium atoms in a range of structurally diverse compounds. \ FMOs have been implicated in the metabolism of a number of pharmaceuticals, pesticides and toxicants. In man, \ lack of hepatic FMO-catalysed trimethylamine metabolism results in trimethylaminuria (fish odour syndrome).\ Five mammalian forms of FMO are now known and have been designated FMO1-FMO5 [MEDLINE:91286259], [MEDLINE:90202836],\ [MEDLINE:92179247], [MEDLINE:93038564], [MEDLINE:93252844]. This is a recent nomenclature based on comparison of amino acid \ sequences, and has been introduced in an attempt to eliminate confusion inherent in multiple, \ laboratory-specific designations and tissue-based classifications [MEDLINE:94145088]. Following the determination \ of the complete nucleotide sequence of S. cerevisiae\ \ \ \ [MEDLINE:94378003], a novel gene was found to encode a protein \ with similarity to mammalian monooygenases.\ \ monooxygenase activity ; GO:0004497 \N electron transport ; GO:0006118 19680 IPR000961 Protein kinases are responsible for the phosphorylation of proteins, potentially for regulating their activity. This domain is found in a large variety of protein kinases with different functions and \ dependencies. Protein kinase C, for example, is a calcium-activated, phospholipid-dependent serine- and \ threonine-specific enzyme. It is activated by diacylglycerol which, in turn, phosphorylates a range of\ cellular proteins. This domain is most often found associated with IPR000719.\ \ ATP binding activity ; GO:0005524 \N protein amino acid phosphorylation ; GO:0006468 19677 IPR000957 Sulfate-binding protein (gene sbp or sbpA) and thiosulfate-binding protein (gene cysP) are two structurally related periplasmic bacterial proteins which specifically bind sulfate and thiosulfate \ and are involved in the transport systems for these nutrients [MEDLINE:90264335], [MEDLINE:91210162]. There are \ two conserved regions in the protein, one located in the N-terminal region and the other in the central \ part of these proteins. The second pattern includes two adjacent amino acids (Ser-Gly) that, in sbp, \ are known to be essential for sulfate binding [MEDLINE:88245181].\ \ sulfate porter activity ; GO:0008271 periplasmic space (sensu Gram-negative Bacteria) ; GO:0030288 sulfate transport ; GO:0008272 19678 IPR000959

A subgroup of serine/threonine protein kinases, Polo or Polo-like kinases (IPR002290) play multiple roles during the cell cycle. Polo kinases are required at several key pointsthrough mitosis, starting from control of the G2/M transition through phosphorylation of Cdc25C and mitotic cyclins. Polo kinases are characterised by an amino terminal catalytic domain, and a carboxy terminal non-catalytic domain consisting of three blocks of conserved\ sequences known as polo boxes which form one single functional domain [MEDLINE:99116035]. The domain is named after its founding member encoded by the polo gene of Drosophila melanogaster\ \ \ \ [MEDLINE:92084090]. This domain of around 70 amino acids has been found in species ranging from yeast to mammals. Polo boxes appear to mediate interaction with multiple proteins through protein:protein interactions; some but not all of these proteins are substrates for the kinase domain of the molecule [MEDLINE:22502988].

The crystal structure of the polo domain of the murine protein, Sak, is dimeric,\ consisting of two -helices and two six-stranded -sheets [MEDLINE:22239887]. The topology of one polypeptide subunit of the\ dimer consists of, from its N- to C-terminus, an extended strand segment, five -strands, one -helix (A) and a\ C-terminal -strand. Beta-strands from one\ subunit form a contiguous antiparallel -sheet with -strands from the second subunit. The two -sheets pack with a\ crossing angle of 110�, orienting the hydrophobic surfaces\ inward and the hydrophilic surfaces outward. Helix A, which is\ colinear with -strand 6 of the same polypeptide, buries a large\ portion of the non-overlapping hydrophobic -sheet surfaces.\ Interactions involving helices A comprise a majority of the\ hydrophobic core structure and also the dimer interface.

Point mutations in the Polo box of the budding yeast Cdc5 protein abolish the ability of overexpressed Cdc5 to interact with the spindle poles and to organize cytokinetic structures [MEDLINE:20063188].

\ \ ATP binding activity ; GO:0005524 \N cell cycle ; GO:0007049 19672 IPR000949

The ELM2 (Egl-27 and MTA1 homology 2) domain is a small domain of unknown function. It is found in the MTA1 protein that is part of the NuRD complex [MEDLINE:99244701]. The domain is usually found to the N terminus of a myb-like DNA binding domain and a GATA binding domain. ELM2 , in some instances, is also found associated with the ARID DNA binding domain IPR001606. This suggests that ELM2 may also be involved in DNA binding, or perhaps is a protein-protein interaction domain.

\ \ \N \N \N 19673 IPR000951 Flavoprotein pyridine nucleotide cytochrome reductases [MEDLINE:92084635] (FPNCR) catalyse the interchange of reducing equivalents between one-electron carriers and the two-electron-carrying nicotinamide \ dinucleotides. The enzymes include ferredoxin:NADP+ reductases (FNR) [MEDLINE:94299474]; plant and fungal \ NAD(P)H:nitrate reductases [MEDLINE:92084635]; NADH:cytochrome B5 reductases; NADPH:P450 reductases; \ NADPH:sulfite reductases; nitric oxide synthases; phthalate dioxygenase reductase [MEDLINE:93088078]; and \ various other flavoproteins. Phthalate dioxygenase reductase (PDR) is a member of a family of\ FPNCR/[2Fe-2S] ferredoxin fusion proteins, found in flavobacteria, that participate in oxidative metabolism \ of a variety of substrates. Other family members are vanillate demethylase reductase [MEDLINE:89008117]; \ phenoxybenzoate dioxygenase; and pentachlorophenol 4-monooxygenase. All of contain a [2Fe-2S] ferredoxin \ domain fused to the C-terminus of an FPNCR domain. The direction of electron flow is from flavin to the \ [2Fe-2S] center. By contrast with most FPNCRs, PDR binds FMN instead of FAD. The 3D-structure of PDR has \ been solved [MEDLINE:93088078]. The overall fold of the FPNCR module is similar to that of ferredoxin:NADP+ \ reductase [MEDLINE:94299474]; the FMN-binding domain (N-terminal) has the topology of an anti-parallel

-barrel; and the NAD(P)-binding domain (C-terminal) has the topology of a classical pyridine \ dinucleotide-binding fold, a central parallel

-sheet flanked by 2 helices on each side.\ \ oxidoreductase activity ; GO:0016491 \N electron transport ; GO:0006118 19674 IPR000952 The following uncharacterized proteins have been shown to share regions of similarities; yeast chromosome II hypothetical protein YBR177c; yeast chromosome XIII hypothetical protein YMR210w; yeast chromosome XVI \ hypothetical protein YPL095c; Escherichia coli hypothetical protein yheT; human protein pHPS1-2; Drosophila \ protein anon-23D; Picea glauca (white spruce) late embryogenesis abundant protein EMB8; and Caenorhabditis \ elegans hypothetical protein C44C1.5. These are proteins of about 38 to 51 kD whose central region contains \ a number of conserved regions.\ \ molecular_function unknown ; GO:0005554 \N \N 19675 IPR000953 The CHROMO (CHRromatin Organization MOdifier) domain [MEDLINE:91205601], [MEDLINE:91204431], [MEDLINE:95396576], [MEDLINE:96091165] is a conserved region of around 60 amino acids, originally identified in Drosophila modifiers of variegation.\ These are proteins that alter the structure of chromatin to the condensed morphology of heterochromatin, \ a cytologically visible condition where gene expression is repressed. In one of these proteins, Polycomb, \ the chromo domain has been shown to be important for chromatin targeting. Proteins that contain a chromo \ domain appear to fall into 3 classes. The first class includes proteins having an N-terminal chromo domain \ followed by a region termed the chromo shadow domain [MEDLINE:95396576], eg. Drosophila and human heterochromatin \ protein Su(var)205 (HP1); and mammalian modifier 1 and modifier 2. The second class includes proteins with \ a single chromo domain, eg. Drosophila protein Polycomb (Pc); mammalian modifier 3; human Mi-2 autoantigenand \ and several yeast and Caenorhabditis elegans hypothetical proteins. In the third class paired tandem chromo domains are \ found, eg. in mammalian DNA-binding/helicase proteins CHD-1 to CHD-4 and yeast protein CHD1.\ \ chromatin binding activity ; GO:0003682 nucleus ; GO:0005634 chromatin assembly/disassembly ; GO:0006333 19676 IPR000956 Stathmin is a ubiquitous phosphorylated protein thought to act as an intracellular relay for diverse regulatory pathways [MEDLINE:90292224], functioning through a variety of second messengers. Its phosphorylation \ and gene expression are regulated throughout development [MEDLINE:93346387] and in response to extracellular \ signals regulating cell proliferation, differentiation and function [MEDLINE:89308626]. Stathmin, and the \ related proteins SCG10 and XB3, contain a N-terminal domain (XB3 contains an additional N-terminal \ hydrophobic region), a 78 amino acid coiled-coil region, and a short C-terminal domain.\ \ \N \N intracellular signaling cascade ; GO:0007242 19671 IPR000948

\ \ \

The sequence of the acidic ribosomal protein S6 from Haloarcula marismortui has been determined \ [MEDLINE:88055606]. The protein consists of 116 amino acid residues, and has a molecular mass of 12,251 Da. \ Sequence comparison with ribosomal proteins of other organisms has revealed that halobacterial protein \ S6 is similar to mammalian protein L7a [MEDLINE:92096469], yeast L4 [MEDLINE:90221868], yeast NHP2 [MEDLINE:91289691],\ B. subtilis hypothetical protein ylxQ and M. jannaschii MJ1203.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 19670 IPR000945 Peptidylglycine

-amidating monooxygenase (PAM) is a multifunctional protein found in secretory granules. The protein contains two enzymes that act sequentially to catalyse the

-amidation of \ neuroendocrine peptides [MEDLINE:93078791], [MEDLINE:91107670].\ \

\
peptidylglycine + ascorbate + O₂ = peptidyl(2-hydroxyglycine) + \
dehydroascorbate + H₂O\

\ The product is unstable and dismutates to glyoxylate \ and the corresponding desglycine peptide amide. The first step of the reaction is catalysed by \ peptidylglycine

-hydroxylating monooxygenase (PHM), and is dependent on copper, ascorbate and \ molecular oxygen; peptidyl-

-hydroxyglycine

-amidating lyase (PAL) catalyses the second step \ of the reaction [MEDLINE:93078791]. Sequence analysis shows the protein to be similar to \ dopamine-

-monooxygenases (DBH), a class of ascorbate-dependent enzymes from the catecholamine \ biosynthetic pathway that requires copper as a cofactor and uses ascorbate as an electron donor. DBH \ catalyses the conversion of dopamine to the neurotransmitter norepinephrine:\

\
3,4-dihydroxyphenethylamine\
+ ascorbate + O₂ = noradrenaline + dehydroascorbate + H₂O\

\ DBH exists in both soluble \ (in chromaffin granules) and membane bound forms. The protein functions as a homotetramer. DBH and PAM \ share a few regions of sequence similarity, some of which contain clusters of conserved histidine residues \ that may be involved in copper binding [MEDLINE:90110082].\ \ dopamine-beta-monooxygenase activity ; GO:0004500 \N catecholamine metabolism ; GO:0006584 19669 IPR000944 The following uncharacterized bacterial proteins have been shown to be evolutionary related, Desulfovibrio vulgaris protein Rrf2; Escherichia coli hypothetical proteins yfhP and yjeB; Bacillus subtilis hypothetical \ proteins yhdE, yrzC and ywgB; Mycobacterium tuberculosis hypothetical protein Rv1287; and Synechocystis \ strain PCC 6803 hypothetical protein slr0846. These are small proteins of 12 to 18 kD which seem to contain \ a signal sequence, and may represent a family of probable transcriptional regulators.\ \ molecular_function unknown ; GO:0005554 \N \N 19668 IPR000943

The bacterial core RNA polymerase complex, which consists of five subunits, is sufficient for transcription elongation and termination but is unable to initiate transcription. Transcription initiation from promoter elements requires a sixth,\ dissociable subunit called a sigma factor, which reversibly associates with the core RNA polymerase complex to form a\ holoenzyme [MEDLINE:89024591]. RNA polymerase recruits alternative sigma factors\ as a means of switching on specific regulons. Most bacteria express a multiplicity of sigma factors. Two of these factors, \ sigma-70 (gene rpoD), generally known as the major or primary sigma factor, and sigma-54 (gene rpoN or ntrA) \ direct the transcription of a wide variety of genes. The other sigma factors, known as alternative sigma \ factors, are required for the transcription of specific subsets of genes.

Each sigma2 domain is composed of a bundle of three -helices that is virtually identical in\ all structures analyzed to date PUB00010647. The second helix of this bundle is a major point for contact with a coiled-coil domain in the '\ subunit of the core RNA polymerase complex. The third helix of the bundle includes conserved residues along one face\ that are involved in DNA melting and in recognition of the -10 promoter element. The sigma3 domain, which is less conserved between members of the sigma70 family is also a\ three-helix domain, the first helix of which contains the residues implicated in contacting DNA upstream of extended -10\ promoters. The sigma4, domain has two pairs of helices; the carboxy-terminal pair forms a helix-turn-helix motif that\ contacts the promoter DNA in the region from -30 to -38.

\ \ \ sigma factor activity ; GO:0016987 \N regulation of transcription, DNA-dependent ; GO:0006355 19666 IPR000941 Enolase (2-phospho-D-glycerate hydrolase) is an essential glycolytic enzyme that catalyses the interconversion of 2-phosphoglycerate and phosphoenolpyruvate [MEDLINE:91316216], [MEDLINE:91222137]. In vertebrates, \ there are 3 different, tissue-specific isoenzymes, designated

and gamma. Alpha is present in \ most tissues,

is localised in muscle tissue, and gamma is found only in nervous tissue. The functional \ enzyme exists as a dimer of any 2 isoforms. In immature organs and in adult liver, it is usually an

homodimer, in adult skeletal muscle, a

homodimer, and in adult neurons, a gamma homodimer. In \ developing muscle, it is usually an

heterodimer, and in the developing nervous system, an

/gamma heterodimer [MEDLINE:88268812]. The tissue specific forms display minor kinetic differences. \ Tau-crystallin, one of the major lens proteins in some fish, reptiles and birds, has been shown \ [MEDLINE:87234351] to be evolutionary related to enolase.\ \ phosphopyruvate hydratase activity ; GO:0004634 phosphopyruvate hydratase complex ; GO:0000015 glycolysis ; GO:0006096 19667 IPR000942 Geminiviruses are characterised by a genome of circular single-strandedDNA encapsidated in twinned (geminate) quasi-isometric particles, from\ which the group derives its name. Most geminiviruses can be divided\ into two subgroups on the basis of host range and/or insect vector: i.e.\ those that infect dicotyledenous plants and are transmitted by the same\ whitefly species, and those that infect monocotyledenous plants and are\ transmitted by different leafhopper vectors. The genomes of the whitefly-transmitted \ cassava latent (CLV), tomato golden mosaic (TGMV) and bean\ golden mosaic (BGMV) viruses possess a bipartite genome. By contrast, only\ a single DNA component has been identified for the leafhopper-transmitted\ maize streak (MSV) and wheat dwarf (WDV) viruses \ [MEDLINE:85126910], [MEDLINE:88124198].\ \ \ structural molecule activity ; GO:0005198 viral capsid ; GO:0019028 \N 19665 IPR000941 Enolase (2-phospho-D-glycerate hydrolase) is an essential glycolytic enzyme that catalyses the interconversion of 2-phosphoglycerate and phosphoenolpyruvate [MEDLINE:91316216], [MEDLINE:91222137]. In vertebrates, \ there are 3 different, tissue-specific isoenzymes, designated

and gamma. Alpha is present in \ most tissues,

is localised in muscle tissue, and gamma is found only in nervous tissue. The functional \ enzyme exists as a dimer of any 2 isoforms. In immature organs and in adult liver, it is usually an

homodimer, in adult skeletal muscle, a

homodimer, and in adult neurons, a gamma homodimer. In \ developing muscle, it is usually an

heterodimer, and in the developing nervous system, an

\ \

Several cytoplasmic vertebrate methyltransferases are evolutionary related [MEDLINE:94237908], including\ nicotinamide N-methyltransferase (EC: 2.1.1.1) (NNMT); phenylethanolamine N-methyltransferase \ (EC: 2.1.1.28) (PNMT); and thioether S-methyltransferase \ (EC: 2.1.1.96) (TEMT). NNMT catalyzes the \ N-methylation of nicotinamide and other pyridines to form pyridinium ions. This activity is important \ for the biotransformation of many drugs and xenobiotic compounds. PNMT catalyzes the last step in \ catecholamine biosynthesis, the conversion of noradrenalin to adrenalin; and TEMT catalyzes the\ methylation of dimethyl sulfide into trimethylsulfonium. These three enzymes use S-adenosyl-L-methionine \ as the methyl donor. They are proteins of 30 to 32 kDa.

\ \ methyltransferase activity ; GO:0008168 \N \N 19661 IPR000937 The capsid proteins of plant icosahedral positive strand RNA viruses form 4 different domains, a positively charged, N-terminal 'R' domain, which interacts with RNA (66 residues); a connecting arm, \ 'a' (35 residues); a central, surface 'S' domain, which forms the virion shell; and a projecting, \ C-terminal 'P' domain [MEDLINE:95219381]. Some of the viruses lack either the R or P domains. The S domain \ contains from 158 to 166 amino acids and comprises 8 anti-parallel

-strands, which form a twisted \ sheet or jelly-roll fold. This structure is shared by a number of plant viral capsid proteins, including \ carmoviruses, dianthoviruses, sobemoviruses, tombusviruses and tobacco necrosis virus\ \ \ \ [MEDLINE:91311399].\ \ structural molecule activity ; GO:0005198 viral capsid ; GO:0019028 \N 19662 IPR000938 Cytoskeleton-associated proteins (CAP) are made of three distinct parts, an N-terminal section that is most probably globular and contains the CAP-Gly domain, a large central region predicted to be in an

-helical coiled-coil conformation and, finally, a short C-terminal globular domain. The CAP-Gly \ domain is a conserved, glycine-rich domain of about 42 residues found in some CAPs [MEDLINE:93242656].\ Proteins known to contain this domain include restin (also known as cytoplasmic linker protein-170 or \ CLIP-170), a 160 kD protein associated with intermediate filaments and that links endocytic vesicles to \ microtubules; vertebrate dynactin (150 kD dynein-associated polypeptide; DAP) and Drosophila glued, a \ major component of activator I; yeast protein BIK1, which seems to be required for the formation or\ stabilization of microtubules during mitosis and for spindle pole body fusion during conjugation; yeast \ protein NIP100 (NIP80); human protein CKAP1/TFCB; Schizosaccharomyces pombe protein alp11 and C. elegans \ hypothetical protein F53F4.3. The latter proteins contain a N-terminal ubiquitin domain and a C-terminal \ CAP-Gly domain.\ \ \N \N \N 19663 IPR000939 Adenoviruses are responsible for diseases such as pneumonia, cystitis, conjunctivitis and diarrhoea, all of which can be fatal to patients who are immunocompromised [MEDLINE:95219386]. Viral infection commences with \ recognition of host cell receptors by means of specialised proteins on viral surfaces. Specific attachment \ of adenovirus is achieved through interactions between host-cell receptors and the adenovirus fiber protein \ and is mediated by the globular carboxy-terminal domain of the adenovirus fiber protein, rather than the \ 'shaft' region represented by this family. The alignment of this family contains two copies of a fifteen\ residue repeat found in the 'shaft' region of adenoviral fiber proteins.\ \ \N \N cell recognition ; GO:0008037 19657 IPR000932 This family contains photosystem II proteins, which are responsible for binding chlorophyll. Membersof the family include Synechococcus iron-stress induced chlorophyll-binding protein, and the plant \ chloroplast encoded P680 chlorophyll A apoprotein and 44 kD reaction centre protein CP43. P680 \ conjugates with chlorophyll and catalyses the primary light-induced photochemical processes of \ photosystem II.\ \ \N membrane ; GO:0016020 electron transport ; GO:0006118 19658 IPR000933

Family 29 (CAZY:GH_29, which is a lysosomal enzyme responsible for\ hydrolyzing the -1,6-linked fucose joined to the reducing-end\ N-acetylglucosamine of the carbohydrate moieties of glycoproteins. Deficiency\ of -L-fucosidase results in the lysosomal storage disease fucosidosis.

\ \ \ alpha-L-fucosidase activity ; GO:0004560 \N carbohydrate metabolism ; GO:0005975 19659 IPR000935

Thrombin is a serine protease with a central role in blood clotting .\ It cleaves various substrates involved in coagulation, and activates cell\ surface receptors via a novel proteolytic action. Thrombin stimulates\ aggregation and secretion in blood platelets at the site of vascular injury,\ and also has inflammatory and reparative actions, stimulating chemotaxis in\ monocytes, proliferation of fibroblasts and lymphocytes, and inducing\ endothelium-dependent relaxation of blood vessels . The protein activates\ a number of substrates involved in coagulation: it cleaves fibrinogen to\ fibrin and activates coagulation factor XIII; it also activates factors V\ and VIII . When bound to thrombomodulin, it activates plasma protein C,\ which, in concert with protein S, inactivates factors Va and VIIIa, leading\ to a decrease in thrombin formation PUB00005905.

The thrombin receptor is expressed in high levels in platelets, vascular\ endothelial cells, and various cell lines . The receptor activates\ phosphoinositide metabolism via a pertussis-toxin-insensitive G-protein,\ and inhibits adenylyl cyclase via a pertussis-toxin-sensitive G-protein PUB00005905.

\ \ G-protein coupled receptor activity ; GO:0004930 integral to membrane ; GO:0016021 blood coagulation ; GO:0007596 19660 IPR000936 E2 is a spike glycoprotein encoded by ssRNA positive-strand viruses, with no DNA stage in their life cycle. E2 forms a heterodimer with E1. The virus spikes are made up of 80 trimers of these heterodimers \ eg. in the sindbis virus\ \ \ \ [MEDLINE:97151146].\ \ structural molecule activity ; GO:0005198 viral capsid ; GO:0019028 \N 19656 IPR000931 Adenoviruses are responsible for diseases such as pneumonia, cystitis, conjunctivitis and diarrhoea, all of which can be fatal to patients who are immunocompromised [MEDLINE:95219386]. Viral infection commences with \ recognition of host cell receptors by means of specialised proteins on viral surfaces. The adenovirus \ fibre protein 'knob domain' at the C-terminus is one such receptor-binding protein subunit. The crystal \ structure of the knob domain reveals a trimeric organisation, each subdomain folded into 2 functionally \ distinct

-sheets. The V sheet is highly conserved, and provides contact surfaces in the formation of \ the trimer, while the R sheet is more variable, and may play a role in viral-receptor interactions. The \ overall shape of the trimer resembles a 3-bladed propeller, with a central surface depression and 3 valleys \ formed by the symmetry-related R sheets. Sequence comparison of different types of adenovirus fibre protein \ suggests an overall similarity in the structure of the knob domain. The main conserved regions lie in the \ central surface depression around the 3-fold symmetry axis [MEDLINE:95219386]. The N-terminus of the protein\ contains the 'shaft' region.\ \ \N \N cell recognition ; GO:0008037 19655 IPR000930

Togavirin, also known as sindbis virus core endopeptidase, is a serine\ protease resident at the N-terminus of the p130 polyprotein of togaviruses\ \ \ \ [MEDLINE:95147689]. The polyprotein also includes structural proteins for the nucleocapsid\ core and for the glycoprotein spikes [MEDLINE:95147689]. Togavirin is only active while\ part of the polyprotein, cleavage at a Trp-Ser bond resulting in total lack\ of activity [MEDLINE:95147689]. Mutagenesis studies have identified the location of the\ His-Asp-Ser catalytic triad, and X-ray studies have revealed the protein\ fold to be similar to that of chymotrypsin [MEDLINE:95147689], [MEDLINE:92049751].

\ \ serine-type endopeptidase activity ; GO:0004252 membrane ; GO:0016020 proteolysis and peptidolysis ; GO:0006508 19654 IPR000929

\ \ dopamine receptor activity ; GO:0004952 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19652 IPR000926

GTP cyclohydrolase II catalyses the first committed step in the biosynthesis of riboflavin. The enzymeconverts GTP and water to formate, 2,5-diamino-6-hydroxy-4-(5-phosphoribosylamino)- pyrimidine and\ pyrophosphate, and requires magnesium as a cofactor. It is sometimes found as a bifunctional enzyme with 3,4-dihydroxy-2-butanone 4-phosphate synthase (DHBP_synthase) IPR000422.

\ \ GTP cyclohydrolase II activity ; GO:0003935 \N vitamin B2 biosynthesis ; GO:0009231 19653 IPR000928

SNAP-25 (synaptosome-associated protein 25 kDa) proteins are components of SNARE complexes, which are proposed to account for the specificity of membrane fusion and to directly execute fusion by forming a tight complex (the SNARE or core\ complex) that brings the synaptic vesicle and plasma membranes\ together. The SNAREs constitute a large family of proteins that\ are characterized by 60-residue sequences known as SNARE motifs (IPR000727),\ which have a high propensity to form coiled coils and often precede\ carboxy-terminal transmembrane regions. The synaptic core complex is formed by four SNARE motifs (two from\ SNAP25 and one each from synaptobrevin and syntaxin 1) that are\ unstructured in isolation but form a parallel four-helix bundle on\ assembly. The crystal structure of the core complex revealed\ that the helix bundle is highly twisted and contains several salt bridges on\ the surface, as well as layers of interior hydrophobic residues.\ However, a polar layer in the centre of the complex is formed by three\ glutamines (two from SNAP25 and one from syntaxin 1) and one arginine\ (from synaptobrevin) PUB00010661.

Members \ of the SNAP-25 family contain a cluster of cysteine residues that can be palmitoylated for membrane attachment \ PUB00010661.

\ \ \N \N \N 19650 IPR000924

\ \

\ \ ATP binding activity ; GO:0005524 \N glutamyl-tRNA aminoacylation ; GO:0006424 19651 IPR000925 This family includes attachment proteins from respiratory synctial virus. Glycoprotein G has not been shown to have any neuraminidase or hemagglutinin activity. The amino terminus is thought to be cytoplasmic, \ and the carboxyl terminus extracellular. The extracellular region contains four completely conserved \ cysteine residues.\ \ \N \N \N 19649 IPR000924

\ \

\ \ ATP binding activity ; GO:0005524 \N glutamyl-tRNA aminoacylation ; GO:0006424 19647 IPR000922 The D-galactoside binding lectin purified from sea urchin (Anthocidaris crassispina) eggs exists as a disulfide-linked homodimer of two subunits; the dimeric form is essential for hemagglutination activity [MEDLINE:91159418]. The sea urchin egg lectin (SUEL) forms a new class of lectins. Although SUEL was first isolated as a D-galactoside binding lectin it was latter shown that it bind to L-rhamnose preferentially [MEDLINE:91159418], [MEDLINE:20033433]. L-rhamnose and D-galactose share the same hydroxyl group orientation at C2 and C4 of the pyranose ring structure.

A cysteine-rich domain homologous to the SUEL protein has been identified in the following proteins [MEDLINE:97407945], [MEDLINE:98334657], [MEDLINE:99121098]:

Plant -galactosidases (EC: 3.2.1.23) (lactases).
Mammalian latrophilin, the calcium independent receptor of -latrotoxin (CIRL). The galactose-binding lectin domain is not required for -latratoxin binding [MEDLINE:99121098].
Human lectomedin-1.
Rhamnose-binding lectin (SAL) from catfish (Parasilurus asotus) eggs. This protein is composed of three tandem repeat domains homologous to the SUEL lectin domain . All cysteine positions of each domain are completely conserved [MEDLINE:20033433].
The hypothetical B0457.1, F32A7.3A and F32A7.3B proteins from Caenorhabditis elegans.
The human KIAA0821 protein.

\ \ sugar binding activity ; GO:0005529 \N \N 19648 IPR000923 Blue (type 1) copper proteins are small proteins which bind a single copper atom and which are characterized by an intense electronic absorption band near 600 nm [MEDLINE:84135769], [MEDLINE:93164266]. The most \ well known members of this class of proteins are the plant chloroplastic plastocyanins, which exchange \ electrons with cytochrome c6, and the distantly related bacterial azurins, which exchange electrons with \ cytochrome c551. This family of proteins also includes amicyanin from bacteria such as Methylobacterium \ extorquens or Thiobacillus versutus that can grow on methylamine; auracyanins A and B from Chloroflexus \ aurantiacus\ \ \ \ [MEDLINE:92202194]; blue copper protein from Alcaligenes faecalis; cupredoxin (CPC) from cucumber \ peelings [MEDLINE:93106154]; cusacyanin (basic blue protein; plantacyanin, CBP) from cucumber; halocyanin from \ Natrobacterium pharaonis\ \ \ \ [MEDLINE:94253046], a membrane associated copper-binding protein; pseudoazurin from \ Pseudomonas; rusticyanin from Thiobacillus ferrooxidans\ \ \ \ [MEDLINE:91348256]; stellacyanin from the Japanese \ lacquer tree; umecyanin from horseradish roots; and allergen Ra3 from ragweed. This pollen protein is \ evolutionary related to the above proteins, but seems to have lost the ability to bind copper. Although \ there is an appreciable amount of divergence in the sequences of all these proteins, the copper ligand \ sites are conserved.\ \ copper ion binding activity ; GO:0005507 \N electron transport ; GO:0006118 19644 IPR000919 Phagocytes form the first line of defence against invasion by microorganisms. Engulfing of bacteria by neutrophils is accompanied by the consumption of large amounts of oxygen, a so-called respiratory burst.\ Defects in phagocytosis involving the lack of a respiratory burst give rise to chronic granulomatous \ disease (CGD), in which patients are predisposed to infection, often from otherwise non-pathogenic bacteria. \ Regulation of the respiratory burst takes place at the phagocytic vacuole. The process is mediated by NADPH \ oxidase, which transports electrons across the plasma membrane to form superoxide (an oxygen molecule with \ an extra electron that is toxic to normal cells) in the vacuole interior. The electrons are carried across \ the membrane by a short electron transport chain in the form of an unusual flavocytochrome B [MEDLINE:96389574].\ To conserve NADPH and avoid the toxic effects of superoxide, the oxidase remains inactive until it receives \ an appropriate stimulus. Activation involves the participation of a number of cytosolic proteins, some of \ which attach to the flavocytochrome. P47phox, p67phox and p40phox are specialised components of phagocytic \ cells. All contain SH3 domains, by means of which they attach to proline-rich regions of other proteins. \ Upon activation, p40phox translocates to the region of the plasma membrane forming the phagocytic vacuole, \ where, with phosphorylated p47phox and p67phox, it associates with hydrophilic regions of the flavocytochrome\ \ \N \N electron transport ; GO:0006118 19645 IPR000920 The myelin sheath is a multi-layered membrane, unique to the nervous system, that functions as an insulator to greatly increase the velocity of axonal impulse conduction. The P0 glycoprotein, absent in the central \ nervous system [MEDLINE:87166035], is a major component of the myelin sheath in peripheral nerves. It comprises \ a large extracellular N-terminal domain, a single transmembrane (TM) region, and a smaller positively\ charged intracellular domain. It is postulated that P0 is a structural element in the formation and \ stabilisation of peripheral nerve myelin [MEDLINE:85124601], holding its characteristic coil structure together \ by the interaction of its positively-charged domain with acidic lipids in the cytoplasmic face of the \ opposed bilayer, and by interaction between hydrophobic globular 'heads' of adjacent extracellular domains \ [MEDLINE:87166035].\ \ \N \N \N 19646 IPR000921

Histamine is distributed within mast cells in all peripheral tissues and\ is a well-characterised mediator of inflammation and allergy PUB00005888. It also\ regulates release of gastric acid from parietal cells in the gastric\ mucosa. H1 receptors mediate increase in vascular permeability induced\ by histamine at sites of inflammation. H1 antagonists are used clinically\ in the treatment of allergic and anaphylactic reactions, various\ inflammatory conditions, and motion sickness. The receptor is distributed\ widely in the periphery, notably smooth muscle, where it stimulates\ contraction, and also in the adrenal medulla, vascular endothelium and\ heart. It is found throughout the CNS, including the cerebral cortex,\ spinal cord and cerebellum.

\ \ histamine receptor activity ; GO:0004969 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19643 IPR000918

Isocitrate lyase (EC: 4.1.3.1) [MEDLINE:90175328], [MEDLINE:90299863] is an enzyme that catalyzes the conversion of isocitrate to succinate and glyoxylate. This is the first step in the glyoxylate bypass, an alternative \ to the tricarboxylic acid cycle in bacteria, fungi and plants. A cysteine, a histidine and a glutamate \ or aspartate have been found to be important for the enzyme's catalytic activity. Only one cysteine \ residue is conserved between the sequences of the fungal, plant and bacterial enzymes; it is located in \ the middle of a conserved hexapeptide.

Other enzymes also belong to this family including carboxyvinyl-carboxyphosphonate phosphorylmutase (EC: 2.7.8.23) which catalyses the conversion of 1-carboxyvinyl carboxyphosphonate to 3-(hydrohydroxyphosphoryl) pyruvate carbon dioxide, and Phosphoenolpyruvate mutase (EC: 5.4.2.9), which is involved in the biosynthesis of phosphinothricin tripeptide antiobiotics.

\ \ enzyme activity ; GO:0003824 \N metabolism ; GO:0008152 19642 IPR000917 Sulfatases (EC: 3.1.6.-) are enzymes that hydrolyze various sulfate esters. The sequence of different types of sulfatases are available and have shown to be structurally related [MEDLINE:90153994], [MEDLINE:91046030], \ [MEDLINE:89384447], including arylsulfatase A (EC: 3.1.6.8) (ASA), a lysosomal enzyme which hydrolyzes cerebroside \ sulfate; arylsulfatase B (EC: 3.1.6.12) (ASB), which hydrolyzes the sulfate ester group from \ N-acetylgalactosamine 4-sulfate residues of dermatan sulfate; arylsulfatase C (ASD) and E (ASE);\ steryl-sulfatase (EC: 3.1.6.2) (STS), a membrane bound microsomal enzyme which hydrolyzes 3-

-hydroxy \ steroid sulfates; iduronate 2-sulfatase precursor (EC: 3.1.6.13) (IDS), a lysosomal enzyme that hydrolyzes \ the 2-sulfate groups from non-reducing-terminal iduronic acid residues in dermatan sulfate and heparan \ sulfate; N-acetylgalactosamine-6-sulfatase (EC: 3.1.6.4), which hydrolyzes the 6-sulfate groups of the \ N-acetyl-d-galactosamine 6-sulfate units of chondroitin sulfate and the D-galactose 6-sulfate units of \ keratan sulfate; glucosamine-6-sulfatase (EC: 3.1.6.14) (G6S), which hydrolyzes the N-acetyl-D-glucosamine \ 6-sulfate units of heparan sulfate and keratan sulfate; N-sulphoglucosamine sulphohydrolase (EC: 3.10.1.1) \ (sulphamidase), the lysosomal enzyme that catalyzes the hydrolysis of N-sulfo-d-glucosamine into glucosamine \ and sulfate; sea urchin embryo arylsulfatase (EC: 3.1.6.1); green algae arylsulfatase (EC: 3.1.6.1), which \ plays an important role in the mineralization of sulfates; and arylsulfatase \ (EC: 3.1.6.1) from E. coli \ (aslA), Klebsiella aerogenes (gene atsA) and Pseudomonas aeruginosa (gene atsA).\ \ sulfuric ester hydrolase activity ; GO:0008484 \N metabolism ; GO:0008152 19640 IPR000915

\ \ \

A number of eukaryotic and archaeabacterial ribosomal proteins can be grouped on the basis of sequence \ similarities. One of these families includes mammalian ribosomal protein L6 (L6 was previously known \ as TAX-responsive enhancer element binding protein 107); Caenorhabditis elegans ribosomal protein L6 \ (R151.3); Saccharomyces cerevisiae ribosomal protein YL16A/YL16B; and Mesembryanthemum crystallinum ribosomal protein \ YL16-like. These proteins have 175 (yeast) to 287 (mammalian) amino acids.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 19641 IPR000916

The allergens in this family include allergens with the following designations: Aln g 1, Api g 1, Bet v 1, Car b 1, Cor a 1, Dau c 1, Mal d 1 and Pru a 1.

Trees within the order \ Fagales possess particularly potent allergens, e.g. Bet v1, the major Birch (Betula verrucosa) pollen \ antigen. Bet v1 is the main cause of type I allergies observed in early spring. Type I, or immunoglobulin \ E-mediated (IgE-mediated) allergies affect 1 in 5 people in Europe and North America. Commonly-observed \ symptoms are hay fever, dermatitis, asthma and, in severe cases, anaphylactic shock. First contact with \ these allergens results in sensitisation; subsequent contact produces a cross-linking reaction of IgE on \ mast cells and concomitant release of histamine. The inevitable symptoms of an allergic reaction ensue.

Recent NMR analysis [MEDLINE:96325031] has confirmed earlier predictions of the protein structure and site of \ the major T-cell epitope [MEDLINE:96254050]. \ The Bet v1 protein comprises 6 anti-parallel -strands and 3 -helices. Four of the strands dominate the global fold, and 2 of the helices form a C-terminal\ amphipathic helical motif. This motif is believed to be the T-cell epitope. Other proteins belonging to \ this family include the major pollen allergens from alder (Aln g I); celery (Api G I); hornbeam (Car b I);\ hazel (Cor a I) and apple (Mal d I); asparagus wound-induced protein AoPR1; pathogenesis-related proteins \ from kidney bean; parsley (PR1-1 and PR1-3) and Potato (STH-2 and STH-21); pea disease resistance response \ proteins pI49, pI176 and DRRG49-C; pea abscisic acid-responsive proteins ABR17 and ABR18; and soybean \ stress-induced protein SAM22.

\ \ \N \N \N 19639 IPR000914 Bacterial high affinity transport systems are involved in active transport of solutes across the cytoplasmic membrane. The protein components of these traffic systems include one or two transmembrane \ protein components, one or two membrane-associated ATP-binding proteins and a high affinity periplasmic \ solute-binding protein. The latter are thought to bind the substrate in the vicinity of the inner membrane, \ and to transfer it to a complex of inner membrane proteins for concentration into the cytoplasm. In \ gram-positive bacteria which are surrounded by a single membrane and therefore have no periplasmic region \ the equivalent proteins are bound to the membrane via an N-terminal lipid anchor. These homolog proteins \ do not play an integral role in the transport process per se, but probably serve as receptors to trigger \ or initiate translocation of the solute throught the membrane by binding to external sites of the integral \ membrane proteins of the efflux system. In addition at least some solute-binding proteins function in the \ initiation of sensory transduction pathways. On the basis of sequence similarities, the vast majority of \ these solute-binding proteins can be grouped [MEDLINE:93330183] into eight families of clusters, which generally \ correlate with the nature of the solute bound. Family 5 currently includes periplasmic oligopeptide-binding\ proteins (oppA) of Gram-negative bacteria and homologous lipoproteins in Gram-positive bacteria (oppA, amiA \ or appA); periplasmic dipeptide-binding proteins of E. coli (dppA) and Bacillus subtilis (dppE); periplasmic \ murein peptide-binding protein of E. coli (mppA); periplasmic peptide-binding proteins sapA of E. coli, \ Salmonella typhimurium and Haemophilus influenzae; periplasmic nickel-binding protein (nikA) of E. coli;\ heme-binding lipoprotein (hbpA or dppA) from Haemophilus influenzae; lipoprotein xP55 from Streptomyces \ lividans; and hypothetical proteins from Haemophilus influenzae (HI0213) and Rhizobium strain NGR234 \ symbiotic plasmid (y4tO and y4wM).\ \ transporter activity ; GO:0005215 \N transport ; GO:0006810 19637 IPR000912 The Herpesvirus major capsid protein (MCP) is the principal protein of the icosahedral capsid, formingthe main component of the hexavalent and probably the pentavalent capsomeres. It shares similarity with\ all other Herpesvirus major capsid proteins.\ \ structural molecule activity ; GO:0005198 viral capsid ; GO:0019028 \N 19638 IPR000913

In the periphery, NK2 receptors are found in smooth muscle of the\ respiratory, gastrointestinal and urogenital systems . NK2 receptors\ activate the phosphoinositide pathway through a pertussis-toxin-insensitive\ G-protein, probably of the Gq/G11 class PUB00005903.

\ \ tachykinin receptor activity ; GO:0004995 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19636 IPR000911

\ \ \

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 19635 IPR000911

\ \ \

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 19632 IPR000908

Group B carboxylesterases constitute a family of enzymes that includes proteins that catalyse the conversion of an acylcholine to a choline and a weak acid:\

\
Acylcholine + H₂O -> Choline + COO^-\

\ and those that catalyse the hydrolysis of acetylcholine to choline and acetate (acetylcholinesterases):\

\
Acetylcholine + H₂O -> Choline + Acetate\

class, \ with a 3-layer

sandwich architecture.

\ \ acetylcholinesterase activity ; GO:0003990 \N acetylcholine breakdown in the synaptic cleft ; GO:0001507 19633 IPR000909 Phosphatidylinositol-specific phospholipase C (EC: 3.1.4.11), a eukaryotic intracellular enzyme, plays an important role in signal transduction processes [MEDLINE:91182830]. It catalyzes the hydrolysis of \ 1-phosphatidyl-D-myo-inositol-3,4,5-triphosphate into the second messenger molecules diacylglycerol \ and inositol-1,4,5-triphosphate. This catalytic process is tightly regulated by reversible phosphorylation \ and binding of regulatory proteins [MEDLINE:93040690], [MEDLINE:92316906], [MEDLINE:93110772]. In mammals, there are at \ least 6 different isoforms of PI-PLC, they differ in their domain structure, their regulation, and their \ tissue distribution. Lower eukaryotes also possess multiple isoforms of PI-PLC. All eukaryotic PI-PLCs \ contain two regions of homology, sometimes referred to as the 'X-box' and 'Y-box'. The order of these two \ regions is always the same (NH2-X-Y-COOH), but the spacing is variable. In most isoforms, the distance\ between these two regions is only 50-100 residues but in the gamma isoforms one PH domain, two SH2 domains, \ and one SH3 domain are inserted between the two PLC-specific domains. The two conserved regions have been \ shown to be important for the catalytic activity. By profile analysis, we could show that sequences with \ significant similarity to the X-box domain occur also in prokaryotic and trypanosome PI-specific \ phospholipases C. Apart from this region, the prokaryotic enzymes show no similarity to their eukaryotic \ counterparts.\ \ phospholipase C activity ; GO:0004629 \N intracellular signaling cascade ; GO:0007242 19634 IPR000910 High mobility group (HMG) proteins are a family of relatively low molecular weight non-histone components in chromatin. HMG1 (also called HMG-T in fish) and HMG2 [MEDLINE:90344865] are two highly related proteins that \ bind single-stranded DNA preferentially and unwind double-stranded DNA. HMG1/2 are proteins of about 200 \ amino acid residues with a highly acidic C-terminal section which is composed of an uninterrupted stretch \ of from 20 to 30 aspartic and glutamic acid residues, the rest of the protein sequence is very basic. The \ profile in this entry describing the HMG-domains is much more general than the signature. In addition to \ the HMG1 and HMG2 proteins, HMG-domains occur in single or multiple copies in the following protein classes; \ the SOX family of transcription factors; SRY sex determining region Y protein and related proteins; LEF1 \ lymphoid enhancer binding factor 1; SSRP recombination signal recognition protein; MTF1 mitochondrial \ transcription factor 1; UBF1/2 nucleolar transcription factors; Abf2 yeast ARS-binding factor; and yeast \ transcription factors Ixr1, Rox1, Nhp6a, Nhp6b and Spp41.\ \ DNA binding activity ; GO:0003677 \N regulation of transcription, DNA-dependent ; GO:0006355 19630 IPR000906 This is a domain of unknown function, present in ZO-1 and Unc5-like netrin receptors. It is also found in different variants of ankyrin, which are responsible for attaching integral membrane proteins to \ cytoskeletal elements.\ \ \N \N \N 19631 IPR000907

\ \ \

Plant lipoxygenases (EC: 1.13.11.12\ \ \ \ IPR001246). Plants express a variety of cytosolic\ isozymes as well as what seems to be a chloroplast isozyme [MEDLINE:94148883] .

Mammalian arachidonate 5-lipoxygenase (EC: 1.13.11.34\ \ \ \ IPR001246/>).

Mammalian arachidonate 12-lipoxygenase (EC: 1.13.11.31\ \ \ \ IPR001885).

Mammalian erythroid cell-specific 15-lipoxygenase (EC: 1.13.11.33\ \ \ \ IPR001885/>).

\ \ \

\ \ lipoxygenase activity ; GO:0016165 \N electron transport ; GO:0006118 19629 IPR000905

Metalloproteases can be split into five clans, and futher sub-divided into families, on the basis of their metal binding residues.

O-Sialoglycoprotein endopeptidase is secreted by the bacterium Mannheimia haemolytica and digests only proteins that are heavily sialylated, in\ particular those with sialylated serine and threonine residues [MEDLINE:95405299].\ Substrate proteins include glycophorin A and leukocyte surface antigens\ CD34, CD43, CD44 and CD45 [MEDLINE:95405261], [MEDLINE:95405299]. Removal of glycosylation, by treatment\ with neuraminidase, completely negates susceptibility to O-sialoglycoprotein\ endopeptidase digestion [MEDLINE:95405261], [MEDLINE:95405299].

\ \

Sequence similarity searches have revealed other members of the M22 family,\ from yeast, Mycobacterium, Haemophilus influenzae and the cyanobacterium\ Synechocystis\ \ \ \ [MEDLINE:95405261]. The zinc-binding and catalytic residues of this family\ have not been determined, although the motif HMEGH may be a zinc-binding\ region [MEDLINE:95405261].

\ \ O-sialoglycoprotein endopeptidase activity ; GO:0008450 \N proteolysis and peptidolysis ; GO:0006508 19626 IPR000903 Myristoyl-CoA:protein N-myristoyltransferase (EC: 2.3.1.97) (Nmt) [MEDLINE:93311238] is the enzyme responsible for transferring a myristate group on the N-terminal glycine of a number of cellular eukaryotics and \ viral proteins. Nmt is a monomeric protein of about 50 to 60 kD whose sequence appears to be well \ conserved.\ \ glycyl-peptide N-tetradecanoyltransferase activity ; GO:0004379 \N N-terminal protein myristoylation ; GO:0006499 19627 IPR000903 Myristoyl-CoA:protein N-myristoyltransferase (EC: 2.3.1.97) (Nmt) [MEDLINE:93311238] is the enzyme responsible for transferring a myristate group on the N-terminal glycine of a number of cellular eukaryotics and \ viral proteins. Nmt is a monomeric protein of about 50 to 60 kD whose sequence appears to be well \ conserved.\ \ glycyl-peptide N-tetradecanoyltransferase activity ; GO:0004379 \N N-terminal protein myristoylation ; GO:0006499 19628 IPR000904 The SEC7 domain was named after the first protein found to contain such a region [MEDLINE:88298841]. It has been shown to be linked with guanine nucleotide exchange function [MEDLINE:97228176], [MEDLINE:98113139].\ The 3D structure of the domain displays several

-helices [MEDLINE:98318585]. It was found to be \ associated with other domains involved in guanine nucleotide exchange (e.g., CDC25, Dbl) in mammalian \ factors [MEDLINE:99085259].\ \ \N \N \N 19624 IPR000898 Indoleamine 2,3-dioxygenase (EC: 1.13.11.42) (IDO) [MEDLINE:91331208] is an enzyme responsible for the conversion of tryptophan and other indole derivatives to kynurenines. In mammals, IDO is induced by interferon-gamma \ (IFN-gamma) and is responsible for some of its anti-proliferative effects. The degradative action of IDO on\ tryptophan leads to cell death by starvation of this essential and relatively scarce amino acid. IDO is a \ heme-containing enzyme of about 400 amino acids. Other proteins that are evolutionarily related to IDO \ include yeast hypothetical protein YJR078w; and myoglobin from the red muscle of the gastropods Haliotis madaka and Sulculus diversicolor\ \ \ \ [MEDLINE:94280526]. These unusual globins lack enzymatic activity but have \ kept the heme group.\ \ \N \N \N 19625 IPR000900 Nebulin is a 600-800 kD protein found in the thin filaments of striated vertebrate muscle. It is presumed to play a role in binding and stabilising F-actin [MEDLINE:96180022], essentially by providing \ a template for actin polymerisation (i.e., acting as an "actin zipper"). The amino acid sequence \ shows a uniform repeating pattern along its length, a repeated 35-residue motif constituting up to \ 97% of the polypeptide. Analysis of individual repeats reveals a progressive N- to C-terminal \ divergence, coupled with an increasing

-helix propensity. This correlates with a higher\ binding affinity for F-actin at the C-terminus. Thus, it is postulated that once the repeats have \ formed an initiation complex, the whole length of the nebulin molecule may then associate in a highly \ co-operative process with the thin filament, in a manner similar to the closing of a zipper [MEDLINE:96180022].\ \ \N \N \N 19622 IPR000897

The signal recognition particle (SRP) is an oligomeric complex that mediates targeting and insertion of the signal sequence of exported proteins into the membrane of the endoplasmic reticulum. SRP \ consists of a 7S RNA and six protein subunits. One of these subunits, the 54 kD protein (SRP54), is \ a GTP-binding protein that interacts with the signal sequence when it emerges from the ribosome. The 54K subunit of the signal recognition particle has a two domain structure: the G-domain that binds GTP and the M-domain (see IPR004125) that binds the 7s RNA and also binds the signal sequence. The \ N-terminal 300 residues of SRP54 include the GTP-binding site (G-domain) and are evolutionary related \ to similar domains in other proteins [MEDLINE:94301771].

These proteins include Escherichia coli and Bacillus \ subtilis ffh protein (P48), which seems to be the prokaryotic counterpart of SRP54; signal recognition \ particle receptor subunit (docking protein), an integral membrane GTP-binding protein which \ ensures, in conjunction with SRP, the correct targeting of nascent secretory proteins to the \ endoplasmic reticulum membrane; bacterial FtsY protein, which is believed to play a similar role to \ that of the docking protein in eukaryotes; the pilA protein from Neisseria gonorrhoeae, the homolog of \ ftsY; and bacterial flagellar biosynthesis protein flhF.

\ \ GTP binding activity ; GO:0005525 signal recognition particle ; GO:0005786 protein targeting ; GO:0006605 19623 IPR000897

The signal recognition particle (SRP) is an oligomeric complex that mediates targeting and insertion of the signal sequence of exported proteins into the membrane of the endoplasmic reticulum. SRP \ consists of a 7S RNA and six protein subunits. One of these subunits, the 54 kD protein (SRP54), is \ a GTP-binding protein that interacts with the signal sequence when it emerges from the ribosome. The 54K subunit of the signal recognition particle has a two domain structure: the G-domain that binds GTP and the M-domain (see IPR004125) that binds the 7s RNA and also binds the signal sequence. The \ N-terminal 300 residues of SRP54 include the GTP-binding site (G-domain) and are evolutionary related \ to similar domains in other proteins [MEDLINE:94301771].

\ \ GTP binding activity ; GO:0005525 signal recognition particle ; GO:0005786 protein targeting ; GO:0006605 19618 IPR000893 The nucleotide sequence of the genomic RNA of beet western yellow virus (BWYV) has been determined [MEDLINE:89057523]. The sequence contains six long open reading frames (ORFs). A cluster of three of \ these ORFs, including the coat protein cistron, display extensive sequence similarity to corresponding \ ORFs of a second luteovirus, the PAV isolate of barley yellow dwarf virus (BYDV)\ \ \ \ [MEDLINE:91108372]. The \ nucleotide sequence of the RNA of potato leafroll luteovirus (PLRV) has been determined [MEDLINE:89171329], \ [MEDLINE:89279282]. The sequence contains six large ORFs. The 3' coding region encodes three polypeptides, \ a 23 kD coat protein, a 17 kD polypeptide encoded in a different frame, and a 53 kD polypeptide, immediately \ following the coat protein sequence in the same frame. It has been suggested that the 53 kD polypeptide \ is translated by readthrough of the amber termination codon of the coat protein gene. The amino acid \ sequences encoded within the 3' region show many similarities to analogous polypeptides of barley \ yellow dwarf virus, PAV strain (BYDV), and beet western yellows virus (BWYV).\ \ molecular_function unknown ; GO:0005554 \N \N 19619 IPR000894 RuBisCO (ribulose-1,5-bisphosphate carboxylase/oxygenase) is a bifunctional enzyme that catalyses both the carboxylation and oxygenation of ribulose-1,5-bisphosphate (RuBP) PUB00000766, thus \ fixing carbon dioxide as the first step of the Calvin cycle. RuBisCO is the major protein in the \ stroma of chloroplasts, and in higher plants exists as a complex of 8 large and 8 small subunits. \ The function of the small subunit is unknown PUB00000766. While the large subunit is coded for by \ a single gene, the small subunit is coded for by several different genes, which are distributed in a \ tissue specific manner. They are transcriptionally regulated by light receptor phytochrome [MEDLINE:86205237], \ which results in RuBisCO being more abundant during the day when it is required.\ \ ribulose-bisphosphate carboxylase activity ; GO:0016984 ribulose bisphosphate carboxylase complex ; GO:0009573 carbon utilization by fixation of carbon dioxide ; GO:0015977 19620 IPR000895 Transthyretin (formerly prealbumin) is one of 3 thyroid hormone-binding proteins found in the blood of vertebrates [MEDLINE:92007844]. It is produced in the liver and circulates in the bloodstream, where \ it binds retinol and thyroxine (T4) [MEDLINE:86031352]. It differs from the other 2 hormone-binding \ proteins (T4-binding globulin and albumin) in 3 distinct ways: (1) the gene is expressed at a high \ rate in the brain choroid plexus; (2) it is enriched in cerebrospinal fluid; and (3) no genetically \ caused absence has been observed, suggesting an essential role in brain function, distinct from that \ played in the bloodstream [MEDLINE:92007844]. The protein consists of around 130 amino acids, which assemble \ as a homotetramer that contains an internal channel in which T4 is bound. Within this complex, T4 \ appears to be transported across the blood-brain barrier, where, in the choroid plexus, the hormone \ stimulates further synthesis of transthyretin. The protein then diffuses back into the bloodstream, \ where it binds T4 for transport back to the brain [MEDLINE:92007844]. A number of uncharacterized proteins \ also belong to this family, including E. coli hypothetical protein yedX; Bacillus subtilis hypothetical \ protein yunM; and C. elegans hypothetical proteins R09H10.3 and ZK697.8.\ \ steroid binding activity ; GO:0005496 \N transport ; GO:0006810 19621 IPR000896

\ \ oxygen transporter activity ; GO:0005344 \N transport ; GO:0006810 19613 IPR000888 The dTDP-4-dehydrorhamnose 3,5-epimerase enzyme (EC: 5.1.3.13) catalyses the isomerisation of dTDP-4-dehydro-6-deoxy-D-glucose with dTDP-4-dehydro-6-deoxy-L-mannose during dTDP-L-rhamnose\ biosynthesis within the O antigen biosynthesis pathway of lipopolysaccharide biosynthesis.\ A related protein is the spore coat polysaccharide biosynthesis protein SPSK from Bacillus\ subtilis.\ \ enzyme activity ; GO:0003824 \N lipopolysaccharide biosynthesis ; GO:0009103 19614 IPR000889 Glutathione peroxidase (GSHPx), an enzyme whose principal function is to protect against damage from endogenously-formed hydroxyperoxides, catalyses the reduction of hydroxyperoxides by glutathione \ PUB00004514, PUB00004514.\

\
2 Glutathione + H₂O(2) = oxidised Glutathione + 2H₂O\

\ In higher vertebrates, several forms of GSHPx are known, including a\ ubiquitous cytosolic form (GSHPx-1); a gastrointestinal cytosolic form (GSHPx-GI); a plasma secreted \ form (GSHPx-P); and an epididymal secretory form (GSHPx-EP). In filarial nematode parasites, the major \ soluble cuticular protein (gp29) is a secreted GSHPx, which may provide a mechanism of resistance to \ the immune reaction of the mammalian host by neutralising the products of the oxidative burst of \ leukocytes [MEDLINE:92335192]. The E.coli protein btuE, a periplasmic protein involved in vitamin B12\ transport, is evolutionarily related to GSHPxs, although the significance of this relationship is \ unclear. The structure of bovine seleno-glutathione peroxidase has been determined [MEDLINE:83209650]. The \ protein belongs to the

class, with a 3-layer(aba) sandwich architecture. The catalyic site \ of GSHPx contains a conserved residue which is either a cysteine or, in many eukaryotic GSHPx, a \ selenocysteine [MEDLINE:90328737].\ \ glutathione peroxidase activity ; GO:0004602 \N peroxidase reaction ; GO:0006804 19615 IPR000890 Acetate kinase, which is predominantly found in micro-organisms, facilitates the production of acetyl-CoA by phosphorylating acetate in the presence of ATP and a divalent cation [MEDLINE:94042910], \ [MEDLINE:93380658]. The enzyme is important in the process of glycolysis, enzyme levels being increased \ in the presence of excess glucose. The growth of a bacterial mutant lacking acetate kinase has \ been shown to be inhibited by glucose, suggesting that the enzyme is involved in excretion of excess \ carbohydrate [MEDLINE:94042910]. A related enzyme, butyrate kinase, facilitates the formation of \ butyryl-CoA by phosphorylating butyrate in the presence of ATP to form butyryl phosphate [MEDLINE:93380658].\ \ phosphotransferase activity, carboxyl group as acceptor ; GO:0016774 intracellular ; GO:0005622 phosphorylation ; GO:0016310 19616 IPR000891

Hydroxymethylglutaryl-CoA lyase (EC: 4.1.3.4)catalyses the conversion of (S)-3-hydroxy-3-methylglutaryl-CoA toacetyl-CoA and acetoacetate during the final step of ketogenesis and leucine catabolism. The HMGL-like signature is found in a diverse set of enzymes including various aldolases and a region of pyruvate \ carboxylase.

\ \ enzyme activity ; GO:0003824 \N \N 19617 IPR000892

\ \ \

A number of eukaryotic ribosomal proteins can be grouped on the basis of sequence similarities. One \ of these families, the S26E family, includes mammalian S26 [MEDLINE:85289112]; Octopus S26 [MEDLINE:89276092];\ Drosophila S26 (DS31) [MEDLINE:89183616]; plant cytoplasmic S26; and fungal S26 [MEDLINE:95121938]. These proteins \ have 114 to 127 amino acids.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 19610 IPR000885 Collagens contain a large number of globular domains in between theregions of triple helical repeats IPR008160.\ These domains are involved in binding diverse substrates.\ One of these domains is found at the C terminus of fibrillar collagens.\ The exact function of this domain is unknown.\ \ extracellular matrix structural constituent ; GO:0005201 collagen ; GO:0005581 \N 19611 IPR000886 Proteins that permanently reside in the lumen of the endoplasmic reticulum (ER) seem to be distinguished from newly synthesized secretory proteins by the presence of the C-terminal sequence \ Lys-Asp-Glu-Leu (KDEL) [MEDLINE:87131101], [MEDLINE:91173477]. While KDEL is the preferred signal in many species, \ and is used in vertebrates, Drosophila, C. elegans and plants, variants of that signal are used by\ different species. For example, HDEL is used in Saccharomyces cerevisiae, Kluyveromyces lactis and \ plants; DDEL in Kluyveromyces lactis; ADEL in fission yeast; and SDEL in Plasmodium falciparum. The \ signal is usually very strictly conserved in major ER proteins but some minor ER proteins have divergent \ sequences (probably because efficient retention of these proteins is not crucial to the cell). Proteins \ bearing the KDEL-type signal are not simply held in the ER, but are selectively retrieved from a post-ER \ compartment by a receptor and returned to their normal location. The currently known ER luminal proteins \ include protein disulphide-isomerase (PDI); ERp60, ERp72, and P5, three minor isoforms of PDI; \ Trypanosoma brucei bloodstream-specific protein 2; hsp70 related protein GRP78; hsp90 related protein \ 'endoplasmin'; Calreticulin; ERC-55; Reticulocalbin; Hsp47; thiol proteases from rice bean and kidney \ bean; esterases from mammalian liver and nematodes;

-2-macroglobulin receptor-associated protein \ (RAP); and yeast peptidyl-prolyl cis-trans isomerase D (CYPD) and KRE5, SEC20 and SCJ1 proteins.\ \ \N \N \N 19612 IPR000887 4-Hydroxy-2-oxoglutarate aldolase (EC: 4.1.3.16) (KHG-aldolase) catalyzes the interconversion of 4-hydroxy-2-oxoglutarate into pyruvate and glyoxylate. Phospho-2-dehydro-3-deoxygluconate aldolase \ (EC: 4.1.2.14) (KDPG-aldolase) catalyzes the interconversion of 6-phospho-2-dehydro-3-deoxy-D-gluconate \ into pyruvate and glyceraldehyde 3-phosphate. These two enzymes are structurally and functionally \ related [MEDLINE:88298837]. They are both homotrimeric proteins of approximately 220 amino-acid residues. \ They are class I aldolases whose catalytic mechanism involves the formation of a Schiff-base \ intermediate between the substrate and the epsilon-amino group of a lysine residue. In both enzymes, \ an arginine is required for catalytic activity.\ \ enzyme activity ; GO:0003824 \N metabolism ; GO:0008152 19609 IPR000884

This repeat was first described in 1986 by Lawler and Hynes [MEDLINE:87057617]. It was found in the thrombospondin protein where it is repeated 3 times. Now a number of proteins involved in the complement pathway (properdin, C6, C7, C8A, C8B, C9) [MEDLINE:89011994] as well as extracellular matrix protein like mindin, F-spondin [MEDLINE:99339921], SCO-spondin and even the circumsporozoite surface protein 2 and TRAP proteins of Plasmodium [MEDLINE:99437997], [MEDLINE:92365736] contain one or more instance of this repeat.It has been involved in cell-cell interraction, inhibition of angiogenesis [MEDLINE:99431835] and\ apoptosis [MEDLINE:97280690].

The intron-exon organisation of the properdin gene confirms the hypothesis \ that the repeat might have evolved by a process involving exon shuffling [MEDLINE:93038568].\ A study of properdin structure provides some information about the structure of\ the thrombospondin type I repeat [MEDLINE:91329374].

\ \ \N \N \N 19606 IPR000879 Guanylin, a 15-amino-acid peptide, is an endogenous ligand of the intestinal receptor guanylate cyclase-C, known as STaR [MEDLINE:95229161], [MEDLINE:93028409]. Upon receptor binding, guanylin increases the \ intracellular concentration of cGMP, it induces chloride secretion and decreases intestinal fluid \ absorption, ultimately causing diarrhoea [MEDLINE:92141235]. The peptide stimulates the enzyme through \ the same receptor binding region as the heat-stable enterotoxins [MEDLINE:93028409].\ \ enzyme activator activity ; GO:0008047 \N \N 19607 IPR000881 Myotoxins [MEDLINE:91071443], [MEDLINE:91320359] are small basic peptides found in rattlesnake venom that cause severe muscle necrosis by a non-enzymatic mechanism. The peptides act very rapidly, causing \ instantaneous paralysis of the limbs to limit the flight of prey, and promoting death by paralysis of \ the diaphragm. Myotoxins have a well-conserved structure containing 6 cysteine residues, which are \ involved in 3 disulphide bridges.\ \ toxin activity ; GO:0015070 extracellular ; GO:0005576 \N 19608 IPR000883 Cytochrome c oxidase (EC: 1.9.3.1) is a key enzyme in aerobic metabolism. Proton pumping heme-copper oxidases represent the terminal, energy-transfer enzymes of respiratory chains in prokaryotes and eukaryotes. The CuB-heme a3 (or heme o) binuclear center, associated with the largest subunit I of cytochrome c and ubiquinol oxidases (EC: 1.10.3.-), is directly involved in the coupling between dioxygen reduction and proton pumping [MEDLINE:94364936], [MEDLINE:94325870].Some terminal oxidases generate a transmembrane proton gradient across the plasma membrane (prokaryotes) or the mitochondrial inner membrane (eukaryotes).

The enzyme complex consists of 3-4 subunits (prokaryotes) up to 13 polypeptides (mammals) of which only the catalytic subunit (equivalent to mammalian subunit I (CO I)) is found in all heme-copper respiratory oxidases. The presence of a bimetallic center (formed by a high-spin heme and copper B) as well as a low-spin heme, both ligated to six conserved histidine residues near the outer side of four transmembrane spans within CO I is common to all family members [MEDLINE:94283376], [MEDLINE:83257235], [MEDLINE:88054981]. In contrast to eukaryotes the respiratory chain of prokaryotes is branched to multiple terminal oxidases. The enzyme complexes \ vary in heme and copper composition, substrate type and substrate affinity. The different respiratory oxidases allow the cells to customize their respiratory systems according to a variety of environmental growth conditions [MEDLINE:94364936]. The PRINTS signature (PR01165) is specific for cytochrome c and does not recognise the other enzymes in this family.

It has been shown that eubacterial quinol oxidase was derived from cytochrome c oxidase in Gram-positive bacteria and that archaebacterial quinol oxidase has an independent origin. A considerable amount of evidence suggests that Proteobacteria (Purple bacteria) acquired quinol oxidase through a lateral gene transfer from Gram-positive bacteria\ \ \ \ [MEDLINE:94364936].

\ \

Nitric oxide reductase (NOR) (EC: 1.7.99.7) exists in denitrifying species of archae and eubacteria and is a heterodimer of cytochromes b and c. Phenazine methosulfate can act as acceptor. The prosite signature in this entry recognises the heme-copper site of the nitric oxidases.

\ \ cytochrome c oxidase activity ; GO:0004129 membrane ; GO:0016020 electron transport ; GO:0006118 19605 IPR000878 Uroporphyrin-III C-methyltransferase (EC: 2.1.1.107) (SUMT) [MEDLINE:91310569], [MEDLINE:91310599] catalyzes thetransfer of two methyl groups from S-adenosyl-L-methionine to the C-2 and C-7 atoms of uroporphyrinogen \ III to yield precorrin-2 via the intermediate formation of precorrin-1. SUMT is the first enzyme \ specific to the cobalamin pathway and precorrin-2 is a common intermediate in the biosynthesis of\ corrinoids such as vitamin B12, siroheme and coenzyme F430. The sequences of SUMT from a variety of \ eubacterial and archaebacterial species are currently available. In species such as Bacillus megaterium \ (gene cobA), Pseudomonas denitrificans (cobA) or Methanobacterium ivanovii (gene corA) SUMT is a protein \ of about 25 to 30 kD. In Escherichia coli and related bacteria, the cysG protein, which is involved in \ the biosynthesis of siroheme, is a multifunctional protein composed of a N-terminal domain, probably\ involved in transforming precorrin-2 into siroheme, and a C-terminal domain which has SUMT activity. The \ sequence of SUMT is related to that of a number of P. denitrificans and Salmonella typhimurium enzymes \ involved in the biosynthesis of cobalamin which also seem to be SAM-dependent methyltransferases \ [MEDLINE:91008976], [MEDLINE:93273696]. The similarity is especially strong with two of these enzymes, cobI/cbiL \ (S-adenosyl-L-methionine--precorrin-2 methyltransferase) and cobM/cbiF, whose exact function is not known.\ \ methyltransferase activity ; GO:0008168 \N metabolism ; GO:0008152 19604 IPR000877 The Bowman-Birk inhibitor family [MEDLINE:80264016] is one of the numerous families of serine proteinase inhibitors. They have a duplicated structure and generally possess two distinct inhibitory sites.\ These inhibitors are found in the seeds of all leguminous plants as well as in cereal grains. In \ cereals they exist in two forms, one of which is a duplication of the basic structure [MEDLINE:88032948].\ \ serine protease inhibitor activity ; GO:0004867 extracellular ; GO:0005576 \N 19602 IPR000875 Cecropins [MEDLINE:88075837], [MEDLINE:91199190], [MEDLINE:92007880] are potent antibacterial proteins that constitute a main part of the cell-free immunity of insects. Cecropins are small proteins of about 35 amino acid \ residues active against both Gram-positive and Gram-negative bacteria. They seem to exert a lytic \ action on bacterial membranes. Cecropins isolated from insects other than Cecropia have been given \ various names; bactericidin, lepidopteran, sarcotoxin, etc. All of these peptides are structurally \ related. Cecropin P1, an intestinal antibacterial peptide from pig, also belongs to this family.\ \ \N \N \N 19603 IPR000876

\ \ \

A number of eukaryotic and archaeal ribosomal proteins can be grouped on the basis of \ sequence similarities. One of these families includes yeast S7 (YS6); archaeal S4e; and \ mammalian and plant cytoplasmic S4 [MEDLINE:91084849]. Two highly similar isoforms of mammalian S4 \ exist, one coded by a gene on chromosome Y, and the other on chromosome X. These proteins have \ 233 to 264 amino acids.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 19599 IPR000872 Tafazzins [MEDLINE:96224398] are expressed at high levels in cardiac and skeletal muscle. As many as 10 isoforms can be present in different amounts in different tissues. Isoforms with hydrophobic N-termini \ are thought to be membrane anchored, while shorter forms, lacking the hydrophobic stretch, may be\ cytoplasmic (these latter are found in leukocytes and fibroblasts, but not in heart and skeletal muscle). \ A central hydrophilic domain may serve as an exposed loop that interacts with other proteins. Defects \ in taz are the cause of Barth syndrome, a severe inherited disorder, often fatal in childhood. The \ disease is characterised by cardiac and skeletal myopathy, short stature and neutropenia [MEDLINE:96224398].\ \ \N \N \N 19600 IPR000873 A number of prokaryotic and eukaryotic enzymes, which appear to act via an ATP-dependent covalent binding of AMP to their substrate, share a region of sequence similarity [MEDLINE:90360984], [MEDLINE:89098418], \ [MEDLINE:91072253]. This region is a Ser/Thr/Gly-rich domain that is further characterised by a conserved \ Pro-Lys-Gly triplet. The family of enzymes includes luciferase, long chain fatty acid Co-A ligase, \ acetyl-CoA synthetase and various other closely-related synthetases.\ \ enzyme activity ; GO:0003824 \N metabolism ; GO:0008152 19595 IPR000868 This is a family of hydrolase enzymes. Isochorismatase, also known as 2,3 dihydro-2,3 dihydroxybenzoatesynthase catalyses the conversion of isochorismate, in the presence of water, to 2,3-dihydroxybenzoate\ and pyruvate.\ \ enzyme activity ; GO:0003824 \N metabolism ; GO:0008152 19596 IPR000869

Fungi-IV (family 11) MTs are \ proteins of about 55-56 residues, with 9 conserved cysteines. Its members are recognised by the sequence pattern C-X-K-C-x-C-x(2)-C-K-C. \ The taxonomic range of the members extends to ascomycotina. \ The protein contains a number of unusual histidine and phenylalanine residues conserved in the N-terminal part of the sequence. This fragment does not contain any Cys. The protein binds to copper ions.

\ \ copper ion binding activity ; GO:0005507 \N \N 19594 IPR000867 The insulin-like growth factors (IGF-I and IGF-II) bind to specific binding proteins in extracellular fluids with high affinity [MEDLINE:93190524], [MEDLINE:92248096], PUB00005513. These IGF-binding\ proteins (IGFBP) prolong the half-life of the IGFs and have been shown to either inhibit or \ stimulate the growth promoting effects of the IGFs on cells culture. They seem to alter the \ interaction of IGFs with their cell surface receptors. There are at least six different IGFBPs and \ they are structurally related. The following growth-factor inducible proteins are structurally \ related to IGFBPs and could function as growth-factor binding proteins PUB00005513, [MEDLINE:92107157], \ mouse protein cyr61 and its probable chicken homolog, protein CEF-10; human connective tissue growth \ factor (CTGF) and its mouse homolog, protein FISP-12; and vertebrate protein NOV.\ \ insulin-like growth factor binding activity ; GO:0005520 extracellular ; GO:0005576 regulation of cell growth ; GO:0001558 19601 IPR000874 Bombesin-like peptides comprise a large family of peptides which were initially isolated from amphibianskin, where they stimulate smooth muscle contraction. They were later found to be widely distributed in \ mammalian neural and endocrine cells. The amphibian peptides which belong to this family are currently \ classified into three subfamilies [MEDLINE:84131098], [MEDLINE:86177052]; the Bombesin group, which includes bombesin and alytesin; the \ Ranatensin group, which includes ranatensins, litorin, and Rohdei litorin; and the Phyllolitorin group, \ which includes Leu(8)- and Phe(8)-phyllolitorins. In mammals and bbirds two categories of bombesin-like \ peptides are known PUB00005536, PUB00005536, gastrin-releasing peptide (GRP), which stimulates the \ release of gastrin as well as other gastrointestinal hormones, and neuromedin B (NMB), a neuropeptide \ whose function is not yet clear. Bombesin-like peptides, like many other active peptides, are synthesized \ as larger protein precursors that are enzymatically converted to their mature forms. The final peptides \ are eight to fourteen residues long.\ \ \N \N neuropeptide signaling pathway ; GO:0007218 19598 IPR000871 Beta-lactamase catalyses the opening and hydrolysis of the

-lactam ring of

-lactam antibiotics such as penicillins and cephalosporins. There are four groups, classed A, B, C and D according to \ sequence, substrate specificity, and kinetic behaviour. Class A (penicillinase-type) is the most \ common [MEDLINE:91311684]. The genes for class A

-lactamases are widely distributed in bacteria, \ frequently located on transmissable plasmids in Gram-negative organisms, although an equivalent \ chromosomal gene has been found in a few species [MEDLINE:89350885]. Class A, C and D

-lactamases are \ serine-utilising hydrolases, while class B enzymes utilise a catalytic zinc centre instead. The 3 \ classes of serine

-lactamase are evolutionarily related and belong to a superfamily that also \ includes DD-peptidases and other penicillin-binding proteins [MEDLINE:88183346]. All these proteins contain \ an S-x-x-K motif, the Ser being the active site residue. Although clearly related, however, the \ sequences of the 3 classes of serine

-lactamases vary considerably outside the active site.\ \ \N \N \N 19597 IPR000870 Saccharomyces cerevisiae strains containing the erg8-1 mutation are temperature sensitive for growth due to a defect in phosphomevalonate kinase, an enzyme of isoprene and ergosterol biosynthesis. \ Subcloning and DNA sequencing have defined the functional ERG8 regulon as an 850bp upstream region \ and an adjacent 1,272bp open reading frame. The deduced ERG8 protein contains 424 residues and shows \ no similarity to known proteins, except within a putative ATP-binding domain present in many kinases \ [MEDLINE:91117228]. Enzymes that share the N-terminal Gly/Ser-rich putative ATP-binding region include \ galactokinase, homoserine kinase, mevalonate kinase and phosphomevalonate kinase. Homoserine kinase \ is a homodimeric enzyme involved in threonine biosynthesis. Sequence comparison of the yeast enzyme \ with the corresponding proteins from bacterial sources reveals the presence of several highly conserved \ regions, the pattern of occurrence of which suggests that the ancestral sequences might have been \ composed from separate (functional) domains. A block of similar residues, found towards the C-terminus,\ is also present in many other proteins involved in threonine (or serine) metabolism; this motif may \ therefore represent the binding site for the hydroxy-amino acids. Limited similarity was detected \ between a motif conserved among the homoserine kinases and consensus sequences found in other mono- \ or dinucleotide-binding proteins [MEDLINE:90336619].\ \ ATP binding activity ; GO:0005524 \N threonine metabolism ; GO:0006566 19593 IPR000866

Peroxiredoxins (Prxs) are a ubiquitous family of antioxidant enzymes that also control cytokine-induced peroxide levels which mediate signal transduction in mammalian cells. Prxs can be regulated by changes to phosphorylation, redox and\ possibly oligomerization states. Prxs are divided into three classes: typical 2-Cys Prxs; atypical 2-Cys Prxs; and 1-Cys\ Prxs. All Prxs share the same basic catalytic mechanism, in which an active-site cysteine (the peroxidatic cysteine) is\ oxidized to a sulfenic acid by the peroxide substrate. The recycling of the sulfenic acid back to a thiol is what\ distinguishes the three enzyme classes. Using crystal structures, a detailed catalytic cycle has been derived for typical\ 2-Cys Prxs, including a model for the redox-regulated oligomeric state proposed to control enzyme activity [MEDLINE:22406502].

\ \ \

Alkyl hydroperoxide reductase (AhpC) is responsible for directly reducing organic hyperoxides in \ its reduced dithiol form. Thiol specific antioxidant (TSA) is a physiologically important antioxidant\ which constitutes an enzymatic defense against sulfur-containing radicals. This family contains AhpC \ and TSA, as well as related proteins.

\ \

The allergens in this family include allergens with the following designations: Asp f 3, Mal f 2 and Mal f 3.

\ \ \N \N \N 19592 IPR000865 Microbodies are a class of small, single membraned organelles to which belong peroxisomes, glyoxysomes, and glycosomes. Microbody proteins are synthesized on free polysomes and imported into the organelle \ post-translationally. Unlike the import of proteins into mitochondria, chloroplasts or the ER/secretion\ pathway, import into microbodies does not generally require the removal of a presequence [MEDLINE:93038490]. \ It has been experimentally shown [MEDLINE:88331117], [MEDLINE:89234155], [MEDLINE:90107964] that, in some peroxisomal \ proteins, the targeting signal (PTS) resides in the last three amino acids of the C-terminus. This \ consensus sequence is known as 'S-K-L' (Ser-Lys-Leu), although some variations are allowed in all three \ positions. As the peroxisomal targeting signal also seems to be recognized by other microbodies, it is \ now known [MEDLINE:93038490] as the C-terminal microbody targeting signal (CMTS). It must be noted that not \ all microbody proteins contain a CMTS, some seem to contain an internal CMTS-like sequence, but it is \ not yet known if it is active as such. A few proteins are synthesized with an N-terminal presequence \ which is cleaved off during import. Microbody proteins known or thought to contain a CMTS include\ mammalian D-amino acid oxidase, acyl-coenzyme A oxidase, carnitine o-acetyltransferase, trifunctional \ fatty acid

oxidation pathway enzyme, sterol carrier protein-2 high molecular form (SCP-X) and soluble \ epoxide hydrolase (sEH); mammalian, insect, plants, and Aspergillus uricase; firefly luciferase; plant \ glycolate oxidase, glyoxisomal isocitrate lyase and glyoxisomal malate synthase; Trypanosoma glycosomal \ glucose-6-phosphate isomerase and glycosomal glyceraldehyde 3-phosphate dehydrogenase; and yeast alcohol \ oxidase (AOX), dihydroxy-acetone synthase (DHAS), catalase A, citrate synthase, peroxisomal malate \ dehydrogenase, hydratase-dehydrogenase-epimerase (HDE) and isocitrate lyase.\ \ \N \N protein targeting ; GO:0006605 19590 IPR000863 This family includes a range of sulfotransferase proteins including flavonyl 3-sulfotransferase, aryl sulfotransferase, alcohol sulfotransferase, estrogen sulfotransferase and phenol-sulfating \ phenol sulfotransferase. These enzymes are responsible for the transfer of sulphate groups to \ specific compounds.\ \ sulfotransferase activity ; GO:0008146 \N \N 19591 IPR000864 Severe leaf damage to potato or tomato plants initiates the synthesis of 2 serine protease inhibitors throughout the plant, this systemic response being triggered by the release of a \ putative plant hormone PUB00004529. The inhibitors (designated type I and II) are also \ synthesised in potato tubers, increasing in concentration as the tuber develops. The family \ is widely distributed throughout nature, and includes type I potato inhibitor analogues such \ as leech eglin PUB00004529, barley endosperm chymotrypsin inhibitor [MEDLINE:87190479], and \ trypsin inhibitor from pumpkin. As such, it is the only family of protease inhibitor found in \ both plant and animal species. In general, the proteins have retained a specificity towards \ chymotrypsin-like and elastase-like proteases PUB00004529. Structurally these inhibitors are \ small (60 to 90 residues) and in contrast with other families of protease inhibitors, they lack \ disulfide bonds. The inhibitor is a wedge-shaped molecule, its pointed edge formed by the \ protease-binding loop, which contains the scissile bond. The loop binds tightly to the protease \ active site, subsequent cleavage of the scissile bond causing inhibition of the enzyme PUB00004529.\ \ serine protease inhibitor activity ; GO:0004867 \N response to wounding ; GO:0009611 19586 IPR000860 Porphobilinogen deaminase (PBGD), or hydroxymethylbilane synthase, is the third enzyme in the biosynthetic pathway of tetrapyrroles, which include the vitally important macrocycles haem, \ chlorophyll and corrin PUB00001079. PBGD catalyses the head-to-tail polymerisation of 4 molecules \ of porphobilinogen to assemble the open chain tetrapyrole, hydroxymethylbilane. PBGD is a \ ubiquitously occurring, monomeric protein, showing high sequence conservation among proteins from \ bacteria, fungi, plants and mammals. The protein contains a dipyrromethane cofactor, which is \ covalently attached to a cysteine side chain. The structure of PBGD shows the same chain fold\ as proteins from 2 classes of binding protein, the transferrins and the group-II periplasmic \ receptors (the sulphate-, phosphate-, maltodextrin- and lysine/arginine/ornithine-binding proteins). \ Despite structural similarities, there is no significant identity between their sequences.\ \ hydroxymethylbilane synthase activity ; GO:0004418 \N porphyrin biosynthesis ; GO:0006779 19587 IPR000860 Porphobilinogen deaminase (PBGD), or hydroxymethylbilane synthase, is the third enzyme in the biosynthetic pathway of tetrapyrroles, which include the vitally important macrocycles haem, \ chlorophyll and corrin PUB00001079. PBGD catalyses the head-to-tail polymerisation of 4 molecules \ of porphobilinogen to assemble the open chain tetrapyrole, hydroxymethylbilane. PBGD is a \ ubiquitously occurring, monomeric protein, showing high sequence conservation among proteins from \ bacteria, fungi, plants and mammals. The protein contains a dipyrromethane cofactor, which is \ covalently attached to a cysteine side chain. The structure of PBGD shows the same chain fold\ as proteins from 2 classes of binding protein, the transferrins and the group-II periplasmic \ receptors (the sulphate-, phosphate-, maltodextrin- and lysine/arginine/ornithine-binding proteins). \ Despite structural similarities, there is no significant identity between their sequences.\ \ hydroxymethylbilane synthase activity ; GO:0004418 \N porphyrin biosynthesis ; GO:0006779 19588 IPR000861 The REM repeat, which is also called rho effector or HR1 domain, wasfirst described as a three times repeated homology region of the\ N-terminal non-catalytic part of protein kinase PRK1(PKN) [MEDLINE:95154310]. \ The first two of these repeats were later shown to bind the small\ G protein rho [MEDLINE:96213692], [MEDLINE:98112814] known to activate PKN in its GTP-bound\ form. Similar rho-binding domains also occur in a number of other\ protein kinases and in the rho-binding proteins rhophilin and rhotekin. Recently, the structure of the N-terminal REM repeat complexed with RhoA has been determined by X-ray crystallography [MEDLINE:20085746]. It forms an antiparallel coiled-coil fold termed an ACC finger.\ \ \N intracellular ; GO:0005622 signal transduction ; GO:0007165 19589 IPR000862 DNA replication or DNA repair requires the concerted action of many enzymes, together with other proteins or cofactors. Among them three main accessory proteins. Replication factor C (RF-C), \ proliferating-cell nuclear antigen (PCNA) and replication protein A (RP-A), are essential for \ accurate and processive DNA synthesis by DNA polymerases. RF-C is a multiprotein complex consisting \ of one large and four small subunits with distinct functions. RF-C can bind to a template-primer \ junction and, in the presence of ATP, load the PCNA clamp onto DNA, thereby recruiting DNA \ polymerases to the site of DNA synthesis [MEDLINE:98321609]. Each of the five RF-C subunits as well as the \ prokaryotic clamp loader share seven regions of high similarity (termed RFC boxes II to VIII).\ These boxes are between 3 to 16 amino acids in length and the distances between them are similar \ in all subunits. In the four small subunits, these boxes are clustered within the N-terminal half \ of the polypeptide while they are centrally located in the large subunit [MEDLINE:95379808]. Proteins currently \ known to include this motif include yeast Replication Factor C (RFC); eukaryotic Activator 1 (AC1) \ protein; bacterial DNA Polymerase III delta' and TAU subunits; Drosophila Germline transcription \ factor 1 (GFN1); yeast RAD17/24 and CHL12 proteins; and bacteriophage DPA4 proteins. This profile is \ directed against a region covering modules VII and VIII. This region has an

-alpha-

structure and could, according to mutant phenotype, amino acids conservation and crystal\ structure, contain two ATP sensors being part of a nucleotide-binding pocket.\ \ DNA binding activity ; GO:0003677 DNA replication factor C complex ; GO:0005663 DNA replication ; GO:0006260 19583 IPR000857 The microtubule-based kinesin motors and actin-based myosin motors generate motions associated with intracellular trafficking, cell division, and muscle contraction. Early studies suggested that these molecular motors work by very different mechanisms. It has now become clear that kinesin and myosin share a common core structure and convert energy from adenosine triphosphate into protein motion using a similar conformational change strategy. Many different types of mechanical amplifiers have evolved that operate in conjunction with the conserved core. This modular design has given rise to a remarkable diversity of kinesin and myosin motors whose motile properties are optimized for performing distinct biological functions [MEDLINE:20217212].\ ATP binding activity ; GO:0005524 cytoskeleton ; GO:0005856 \N 19584 IPR000858 In Brassicaceae, self-incompatible plants have a self/non-self recognition system, which involves the inability of flowering plants to achieve self-fertilization. This is sporophytically controlled \ by multiple alleles at a single locus (S). There are a total of 50 different S alleles in B. oleracea.\ S-locus glycoproteins, as well as S-receptor kinases, are in linkage with the S-alleles [MEDLINE:95402702]. Most of the proteins within this family contain apple-like domain (IPR003609), which is predicted to possess protein- and/or carbohydrate-binding functions.\ \ \N \N \N 19585 IPR000859 The CUB domain is an extracellular domain of approximately 110 residues which is found in functionally diverse, mostly developmentally regulated proteins [MEDLINE:93287125], [MEDLINE:91224351]. Almost all CUB domains \ contain four conserved cysteines which probably form two disulfide bridges (C1-C2, C3-C4). The structure \ of the CUB domain has been predicted to be a

-barrel similar to that of immunoglobulins. Proteins \ that have been found to contain the CUB domain include mammalian complement subcomponents C1s/C1r, which \ form the calcium-dependent complex C1, the first component of the classical pathway of the complement \ system; hamster serine protease Casp, which degrades type I and IV collagen and fibronectin in the \ presence of calcium; mammalian complement-activating component of Ra-reactive factor (RARF), a protease \ that cleaves the C4 component of complement; vertebrate enteropeptidase (EC: 3.4.21.9), a type II \ membrane protein of the intestinal brush border, which activates trypsinogen; vertebrate bone \ morphogenic protein 1 (BMP-1), a protein which induces cartilage and bone formation and expresses \ metalloendopeptidase activity; sea urchins blastula proteins BP10 and SpAN; Caenorhabditis elegans \ hypothetical proteins F42A10.8 and R151.5; neuropilin (A5 antigen), a calcium-independent cell adhesion \ molecule that functions during the formation of certain neuronal circuits; fibropellins I and III from \ sea urchin; mammalian hyaluronate-binding protein TSG-6 (or PS4), a serum and growth factor induced \ protein; mammalian spermadhesins; and Xenopus embryonic protein UVS.2, which is expressed during \ dorsoanterior development.\ \ \N \N \N 19582 IPR000856

By contrast with vertebrate rhodopsin, which is found in rod cells, insectphotoreceptors are found in the ommatidia that comprise the compound eyes.\ Each Drosophila eye has 800 ommatidia, each of which contains 8 photoreceptor cells (designated R1-R8): R1-R6 are outer cells, while R7 and R8\ are inner cells. Opsins RH3 and RH4 are sensitive to UV light [MEDLINE:87218500], [MEDLINE:87197540], [MEDLINE:87197541].

\ \ rhodopsin-like receptor activity ; GO:0001584 integral to membrane ; GO:0016021 phototransduction ; GO:0007602 19580 IPR000853

Nematode (family 6) MTs are 62-74 \ residue proteins, containing 18 conserved cysteines and binding 6 cadmium ions. The protein also binds cations of several transition elements. The cysteine residues are arranged in C-X-C and X-C-C-X groups. In particular, the consensus pattern K-C-C-x(3)-C-C has been found to be diagnostic of family 6 metallothioneins. The protein is induced by cadmium, and is abundantly and exclusively expressed in the intestinal cells of larvae and adult animals \ Subfamilies of this family, n1 and n2, hit the same entry. It is known that the identity between n1 and n2 is about 60% and n2 is longer than n1.

\ \ \ calcium ion binding activity ; GO:0005509 \N \N 19581 IPR000855

Cysteine protease activity is dependent on an active dyad of cysteine andhistidine, the order and spacing of these residues varying in the 20 or so\ known families. Families C1, C2 and C10 are loosely termed papain-like.\ Nearly half of all cysteine proteases are found exclusively in viruses [MEDLINE:95147707].

\ \

Several adenovirus proteins are synthesised as precursors, requiring\ processing by a protease before the virion is assembled [MEDLINE:95147707], [MEDLINE:89024588]. Until\ recently, the adenovirus endopeptidase was classified as a serine protease,\ having been reported to be inhibited by serine protease inhibitors [MEDLINE:95147707], [MEDLINE:79226892].\ However, it has since been shown to be inhibited by cysteine protease\ inhibitors, and the catalytic residues are believed to be His-54 and\ Cys-104 [MEDLINE:95147707], [MEDLINE:89024588].

\ \ cysteine-type endopeptidase activity ; GO:0004197 \N proteolysis and peptidolysis ; GO:0006508 19579 IPR000852

Glycoside hydrolase family 52 CAZY:GH_52\ comprises enzymes with only one known activity; -xylosidase (EC: 3.2.1.37).

\ \

Proteins harboring -xylosidase and xylanase activities [MEDLINE:94354640]have been\ identified in the Gram-positive, facultative thermophilic aerobe Bacillus\ stearothermophilus 21 [MEDLINE:94354640]. This microbe, which functions in xylan\ degradation, can utilise xylan as a sole source of carbon. The enzyme\ hydrolyses 1,4--D-xylans, removing successive D-xylose residues from\ the non-reducing termini. It also hydrolyses xylobiose.

\ \ xylan 1,4-beta-xylosidase activity ; GO:0009044 \N carbohydrate metabolism ; GO:0005975 19577 IPR000850 Adenylate kinases (ADK) are phosphotransferases that catalyse the reversible reaction

\
AMP + MgATP = ADP + MgADP\

\ an essential reaction for many processes in living cells. Two ADK isozymes \ have been identified in mammalian cells. These specifically bind AMP and favour binding to ATP over \ other nucleotide triphosphates (AK1 is cytosolic and AK2 is located in the mitochondria). A third ADK \ has been identified in bovine heart and human cells [MEDLINE:84285416], this is a mitochondrial GTP:AMP \ phosphotransferase, also specific for the phosphorylation of AMP, but can only use GTP or ITP as a\ substrate [MEDLINE:79148362]. ADK has also been identified in different bacterial species and in yeast \ [MEDLINE:92267376]. Two further enzymes are known to be related to the ADK family, i.e. yeast uridine \ monophosphokinase and slime mold UMP-CMP kinase. Within the ADK family there are several conserved \ regions, including the ATP-binding domains. One of the most conserved areas includes an Arg residue, \ whose modification inactivates the enzyme, together with an Asp that resides in the catalytic cleft \ of the enzyme and participates in a salt bridge.\ \ ATP binding activity ; GO:0005524 \N \N 19578 IPR000851

\ \ \

Ribosomal protein S5 is one of the proteins from the small ribosomal subunit, and is a protein of \ 166 to 254 amino-acid residues. In Escherichia coli, S5 is known to be important in the assembly and \ function of the 30S ribosomal subunit. Mutations in S5 have been shown to increase translational \ error frequencies. It belongs to a family of ribosomal proteins which, on the basis of sequence \ similarities [MEDLINE:91061762], PUB00005070, groups bacterial, cyanelle, red algal chloroplast, \ archaeal and fungal mitochondrial S5; mammalian, C. elegans, Drosophila and plant S2; and yeast \ S4 (SUP44).

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 19572 IPR000846 Dihydrodipicolinate reductase (EC: 1.3.1.26) catalyzes the second step in the biosynthesis of diaminopimelic acid and lysine, the NAD or NADP-dependent reduction of 2,3-dihydrodipicolinate \ into 2,3,4,5-tetrahydrodipicolinate. This enzyme is present in bacteria (gene dapB) and higher \ plants.\ \ dihydrodipicolinate reductase activity ; GO:0008839 \N lysine biosynthesis via diaminopimelate ; GO:0009089 19573 IPR000846 Dihydrodipicolinate reductase (EC: 1.3.1.26) catalyzes the second step in the biosynthesis of diaminopimelic acid and lysine, the NAD or NADP-dependent reduction of 2,3-dihydrodipicolinate \ into 2,3,4,5-tetrahydrodipicolinate. This enzyme is present in bacteria (gene dapB) and higher \ plants.\ \ dihydrodipicolinate reductase activity ; GO:0008839 \N lysine biosynthesis via diaminopimelate ; GO:0009089 19574 IPR000847 Numerous bacterial transcription regulatory proteins bind DNA via a helix-turn-helix (HTH) motif. These proteins are very diverse, but for convenience may be grouped into subfamilies on the basis \ of sequence similarity. One such family, the lysR family, groups together a range of proteins, \ including ampR, catM, catR, cynR, cysB, gltC, iciA, ilvY, irgB, lysR, metR, mkaC, mleR, nahR, nhaR, \ nodD, nolR, oxyR, pssR, rbcR, syrM, tcbR, tfdS and trpI [MEDLINE:91317745], [MEDLINE:92276346], [MEDLINE:92106347], \ [MEDLINE:88320486], [MEDLINE:91239508]. The majority of these proteins appear to be transcription activators\ and most are known to negatively regulate their own expression. All possess a potential HTH \ DNA-binding motif towards their N-termini.\ \ transcription factor activity ; GO:0003700 \N regulation of transcription, DNA-dependent ; GO:0006355 19575 IPR000848

It has been suggested that the cAMP receptors coordinate aggregation of\ individual cells into a multicellular organism, and regulate the expression\ of a large number of developmentally-regulated genes [MEDLINE:88336877], [MEDLINE:93170665], [MEDLINE:93170666]. The amino acid\ sequences of the receptors contain high proportions of hydrophobic residues\ grouped into 7 domains, in a manner reminiscent of the rhodopsins and other\ receptors believed to interact with G-proteins. However, while a similar\ 3D framework has been proposed to account for this, there is no significant\ sequence similarity between these families: the cAMP receptors thus bear\ their own unique '7TM' signature.

\ \ \ G-protein coupled receptor activity ; GO:0004930 membrane ; GO:0016020 \N 19576 IPR000849

Proteins in this group are involved in the transport system that mediates the uptake of a number of sugar phosphates as well as the regulatory components that are responsible for induction of this transport system by external glucose 6-phosphate. In Escherichia coli its role in transmembrane signaling may involve sugar-phosphate-binding sites and transmembrane orientations similar to those of the transport protein [MEDLINE:87279903]. The following proteins in this entry, involved in the uptake of phosphorylated metabolites,are evolutionary related [MEDLINE:88298646], [MEDLINE:93174460]:\

E. coli, Bacillus subtilis and Haemophilus influenzae glycerol-3- phosphate transporter (gene glpT).
Salmonella typhimurium phosphoglycerate transporter (gene pgtP).
E. coli and S. typhimurium hexose-6-phosphate transporter (gene uhpT).
E. coli and S. typhimurium protein uhpC. UhpC is necessary for the expression of uhpT and seems to act jointly with the uhpB sensor/kinase protein.
Human glucose 6-phosphate translocase [MEDLINE:98088917].

These proteins of about 50 Kd apparently contain 12 transmembrane regions.

\ \ transporter activity ; GO:0005215 membrane ; GO:0016020 transport ; GO:0006810 19571 IPR000845 The following phosphorylases belong to the same family, purine nucleoside phosphorylase (EC: 2.4.2.1) (PNP) from most bacteria (gene deoD), which catalyzes the cleavage of guanosine or inosine to\ respective bases and sugar-1-phosphate molecules [MEDLINE:96068952]; uridine phosphorylase (EC: 2.4.2.3) \ (UdRPase) from bacteria (gene udp) and mammals, which catalyzes the cleavage of uridine into uracil \ and ribose-1-phosphate, the products of the reaction are used either as carbon and energy sources or \ in the rescue of pyrimidine bases for nucleotide synthesis [MEDLINE:95263571]; and 5'-methylthioadenosine \ phosphorylase (EC: 2.4.2.28) (MTA phosphorylase) from Sulfolobus solfataricus\ \ \ \ [MEDLINE:95014242]. It should \ be noted that mammalian and some bacterial PNP as well as eukaryotic MTA phosphorylase belong to a \ different family of phosphorylases.\ \ enzyme activity ; GO:0003824 \N nucleoside metabolism ; GO:0009116 19570 IPR000844

\ \

SUR1 is thought to be the sulphonylurea receptor isoform that is a\ constituent of the pancreatic cell KATP channel. Several mutations\ have been characterised in the human SUR1 gene, some of which are thought\ to be responsible for the rare inheritable metabolic disorder, familial\ persistent hyperinsulinemic hypoglycemia of infancy, which is characterised\ by excessive unregulated insulin secretion. SUR1 gene mutations may also\ underlie the varying sensitivity of some individuals to sulphonylurea\ oral hypoglycaemic agents [MEDLINE:98227644].

\ \ sulfonylurea receptor activity ; GO:0008281 membrane ; GO:0016020 potassium ion transport ; GO:0006813 19568 IPR000842 Phosphoribosyl pyrophosphate synthetase (EC: 2.7.6.1) (PRPP synthetase) catalyzes the formation of PRPP from ATP and ribose 5-phosphate. PRPP is then used in various biosynthetic pathways, for example \ in the formation of purines, pyrimidines, histidine and tryptophan. PRPP synthetase requires inorganic \ phosphate and magnesium ions for its stability and activity. In mammals, three isozymes of PRPP \ synthetase are found, while in yeast there are at least four isozymes. A very conserved region \ containing two conserved aspartic acid residues as well as a histidine has been suggested to be \ involved in binding divalent cations [MEDLINE:89255522]. These residues are all potential ligands for \ a cation such as magnesium.\ \ lipoate-protein ligase B activity ; GO:0016978 \N ribonucleoside monophosphate biosynthesis ; GO:0009156 19569 IPR000843 Numerous bacterial transcription regulatory proteins bind DNA via a helix-turn-helix (HTH) motif. These proteins are very diverse, but for convenience may be grouped into subfamilies on the basis \ of sequence similarity. One such family groups together a range of proteins, including ascG, ccpA, \ cytR, ebgR, fruR, galR, galS, lacI, malI, opnR, purF, rafR, rbtR and scrR [MEDLINE:92348454], [MEDLINE:92213266]. \ Within this family, the HTH motif is situated towards the N-terminus.\ \ transcription factor activity ; GO:0003700 intracellular ; GO:0005622 regulation of transcription, DNA-dependent ; GO:0006355 19565 IPR000839

The outer membrane-spanning (Oms) proteins of Borrelia burgdorferi have beenisolated and their porin activities characterised; 0.6-nS porin activity\ was found to reside in a 28 kD protein, designated Oms28 [MEDLINE:96326336]. The gene\ sequence of oms28 was found to encode a 257-amino-acid precursor protein\ with a putative 24-amino-acid leader peptidase I signal sequence [MEDLINE:96326336]. The\ Oms28 protein partly fractionated to the outer membrane, and was\ characterised by an average single-channel conductance of 1.1 nS in a\ planar lipid bilayer assay, confirming Oms28 to be a porin [MEDLINE:96326336].

\ \ transporter activity ; GO:0005215 membrane ; GO:0016020 transport ; GO:0006810 19566 IPR000840

The matrix protein (MA), also known as p15, is encoded along with other proteins by the gag gene of retroid viruses. The propeptide is enzymatically cleaved to release the mature proteins. MA is \ involved in pathogenicity of the virus [MEDLINE:93381801].

\ \ structural molecule activity ; GO:0005198 viral capsid ; GO:0019028 \N 19567 IPR000841

Metalloproteases can be split into five clans, and futher sub-divided into families, on the basis of their metal binding residues.

B-lytic endopeptidases are bacterial metallopeptidases that belong to the\ M23 protease family [MEDLINE:95405261], see protease database http://merops.sanger.ac.uk/merops.htm]. Cleavage is specific for glycine bonds,\ especially in -Gly-Gly+Xaa sequences (Xaa is any aliphatic hydrophobic\ residue). They lyse the cell walls of Gram positive bacteria in which the\ peptidoglycan cross-links contain glycine residues. The enzymes contain\ zinc, but the exact position of the metal-binding ligands is uncertain. On\ the basis of similarity with D-Ala-D-Ala-carboxypeptidase, it has been\ suggested that a conserved His-X-His motif (where X is any amino acid)\ forms part of the binding site [MEDLINE:95405261].

\ \

The protein sequence deduced from the nucleotide sequence reveals a mature\ enzyme of 179 residues [MEDLINE:91035265]. In the gene product from Achromobacter lyticus,\ an additional 195 amino acids at the N-terminal end of the protein include\ the signal peptide, indicating that the enzyme is synthesised as a\ precursor [MEDLINE:91035265].

\ \ metalloendopeptidase activity ; GO:0004222 \N proteolysis and peptidolysis ; GO:0006508 19563 IPR000837 Both the cellular and viral forms of the fos oncogene encode a phosphoprotein that is located in the nucleus of cells, and forms a noncovalent complex with several other proteins. A leucine zipper \ holds the dimer together. The dimer is associated with chromatin and demonstrates specific and non-specific DNA-binding properties [MEDLINE:88261282], the DNA being bound by a highly basic area in the \ protein sequence immediately preceding the zipper domain. Expression of the fos gene is stimulated by \ mitogens, suggesting that the gene product is involved in cell growth [MEDLINE:83221560], and may act as a \ nuclear signal in a more general sense. The 'leucine zipper' is a structure that is believed to mediate \ the function of several eukaryotic gene regulatory proteins. The zipper consists of a periodic \ repetition of leucine residues at every seventh position, and regions containing them appear to span \ 8 turns of

-helix. The leucine side chains that extend from one helix interact with those from a \ similar helix, hence facilitating dimerisation in the form of a coiled-coil. Leucine zippers are present \ in many gene regulatory proteins, including the CREB proteins, Jun/AP1 transcription factors, fos \ oncogene and fos-related proteins, C-myc, L-myc and N-myc oncogenes, and so on.\ \ DNA binding activity ; GO:0003677 nucleus ; GO:0005634 \N 19564 IPR000838 Sigma factors [MEDLINE:89024591] are bacterial transcription initiation factors that promote the attachment of the core RNA polymerase to specific initiation sites and are then released. They alter \ the specificity of promoter recognition. Most bacteria express a multiplicity of sigma factors. With \ regards to sequence similarity, sigma factors can be grouped into two classes, the sigma-54 and\ sigma-70 families. The sigma-70 family includes, in addition to the primary sigma factors, a wide \ variety of sigma factors. It also includes a divergent subfamily [MEDLINE:94329558] that regulates \ genes encoding proteins with extracytoplasmic functions. The proteins that are currently known to \ belong to this sigma factor subfamily, known as ECF, include Pseudomonas aeruginosa algU; Myxococcus \ xanthus carQ; Alcaligenes eutrophus plasmid pMOL28-encoded cnrH; E. coli fecI; Pseudomonas syringae\ hrpL; rpoE from E. coli, Salmonella typhimurium and Haemophilus influenzae; Streptomyces coelicolor\ sigE; and Bacillus subtilis sigma factors sigV, sigX, sigY and sigZ.\ \ sigma factor activity ; GO:0016987 \N regulation of transcription, DNA-dependent ; GO:0006355 19559 IPR000833 Alpha amylase inhibitor inhibits mammalian

-amylases specifically, by forming a tight stoichiometric 1:1 complex with

-amylase. The inhibitor has no action on plant and microbial

amylases.\ \ endopeptidase inhibitor activity ; GO:0004866 \N \N 19560 IPR000834

The carboxypeptidase A family (M14) can be divided into two subfamilies:carboxypeptidase H (regulatory) and carboxypeptidase A (digestive) [MEDLINE:95405261].\ Members of the H family have longer C-termini than those of family A [MEDLINE:93080735],\ and carboxypeptidase M (a member of the H family) is bound to the membrane\ by a glycosylphosphatidylinositol anchor, unlike the majority of the M14\ family, which are soluble [MEDLINE:95405261].

\ \

The zinc ligands have been determined as two histidines and a glutamate,\ and the catalytic residue has been identified as a C-terminal glutamate,\ but these do not form the characteristic metalloprotease HEXXH motif [MEDLINE:95405261], [MEDLINE:83294519].\ Members of the carboxypeptidase A family are synthesised as inactive\ molecules with propeptides that must be cleaved to activate the enzyme.\ Structural studies of carboxypeptidases A and B reveal the propeptide to\ exist as a globular domain, followed by an extended -helix; this\ shields the catalytic site, without specifically binding to it, while the\ substrate-binding site is blocked by making specific contacts [MEDLINE:95405261], [MEDLINE:92194312].

\ \ \ carboxypeptidase A activity ; GO:0004182 \N proteolysis and peptidolysis ; GO:0006508 19561 IPR000835 Numerous bacterial transcription regulatory proteins bind DNA via a helix-turn-helix (HTH) motif. These proteins are very diverse, but for convenience may be grouped into subfamilies on the basis \ of sequence similarity [MEDLINE:95247664], [MEDLINE:95302970]. One such family, marR, groups together a range \ of proteins, including emrR, hpcR, hpR, marR, pecS, petP, papX, prsX, ywaE, yxaD and yybA. The Mar \ proteins are involved in the multiple antibiotic resistance, a non-specific resistance system. The \ expression of the mar operon is controlled by a repressor, MarR. A large number of compounds \ induce transcription of the mar operon. This is thought to be due to the compound binding to MarR, \ and the resulting complex stops MarR binding to the DNA. With the MarR repression lost, transcription \ of the operon proceeds [MEDLINE:97221583].\ \ transcription factor activity ; GO:0003700 intracellular ; GO:0005622 regulation of transcription, DNA-dependent ; GO:0006355 19562 IPR000836 Members of PRT family are catalytic and regulatory proteins involved in nucleotide synthesis and salvage. The name PRT comes from phosphoribosyltransferase enzymes, which carry out phosphoryl transfer reactions on PRPP, an activated form of ribose-5-phosphate. This family includes a range of diverse phosphoribosyl transferase enzymes including adenine phosphoribosyltransferase (EC: 2.4.2.7); hypoxanthine-guanine-xanthine phosphoribosyltransferase; hypoxanthine phosphoribosyltransferase (EC: 2.4.2.8); ribose-phosphate pyrophosphokinase (EC: 2.7.6.1);\ amidophosphoribosyltransferase (EC: 2.4.2.14); orotate phosphoribosyltransferase (EC: 2.4.2.10);\ uracil phosphoribosyltransferase (EC: 2.4.2.9); and xanthine-guanine phosphoribosyltransferase \ (EC: 2.4.2.22). Not all PRT proteins are enzymes. For example, in some bacteria PRT proteins regulate the expression of purine and pyrimidine synthetic genes. Members of the family are defined by the protein fold and by a short sequence motif, that was correctly predicted to be a PRPP-binding site. Apart of this motif, different PRT proteins have a low level of sequence identity, less than 15%. The PRT sequence motif is only found in PRTases from the nucleotide synthesis and salvage pathways. Other PRTases, from the tryptophan, histidine and nicotinamide synthetic and salvage pathways, lack the PRT sequence motif and are not members of this family.\ \ \N \N nucleoside metabolism ; GO:0009116 19557 IPR000831 This protein is an aporepressor that works as a homodimer. When complexed with L-Trp, it binds to the operator region of the Trp operon at a specific sequence (5'-ACTAGT-3'), and prevents the \ initiation of transcription. The complex also regulates Trp repressor biosynthesis by binding to \ its own regulatory region.\ \ transcription factor activity ; GO:0003700 \N regulation of transcription, DNA-dependent ; GO:0006355 19558 IPR000832

\ \ \ G-protein coupled receptor activity ; GO:0004930 membrane ; GO:0016020 \N 19554 IPR000828 Monellin is an intensely sweet-tasting protein derived from African berries. The protein has a very high specificity for the sweet receptors, making it ~100,000 times sweeter than sugar on a molar \ basis and several thousand times sweeter on a weight basis. Like the sweet-tasting protein thaumatin, \ it neither contains carbohydrates nor modified amino acids. Although there is no sequence similarity \ between the proteins, antibodies for thaumatin compete for monellin (and other sweet compounds, but \ not for chemically modified non-sweet monellin) and vice versa [MEDLINE:87287292]. It is thought that native \ conformations are important for the sweet taste. Monellin is a heterodimer, comprising an A chain of \ 44 amino acid residues, and a B chain of 50 residues. The individual subunits are not sweet, nor do \ they block the sweet sensation of sucrose or monellin. However, blocking the single SH of monellin \ abolishes its sweetness, as does reaction of its methionyl residue with CNBr [MEDLINE:91136778]. The \ cysteinyl and methionyl residues are adjacent, and it has therefore been suggested that this part of \ the molecule is essential for its sweetness [MEDLINE:76161292]. The structure of monellin belongs to the

class, a 5-stranded

-sheet sequestering a single

-helix. The A chain contributes \ 3 strands to the sheet.\ \ \N \N \N 19555 IPR000829 Diacylglycerol kinase (EC: 2.7.1.107) (DAGK) is an enzyme that catalyzes the formation of phosphatidic acid from diacylglycerol and ATP, an important step in phospholipid biosynthesis. In bacteria DAGK is \ very small (13 to 15 kD) membrane protein which seems to contain three transmembrane domains [MEDLINE:94350829]. \ The best conserved region, is a stretch of 12 residues which are located in a cytoplasmic loop between \ the second and third transmembrane domains.\ \ diacylglycerol kinase activity ; GO:0004143 membrane ; GO:0016020 phospholipid biosynthesis ; GO:0008654 19556 IPR000830 The outer segments of vertebrate rod photoreceptor cells are specialised organelles that function in the transduction of light into electrical signals as part of the visual excitation process. These \ organelles contain thousands of closely-stacked disk membranes, which have distinctly different protein \ compositions in their lamellar and rim regions [MEDLINE:90321927]. Peripherin (or RDS) and rom-1 are related \ retinal-specific integral membrane proteins which are located at the rims of the photoreceptor disks, \ where they may act jointly in disk morphogenesis [MEDLINE:92304584]. Both peripherin and rom-1 form\ disulfide-linked homodimers. Defects in the peripherin gene (RDS) cause various human diseases such as\ autosomal dominant retinitis pigmentosa, autosomal dominant punctata albescens and butterfly-shaped \ pigment dystrophy. In mice it causes retinopathy known as 'retinal degeneration slow' (rds). These \ proteins contain about 350 amino acid residues. Structurally they consist of a short cytoplasmic \ N-terminal domain, followed by four transmembrane segments that delimit two lumenal and one cytoplasmic \ loops; the C-terminal domain is cytoplasmic. The second lumenal loop is very large (about 140 amino acid \ residues) and contains seven conserved cysteines.\ \ \N \N \N 19551 IPR000825 A number of hypothetical proteins have been shown to share sequence similarities. These have beenclassified into the uncharacterized protein family UPF0051. The functions of these proteins are not \ known.\ \ molecular_function unknown ; GO:0005554 \N \N 19552 IPR000826

Accumulation of phagocytic cells at sites of injury or infection is\ regulated by substances that stimulate chemotaxis, granule secretion,\ superoxide generation and up-regulation of cell surface adhesion molecules\ in cells of the immune system . The chemoattractant substances include\ bacterial N-formyl-methionyl peptides (typified by fMet-Leu-Phe (fMLP)),\ many of which participate in pathophysiological conditions, such as\ anaphylactic and septic shock . Three fMLP receptors have been\ identified: fMLP selectively activates the FPR1 receptor relative to\ the FPR2 receptor; its action on FPR3 is unknown. The FPR1 receptor is\ found in differentiated myeloid cells (i.e., neutrophils and monocytes),\ and in related cell lines; the FPR2 receptor is found only in neutrophils\ and monocytes (it binds fMLP at >1000 times higher concentrations than\ at the FPR1 receptor, and may bind other N-formyl-methionyl peptides\ with higher affinity) PUB00005670.

\ \ \ N-formyl peptide receptor activity ; GO:0004982 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19550 IPR000824 The mtr operon encodes a presumed RNA-binding regulatory protein that is required for attenuation control of the trp operon [MEDLINE:91062353]. The operon consists of two structural \ genes, mtrA and mtrB, predicted to encode 22-kD and 6-kD polypeptides respectively [MEDLINE:92202128]. \ MtrB is similar to RegA, an RNA-binding regulatory protein of bacteriophage T4. Both mtrA and mtrB \ have been shown to be necessary for regulation of

-galactosidase production. The crystal structure \ of the Trp RNA-binding attenuation protein of B. subtilis has been solved [MEDLINE:95055737], [MEDLINE:95231646]. \ The protein is an ondecamer of 7-stranded

-sandwiches. The 11 subunits are stabilised by 11 inter-subunit strands, forming a

-wheel with a large central hole. The binding of L-tryptophan in clefts \ between adjacent strands induces conformational changes in the protein. It is possible that, on binding, \ the mRNA target forms a matching circle in which 11 U/GAG repeats are bound to the surface of the \ protein ondecamer modified by the binding of L-tryptophan [MEDLINE:95231646].\ \ RNA binding activity ; GO:0003723 \N regulation of transcription, DNA-dependent ; GO:0006355 19553 IPR000827 Many low-molecular weight factors secreted by cells including fibroblasts, macrophages and endothelial cells, in response to a variety of stimuli such as growth factors, interferons, viral transformation \ and bacterial products, are structurally related [MEDLINE:92000517], [MEDLINE:91145332], [MEDLINE:90076753]. \ Most members of this family of proteins seem to have mitogenic, chemotactic or inflammatory activities. \ These small cytokines are also called intercrines or chemokines. They are cationic proteins of 70 to 100 \ amino acid residues that share four conserved cysteine residues involved in two disulfide bonds. These \ proteins can be sorted into two groups based on the spacing of the two amino-terminal cysteines. In the \ first group, the two cysteines are separated by a single residue (C-x-C), while in the second group, they \ are adjacent (C-C). The 'C-C' group is currently known to include monocyte chemotactic proteins 1 (MCP-1),\ 2 (MCP-2), 3 and 4; macrophage inflammatory protein 1

(MIP-1-

) and gamma \ (MIP-1-gamma); macrophage inflammatory protein 3

and

, 4 and 5; LD78

; SIS-epsilon (p500);\ thymus and activation-regulated chemokine (TARC); Eotaxin; I-309; human proteins HCC-1/NCC-2 and HCC-3;\ and mouse protein C10.\ \ chemokine activity ; GO:0008009 extracellular ; GO:0005576 immune response ; GO:0006955 19549 IPR000823 Peroxidases are haem-containing enzymes that use hydrogen peroxide asthe electron acceptor to catalyse a number of oxidative reactions.\ Most haem peroxidases follow the reaction scheme:\

\
Fe³⁺ + H₂O₂            --> [Fe⁴⁺=O]R' (Compound I) + H₂O\

\ \ \ \

\
[Fe⁴⁺=O]R' + substrate --> [Fe⁴⁺=O]R (Compound II) + oxidised substrate\

\ \ \ \

\
[Fe⁴⁺=O]R  + substrate -->  Fe³⁺ + H₂O + oxidised substrate\

\ \

Peroxidases are found in bacteria, fungi, plants and animals and can be\ viewed as members of a superfamily consisting of 3 major classes PUB00001075. Class III comprises the secretory \ plant peroxidases, which have multiple tissue-specific functions e.g., removal of hydrogen peroxide \ from chloroplasts and cytosol; oxidation of toxic compounds; biosynthesis of the cell wall; defence \ responses towards wounding; indole-3-acetic acid (IAA) catabolism; ethylene biosynthesis; and so on. \ The wide spectrum of peroxidase activity, coupled with the participation in various physiological \ processes, is in keeping with its relative lack of specificity for substrates and the occurence of \ a variety of isozymes PUB00001075. \ Plant peroxidases are monomeric glycoproteins containing 4 conserved disulphide bridges and 2 calcium \ ions. The 3D structure of peanut peroxidase has been shown to possess the same helical fold as class \ I and II peroxidases [MEDLINE:96398617].

\ \ \ peroxidase activity ; GO:0004601 \N peroxidase reaction ; GO:0006804 19547 IPR000820 The mas oncogene was discovered following co-transfection with DNA isolated from a human epidermal carcinoma PUB00005897. It efficiently induces tumorigenicity\ and has weak focus-inducing activity in NIH 3T3 cells. To date, it is the\ only oncogene to have been sequenced that encodes a 7TM protein . It has\ been claimed that mas is a receptor for angiotensin, but this view has not\ found wide acceptance. In the CNS, high levels of the mas oncogene\ transcript are present in the cerebral cortex, with lower amounts in the\ hippocampus and cerebellum. In the periphery, it is expressed in low levels\ in the kidney, adrenals and liver PUB00005897. The rat RTA protein has some\ similarity to the mas oncogene sequence.\ \ G-protein coupled receptor activity ; GO:0004930 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19548 IPR000821 Alanine racemase catalyses the pyridoxal-dependent conversion of L-alanine into D-alanine, a key component of bacterial peptidoglycan [MEDLINE:90328763]. In E. coli and S. typhimurium, there are two \ alanine racemase isoforms, alr is a biosynthetic form required for cell wall formation; and dadB \ functions in L-alanine catabolism. By contrast with dadB and alr, both of which are monomeric \ enzymes, the alanine racemase of Bacillaceae are homodimers. In P. putida, a broad-specificity \ amino acid racemase is structurally and functionally related to alanine racemase. The 3D-structure \ of the dimeric alanine racemase from B. stearothermophilus has been determined to a resolution of \ 1.9 A [MEDLINE:97178818]. Each monomer comprises two domains, with an eight-stranded

barrel \ at the N-terminus, and a C-terminal

-strand domain. In the dimer, the mouth of the

barrel of one monomer faces the second domain of the other monomer. The pyridoxal 5'-phosphate \ (PLP) cofactor lies in and above the barrel mouth and is covalently linked via an aldimine linkage \ to Lys39. Several other residues are involved in anchoring the PLP, for example, Arg219 forms a \ hydrogen bond with the pyridine nitrogen of the cofactor, which is assumed to influence electron \ delocalisation in PLP-alanine intermediates; Arg136 donates a hydrogen bond to the phenolic oxygen \ of PLP, and may be involved in substrate binding and stabilisation of intermediates; and Tyr265' \ is postulated to be a 2 proton donor to the carbanion intermediate [MEDLINE:97178818].\ \ alanine racemase activity ; GO:0008784 \N alanine metabolism ; GO:0006522 19546 IPR000819

Aminopeptidases are exopeptidases involved in the processing and regular\ turnover of intracellular proteins, although their precise role in cellular\ metabolism is unclear [MEDLINE:92209533], [MEDLINE:90370887]. Leucine aminopeptidases cleave leucine residues\ from the N-terminal of polypeptide chains, but substantial rates are evident\ for all amino acids [MEDLINE:90370887].

\ \

The enzymes exist as homo-hexamers, comprising 2 trimers stacked on top of\ one another [MEDLINE:90370887]. Each monomer binds 2 zinc ions and folds into 2 /-type quasi-spherical globular domains, producing a comma-like shape [MEDLINE:90370887]. The\ N-terminal 150 residues form a 5-stranded -sheet with 4 parallel and 1\ anti-parallel strand sandwiched between 4 -helices [MEDLINE:90370887]. An -helix\ extends into the C-terminal domain, which comprises a central 8-stranded\ saddle-shaped -sheet sandwiched between groups of helices, forming the\ monomer hydrophobic core [MEDLINE:90370887]. A 3-stranded -sheet resides on the surface\ of the monomer, where it interacts with other members of the hexamer [MEDLINE:90370887].\ The 2 zinc ions and the active site are entirely located in the C-terminal\ catalytic domain [MEDLINE:90370887].

\ \ \ aminopeptidase activity ; GO:0004177 intracellular ; GO:0005622 proteolysis and peptidolysis ; GO:0006508 19544 IPR000818 Transcriptional enhancer activators are nuclear proteins that contain a TEA/ATTSdomain, a DNA-binding region of 66-68 amino acids. The TEA/ATTS domain is found in the N-termini of certain gene regulatory proteins, such as the SV40 enhancer factor TEF-1, yeast trans-acting factor TEC-1 (which is required for TY1\ enhancer activity), and the Aspergillus abaA regulatory gene product.\ SV40 and retroviral enhancers, and those to which TEF-1, TEC-1 and abaA\ proteins bind, contain GT-IIC sites: the TEA/ATTS domain may therefore recognise\ and bind such sites.\ Secondary structure predictions suggest the presence of 3 helices, but have\ not confirmed the presence of the helix-turn-helix motif characteristic of\ many DNA-binding proteins: DNA-binding may therefore be effected by a\ different mechanism [MEDLINE:91300541].\ \ transcription factor activity ; GO:0003700 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 19545 IPR000819

\ \

\ \ \ aminopeptidase activity ; GO:0004177 intracellular ; GO:0005622 proteolysis and peptidolysis ; GO:0006508 19543 IPR000817

Prion protein (PrP-c) [MEDLINE:90024956], [MEDLINE:92008960], [MEDLINE:91134832] is a small glycoprotein found in high quantity in the brain of animals infected with certain degenerative neurological diseases, such as \ sheep scrapie and bovine spongiform encephalopathy (BSE), and the human dementias Creutzfeldt-Jacob \ disease (CJD) and Gerstmann-Straussler syndrome (GSS). PrP-c is encoded in the host genome and is \ expressed both in normal and infected cells. During infection, however, the PrP-c molecule become \ altered (conformationally rather than at the amino acid level) to an abnormal isoform, PrP-sc. In detergent-treated brain extracts from infected individuals, fibrils\ composed of polymers of PrP-sc, namely scrapie-associated fibrils or prion rods, can be evidenced by electron microscopy. The precise function of the normal PrP isoform in healthy individuals remains unknown. Several results, mainly obtained in transgenic animals, indicate that PrP-c\ might play a role in long-term potentiation, in sleep physiology, in oxidative burst compensation (PrP can fix four Cu2+ through its octarepeat domain), in\ interactions with the extracellular matrix (PrP-c can bind to the precursor of the laminin receptor, LRP), in apoptosis and in signal transduction (costimulation of\ PrP-c induces a modulation of Fyn kinase phosphorylation) [MEDLINE:22241617].

The normal isoform, PrP-c, is anchored at the cell membrane, in rafts, through a glycosyl phosphatidyl inositol (GPI); its half-life at the cell surface is 5 h, after which\ the protein is internalised through a caveolae-dependent mechanism and degraded in the endolysosome compartment. Conversion between PrP-c and PrP-sc\ occurs likely during the internalisation process.

In humans, PrP is a 253 amino acid protein, which has a molecular weight of 3536 kDa. It has two hexapeptides\ and repeated octapeptides at the N-terminus, a disulphide bond and is associated at the C-terminus with a GPI, which enables it to anchor to the external part of the\ cell membrane. The\ secondary structure of PrP-c is mainly composed of -helices, whereas PrP-sc is mainly -sheets: transconformation of -helices into -sheets has been\ proposed as the structural basis by which PrP acquires pathogenicity in TSEs. The three-dimensional structures shows the protein to be made of a globular domain which includes three -helices and two small antiparallel -sheet\ structures, and a long flexible tail whose conformation depends on the biophysical parameters of the environment. Crystals of the globular domain of PrP\ have recently been obtained; their analysis suggests a possible dimerisation of the protein through the three-dimensional swapping of the C-terminal helix 3 and\ rearrangement of the disulphide bond.

\ \ \N \N \N 19542 IPR000817

\ \ \N \N \N 19537 IPR000812 In eukaryotes, transcription initiation by polymerase II is modulated by both general and specific transcription factors. The general factors (which include TFIIA, TFIIB, TFIID, TFIIE, TFIIF, TFIIG \ and TFIIH) operate through common promoter elements, such as the TATA box. Transcription factor IIB \ (TFIIB) is of central importance in transcription of class II genes. It associates with TFIID-TFIIA \ bound to DNA (the DA complex) to form a ternary TFIID-IIA-IBB (DAB) complex, which is recognized by \ RNA polymerase II [MEDLINE:91342994], [MEDLINE:92055930]. TFIIB comprises ~315-340 residues and contains an \ imperfect C-terminal repeat of a 75-residue domain that may contribute to the symmetry of the folded \ protein.\ \ RNA polymerase II transcription factor activity ; GO:0003702 transcription factor complex ; GO:0005667 transcription initiation from Pol II promoter ; GO:0006367 19538 IPR000813 Ferredoxins [MEDLINE:86037262] are iron-sulphur proteins that mediate electron transfer in a range of metabolic reactions. The proteins fall into several subgroups according to the nature of their \ iron-sulphur cluster(s). The 7Fe ferredoxins [MEDLINE:90181428], [MEDLINE:89178673] contain both 4Fe-4S and \ 3Fe-4S centres. The 4Fe-4S domain is similar to those found in other bacterial-type ferredoxins.\ The 3D structure of the 7Fe ferredoxin from Azotobacter vinelandii has been determined to 1.9 A \ resolution [MEDLINE:89178673]. The fold belongs to the

class, with 3 helices and 4 strands \ forming a barrel-like structure, and an extruded loop containing 3 of the 4 cysteinyl residues of \ the iron-sulphur cluster.\ \ electron transporter activity ; GO:0005489 \N electron transport ; GO:0006118 19539 IPR000814 Transcription factor TFIID (also known as TATA-binding protein, TBP) is a general factor that plays a central role in the activation of eukaryotic genes transcribed by RNA polymerase II \ [MEDLINE:90326195], [MEDLINE:90326196]. TFIID binds specifically to the TATA-box promoter element, which \ lies close to the position of transcription initiation. The C-terminal domain (~180 residues) \ of eukaryotic TFIID sequences is highly conserved and is involved in TATA-box binding. The most \ striking feature of the domain is the presence of 2 conserved 77 amino-acid repeats. The \ symmetrical disposition of these features generates a saddle-shaped structure that straddles the \ DNA [MEDLINE:93063314]. Drosophila TRF (TBP-related factor), a sequence-specific transcription factor \ that also binds to the TATA-box, is highly similar to TFIID [MEDLINE:93156846].\ \ RNA polymerase II transcription factor activity ; GO:0003702 transcription factor TFIID complex ; GO:0005669 transcription initiation from Pol II promoter ; GO:0006367 19540 IPR000815 Proteins that transport heavy metals in micro-organisms and mammals share similarities in their sequences and structures. \

A conserved 30-residue domain has been found in a number of these heavy\ metal transport or detoxification proteins. The domain, which has been termed Heavy-Metal-Associated (HMA), contains two conserved cysteines that\ are probably involved in metal binding. \ The HMA domain has been identified in the N-terminal regions of a variety of cation-transporting ATPases (E1-E2 ATPases). In addition, the domain has been found in bacterial \ mercuric reductase; the copP copper-binding protein of Helicobacter pylori; and in the N-terminal \ regions of mercuric transport protein periplasmic component (gene merP) and plasmids carried by \ mercury-resistant Gram-negative bacteria, where it seems to be a mercury scavenger that specifically \ binds to one Hg⁽²⁺⁾ ion, passing this to mercuric reductase via the merT protein.

Mercuric reductase, \ which contains a single copy of the HMA domain, is involved in a specialised system that confers \ resistance to Hg⁽²⁺⁾ on catalysing the reaction:\

\
Hg + NADP⁺ + H⁺ = Hg²⁺ + NADPH\

\ The protein functions as a homodimer, with an FAD flavoprotein; its active site is a redox-active \ disulphide bond.

\ \ heavy metal binding activity ; GO:0005505 \N \N 19541 IPR000816

\ \

Pyrrolidone carboxyl peptidase (Pcp or PYRase) is an exopeptidase that\ hydrolytically removes the pGlu from pGlu-peptides or pGlu-proteins [MEDLINE:95124985], [MEDLINE:92339527].\ PYRase has been found in a variety of bacterial, plant and animal tissues.\ At least two different classes have been characterised, the first\ containing bacterial and animal type I PYRases, and the second containing\ animal type II and serum PYRases. Type I and bacterial PYRases are soluble\ enzymes, while type II PYRases are membrane-bound. The primary application\ of PYRase has been its utilisation for protein or peptide sequencing, and\ bacterial diagnosis [MEDLINE:92339527]. The conserved residues Cys-144 and His-168 have\ been identified by inhibition and mutagenesis studies [MEDLINE:95124985], [MEDLINE:94222834].

\ \ pyroglutamyl-peptidase I activity ; GO:0004219 \N proteolysis and peptidolysis ; GO:0006508 19536 IPR000811

Glycosyltransferase family 35 CAZY:GT_35\ comprises enzymes with only one known activity; glycogen and starch phosphorylase (EC: 2.4.1.1).

\ \

The main role of glycogen phosphorylase (GPase) is to provide phosphorylated glucose molecules (G-1-P) PUB00007032. GPase is a highly regulated allosteric enzyme. The net effect of the regulatory site allows the enzyme to operate at a variety of rates; the enzyme is not simply regulated as "on" or "off", but rather it can be thought of being set to operate at an ideal rate based on changing conditions at in the cell. The most important allosteric effector is the phosphate molecule covalently attached to Ser14.\ This switches GPase from the b (inactive) state to the a (active) state. Upon phosphorylation, GPase attains about 80% of its Vmax. When the enzyme is not phosphorylated, GPase activity is practically non-existent at low AMP levels PUB00006594.

\ There is some apparent controversy as to the structure of GPase. All sources agree that the enzyme is multimeric, but there is apparent controversy as to the enzyme being a tetramer or a dimer. Apparently, GPase (in the a\ form) forms tetramers in the crystal form. The consensus seems to be that 'regardless of the a or b form, GPase functions as a dimer in vivo PUB00006594. The GPase monomer is best described as consisting of two domains, an N-terminal domain and a C-terminal domain [MEDLINE:96394282]. The C-terminal domain is often referred to as the catalytic domain. It consists of a -sheet core surrounded by layers of helical segments [MEDLINE:89337752]. The vitamin cofactor pyridoxal phosphate (PLP) is covalently attached to the amino acid backbone. The N-terminal domain also consists of a central -sheet core and is surrounded by layers of helical segments. The N-terminal domain contains different allosteric effector sites to regulate the enzyme.

Bacterial phosphorylases follow the same catalytic mechanisms as their plant and animal counterparts, but differ considerably in terms of their substrate specificity and regulation. The catalytic domains are highly conserved while the regulatory sites are only poorly conserved. For maltodextrin phosphorylase from E.coli the physiological role of the enzyme in the utilisation of maltidextrins is known in detail; that of all the other bacterial phosphorylases is still unclear. Roles in regulatuon of endogenous glycogen metabolism in periods of starvation, and sporulation, stress response or quick adaptation to changing environments are possible [MEDLINE:99177556].

\ \ phosphorylase activity ; GO:0004645 \N carbohydrate metabolism ; GO:0005975 19534 IPR000809 Many flagellar proteins are exported by a flagellum-specific export pathway. Attempts have been made to characterise the apparatus responsible for this process, by designing assays to screen \ for mutants with export defects [MEDLINE:91258342]. Experiments involving filament removal from \ temperature-sensitive flagellar mutants of Salmonella typhimurium have shown that, while most \ mutants were able to regrow filaments, flhA, fliH, fliI and fliN mutants showed no or greatly \ reduced regrowth. This suggests that the corresponding gene products are involved in the process \ of flagellum-specific export. The sequences of fliH, fliI and the adjacent gene, fliJ, have been \ deduced. FliJ was shown to encode a protein of molecular mass 17,302 Da [MEDLINE:91258342]. It is a \ membrane-associated protein that affects chemotactic events, mutations in FliJ result in failure \ to respond to chemotactic stimuli.\ \ motor activity ; GO:0003774 flagellum (sensu Bacteria) ; GO:0009288 chemotaxis ; GO:0006935 19535 IPR000810

\ \ cannabinoid receptor activity ; GO:0004949 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19533 IPR000808 The Escherichia coli protein mrp is a 41 kD ATP-binding protein of unknown function. Homologs are present in other bacteria including Bacillus subtilis ybaL, Haemophilus influenzae HI1277, \ Synechocystis PCC 6803 slr0067; and also in eukaryotes, for example human NBP, yeast NBP35 and \ YIL003w, Caenorhabditis elegans F10G8.6; and in archaebacteria, for example Methanococcus jannaschii \ MJ0283.\ \ molecular_function unknown ; GO:0005554 \N \N 19532 IPR000807 Imidazoleglycerol-phosphate dehydratase (EC: 4.2.1.19) is the enzyme that catalyzes the seventh step in the biosynthesis of histidine in bacteria, fungi and plants. In most organisms it is a \ monofunctional protein of about 22 to 29 kD. In some bacteria such as Escherichia coli, it is the \ C-terminal domain of a bifunctional protein that include a histidinol-phosphatase domain \ [MEDLINE:89094829].\ \ imidazoleglycerol-phosphate dehydratase activity ; GO:0004424 \N histidine biosynthesis ; GO:0000105 19530 IPR000805

Glycoside hydrolase family 26 CAZY:GH_26).

\ \

Family 26 encompasses mainly mannan endo-1,4--mannosidases.\ Mannan endo-1,4--mannosidase hydrolyses mannan and galactomannan, but\ displays little activity towards other plant cell wall polysaccharides [MEDLINE:95150994]. The enzyme randomly hydrolyses 1,4--D-linkages in mannans, galacto-mannans, glucomannans and galactoglucomannans.

\ \ mannan endo-1,4-beta-mannosidase activity ; GO:0016985 \N mannan metabolism ; GO:0006080 19531 IPR000806 Rab proteins, a family of small Ras-related GTP-binding proteins, are involved in regulation of intracellular vesicle trafficking [MEDLINE:96062207]. Rab GDP dissociation inhibitor (GDI) forms a \ soluble complex with Rab proteins, thereby preventing exchange of GDP for GTP. Rab GDI exists in \ several isoforms, and belongs to the TCD/MRS6 family of GDP dissociation inhibitors. \

\ \ RAB GDP-dissociation inhibitor activity ; GO:0005093 \N protein transport ; GO:0015031 19529 IPR000804 Clathrin coated vesicles (CCV) mediate intracellular membrane traffic such as receptor mediated endocytosis. In addition to clathrin, the CCV are composed of a number of other components including \ oligomeric complexes which are known as adaptor or clathrin assembly proteins (AP) complexes \ [MEDLINE:91113395]. The adaptor complexes are believed to interact with the cytoplasmic tails of \ membrane proteins, leading to their selection and concentration. In mammals two type of adaptor \ complexes are known, AP-1 which is associated with the Golgi complex and AP-2 which is associated \ with the plasma membrane. Both AP-1 and AP-2 are heterotetramers that consist of two large chains, \ the adaptins, (gamma and

' in AP-1;

and

in AP-2); a medium chain (AP47 in AP-1; AP50 \ in AP-2) and a small chain (AP19 in AP-1; AP17 in AP-2). The small chains of AP-1 and AP-2 are \ evolutionary related proteins of about 18 kD. Homologs of AP17 and AP19 have also been found in yeast \ (genes APS1/YAP19 and APS2/YAP17) [MEDLINE:91250426], [MEDLINE:93385156], [MEDLINE:94208541]. AP17 and \ AP19 are also related to the zeta-chain [MEDLINE:94103328] of coatomer (zeta-cop), a cytosolic \ protein complex that reversibly associates with Golgi membranes to form vesicles that mediate \ biosynthetic protein transport from the endoplasmic reticulum, via the Golgi up to the trans Golgi \ network.\ \ \N clathrin vesicle coat ; GO:0030125 intracellular protein transport ; GO:0006886 19526 IPR000801 This family contains several seemingly unrelated proteins, including human esterase D; mycobacterial antigen 85, which is responsible for the high affinity of mycobacteria to \ fibronectin; Corynebacterium glutamicum major secreted protein PS1; and hypothetical proteins \ from E. coli, yeast, mycobacteria and Haemophilus influenzae.\ \ \N \N \N 19527 IPR000802

Arsenic is a toxic metalloid whose trivalent and pentavalent ions inhibita variety of biochemical processes. Operons that encode arsenic resistance\ have been found in multicopy plasmids from both gram-positive and\ gram-negative bacteria [MEDLINE:95238276]. The resistance mechanism is encoded from a single\ operon, which houses an anion pump. The pump has two polypeptide components:\ a catalytic subunit (the ArsA protein), which functions as an\ oxyanion-stimulated ATPase; and an arsenite export component (the ArsB protein),\ which is associated with the inner membrane [MEDLINE:90094396]. The ArsA and ArsB proteins\ are thought to form a membrane complex that functions as an\ anion-translocating ATPase.

The ArsB protein is distinguished by its overall hydrophobic character,\ in keeping with its role as a membrane-associated channel. Sequence\ analysis reveals the presence of 13 putative transmembrane (TM) regions.

\ \ arsenite transporter activity ; GO:0015105 integral to membrane ; GO:0016021 \N 19528 IPR000803

\ \ glucose transporter activity ; GO:0005355 membrane ; GO:0016020 transport ; GO:0006810 19524 IPR000799 Steroidogenic cells respond to trophic hormone stimulation by mobilisation of cholesterol from cellular stores to the mitochondrial outer membrane, and thence to the inner membrane, where the \ first enzymatic step in steroidogenesis occurs. Cholesterol transfer across the membranes is\ dependent on de novo protein synthesis, which is the regulated step in the process [MEDLINE:95050616]. \ The newly-synthesised regulatory protein(s) have yet to be identified. Nevertheless, a candidate \ mitochondrial protein has been characterised that is synthesised in response to luteinising hormone \ stimulation [MEDLINE:95050616]. Expression of the protein in the absence of hormone stimulation is \ sufficient to induce steroid production, suggesting that this protein is required in the acute \ regulation of steroidogenesis. This novel protein has been termed Steroidogenic Acute Regulatory \ protein (StAR).\ \ cholesterol transporter activity ; GO:0017127 \N steroid biosynthesis ; GO:0006694 19525 IPR000800 The Notch domain is also called the 'DSL' domain or the Lin-12/Notch repeat (LNR). The LNR region is present only in Notch related proteins C-terminal to EGF repeats. The lin-12/Notch proteinsact as transmembrane receptors for intercellular signals that specify cell fates during animal\ development. In response to a ligand, proteolytic cleavages release the intracellular domain of\ Notch, which then gains access to the nucleus and acts as a transcriptional co-activator [MEDLINE:88052858]. The\ LNR region is supposed to negatively regulate the Lin-12/Notch proteins activity. It is a triplication\ of an around 35-40 amino acids module present on the extracellular part of the protein [MEDLINE:95211842], [MEDLINE:94187845]. Each\ module contains six cysteine residues engaged in three disulfide bonds and three conserved aspartate\ and asparagine residues [MEDLINE:88052858]. The biochemical characterization of a recombinantly expressed LIN-12.1\ module from the human Notch1 receptor indicate that the disulfide bonds are formed between the first\ and fifth, second and fourth, and third and sixth cysteines. The formation of this particular disulfide\ isomer is favored by the presence of Ca²⁺, which is also required to maintain the structural integrity\ of the rLIN-12.1 module. The conserved aspartate and asparagine residues are likely to be important for\ Ca²⁺ binding, and thereby contribute to the native fold.\ \ \N membrane ; GO:0016020 cell differentiation ; GO:0030154 19523 IPR000798 The ERM family consists of three closely-related proteins, ezrin, radixin and moesin [MEDLINE:97200562].Ezrin was first identified as a constituent of microvilli [MEDLINE:83291254], radixin as a barbed, \ end-capping actin-modulating protein from isolated junctional fractions [MEDLINE:89291974], and moesin as a heparin\ binding protein [MEDLINE:88326223]. A tumour suppressor molecule responsible for neurofibromatosis type 2 (NF2)\ is highly similar to ERM proteins and has been designated merlin (moesin-ezrin-radixin-like protein).\ ERM molecules contain 3 domains, an N-terminal globular domain; an extended

-helical domain; and a\ charged C-terminal domain [MEDLINE:97200562]. Ezrin, radixin and merlin also contain a polyproline region between\ the helical and C-terminal domains. The N-terminal domain is highly conserved, and is also found in merlin,\ band 4.1 proteins and members of the band 4.1 superfamily. ERM proteins crosslink actin filaments with\ plasma membranes. They co-localise with CD44 at actin filament-plasma membrane interaction sites,\ associating with CD44 via their N-terminal domains and with actin filaments via their C-terminal domains\ [MEDLINE:97200562].\ \ \N \N \N 19521 IPR000796 Aspartate aminotransferase is important for the metabolism of amino acids and Krebs-cycle related organic acids. In plants, it is involved in nitrogen metabolism and in aspects of carbon and energy \ metabolism. The enzyme catalyses the reaction:\

\
L-aspartate + 2-oxoglutarate = oxaloacetate + L-glutamate\

\ Aminotransferases share certain mechanistic features with other pyridoxal-phosphate-dependent enzymes, such as the covalent binding of the pyridoxal-phosphate group to a lysine residue \ [MEDLINE:91115885]. This family includes some aromatic-amino-acid aminotransferases too.\ \ transaminase activity ; GO:0008483 \N amino acid metabolism ; GO:0006520 19522 IPR000797

The NSS proteins are encoded in the S RNA from ssRNA negative-strand viruses. The S RNA also codes for the nucleoprotein N. The two main products are read from overlapping reading frames in the viral complementary sequence.

\ \N \N \N 19519 IPR000794 Beta-ketoacyl-ACP synthase (EC: 2.3.1.41) (KAS) [MEDLINE:89351280] is the enzyme that catalyzesthe condensation of malonyl-ACP with the growing fatty acid chain. It is found as a component\ of a number of enzymatic systems, including fatty acid synthetase (FAS), which catalyzes the\ formation of long-chain fatty acids from acetyl-CoA, malonyl-CoA and NADPH; the \ multi-functional 6-methysalicylic acid synthase (MSAS) from Penicillium patulum\ \ \ \ [MEDLINE:91006137], which is\ involved in the biosynthesis of a polyketide antibiotic; polyketide antibiotic synthase enzyme\ systems; Emericella nidulans multifunctional protein Wa, which is involved in the biosynthesis\ of conidial green pigment; Rhizobium nodulation protein nodE, which probably acts as a

-ketoacyl synthase in the synthesis of the nodulation Nod factor fatty acyl chain; and yeast\ mitochondrial protein CEM1. The condensation reaction is a two step process, first the acyl\ component of an activated acyl primer is transferred to a cysteine residue of the enzyme and\ is then condensed with an activated malonyl donor with the concomitant release of carbon\ dioxide.\ \ enzyme activity ; GO:0003824 \N fatty acid biosynthesis ; GO:0006633 19520 IPR000795 Elongation factors belong to a family of proteins that promote the GTP-dependent binding of aminoacyltRNA to the A site of ribosomes during protein biosynthesis, and catalyse the translocation of the\ synthesised protein chain from the A to the P site. The proteins are all relatively similar in the vicinity of\ their C-termini, and are also highly similar to a range of proteins that includes the nodulation Q protein from\ Rhizobium meliloti, bacterial tetracycline resistance proteins [MEDLINE:88298672] and the omnipotent supressor\ protein 2 from yeast.

In both prokaryotes and eukaryotes, there are three distinct types of elongation\ factors, EF-1alpha (EF-Tu), which binds GTP and an aminoacyl-tRNAand delivers the latter to the A site of\ ribosomes; EF-1beta (EF-Ts), which interacts with EF-1a/EF-Tu to displace GDP and thus allows the\ regeneration of GTP-EF-1a; and EF-2 (EF-G), which binds GTP and peptidyl-tRNA and translocates the\ latter from the A site to the P site. In EF-1-, a specific region has been shown [MEDLINE:88163808] to be\ involved in a conformational change mediated by the hydrolysis of GTP to GDP. This region is conserved\ in both EF-1alpha/EF-Tu as well as EF-2/EF-G and thus seems typical for GTP-dependent proteins which\ bind non-initiator tRNAs to the ribosome. The GTP-binding elongation factor family also includes the\ eukaryotic peptide chain release factor GTP-binding subunits [MEDLINE:96016209] and prokaryotic peptide chain\ release factor 3 (RF-3) [MEDLINE:95256223]; the prokaryotic GTP-binding protein lepA and its homolog in yeast\ (GUF1) and C. elegans (ZK1236.1); yeast HBS1 [MEDLINE:93008247]; rat statin S1 [MEDLINE:91244818]; and the prokaryotic\ selenocysteine-specific elongation factor selB [MEDLINE:90066680].

\ \ \ GTP binding activity ; GO:0005525 \N translational elongation ; GO:0006414 19518 IPR000794 Beta-ketoacyl-ACP synthase (EC: 2.3.1.41) (KAS) [MEDLINE:89351280] is the enzyme that catalyzesthe condensation of malonyl-ACP with the growing fatty acid chain. It is found as a component\ of a number of enzymatic systems, including fatty acid synthetase (FAS), which catalyzes the\ formation of long-chain fatty acids from acetyl-CoA, malonyl-CoA and NADPH; the \ multi-functional 6-methysalicylic acid synthase (MSAS) from Penicillium patulum\ \ \ \ [MEDLINE:91006137], which is\ involved in the biosynthesis of a polyketide antibiotic; polyketide antibiotic synthase enzyme\ systems; Emericella nidulans multifunctional protein Wa, which is involved in the biosynthesis\ of conidial green pigment; Rhizobium nodulation protein nodE, which probably acts as a

-ketoacyl synthase in the synthesis of the nodulation Nod factor fatty acyl chain; and yeast\ mitochondrial protein CEM1. The condensation reaction is a two step process, first the acyl\ component of an activated acyl primer is transferred to a cysteine residue of the enzyme and\ is then condensed with an activated malonyl donor with the concomitant release of carbon\ dioxide.\ \ enzyme activity ; GO:0003824 \N fatty acid biosynthesis ; GO:0006633 19513 IPR000789 In eukaryotes, cyclin-dependent protein kinases interact with cyclins to regulate cell cycleprogression, and are required for the G1 and G2 stages of cell division [MEDLINE:88111540]. The\ proteins bind to a regulatory subunit, cyclin-dependent kinase regulatory subunit (CKS),\ which is essential for their function. This regulatory subunit is a small protein of 79 to 150\ residues. In yeast (gene CKS1) and in fission yeast (gene suc1) a single isoform is known,\ while mammals have two highly related isoforms. The regulatory subunits exist as hexamers,\ formed by the symmetrical assembly of 3 interlocked homodimers, creating an unusual \ 12-stranded

-barrel structure [MEDLINE:94023980]. Through the barrel centre runs a 12A diameter\ tunnel, lined by 6 exposed helix pairs [MEDLINE:93259467]. Six kinase units can be modelled to bind the\ hexameric structure, which may thus act as a hub for cyclin-dependent protein kinase\ multimerisation [MEDLINE:93259467], [MEDLINE:94023980].\ \ cyclin-dependent protein kinase activity ; GO:0004693 \N cell cycle ; GO:0007049 19514 IPR000790

\ \

\ \ \ \ \ \ \

The\ sequences of subunits and are related and both contain a\ nucleotide-binding site for ATP and ADP. They have a common amino terminal domain but vary at the C-terminal. The chain has catalytic\ activity, while the chain is a regulatory subunit.

\ \ ATP binding activity ; GO:0005524 \N proton transport ; GO:0015992 19515 IPR000791 Several uncharacterized proteins are evolutionary related, including Yarrowia lipolytica glyxoxylate pathway regulator GPR1; yeast protein FUN34 and hypothetical proteins YCR10c and YDR384c; fission \ yeast hypothetical protein SpAC5D6.09c; E. coli hypothetical protein yaaH; and Methanobacterium \ thermoautotrophicum hypothetical protein Mth215. They are hydrophobic proteins that seem to contain \ six transmembrane regions and which could therefore be involved in transport. They have from 188 to \ 283 amino acids.\ \ molecular_function unknown ; GO:0005554 membrane ; GO:0016020 \N 19516 IPR000792 The many bacterial transcription regulation proteins which bind DNA through a 'helix-turn-helix' motif can be classified into subfamilies on the basis of sequence similarities. One of\ these subfamilies [MEDLINE:91154130], [MEDLINE:90190362], [MEDLINE:91312138] which includes proteins with sizes ranging\ from 74 (gerE) to 901 amino acids (malT), can be further subdivided into two classes on the\ basis of the mechanism by which they are activated. The first is a class of regulators which\ belong to a two-component sensory transduction system where the protein is activated by its\ phosphorylation, generally on an aspartate residue, by a transmembrane kinase. The proteins\ that belong to this class include bvgA, comA, dctR; degU, evgA, fimZ, fixJ, gacA, glpR, narL,\ narP, nodW, rcsB and uhpA. The second is a class of regulators which is activated when\ bound to autoinducer molecules such as N-(3-oxohexanoyl)-L-homoserine lactone (OHHL)\ [MEDLINE:95058194]. The proteins that belong to this class are carR, echR, esaR, expR, lasR, luxR, phzR,\ rhlR, traR and yenR. The 'helix-turn-helix' DNA-binding motif of these proteins is located in the\ C-terminal section of the sequence.\ \ transcription factor activity ; GO:0003700 intracellular ; GO:0005622 regulation of transcription, DNA-dependent ; GO:0006355 19517 IPR000793

\ \

\ \ \ \ \ \ \

Vacuolar ATPases [MEDLINE:90078145] (V-ATPases) are responsible for acidifying a variety of\ intracellular compartments in eukaryotic cells. Like F-ATPases, they are\ oligomeric complexes of a transmembrane and a catalytic sector. The sequence\ of the largest subunit of the catalytic sector (70 Kd) is related to that of\ F-ATPase subunit, while a 60 Kd subunit, from the same sector, is related\ to the F-ATPases subunit [MEDLINE:89367309].\ Archaebacterial membrane-associated ATPases are composed of three subunits.\ The chain is related to F-ATPases chain and the chain is\ related to F-ATPases chain [MEDLINE:89367309].\ A protein highly similar to F-ATPase subunits is found [MEDLINE:93259961] in some\ bacterial apparatus involved in a specialized protein export pathway that\ proceeds without signal peptide cleavage. This protein is known as fliI in\ Bacillus subtilis and Salmonella typhimurium, Spa47 (mxiB) in Shigella flexneri, HrpB6 in\ Xanthomonas campestris and yscN in Yersinia pestis virulence plasmids.

In bacteria the chain is the regulatory subunit and the chain is the catalytic subunit. In V-type ATP synthase the archaeal chain is the catalytic subunit while the chain is the regulatory subunit.

\ \ \ ATP-binding and phosphorylation-dependent chloride channel activity ; GO:0005224 \N proton transport ; GO:0015992 19512 IPR000788

Ribonucleotide reductase (EC: 1.17.4.1) [MEDLINE:88225729], [MEDLINE:93289354] catalyzes the reductivesynthesis of deoxyribonucleotides from their corresponding ribonucleotides. It provides\ the precursors necessary for DNA synthesis. RNRs divide into three classes on the basis of their\ metallocofactor usage. Class I RNRs, found in eukaryotes, bacteria, bacteriophage and viruses, use a diiron-tyrosyl\ radical, Class II RNRs, found in bacteria, bacteriophage, algae and archaea, use coenzyme B12\ (adenosylcobalamin, AdoCbl). Class III RNRs, found in anaerobic bacteria and bacteriophage, use an FeS cluster\ and S-adenosylmethionine to generate a glycyl radical. Many organisms have more than one class of RNR present in\ their genomes.

Ribonucleotide reductase is an oligomeric\ enzyme composed of a large subunit (700 to 1000 residues) and a small subunit (300 to\ 400 residues) - class II RNRs are less complex, using the small molecule B12 in place of the small\ chain [MEDLINE:21912423].

The reduction of ribonucleotides to deoxyribonucleotides involves the transfer of free radicals,\ the function of\ each metallocofactor is to generate an active site thiyl radical. This thiyl radical then initiates the nucleotide reduction\ process by hydrogen atom abstraction from the ribonucleotide [MEDLINE:97454793]. The radical-based reaction involves five\ cysteines: two of these are located at adjacent anti-parallel strands in a\ new type of ten-stranded /-barrel; two others reside at the\ carboxyl end in a flexible arm; and the fifth, in a loop in the centre of\ the barrel, is positioned to initiate the radical reaction [MEDLINE:94329174]. There are several regions of similarity in the sequence of the large \ chain of prokaryotes, eukaryotes and viruses spread across 3 domains:\ an N-terminal domain common to the mammalian and bacterial enzymes; a\ C-terminal domain common to the mammalian and viral ribonucleotide \ reductases; and a central domain common to all three [MEDLINE:97454793].

\ \ ribonucleoside-diphosphate reductase activity ; GO:0004748 ribonucleoside-diphosphate reductase complex ; GO:0005971 DNA replication ; GO:0006260 19511 IPR000788

\ \ ribonucleoside-diphosphate reductase activity ; GO:0004748 ribonucleoside-diphosphate reductase complex ; GO:0005971 DNA replication ; GO:0006260 19505 IPR000782 The BIGH3 domain is an extracellular module of about 140 amino acids occurring as multiplerepeats in a limited number of proteins, including Drosophila fasciclin I, TGF-

induced\ protein Ig-H3, osteoblast-specific factor 2 (OSF-2) [MEDLINE:93371373], as\ well as several hypothetical proteins from plants, fungi, and protozoans. Interestingly, a few\ bacterial proteins also contain one copy of this domain, e.g. MPB70 from Mycobacterium\ bovis which has been implicated in vaccination-induced osteitis [MEDLINE:95122204].\ \ \N \N cell adhesion ; GO:0007155 19506 IPR000783 In eukaryotes, there are three different forms of DNA-dependent RNA polymerases (EC: 2.7.7.6)transcribing different sets of genes. Each class of RNA polymerase is an assemblage of ten to\ twelve different polypeptides. In archaebacteria, there is generally a single form of RNA\ polymerase which also consists of an oligomeric assemblage of 10 to 13 polypeptides.\ Archaebacterial subunit H (gene rpoH) [MEDLINE:99208760], [MEDLINE:92108064] is a small protein of about 8.5 to\ 10 kD, it is evolutionary related to the C-terminal part of a 23 kD component shared by all three\ forms of eukaryotic RNA polymerases (gene RPB5 in yeast and POLR2E in mammals).\ \ DNA-directed RNA polymerase activity ; GO:0003899 \N transcription ; GO:0006350 19507 IPR000784 This family includes the L2 minor capsid protein, a late protein from papillomaviruses.The papillomaviruses are dsDNA viruses with no RNA stage in their replication cycle.\ \ structural molecule activity ; GO:0005198 viral capsid ; GO:0019028 \N 19508 IPR000785 The equine Herpesvirus EHV1 protein belongs to a family of sequences that groups together HSV1 UL10, EHV1 52, VZV 50, EBV BBRF3, HVS1 39 and HCMV UL100. Little is yet known about the properties \ of the protein. However, its amino acid sequence is highly hydrophobic, containing 8 putative\ membrane-spanning regions, and it is therefore believed to be either membrane-associated or transmembrane.\ \ molecular_function unknown ; GO:0005554 membrane ; GO:0016020 \N 19509 IPR000786 The green fluorescent protein is found in the jellyfish (Aequorea victoria), and functions asan energy-transfer acceptor. It fluoresces in vivo upon receiving energy from the \ Ca²⁺-activated photoprotein aequorin. The protein absorbs light maximally at 395 nm and exhibits\ a smaller absorbance peak at 470 nm. The fluorescence emission spectrum peaks at 509 nm\ with a shoulder at 540 nm. The protein is produced in the photocytes and contains a covalently\ attached chromophore, which is composed of modified amino acid residues. The chromophore\ is formed upon cyclization of the residues ser-dehydrotyr-gly.\ \ \N \N energy pathways ; GO:0006091 19510 IPR000787

Metalloproteases can be split into five clans, and futher sub-divided into families, on the basis of their metal binding residues.

\ \

The thermophilic metallo-aminopeptidases (M29) are homo-dimeric enzymes that\ fall into the latter group, in which the metal-binding residues remain\ unknown.

\ \ \ aminopeptidase activity ; GO:0004177 \N proteolysis and peptidolysis ; GO:0006508 19503 IPR000780

\ \

Flagellated bacteria swim towards favourable chemicals and away from deleterious ones. Sensing of \ chemoeffector gradients involves chemotaxis receptors, transmembrane (TM) proteins that detect \ stimuli through their periplasmic domains and transduce the signals via their cytoplasmic domains \ PUB00005932, PUB00005932. Signalling outputs from these \ receptors are influenced both by the binding of the chemoeffector ligand to their periplasmic \ domains and by methylation of specific glutamate residues on their cytoplasmic domains. Methylation \ is catalysed by CheR, an S-adenosylmethionine-dependent methyltransferase [MEDLINE:97277239], which \ reversibly methylates specific glutamate residues within a coiled coil region, to form gamma-glutamyl methyl ester residues [MEDLINE:97277239], [MEDLINE:98290446]. The structure of the S. typhimurium \ chemotaxis receptor methyltransferase CheR, bound to S-adenosylhomocysteine, has been determined \ to a resolution of 2.0 A [MEDLINE:97277239]. The structure reveals CheR to be a two-domain protein, with \ a smaller N-terminal helical domain linked via a single polypeptide connection to a larger \ C-terminal / domain. The C-terminal domain has the characteristics of a nucleotide-binding \ fold, with an insertion of a small anti-parallel -sheet subdomain. The S-adenosylhomocysteine-binding site is formed mainly by the large domain, with contributions from residues within the \ N-terminal domain and the linker region [MEDLINE:97277239].

\ \ S-adenosylmethionine-dependent methyltransferase activity ; GO:0008757 \N chemotaxis ; GO:0006935 19502 IPR000780

\ \

\ \ S-adenosylmethionine-dependent methyltransferase activity ; GO:0008757 \N chemotaxis ; GO:0006935 19504 IPR000781 The Drosophila protein 'enhancer of rudimentary' (gene (e(r)) is a small protein of 104residues whose function is not yet clear. From an evolutionary point of view, it is highly\ conserved [MEDLINE:97228417] and has been found to exist in probably all multicellular\ eukaryotic organisms. It has been proposed that this protein plays a role in the cell cycle.\ \ molecular_function unknown ; GO:0005554 \N \N 19499 IPR000777 The entry of HIV requires interaction of viral GP120, an envelope glycoprotein with humanT-cell surface glycoprotein CD4 and a chemokine receptor on the cell surface. Proteins\ belonging to this family are found in HIV types 1 and 2, and Simian Immunodeficiency virus\ (SIV).\ \ \N viral envelope ; GO:0019031 \N 19500 IPR000778 Phagocytes form the first line of defence against invasion by micro-organisms.Engulfing of bacteria by neutrophils during phagocytosis is accompanied by a respiratory burst.\ Defects in phagocytosis involving the lack of a respiratory burst give rise to chronic \ granulomatous disease (CGD) [MEDLINE:96389574]. \

Regulation of the respiratory burst takes place at \ the phagocytic vacuole. The process is mediated by NADPH oxidase, which transports electrons \ across the plasma membrane to form superoxide in the vacuole interior. The electrons are carried \ across the membrane by a short electron transport chain in the form of an unusual flavocytochrome b.

The flavoprotein comprises 2 subunits, p21phox and gp91phox. Gp91phox has 2 major domains, an \ N-terminal, hydrophobic domain with a number of putative transmembrane helices that could associate \ to form a barrel-like pore in the membrane; and a more hydrophilic C-terminal domain, which\ probably lies on the cytosolic side of the membrane, capping the transmembrane structure \ [MEDLINE:96389574]. The C-terminal domain is similar to a number of electron-transport proteins, one of \ which, ferredoxin-NADP reductase, has provided a structural framework upon which to model this \ domain [MEDLINE:94073082].

Around two thirds of individuals with CGD inherit the disease in an X-linked, \ recessive manner. The gene responsible for X-linked CGD is that coding for the large subunit of \ flavocytochrome b, gp91phox.

\ \ oxidoreductase activity ; GO:0016491 membrane ; GO:0016020 electron transport ; GO:0006118 19501 IPR000779 T-Lymphocytes regulate the growth and differentiation of certain lymphopoietic andhaemopoietic cells through the release of various secreted protein factors [MEDLINE:85113172].\ These factors, which include interleukin-2 (IL2), are secreted by lectin- or antigen-stimulated\ T-cells, and have various physiological effects. IL2 is a lymphokine that induces the\ proliferation of responsive T-cells. In addition, it acts on some B-cells, via receptor-specific\ binding [MEDLINE:86205869], as a growth factor and antibody production stimulant [MEDLINE:92379010]. The\ protein is secreted as a single glycosylated polypeptide, and cleavage of a signal sequence\ is required for its activity [MEDLINE:86205869]. Solution NMR suggests that the structure of IL2 comprises a\ bundle of 4 helices (termed A-D), flanked by 2 shorter helices and several poorly-defined\ loops. Residues in helix A, and in the loop region between helices A and B, are important for\ receptor binding. Secondary structure analysis has suggested similarity to IL4 and \ granulocyte-macrophage colony stimulating factor (GMCSF) [MEDLINE:92379010].\ \ \ growth factor activity ; GO:0008083 extracellular ; GO:0005576 immune response ; GO:0006955 19496 IPR000774 Peptidyl-prolyl isomerases accelerate the folding of proteins, and the FKPA-type enzymes probablyact in the folding of extracytoplasmic proteins. They catalyze the cis-trans isomerization of \ proline imidic peptide bonds in oligopeptides. This family is only found at the amino terminus\ of proteins belonging to the IPR001179 family. This particular domain is of unknown function.\ \ \N \N protein folding ; GO:0006457 19497 IPR000775 Bindin, the major protein component of the acrosome granule of sea urchin sperm, mediates species-specific adhesion of sperm to the egg surface during fertilisation [MEDLINE:91122442], [MEDLINE:92130802]. The protein coats the acrosomal process after externalisation by the acrosome reaction; it binds to \ sulphated, fucose-containing polysaccharides on the vitelline-layer receptor proteoglycans that \ cover the egg plasma membrane. Bindins from different genera show high levels of sequence similarity \ in both the mature bindin domain and in the probindin precursor region. The most highly conserved \ region is a 42-residue segment in the central portion of the mature bindin protein. This domain may \ be responsible for conserved functions of bindin, while the more highly divergent flanking regions \ may be responsible for its species-specific properties [MEDLINE:91122442].\ \ \N \N binding/fusion of sperm to egg plasma membrane ; GO:0007342 19498 IPR000776 The fusion glycoproteins from this family are found in ssRNA negative-strand viruses.This protein directs fusion of viral and cellular membranes, resulting in viral penetration,\ and can direct fusion of infected cells with adjoining cells, resulting in the formation of\ syncytia. The mature form is a dimer of polypeptides F-1 and F-2 linked by a disulphide\ bond.\ \ viral-cell fusion molecule activity ; GO:0019039 \N viral-induced cell-cell fusion ; GO:0006948 19495 IPR000773 Granulocyte-macrophage colony-stimulating factor (GMCSF) is a cytokine that acts inhematopoiesis to stimulate growth and differentiation of hematopoietic precursor cells\ from various lineages including granulocytes, macrophages, eosinophils and erythrocytes\ [MEDLINE:89002704], [MEDLINE:92235844]. GMCSF is a glycoprotein of ~120 residues that contains 4 conserved\ cysteines that participate in disulphide bond formation. The crystal structure of recombinant\ human GMCSF has been determined [MEDLINE:92235844]. There are two molecules in the asymmetric\ unit, which are related by an approximate non-crystallographic 2-fold axis. The overall\ structure, which is highly compact and globular with a predominantly hydrophobic core, is\ characterised by a 4-

-helix bundle. The helices are arranged in a left-handed anti-parallel\ fashion, with two overhand connections. Within the connections is a two-stranded \ anti-parallel

-sheet. The tertiary structure has a topology similar to that of porcine growth\ factor and interferon-

. Most of the proposed critical regions for receptor binding are\ located on a continuous surface at one end of the molecule that includes the C terminus\ [MEDLINE:92235844].\ \ growth factor activity ; GO:0008083 extracellular ; GO:0005576 immune response ; GO:0006955 19493 IPR000771 Fructose-bisphosphate aldolase (EC: 4.1.2.13) [MEDLINE:90336970], [MEDLINE:93032118] is a glycolytic enzyme that catalyzes the reversible aldol cleavage or condensation of fructose-1,6-bisphosphate into \ dihydroxyacetone-phosphate and glyceraldehyde 3-phosphate. There are two classes of fructose-bisphosphate aldolases with different catalytic mechanisms. Class-II aldolases [MEDLINE:93032118], \ mainly found in prokaryotes and fungi, are homodimeric enzymes which require a divalent metal ion, \ generally zinc, for their activity. This family also includes the E. coli galactitol operon protein,\ gatY, which catalyzes the transformation of tagatose 1,6-bisphosphate into glycerone phosphate and \ D-glyceraldehyde 3-phosphate; and E. coli N-acetyl galactosamine operon protein, agaY, which \ catalyzes the same reaction. There are two histidine residues in the first half of the sequence of \ these enzymes that have been shown [MEDLINE:93170474] to be involved in binding a zinc ion.\ \ zinc ion binding activity ; GO:0008270 \N glycolysis ; GO:0006096 19494 IPR000772 Ricin is a legume lectin from the seeds of the castor bean plant, Ricinus communis. The seeds are poisonous to \ people, animals and insects and just one milligram of ricin can kill an adult. \ \

Primary structure analysis has shown the presence of a similar domain in many carbohydrate-recognition proteins like plant and bacterial AB-toxins, glycosidases or proteases [MEDLINE:98269113], [MEDLINE:95393205], [MEDLINE:97001848]. This domain, known as the ricin B lectin domain, can be present in one or more copies and has been shown in some instance to bind simple sugars, such as galactose or lactose.

The ricin B lectin domain is composed of three homologous subdomains of 40 amino acids (, and gamma) and a linker peptide of around 15 residues (lambda). It has been proposed that the ricin B lectin domain arose by gene triplication from a primitive 40 residue galactoside-binding peptide [MEDLINE:87173044], [MEDLINE:91352005]. The most characteristic, though not completely conserved, sequence feature is the presence of a Q-W pattern. Consequently, the ricin B lectin domain as also been refered as the (QxW)₃ domain and the three homologous regions as the QxW repeats [MEDLINE:95393205], [MEDLINE:97001848]. A disulfide bond is also conserved in some of the QxW repeats [MEDLINE:95393205].

The 3D structure of the ricin B chain has shown that the three QxW repeats pack around a pseudo threefold axis that is stabilised by the lambda linker [MEDLINE:87173044]. The ricin B lectin domain has no major segments of a helix or sheet but each of the QxW repeats contains an omega loop [MEDLINE:91352005]. An idealized omega-loop is a compact, contiguous segment of polypeptide that traces a 'loop-shaped' path in three-dimensional space; the main chain resembles a Greek omega.

\ \ \N \N \N 19490 IPR000768 Mono-ADP-ribosylation is a post-translational modification of proteins in which the ADP-ribose moiety of NAD is transferred to proteins. This process is responsible for the toxicity\ of some bacterial toxins (e.g., cholera and pertussis toxins). A family of \ mono(ADP-ribosyl)transferases exists in vertebrates that transfer ADP-ribose to arginine [MEDLINE:96355602].\

\
NAD⁺ + L-arginine = nicotinamide + N2-(ADP-D-ribosyl)-L-arginine\

\ At least five forms of the enzyme have been characterised to date, some of which are\ attached to the membrane via glycosylphosphatidylinositol (GPI) anchors, while others\ appear to be secreted. The enzymes contain ~250-300 residues, which encode putative\ signal sequences and carbohydrate attachment sites. In addition, the N- and C-termini are\ predominantly hydrophobic, a characteristic of GPI-anchored proteins [MEDLINE:95034708].\ \ NAD(P)+-arginine ADP-ribosyltransferase activity ; GO:0003956 \N protein amino acid ADP-ribosylation ; GO:0006471 19491 IPR000769 The Rop protein regulates plasmid DNA replication by modulating the initiation of transcription of the primer RNA precursor. Processing of the precursor, RNAII, is inhibited by hydrogen bonding \ of RNAII to its complementary sequence in RNAI. Rop increases the affinity of RNAI for RNAII and \ thus decreases the rate of replication initiation events. The 3D structure of Rop has been \ determined by X-ray crystallography and refined to 1.7A resolution. The 63 amino acid protein is \ a homodimer, each monomer consisting almost entirely of two

-helices, the whole molecule \ forming a highly regular four-

-helix bundle [MEDLINE:88062701]. This can be approximated by a \ four-stranded rope, with radius 7.0 A, a left-handed helical twist, and pitch 172.5 A. A very compact \ packing of side chains in the helix interfaces of the Rop coiled-coil structure is presumed to \ account for its high stability [MEDLINE:93044343]. The overall details of the structure have been\ confirmed by proton NMR [MEDLINE:93044343], [MEDLINE:91027752].\ \ transcription regulator activity ; GO:0030528 \N \N 19492 IPR000770

The SAND domain (named after Sp100, AIRE-1, NucP41/75, DEAF-1) is a conserved~80 residue region found in a number of nuclear proteins, many of which\ function in chromatin-dependent transcriptional control. These include\ proteins linked to various human diseases, such as the Sp100 (Speckled protein\ 100 kDa), NUDR (Nuclear DEAF-1 related), GMEB (Glucocorticoid Modulatory\ Element Binding) proteins and AIRE-1 (Autoimmune regulator 1) proteins.

\ Proteins containing the SAND domain have a modular structure; the SAND domain\ can be associated with a number of other modules, including the bromodomain, the PHD finger and the MYND finger.\ Because no SAND domain has been found in yeast, it is thought that the SAND\ domain could be restricted to animal phyla. Many SAND domain-containing\ proteins, including NUDR, DEAF-1 (Deformed epidermal autoregulatory factor-1)\ and GMEB, have been shown to bind DNA sequences specifically. The SAND domain\ has been proposed to mediate the DNA binding activity of these proteins [MEDLINE:98362750], [MEDLINE:21320923].

\ The resolution of the 3D structure of the SAND domain from Sp100b has revealed\ that it consists of a novel / fold. The SAND domain\ adopts a compact fold consisting of a strongly twisted, five-stranded\ antiparallel -sheet with four -helices packing against one side of\ the -sheet. The opposite side of the -sheet is solvent exposed. The -sheet and -helical parts of the structure form two distinct regions.\ Multiple hydrophobic residues pack between these regions to form a structural\ core. A conserved KDWK sequence motif is found within the -helical,\ positively charged surface patch. The DNA binding surface has been mapped to\ the -helical region encompassing the KDWK motif [MEDLINE:21320923].

\ \ DNA binding activity ; GO:0003677 nucleus ; GO:0005634 \N 19489 IPR000767

Plants are attacked by a range of phytopathegenic organisms, including viruses, mycoplasma, bacteria, fungi, nematodes, protozoa and parasites. Resistance to a pathogen is manifested in \ several ways and is often correlated with a hypersensitive response (HR), localised induced cell\ death in the host plant at the site of infection [MEDLINE:95249974]. The induction of the plant \ defense response that leads to HR is initiated by the plants recognition of specific signal \ molecules (elicitors) produced by the pathogen; R genes are thought to encode receptors for these \ elicitors. RPS2, N and L6 genes confer resistance to bacterial, viral and fungal pathogens.

\ Sequence analysis has shown that they contain C-terminal leucine-rich repeats, which are \ characteristic of plant and animal proteins involved in protein-protein interactions [MEDLINE:95249974]. \ In addition, the sequences contain a conserved nucleotide-binding site towards their N-termini.

\ \ defense/immunity protein activity ; GO:0003793 \N defense response ; GO:0006952 19487 IPR000764

Uridine kinase (pyrimidine ribonucleoside kinase) is the rate-limiting enzyme in the pyrimidinesalvage pathway. It catalyzes the following reaction:\

\
ATP + Uridine = ADP + UMP\

\ A cDNA for uridine kinase from mouse brain was found which encodes a protein of 277 amino\ acids. A truncated form of the cDNA was expressed in Escherichia coli, and shown to display uridine\ kinase activity and to readily form a tetramer, the most active form of the wild-type enzyme.\ Sequence analysis has identified three ATP-binding site consensus motifs. The predicted\ secondary structure, and sequence comparison with kinases of known structure, is consistent\ with uridine kinase having the

core nucleotide-binding fold common to many\ kinases [MEDLINE:97108719].

\ \ ATP binding activity ; GO:0005524 \N uridine kinase reaction ; GO:0006224 19488 IPR000766

\ \ UTP-hexose-1-phosphate uridylyltransferase activity ; GO:0003982 \N galactose metabolism ; GO:0006012 19485 IPR000762 Several extracellular heparin-binding proteins involved in regulation of growth and differentiationbelong to a new family of growth factors. These growth factors are highly related proteins of about\ 140 amino acids that contain 10 conserved cysteines probably involved in disulfide bonds, and\ include pleiotrophin [MEDLINE:91102543] (also known as heparin-binding growth-associated molecule HB-GAM,\ heparin-binding growth factor 8 HBGF-8, heparin-binding neutrophic factor HBNF and osteoblast specific\ protein OSF-1); midkine (MK) [MEDLINE:95408268]; retinoic acid-induced heparin-binding protein (RI-HB)\ [MEDLINE:91207359]; and pleiotrophic factors

-1and -2 and

Peroxidases are haem-containing enzymes that use hydrogen peroxide asthe electron acceptor to catalyse a number of oxidative reactions.\ Most haem peroxidases follow the reaction scheme:

\
Fe³⁺ + H₂O₂            --> [Fe⁴⁺=O]R' (Compound I) + H₂O\

\ \ \ \

\
[Fe⁴⁺=O]R' + substrate --> [Fe⁴⁺=O]R (Compound II) + oxidised substrate\

\ \ \ \

\
[Fe⁴⁺=O]R  + substrate -->  Fe³⁺ + H₂O + oxidised substrate\

\ \

Peroxidases are found in bacteria, fungi, plants and animals. In certain\ bacterial species, haemoproteins of 575-745 residues have been found that\ exhibit both peroxidase and catalase

\
2 H₂O₂ --> O2 + 2 H2O\

activities. It is thought that catalase-peroxidase provides protection to cells under\ oxidative stress [MEDLINE:92250436].

Bacterial catalase-peroxidases are approximately twice the size of plant \ and fungal haem peroxidases. Sequence analysis suggests that this doubling\ in length can be ascribed to gene duplication, whereby each half is similar\ to monomeric plant or fungal peroxidases. However, the C-terminal half does\ not bind haem, so the bacterial enzymes have a single haem per subunit [MEDLINE:92062697].

\ \ \ peroxidase activity ; GO:0004601 \N response to oxidative stress ; GO:0006979 19483 IPR000761

Melanocyte-stimulating hormones (MSH), adrenocorticotrophin (ACTH) and -endorphin are peptide products of pituitary pro-opiomelanocortin.\ MSH has a trophic action on melanocytes, and regulates pigment production\ in fish and amphibia . The MSH receptor is expressed in high levels in\ melanocytes, melanomas and their derived cell lines PUB00005891. Receptors are\ found in low levels in the CNS. MSH regulates temperature control in the\ septal region of the brain and releases prolactin from the pituitary.

\ \ \ melanocyte stimulating hormone receptor activity ; GO:0004980 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19484 IPR000762 Several extracellular heparin-binding proteins involved in regulation of growth and differentiationbelong to a new family of growth factors. These growth factors are highly related proteins of about\ 140 amino acids that contain 10 conserved cysteines probably involved in disulfide bonds, and\ include pleiotrophin [MEDLINE:91102543] (also known as heparin-binding growth-associated molecule HB-GAM,\ heparin-binding growth factor 8 HBGF-8, heparin-binding neutrophic factor HBNF and osteoblast specific\ protein OSF-1); midkine (MK) [MEDLINE:95408268]; retinoic acid-induced heparin-binding protein (RI-HB)\ [MEDLINE:91207359]; and pleiotrophic factors

-1and -2 and

-1 and -2 from Xenopus laevis\ \ \ \ [MEDLINE:95408268],\ the homologs of midkine and pleiotrophin respectively. Pleiotrophin is a heparin-binding protein that\ has neurotrophic activity [MEDLINE:91054508] and has mitogenic activity towards fibroblasts [MEDLINE:91102543].\ It is highly expressed in brain and uterus tissues, but is also found in gut, muscle and skin. It is\ thought to possess an important brain-specific function [MEDLINE:91054508]. Midkine is a regulator of\ differentiation whose expression is regulated by retinoic acid, and, like pleiotrophin, is a \ heparin-binding growth/differentiation factor that acts on fibroblasts and nerve cells [MEDLINE:92348340].\ \ \N \N \N 19481 IPR000759 Mitochondrial P450-containing systems comprise 3 components, an FAD-containing flavoprotein NADPH:adrenodoxin reductase (AR); an iron-sulphur protein, adrenodoxin; and P450 PUB00003474. \ The direction of electron flow is NADPH to AR to adrenodoxin to P450. FAD can be reduced by 2 \ electrons from NADPH, which are transferred one at a time to adrenodoxin, a one-electron carrier. \ Both AR and adrenodoxin are soluble proteins located on the matrix side of the inner mitochondrial \ membrane. Despite functional parallels, AR shows no global similarity either to flavoprotein \ pyridine nucleotide cytochrome reductases (FPNCR) or to FAD-dependent pyridine nucleotide \ reductases (FADPNR) PUB00003474. However, BLAST searches reveal local similarity of the \ N-terminal region of AR to glutamate synthase and NADH peroxidase, especially in the nucleotide-binding regions, suggesting that AR and FADPNR may be distantly related.\ \ \N \N electron transport ; GO:0006118 19482 IPR000760 It has been shown that several proteins share two sequence motifs [MEDLINE:92077133]. Two of theseproteins, vertebrate and plant inositol monophosphatase (EC: 3.1.3.25), and vertebrate inositol\ polyphosphate 1-phosphatase (EC: 3.1.3.57), are enzymes of the inositol phosphate second messenger\ signalling pathway, and share similar enzyme activity. Both enzymes exhibit an absolute requirement\ for metal ions (Mg²⁺ is preferred), and their amino acid sequences contain a number of conserved\ motifs, which are also shared by several other proteins related to MPTASE (including products of\ fungal QaX and qutG, bacterial suhB and cysQ, and yeast hal2) [MEDLINE:95281614]. The function of the\ other proteins is not yet clear, but it is suggested that they may act by enhancing the synthesis\ or degradation of phosphorylated messenger molecules [MEDLINE:92077133]. Structural analysis of these\ proteins has revealed a common core of 155 residues, which includes residues essential for metal\ binding and catalysis. An interesting property of the enzymes of this family is their sensitivity\ to Li⁺. The targets and mechanism of action of Li⁺ are unknown, but overactive inositol phosphate\ signalling may account for symptoms of manic depression [MEDLINE:90030415].\ \ inositol/phosphatidylinositol phosphatase activity ; GO:0004437 \N \N 19480 IPR000758 Virulence-related outer membrane proteins are expressed in Gram-negative bacteria and are essential to bacterial survival within macrophages and for eukaryotic cell invasion. Members of this group include:

PagC, required by Salmonella typhimurium for survival in macrophages and for virulence in mice [MEDLINE:92114784]

Rck outer membrane protein of the Salmonella typhimurium virulence plasmid [MEDLINE:96239012]

Ail, a product of the Yersinia enterocolitica chromosome capable of mediating bacterial adherence to and invasion of epithelial cell lines [MEDLINE:90130261]

OmpX from Escherichia coli that promotes adhesion to and entry into mammalian cells. It also has a role in the resistance against attack by the human complement system [MEDLINE:91100276]

a bacteriophage lambda outer membrane protein, Lom [MEDLINE:91100323]

The crystal structure of OmpX from Escherichia coli reveals that OmpX consists of an eight-stranded antiparallel all-next-neighbour barrel [MEDLINE:20015380]. The structure shows two girdles of aromatic amino acid residues and a ribbon of nonpolar residues that attach to the membrane interior. The core of the barrel consists of an extended hydrogen-bonding network of highly conserved residues. OmpX thus resembles an inverse micelle. The OmpX structure shows that the membrane-spanning part of the protein is much better conserved than the extracellular loops. Moreover, these loops form a protruding sheet, the edge of which presumably binds to external proteins. It is suggested that this type of binding promotes cell adhesion and invasion and helps defend against the complement system. Although OmpX has the same -sheet topology as the structurally related outer membrane protein A (OmpA) IPR000498, their barrels differ with respect to the shear numbers and internal hydrogen-bonding networks.

\ \ \N external outer membrane (sensu Gram-negative Bacteria) ; GO:0009279 \N 19477 IPR000755 The D-alanyl-D-alanine dipeptidase enzyme from Enterococcus is also known as thevancomycin resistance protein VanX, and hydrolyses D-ala-D-ala. It has a 250-fold\ differential in catalytic efficiency for hydrolysis of D-ala-D-ala versus D-ala-D-lactate.\ The latter therefore remains intact for subsequent incorporation into peptidoglycan\ precursors that terminate in the depsipeptide D-ala-D-lactate rather than the dipeptide\ D-ala-D-ala, thereby preventing vancomycin from binding. The enzyme requires a metal\ cofactor, and is induced by vancomycin through regulation by VanS and VanR.\ \ dipeptidase activity ; GO:0016805 cell wall ; GO:0005618 proteolysis and peptidolysis ; GO:0006508 19478 IPR000756 Diacylglycerol (DAG) is a second messenger that acts as a protein kinase C activator. The DAGkinase domain is assumed to be an accessory domain. Upon cell stimulation, DAG kinase converts\ DAG into phosphatidate, initiating the resynthesis of phosphatidylinositols and attenuating\ protein kinase C activity. It catalyzes the reaction: ATP + 1,2-diacylglycerol = ADP +\ 1,2-diacylglycerol 3-phosphate. The enzyme is stimulated by calcium and phosphatidylserine\ and phosphorylated by protein kinase C. This domain is always associated with IPR001206.\ \ diacylglycerol kinase activity ; GO:0004143 \N protein kinase C activation ; GO:0007205 19479 IPR000757

Glycoside hydrolase family 16 CAZY:GH_16).

\ \ hydrolase activity, hydrolyzing O-glycosyl compounds ; GO:0004553 \N carbohydrate metabolism ; GO:0005975 19473 IPR000751 M-phase inducer phosphatases function as dosage-dependent inducers in mitotic control[MEDLINE:92103683], [MEDLINE:91006056], [MEDLINE:94208523], [MEDLINE:93004945]. They are tyrosine protein phosphatases\ required for progression of the cell cycle. They may directly dephosphorylate p34(cdc2) and\ activate p34(cdc2) kinase activity. They catalyze the reaction:\

 \
protein tyrosine phosphate + H₂O = protein tyrosine + P_i\

\ \ protein tyrosine phosphatase activity ; GO:0004725 intracellular ; GO:0005622 protein amino acid dephosphorylation ; GO:0006470 19474 IPR000752 NS2A is a hydrophobic protein about 25 kD in size, which is cleaved from NS1 by a membrane bound host protease [MEDLINE:96013828]. NS2A has been found to associate with the dsRNA within the \ vesicle packages. It has also been found that NS2A associates with the known replicase \ components and so NS2A has been postulated to be part of this replicase complex [MEDLINE:98299989].\ \ \N \N \N 19475 IPR000753

Clusterin is a vertebrate glycoprotein [MEDLINE:92263476], the exact function of which is not yet clear. Clusterin expression is complex, appearing as different forms in\ different cell compartments. One set of proteins is directed for secretion, and other clusterin species are expressed in the\ cytoplasm and nucleus. The secretory form of the clusterin protein (sCLU) is targeted to the ER by an initial\ leader peptide. This ~60-kDa pre-sCLU protein is further glycosylated and proteolytically cleaved into - and -subunits, held together by disulfide bonds.\ External sCLU is an 80-kDa protein and may act as a molecular chaperone, scavenging denatured proteins outside cells following specific stress-induced injury such as heat shock. sCLU possesses nonspecific binding activity to hydrophobic domains of various proteins in vitro PUB00010653.

A specific nuclear form of CLU (nCLU) acts as a pro-death signal, inhibiting cell growth and\ survival. The\ nCLU protein has two coiled-coil domains, one at its N terminus that is unable to bind Ku70, and a C-terminal coiled-coil domain that is uniquely able to associate\ with Ku70 and is minimally required for cell death.

Clusterin is synthesized as a precursor \ polypeptide of about 400 amino acids which is post-translationally cleaved to form two subunits \ of about 200 amino acids each. The two subunits are linked by five disulfide bonds to form an\ antiparallel ladder-like structure PUB00010653. In each of the mature subunits the five \ cysteines that are involved in disulfide bonds are clustered in domains of about 30 amino acids \ located in the central part of the subunits.

\ \ \N \N cell death ; GO:0008219 19476 IPR000754

\ \ \

Ribosomal protein S9 is one of the proteins from the small ribosomal subunit. It belongs to a\ family of ribosomal proteins which, on the basis of sequence similarities [MEDLINE:90235982], PUB00005070,\ groups bacterial; algal chloroplast; cyanelle and archaeal S9 proteins; and mammalian;\ plant; and yeast mitochondrial ribosomal S9 proteins.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 19472 IPR000750 Vertebrate endogenous opioid neuropeptides are released by post-translational proteolytic cleavage of precursor proteins. The precursors consist of the following components: a signal sequence that precedes a conserved region of about 50 residues; a variable-length region; and the sequence of the neuropeptide itself. Three types of precursor are known: preproenkephalin A \ (gene PENK), which is processed to produce 6 copies of Met-enkephalin, plus \ Leu-enkephalin; preproenkephalin B (gene PDYN), which is processed to\ produce neoendorphin, dynorphin, leumorphin, rimorphin and Leu-enkephalin; \ and prepronocipeptin (gene PNOC), whose processing produces nociceptin\ (orphanin FQ) and two other potential neuropeptides.\

The primary structure of porcine preproenkephalin B has been elucidated and\ shown to contain neoendorphin, dynorphin and leumorphin (containing rimorphin as its N-terminus). \ These opioid peptides, each having a Leu-enkephalin structure, act on the kappa-receptor. The sequence \ similarity observed between preproenkephalin B and preproenkephalin A, coupled with the similarity \ between their gene organisations, suggests that the two genes have been generated from a common \ ancestor by gene duplication [MEDLINE:84068211].

\ \ \N \N neuropeptide signaling pathway ; GO:0007218 19471 IPR000749 ATP:guanido phosphotransferases are a family of structurally and functionally related enzymes [MEDLINE:90216675], [MEDLINE:95119082] that reversibly catalyze the transfer of phosphate between \ ATP and various phosphogens. The enzymes belonging to this family include glycocyamine kinase \ (EC: 2.7.3.1), which catalyzes the transfer of phosphate from ATP to guanidoacetate; arginine \ kinase (EC: 2.7.3.3), which catalyzes the transfer of phosphate from ATP to arginine; taurocyamine \ kinase (EC: 2.7.3.4), an annelid-specific enzyme that catalyzes the transfer of phosphate from ATP \ to taurocyamine; lombricine kinase (EC: 2.7.3.5), an annelid-specific enzyme that catalyzes the \ transfer of phosphate from ATP to lombricine; Smc74, a cercaria-specific enzyme from Schistosoma \ mansoni\ \ \ \ [MEDLINE:90216675]; and creatine kinase (EC: 2.7.3.2) (CK) [MEDLINE:85278009], [MEDLINE:90216724], which plays an important role in energy metabolism of vertebrates. It catalyzes the \ reversible transfer of high energy phosphate from ATP to creatine, generating phosphocreatine and \ ADP. There are at least four different, but very closely related, forms of CK. Two isozymes, M \ (muscle) and B (brain), are cytosolic, while the other two are mitochondrial. In sea urchin there \ is a flagellar isozyme, which consists of the triplication of a CK-domain. A cysteine residue is \ implicated in the catalytic activity of these enzymes and the region around this active site residue \ is highly conserved.\ \ transferase activity, transferring phosphorus-containing groups ; GO:0016772 \N \N 19469 IPR000748 Pseudouridine synthases (EC: 4.2.1.70) are responsible for the synthesis of pseudouridine from uracilin ribosomal RNA. Several bacterial proteins from the Rsu family of pseudouridine synthases [MEDLINE:95337112] have been shown to share regions of similarities, including Escherichia coli and Haemophilus \ influenzae 16S pseudouridylate 516 synthase (gene rsuA); Escherichia coli hypothetical proteins yciL and ymfC\ and the corresponding Haemophilus influenzae proteins HI1199 and HI0694 respectively; Aquifex aeolicus \ hypothetical proteins AQ_554 and AQ_1464; Bacillus subtilis hypothetical proteins ypuL and ytzF;\ Borrelia burgdorferi hypothetical protein BB0129; Helicobacter pylori hypothetical protein HP1459; and\ Synechocystis strain PCC 6803 hypothetical proteins slr0361 and slr0612. These are proteins of from 25 \ to 40 kD which contain a number of conserved regions in their central section.\ \ pseudouridylate synthase activity ; GO:0004730 \N \N 19470 IPR000749 ATP:guanido phosphotransferases are a family of structurally and functionally related enzymes [MEDLINE:90216675], [MEDLINE:95119082] that reversibly catalyze the transfer of phosphate between \ ATP and various phosphogens. The enzymes belonging to this family include glycocyamine kinase \ (EC: 2.7.3.1), which catalyzes the transfer of phosphate from ATP to guanidoacetate; arginine \ kinase (EC: 2.7.3.3), which catalyzes the transfer of phosphate from ATP to arginine; taurocyamine \ kinase (EC: 2.7.3.4), an annelid-specific enzyme that catalyzes the transfer of phosphate from ATP \ to taurocyamine; lombricine kinase (EC: 2.7.3.5), an annelid-specific enzyme that catalyzes the \ transfer of phosphate from ATP to lombricine; Smc74, a cercaria-specific enzyme from Schistosoma \ mansoni\ \ \ \ [MEDLINE:90216675]; and creatine kinase (EC: 2.7.3.2) (CK) [MEDLINE:85278009], [MEDLINE:90216724], which plays an important role in energy metabolism of vertebrates. It catalyzes the \ reversible transfer of high energy phosphate from ATP to creatine, generating phosphocreatine and \ ADP. There are at least four different, but very closely related, forms of CK. Two isozymes, M \ (muscle) and B (brain), are cytosolic, while the other two are mitochondrial. In sea urchin there \ is a flagellar isozyme, which consists of the triplication of a CK-domain. A cysteine residue is \ implicated in the catalytic activity of these enzymes and the region around this active site residue \ is highly conserved.\ \ transferase activity, transferring phosphorus-containing groups ; GO:0016772 \N \N 19466 IPR000744

Regulated exocytosis of neurotransmitters and hormones, as well as intracellular traffic, requires fusion of two lipidbilayers. SNARE proteins are thought to form a protein bridge, the SNARE complex, between an\ incoming vesicle and the acceptor compartment. SNARE proteins contribute to the specificity of membrane fusion , implying that the mechanisms by which SNAREs are targeted to subcellular compartments are important for specific docking and\ fusion of vesicles. This mechanism involves a family of conserved proteins, members of which appear to function at all sites of constitutive and regulated secretion in eukaryotes [MEDLINE:95149367]. Among them are 2 types of cytosolic protein, NSF (N-ethyl-maleimide-sensitive protein) and the SNAPs (-, - and gamma-soluble NSF attachment proteins). The yeast vesicular fusion protein,sec17, a cytoplasmic peripheral membrane protein involved in vesicular transport between the\ endoplasmic reticulum and the golgi apparatus, shows a high degree of sequence similarity to the -SNAP family.

SNAP-25 and its non-neuronal homologue Syndet/SNAP-23 are synthesized as soluble proteins in the cytosol. Both SNAP-25 and Syndet/SNAP-23 are palmitoylated at cysteine residues clustered in a loop\ between two N- and C-terminal coils and palmitoylation is essential for membrane binding and plasma membrane targeting. The C-terminal and the N-terminal helices of SNAP-25, are each targeted to the plasma membrane by two distinct cysteine-rich domains and appear to regulate the availability of SNAP to form complexes with SNARE [MEDLINE:22135753].

\ \ intracellular transporter activity ; GO:0005478 Golgi apparatus ; GO:0005794 intracellular protein transport ; GO:0006886 19467 IPR000745 NS4a (non-structural protein) forms an integral part of the NS3 serine protease in Hepatitis C virus, as it is required in a number of cases as a cofactor of cleavage [MEDLINE:98227846], [MEDLINE:97404652]. It has \ also been reported that NS4a interacts with NS4b and NS3 to form a multi-subunit replicase complex \ [MEDLINE:97404652].\ \ \N \N \N 19468 IPR000747 Proteins that regulate developmental gene expression are nuclear proteins [MEDLINE:89252815] that containa conserved domain known as the homeobox, the flanking sequences of which differ considerably among\ different proteins. The homeodomain includes the helix-turn-helix (HTH) motif which binds to DNA\ [MEDLINE:90245562]. Most proteins which contain a homeobox domain can be classified [MEDLINE:89323170], [MEDLINE:87234329],\ on the basis of their sequence characteristics, into three subfamilies, engrailed, antennapedia and\ paired. The engrailed subfamily plays an important role in Drosophila segmentation and neurogenesis,\ affecting genes in posterior compartments of the developing embryo. It is also required for the\ development of the central nervous system. Homologues found in other species may play a role in\ neurogenesis, possibly in both the compartmentalisation of the developing neural tube and specification\ of particular neuronal populations. Other members of the engrailed subfamily include Drosophila invected\ protein (inv); honeybee E30 and E60; grasshopper G-En; mammalian and birds En-1 and En-2; Zebrafish\ Eng-1, -2 and -3; leech Ht-En; and C. elegans ceh-16. The member proteins contain a conserved region of\ 20 amino acids located to the -terminal of the homeobox, the specific function of which is unclear.\ \ DNA binding activity ; GO:0003677 nucleus ; GO:0005634 development ; GO:0007275 19465 IPR000743

Glycoside hydrolase family 28 CAZY:GH_28); rhamnogalacturonase (EC not defined).

\ \

Polygalacturonase (PG) (pectinase) [MEDLINE:90381308], [MEDLINE:90299812] catalyzes the random\ hydrolysis of 1,4--D-galactosiduronic linkages in pectate and other galacturonans. In fruit,\ polygalacturonase plays an important role in cell wall metabolism during ripening. In plant\ bacterial pathogens such as Erwinia carotovora or Pseudomonas solanacearum and fungal\ pathogens such as Aspergillus niger, polygalacturonase is involved in maceration and \ soft-rotting of plant tissue. Exo-poly--D-galacturonosidase (EC: 3.2.1.82) (exoPG) [MEDLINE:90368550]\ hydrolyzes peptic acid from the non-reducing end, releasing digalacturonate. PG and exoPG share a\ few regions of sequence similarity, and belong to family 28 of the glycosyl hydrolases.

\ \ polygalacturonase activity ; GO:0004650 \N carbohydrate metabolism ; GO:0005975 19461 IPR000738 A conserved domain of 46 amino acids, called WHEP-TRS has been shown [MEDLINE:92097547] to exist in a number of higher eukaryote aminoacyl-transfer RNA synthetases. This domain is present one to six\ times in the several enzymes. There are three copies in mammalian multifunctional aminoacyl-tRNA \ synthetase in a region that separates the N-terminal glutamyl-tRNA synthetase domain from the \ C-terminal prolyl-tRNA synthetase domain, and six copies in the intercatalytic region of the Drosophila enzyme. The domain is found at the N-terminal extremity of the mammalian tryptophanyl-\ tRNA synthetase and histidyl-tRNA synthetase, and the mammalian, insect, nematode and plant glycyl-\ tRNA synthetases [MEDLINE:93216727]. This domain could contain a central

-helical region and \ may play a role in the association of tRNA-synthetases into multienzyme complexes.\ \ ATP binding activity ; GO:0005524 \N amino acid activation ; GO:0006418 19462 IPR000740 In prokaryotes the grpE protein [MEDLINE:94107583] stimulates, jointly with dnaJ, the ATPase activityof the dnaK chaperone. It seems to accelerate the release of ADP from dnaK thus allowing dnaK to\ recycle more efficiently. GrpE is a protein of about 22 to 25 kD. In yeast, an evolutionary related\ mitochondrial protein (gene GRPE) has been shown [MEDLINE:94222047] to associate with the mitochondrial\ hsp70 protein and to thus play a role in the import of proteins from the cytoplasm.\ \ \N \N \N 19463 IPR000741 Fructose-bisphosphate aldolase (EC: 4.1.2.13) [MEDLINE:90336970], [MEDLINE:93032118] is a glycolytic enzyme that catalyzes the reversible aldol cleavage or condensation of fructose-1,6-bisphosphate into \ dihydroxyacetone-phosphate and glyceraldehyde 3-phosphate. There are two classes of fructose-\ bisphosphate aldolases with different catalytic mechanisms. Class-I aldolases [MEDLINE:88183272], \ mainly found in higher eukaryotes, are homotetrameric enzymes which form a Schiff-base intermediate\ between the C-2 carbonyl group of the substrate (dihydroxyacetone phosphate) and the epsilon-amino \ group of a lysine residue. In vertebrates, three forms of this enzyme are found, aldolase A in muscle,\ aldolase B in liver and aldolase C in brain. The sequence around the lysine involved in the Schiff-base \ is highly conserved.\ \ fructose-bisphosphate aldolase activity ; GO:0004332 \N glycolysis ; GO:0006096 19464 IPR000742 A sequence of about thirty to forty amino-acid residues long found in the sequence of epidermalgrowth factor (EGF) has been shown [MEDLINE:91145344], [MEDLINE:85063790], PUB00004964, PUB00004964, [MEDLINE:88196363], PUB00001077\ to be present, in a more or less conserved form, in a large number of other, mostly animal proteins.\ The functional significance of EGF domains in what appear to be unrelated proteins is not yet clear.\ However, a common feature is that these repeats are found in the extracellular domain of \ membrane-bound proteins or in proteins known to be secreted (exception: prostaglandin G/H synthase). The\ EGF domain includes six cysteine residues which have been shown (in EGF) to be involved in\ disulfide bonds. The main structure is a two-stranded

-sheet followed by a loop to a C-terminal\ short two-stranded sheet. Subdomains between the conserved cysteines vary in length.\ \ \N \N \N 19458 IPR000736 Hexon is the major coat protein from adenovirus type 2, and is synthesised during late infection.It forms a homo-trimer. The 240 copies of the hexon trimer are organised so that 12 lie on each\ of the 20 facets. The central 9 hexons in a facet are cemented together by 12 copies of polypeptide\ IX. The penton complex, formed by the peripentonal hexons and base hexon (holding in place a\ fibre), lie at each of the 12 vertices [MEDLINE:95018210].\ \ structural molecule activity ; GO:0005198 viral capsid ; GO:0019028 \N 19459 IPR000736 Hexon is the major coat protein from adenovirus type 2, and is synthesised during late infection.It forms a homo-trimer. The 240 copies of the hexon trimer are organised so that 12 lie on each\ of the 20 facets. The central 9 hexons in a facet are cemented together by 12 copies of polypeptide\ IX. The penton complex, formed by the peripentonal hexons and base hexon (holding in place a\ fibre), lie at each of the 12 vertices [MEDLINE:95018210].\ \ structural molecule activity ; GO:0005198 viral capsid ; GO:0019028 \N 19460 IPR000737 The squash inhibitors form one of a number of serine protease inhibitor families. The proteins,found in the seeds of cucurbitaceae plants (squash, cucumber, balsam pear, etc.), are\ approximately 30 residues in length and contain 6 Cys residues, which form 3 disulphide bonds\ [MEDLINE:89121085]. The inhibitors function by being taken up by a serine protease (such as trypsin),\ which cleaves the peptide bond between Arg/Lys and Ile residues in the N-terminal portion of the\ protein [MEDLINE:92118901], [MEDLINE:89121085]. Structural studies have shown that the inhibitor has an\ ellipsoidal shape, and is largely composed of

-turns [MEDLINE:89121085]. The fold and Cys connectivity\ of the proteins resembles that of potato carboxypeptidase A inhibitor [MEDLINE:92118901].\ \ serine protease inhibitor activity ; GO:0004867 \N \N 19456 IPR000734 Triglyceride lipases (EC: 3.1.1.3) are lipolytic enzymes that hydrolyse ester linkages oftriglycerides [MEDLINE:89150316]. Lipases are widely distributed in animals, plants and prokaryotes.\ At least three tissue-specific isozymes exist in higher vertebrates, pancreatic, hepatic and\ gastric/lingual. These lipases are closely related to each other and to lipoprotein lipase\ (EC: 3.1.1.34), which hydrolyses triglycerides of chylomicrons and very low density lipoproteins\ (VLDL) [MEDLINE:89137092]. The most conserved region in all these proteins is centered around a serine\ residue which has been shown [MEDLINE:90158808] to participate, with an histidine and an aspartic acid\ residue, in a charge relay system. Such a region is also present in lipases of prokaryotic\ origin and in lecithin-cholesterol acyltransferase (EC: 2.3.1.43) (LCAT) [MEDLINE:86205950], which\ catalyzes fatty acid transfer between phosphatidylcholine and cholesterol.\ \ enzyme activity ; GO:0003824 \N lipid metabolism ; GO:0006629 19457 IPR000735

Northern analysis has demonstrated the presence of -2C receptor mRNA\ in rat brain (including the cerebral cortex, cerebellum, hippocampus and\ brainstem), but not in peripheral tissues . The receptor inhibits\ adenylyl cyclase through a pertussis-toxin-insensitive G-protein belonging\ to the Gi/G0 class PUB00005869.

\ \ alpha2-adrenergic receptor activity ; GO:0004938 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19454 IPR000732

\ \ \ rhodopsin-like receptor activity ; GO:0001584 integral to membrane ; GO:0016021 phototransduction ; GO:0007602 19455 IPR000733

Synonym(s): Aromatic-ring hydroxylase

Dioxygen can be incorporated directly into organic compounds in reactions catalyzed by\ enzymes termed oxygenases or hydroxylases. Oxygenases that catalyze the incorporation\ of both atoms of dioxygen into substrates are known as dioxygenases; those that catalyze\ the incorporation of only one atom of dioxygen are termed monooxygenases, or \ mixed-function oxygenases. The second atom of dioxygen is reduced to water either by the\ substrates themselves or by a co-substrate reductant [MEDLINE:93073723]. One of the first steps\ in aerobic degradation of aromatic compounds involves introduction of one or two hydroxyl\ groups onto the aromatic ring. Incorporation of single hydroxyl groups (monohydroxylation)\ is generally catalyzed by monooxygenases. In bacteria, the majority of monooxygenases\ catalyzing monohydroxylation of aromatic rings of substituted phenols are single-component\ flavoenzymes, although multi-component monooxygenases, such as phenol and toluene-4 monooxygenase,\ have also been found. There are 2 conserved regions of hydroxylases, a conserved ADP-binding motif\ at the N-terminus, which binds the ADP portion of FAD; and a second region of similarity (residues\ 276-329 in PHBH), which may be involved in FAD binding. With the exception of these 2 regions, the\ sequences of flavoprotein monooxygenases vary significantly.

\ \ monooxygenase activity ; GO:0004497 \N aromatic compound metabolism ; GO:0006725 19453 IPR000731

The sterol-sensing domain (SSD) consists of approximately 180 amino acids organized intoa cluster of five consecutive membrane-spanning domains and is found in proteins which have key roles in different aspects of cholesterol homeostasis or cholesterol-linked signalling such as sterol-regulated movement or the trafficking of specific cargoes. Examples of proteins containing SSDs include the Hedgehog signaling protein (Patched protein) from Drosophila;\ 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), which is involved in the control\ of cholesterol biosynthesis; SREBP cleavage-activating protein (SCAP); the Niemann-Pick type\ C (NPC1) protein [MEDLINE:97362324]; and a number of bacterial drug resistance proteins.

\ \

The role of the SSD is still open to debate [MEDLINE:21930756]. The domain may may either bind directly to sterols, sterol-modified proteins or proteins that change conformation in response to sterol levels, or trigger an intramolecular response in response to sterols.

\ \ \N \N \N 19451 IPR000730 Proliferating cell nuclear antigen (PCNA), or cyclin, is a non-histone acidic nuclear protein[MEDLINE:87218522] that plays a key role in the control of eukaryotic DNA replication [MEDLINE:92137220].\ It acts as a co-factor for DNA polymerase delta, which is responsible for leading strand DNA\ replication [MEDLINE:89214190]. The sequence of PCNA is well conserved between plants and animals,\ indicating a strong selective pressure for structure conservation, and suggesting that this type\ of DNA replication mechanism is conserved throughout eukaryotes [MEDLINE:91146597]. Homologues of\ PCNA have also been identified in yeast (gene POL30), baculovirus (ETL protein) and archaebacteria.\ Yeast POL30 is associated with polymerase III, the yeast analog of polymerase delta.\ \ DNA polymerase processivity factor activity ; GO:0030337 delta-DNA polymerase cofactor complex ; GO:0005660 regulation of DNA replication ; GO:0006275 19452 IPR000730 Proliferating cell nuclear antigen (PCNA), or cyclin, is a non-histone acidic nuclear protein[MEDLINE:87218522] that plays a key role in the control of eukaryotic DNA replication [MEDLINE:92137220].\ It acts as a co-factor for DNA polymerase delta, which is responsible for leading strand DNA\ replication [MEDLINE:89214190]. The sequence of PCNA is well conserved between plants and animals,\ indicating a strong selective pressure for structure conservation, and suggesting that this type\ of DNA replication mechanism is conserved throughout eukaryotes [MEDLINE:91146597]. Homologues of\ PCNA have also been identified in yeast (gene POL30), baculovirus (ETL protein) and archaebacteria.\ Yeast POL30 is associated with polymerase III, the yeast analog of polymerase delta.\ \ DNA polymerase processivity factor activity ; GO:0030337 delta-DNA polymerase cofactor complex ; GO:0005660 regulation of DNA replication ; GO:0006275 19448 IPR000727 The process of vesicular fusion with target membranes depends on a set of SNAREs (SNAP-Receptors), which are associated with the fusing membranes [MEDLINE:97383780], [MEDLINE:97378348]. Target SNAREs \ (t-SNAREs) are localized on the target membrane and belong to two different families, the \ syntaxin-like family and the SNAP-25 like family. One member of each family, together with a\ v-SNARE localized on the vesicular membrane, are required for fusion. The Syntaxins are type-I \ transmembrane proteins that contain several regions with coiled-coil propensity in their cytosolic \ part. SNAP-25 (IPR000928) is a protein consisting of two coiled-coil regions, which is associated with the \ membrane by lipid anchors. Recently, it was shown that the two coiled-coil regions of SNAP-25 and\ one of the coiled-coil regions of the syntaxins are related [MEDLINE:97250487]. Moreover, there are \ some proteins with similarity to this region that cannot be classified into the classical subgroups.\ This domain is found in both Syntaxin and SNAP-25 families as well as in other proteins.\ \ \N \N \N 19446 IPR000725

The olfactory system is a highly-specialised chemical recognition systemthat, like the immune system, is capable of discriminating with tremendous\ sensitivity between numerous foreign molecules in the environment.\ Olfactory transduction is believed to be initiated by the binding of\ odorants to specific receptor proteins in the cilia of olfactory receptor\ cells. Although little is known about the precise mechanism by which\ odorant binding might initiate membrane depolarisation, it is believed\ that cyclic AMP may serve as an intracellular messenger for olfactory\ transduction PUB00001028, PUB00001028, PUB00005330.

The olfactory receptors are integral membrane proteins that belong to a\ superfamily of G-protein-coupled receptors. The activating ligands of the\ different superfamily members vary widely in structure and character, yet\ the proteins appear faithfully to have conserved a basic structural framework, believed to consist of 7 transmembrane (TM) helices. Although the\ sequences of these proteins are very diverse, reflecting to some extent\ this broad range of activating ligands, nevertheless, motifs have been\ identified in the TM regions that are characteristic of virtually the\ entire superfamily PUB00005330, [MEDLINE:94224751]. Amongst the exceptions are the olfactory\ receptors, which cluster together in a subfamily that lacks significant\ matches with domains 2, 4 and 6 [MEDLINE:94224751].

\ \ \ olfactory receptor activity ; GO:0004984 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19447 IPR000726

Glycoside hydrolase family 19 CAZY:GH_19).

\ \

Chitinases [MEDLINE:92387339] are enzymes that catalyze the hydrolysis of the -1,4-N-acetyl-D-glucosamine linkages in chitin polymers. Chitinases belong to glycoside hydrolase families 18 or 19 [MEDLINE:92082464]. Chitinases of family 19 (also known as classes IA or I and IB \ or II) are enzymes from plants that function in the defense against fungal and insect pathogens \ by destroying their chitin-containing cell wall. Class IA/I and IB/II enzymes differ in the\ presence (IA/I) or absence (IB/II) of a N-terminal chitin-binding domain. The catalytic domain \ of these enzymes consist of about 220 to 230 amino acid residues.

\ \ chitinase activity ; GO:0004568 \N cell wall catabolism ; GO:0016998 19449 IPR000728 This family includes Hydrogen expression/formation protein, HypE, which may be involved inthe maturation of NifE hydrogenase; AIR synthase and FGAM synthase, which are involved in\ de novo purine biosynthesis; and selenide, water dikinase, an enzyme which synthesizes\ selenophosphate from selenide and ATP.\ \ enzyme activity ; GO:0003824 \N \N 19450 IPR000728 This family includes Hydrogen expression/formation protein, HypE, which may be involved inthe maturation of NifE hydrogenase; AIR synthase and FGAM synthase, which are involved in\ de novo purine biosynthesis; and selenide, water dikinase, an enzyme which synthesizes\ selenophosphate from selenide and ATP.\ \ enzyme activity ; GO:0003824 \N \N 19445 IPR000724 This domain is found as a tandem repeat in Streptococcal cell surface proteins, such as theIgG binding proteins G and MIG. These proteins are type I membrane proteins that bind to\ the constant Fc region of IgG with high affinity. The N-terminus of MIG mediates binding to\ plasma proteinase inhibitor

2-macroglobulin after complex formation with proteases.\ \ protein binding activity ; GO:0005515 cell wall ; GO:0005618 \N 19443 IPR000722

RNA polymerases catalyze the DNA dependent polymerisation of RNA from DNA, using thefour ribonucleoside triphosphates as substrates. Prokaryotes contain a single RNA polymerase\ compared to three in eukaryotes (not including mitochondrial and chloroplast polymerases).\ Eukaryotic RNA polymerase I is essentially used to transcribe ribosomal RNA units, polymerase II\ is used for mRNA precursors, and III is used to transcribe 5S and tRNA genes. Each class of RNA\ polymerase is assembled from nine to fourteen different polypeptides. Members of the family\ include the largest subunit from eukaryotes; the gamma subunit from Cyanobacteria; the '\ subunit from bacteria; the A' subunit from archaea; and the B'' subunit from chloroplast\ RNA polymerases.

\ \ DNA-directed RNA polymerase activity ; GO:0003899 nucleus ; GO:0005634 transcription ; GO:0006350 19441 IPR000720 Peptidylglycine

-amidating monooxygenase (PAM) is a multifunctional protein found insecretory granules. The protein contains two enzymes that act sequentially to catalyze the

-amidation of neuroendocrine peptides [MEDLINE:91107670], [MEDLINE:93078791]: \

\
peptidylglycine + ascorbate + O₂ = peptidyl(2-hydroxyglycine) + dehydroascorbate + H₂O\

\ The product is unstable and dismutates to glyoxylate and the corresponding desglycine peptide amide. The\ first step of the reaction is catalyzed by peptidylglycine

-hydroxylating monooxygenase\ (PHM), and is dependent on copper, ascorbate and molecular oxygen; peptidyl-

-hydroxyglycine

-amidating lyase (PAL) catalyzes the second step of the reaction [MEDLINE:93078791]. Sequence\ analysis shows the protein to be similar to dopamine-

-monooxygenases (DBH), a class of\ ascorbate-dependent enzymes that requires copper as a cofactor and uses ascorbate as an electron\ donor. PAM and DBH share a few regions of sequence similarity, some of which contain clusters\ of conserved histidine residues that may be involved in copper binding.\ \ copper ion binding activity ; GO:0005507 membrane ; GO:0016020 peptide metabolism ; GO:0006518 19442 IPR000721 The Gag protein from retroviruses, also known as p24, forms the inner protein layer of thenucleocapsid. This protein performs highly complex orchestrated tasks during the assembly,\ budding, maturation and infection stages of the viral replication cycle. During viral assembly,\ the proteins form membrane associations and self-associations that ultimately result in\ budding of an immature virion from the infected cell. Gag precursors also function during\ viral assembly to selectively bind and package two plus strands of genomic RNA. ELISA tests\ for p24 is the most commonly used method to demonstrate virus replication both in vivo and in\ vitro.\ \ \N \N viral life cycle ; GO:0016032 19440 IPR000719 Eukaryotic protein kinases PUB00001071, PUB00001071, [MEDLINE:92065854], [MEDLINE:92065863], [MEDLINE:88264399] are enzymesthat belong to a very extensive family of proteins which share a conserved catalytic core common with\ both serine/threonine and tyrosine protein kinases. There are a number of conserved regions in the\ catalytic domain of protein kinases. In the N-terminal extremity of the catalytic domain there is a\ glycine-rich stretch of residues in the vicinity of a lysine residue, which has been shown to be involved\ in ATP binding. In the central part of the catalytic domain there is a conserved aspartic acid residue\ which is important for the catalytic activity of the enzyme [MEDLINE:91320112]. This entry includes protein kinases from eukaryotes and viruses and may include some bacterial hits too.\ \ ATP binding activity ; GO:0005524 \N protein amino acid phosphorylation ; GO:0006468 19438 IPR000717 A homology domain of unclear function, occurs in the C-terminal region of severalregulatory components of the 26S proteasome as well as in other proteins. This domain\ has also been called the PINT motif (Proteasome, Int-6, Nip-1 and TRIP-15) [MEDLINE:98308842].\ Apparently, all of the characterized proteins containing PCI domains are parts of larger\ multi-protein complexes. Proteins with PCI domains include budding yeast proteasome\ regulatory components Rpn3(Sun2), Rpn5, Rpn6, Rpn7and Rpn9 [MEDLINE:98252903]; mammalian proteasome regulatory components p55, p58 and p44.5, and translation\ initiation factor 3 complex subunits p110 and INT6 [MEDLINE:97150873], [MEDLINE:98001678]; Arabidopsis\ COP9 and FUS6/COP11 [MEDLINE:96291404]; mammalian G-protein pathway suppressor GPS1, and several\ uncharacterized ORFs from plant, nematodes and mammals. The complete homology domain comprises\ approx. 200 residues, the highest conservation is found in the C-terminal half. Several of the\ proteins mentioned above have no detectable homology to the N-terminal half of the domain.\ \ \N \N \N 19439 IPR000718

Metalloproteases can be split into five clans, and futher sub-divided into families, on the basis of their metal binding residues.

Neprilysin (EC: 3.4.24.11) is variously known as common acute lymphoblastic leukemia antigen (CALLA), enkephalinase (gp100) and neutral endopeptidase metalloendopeptidase (NEP). It is a plasma membrane-bound\ mammalian enzyme that is able to digest biologically-active peptides,\ including enkephalins [MEDLINE:95405261]. The family includes eukaryote and prokaryote\ oligopeptidases, as well as a mammalian blood group antigen Kell [MEDLINE:95405261]. The\ zinc ligands of neprilysin are known and are analogous to those in\ thermolysin, a related peptidase [MEDLINE:95405261], [MEDLINE:93285335].

\ \

Neprilysins, like thermolysin, are inhibited by phosphoramidon, which\ appears to selectively inhibit this family in mammals. The enzymes are all\ oligopeptidases, digesting oligo- and polypeptides, but not proteins [MEDLINE:95405261].\ Neprilysin consists of a short cytoplasmic domain, a membrane-spanning\ region and a large extracellular domain. The cytoplasmic domain contains a\ conformationally-restrained octapeptide, which is thought to act as a stop\ transfer sequence that prevents proteolysis and secretion [MEDLINE:95405261], [MEDLINE:87213218].

Some of the proteins in this group are responsible for the molecular basis of the blood group antigens, surface markers on the outside of the red blood cell membrane. Most of these markers are proteins, but some are carbohydrates attached to lipids or proteins [Reid M.E., Lomas-Francis C. The Blood Group Antigen FactsBook Academic Press, London / San Diego, (1997)]. Kell blood group glycoprotein (EC: 3.4.24.-) belongs to the Kell blood group system and is associated with K/k, Kp(a/b/c), Js(a/b), Ul(a), KEL11/17 and KEL14/24 antigens.

\ \

CD molecules are leucocyte antigens on cell surfaces. CD antigens nomenclature is updated at http://www.ncbi.nlm.nih.gov/PROW/guide/45277084.htm \

\ \ neprilysin activity ; GO:0004245 membrane ; GO:0016020 proteolysis and peptidolysis ; GO:0006508 19444 IPR000723

\ \ G-protein coupled receptor activity, unknown ligand ; GO:0016526 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19436 IPR000715 This pattern describes a family of UDP-GlcNAc/MurNAc: polyisoprenol-P GlcNAc/MurNAc-1-Ptransferases. Members of the family include eukaryotic N-acetylglucosamine-1-phosphate\ transferases, which catalyze the conversion of UDP-N-acteyl-D-glucosamine and dolichyl\ phosphate to UMP and N-acetyl-D-glucosaminyl-diphosphodolichol in the glycosylation pathway;\ and bacterial phospho-N-acetylmuramoyl-pentapeptide-transferases, which catalyze the first step\ of the lipid cycle reactions in the biosynthesis of cell wall peptidoglycan.\ \ enzyme activity ; GO:0003824 membrane ; GO:0016020 lipid metabolism ; GO:0006629 19437 IPR000716 Thyroglobulin (Tg) is a large glycoprotein specific to the thyroid gland and is the precursor of the iodinated thyroid hormones thyroxine (T4) and triiodothyronine (T3). The N-terminal section \ of Tg contains 10 repeats of a domain of about 65 amino acids which is known as the Tg type-1 \ repeat [MEDLINE:87246630], [MEDLINE:96390872]. Such a domain has also been found as a single \ or repeated sequence in the HLA class II associated invariant chain [MEDLINE:87275861]; human \ pancreatic carcinoma marker proteins GA733-1 and GA733-2 [MEDLINE:90239051]; nidogen (entactin), \ a sulfated glycoprotein which is widely distributed in basement membranes and that is tightly \ associated with laminin; insulin-like growth factor binding proteins (IGFBP) [MEDLINE:91225006];\ saxiphilin, a transferrin-like protein from frog that binds specifically to the neurotoxin saxitoxin \ [MEDLINE:94195765]; and equistatin, a thiol-protease inhibitor from sea anemone\ \ \ \ [MEDLINE:97298102].\ The domain contains six cysteines (Tg type-1a) but also exists in a variant that lacks the third and \ fourth cysteines (Tg type-1b). One Gln residue is always conserved.\ \ \N \N \N 19433 IPR000712 Active cell suicide (apoptosis) is induced by events such as growth factor withdrawal and toxins.It is controlled by regulators, which have either an inhibitory effect on programmed cell death\ (anti-apoptotic) or block the protective effect of inhibitors (pro-apoptotic) PUB00001030,\ PUB00001030. Many viruses have found a way of countering defensive apoptosis by encoding their own\ anti-apoptosis genes preventing their target-cells from dying too soon. All proteins belonging to\ the Bcl-2 family [MEDLINE:97067261] contain either a BH1, BH2, BH3, or BH4 domain. All anti-apoptotic\ proteins contain BH1 and BH2 domains, some of them contain an additional N-terminal BH4 domain\ (Bcl-2, Bcl-x(L), Bcl-w), which is never seen in pro-apoptotic proteins, except for Bcl-x(S). On the\ other hand, all pro-apoptotic proteins contain a BH3 domain (except for Bad) necessary for\ dimerization with other proteins of Bcl-2 family and crucial for their killing activity, some of them\ also contain BH1 and BH2 domains (Bax, Bak). The BH3 domain is also present in some anti-apoptotic\ protein, such as Bcl-2 or Bcl-x(L). Proteins that are known to contain these domains include vertebrate\ Bcl-2 (

and

This family contains a number of related ligase enzymes that catalyse consecutive steps in the synthesis of peptidoglycan. This family also includes folylpolyglutamate synthase that transfers glutamate to folylpolyglutamate and cyanophycin synthetase that catalyses the biosynthesis of the cyanobacterial reserve material multi-L-arginyl-poly-L-aspartate (cyanophycin) [MEDLINE:98314516].

The N-terminal domain is almost always associated with the cytoplasmic peptidoglycan synthetases C-terminal domain (see IPR004101).

\ \ ATP binding activity ; GO:0005524 \N \N 19435 IPR000714 The IR5 open reading frame (ORF) of the equine herpesvirus type 1 (EHV-1) genome maps within the inverted repeat segments. Sequence analyses of the gene region revealed an ORF of 236 amino acids \ that showed a high degree of similarity to ORF64 of varicella zoster virus and ORF3 of EHV-4, both \ of which map within the inverted repeats, and to the US10 ORF of herpes simplex virus type 1 (HSV-1), \ which maps within the unique short segment. The IR5 ORF houses a sequence of 13 residues (CAYWCCLGHAFAC) \ that matches perfectly the consensus zinc finger motif (C-X2-4-C-X2-15-C/H-X2-4-C/H) [MEDLINE:92263774].\ Putative cis-acting elements flanking the IR5 ORF include a TATA box, a CAAT box, and a polyadenylation \ signal. Coupled with various experimental data, the IR5 gene of EHV-1 thus exhibits characteristics \ representative of a late gene of the gamma-1 class. The DNA sequence covering ~70% of the short unique \ region (Us) and part of the short inverted repeat of the Mareks disease virus type 1 GA strain has\ been determined. Sequence analysis showed the presence of nine potential ORFs in the Us region, four \ of which were found to be similar to US10 (minor virion protein) [MEDLINE:93118245].\ \ \N \N \N 19432 IPR000711

\ \

\ \ \ \ \ \ \

The catalytic core delta subunit (referred to as oligomycin\ sensitivity conferral protein, OSCP, in mitochondria) appears to be part of the stalk that links\ CF0 and CF1, in which context it either transmits conformational changes from CF0 into CF1, or is\ implicated in proton conduction [MEDLINE:90148989]. Delta subunits contain around 200 amino acids, the\ proteins from different sources exhibiting only moderate sequence similarity.

\ \ hydrogen-transporting two-sector ATPase activity ; GO:0003936 \N proton transport ; GO:0015992 19430 IPR000709 Leu/Ile/Val/Thr- and Leu-binding proteins, which share a high degree of sequence similarity, are components of the leucine-specific transport system. This is one of two periplasmic binding protein-dependent systems in the high-affinity transport of branched-chain amino acids in bacteria \ [MEDLINE:85234531], [MEDLINE:89199638]. A much weaker sequence relationship has been reported between the\ periplasmic binding proteins and the aliphatic amidase expression-regulating protein, AmiC. On this \ basis, it has been suggested that AmiC may be capable of adopting a similar 3D fold [MEDLINE:94074562].\ \ amino acid-polyamine transporter activity ; GO:0005279 periplasmic space (sensu Gram-negative Bacteria) ; GO:0030288 amino acid transport ; GO:0006865 19431 IPR000710

Proteins from the chymotrypsin clan (SA) have a conserved GXSG pattern at\ the active serine site. The S6 family of the PA(S) clan include IgA-specific\ endopeptidases [MEDLINE:95147689], see protease Database http://merops.sanger.ac.uk/merops.htm], which cleave prolyl bonds in the hinge regions of\ immunoglobulin A heavy chains. Similar specificity is shown by the unrelated\ family of M26 metalloendopeptidases.

\ \ \ serine-type endopeptidase activity ; GO:0004252 \N proteolysis and peptidolysis ; GO:0006508 19428 IPR000707 ParA is a family of ATPases involved in active partitioning of diverse bacterial plasmids, andincludes the bacterial proteins IncC, MinD, SopA and RepA. These proteins are thought to play\ a role in plasmid maintenance and replication, and ensure the proper distribution of newly\ replicated plasmids to daughter cells during cell division. MinD is a membrane ATPase required\ for the correct placement of the division site.\ \ \ \N \N \N 19429 IPR000708

EP1 receptors mediate contraction of gastrointestinal smooth muscles in\ various species, and relaxation of airway and uterine smooth muscles,\ especially in rodents. The receptors activate the phosphoinositide\ pathway via a pertussis-toxin-insensitive G-protein, probably of the\ Gq/G11 class PUB00005901.

\ \ prostaglandin E receptor activity ; GO:0004957 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19426 IPR000705 Galactokinase catalyses the first reaction in the galactose metabolism pathway, the ATP-dependent phosphorylation of galactose, yielding galactose-1-phosphate [MEDLINE:89096937], [MEDLINE:93066348].\ Deficiency in this enzyme results in the disease galactosemia, which is responsible for the\ formation of cataracts in newborn babies, and is possibly responsible for presenile cataracts in\ adults [MEDLINE:93066348]. In yeast, the GAL3 gene product is required for the GAL4-mediated induction\ of other enzymes involved in galactose metabolism. The induction of GAL1 production then reinforces\ this process, increasing the expression of other galactose-inducible genes. GAL3 has been shown to\ be similar to the GAL1 protein [MEDLINE:89096937].\ \ ATP binding activity ; GO:0005524 \N galactose metabolism ; GO:0006012 19427 IPR000706 N-acetyl-gamma-glutamyl-phosphate reductase (EC: 1.2.1.38) (AGPR) [MEDLINE:92325051], [MEDLINE:94179195] is theenzyme that catalyzes the third step in the biosynthesis of arginine from glutamate, the NADP-dependent reduction of N-acetyl-5-glutamyl phosphate into N-acetylglutamate 5-semialdehyde. In \ bacteria it is a monofunctional protein of 35 to 38 kD (gene argC), while in fungi it is part of \ a bifunctional mitochondrial enzyme (gene ARG5,6, arg11 or arg-6) which contains a N-terminal \ acetylglutamate kinase (EC: 2.7.2.8) domain and a C-terminal AGPR domain. In the Escherichia coli \ enzyme, a cysteine has been shown to be implicated in the catalytic activity, and the region \ around this residue is well conserved.\ \ N-acetyl-gamma-glutamyl-phosphate reductase activity ; GO:0003942 \N arginine biosynthesis ; GO:0006526 19425 IPR000704 Casein kinase, a ubiquitous, well-conserved protein kinase involved in cell metabolism anddifferentiation, is characterized by its preference for Ser or Thr in acidic stretches of amino acids.\ The enzyme is a tetramer of 2

- and 2

-subunits [MEDLINE:89325340], [MEDLINE:91310643]. However, some\ species (e.g., mammals) possess 2 related forms of the

-subunit (

and

'), while others\ (e.g., fungi) possess 2 related

-subunits (

and

') [MEDLINE:95256195]. The

-subunit is the\ catalytic unit and contains regions characteristic of serine/threonine protein kinases. The

-subunit\ is believed to be regulatory, possessing an N-terminal auto-phosphorylation site, an internal acidic\ domain, and a potential metal-binding motif [MEDLINE:95256195]. The

subunit is a highly conserved protein\ of about 25 kD that contains, in its central section, a cysteine-rich motif that could be involved in\ binding a metal such as zinc [MEDLINE:94299539]. The mammalian

-subunit gene promoter shares common\ features with those of other mammalian protein kinases and is closely related to the promoter of the\ regulatory subunit of cAMP-dependent protein kinase [MEDLINE:95256195].\ \ protein kinase CK2, regulator activity ; GO:0008605 protein kinase CK2 complex ; GO:0005956 \N 19424 IPR000703 Vertebrate endogenous opioid neuropeptides are released by post-translational proteolytic cleavage of precursor proteins. The precursors consist of the following components: a signal sequence that precedes a conserved region of about 50 residues; a variable-length region; and the sequence of the neuropeptide itself. Three types of precursor are known: preproenkephalin A \ (gene PENK), which is processed to produce 6 copies of Met-enkephalin, plus \ Leu-enkephalin; preproenkephalin B (gene PDYN), which is processed to\ produce neoendorphin, dynorphin, leumorphin, rimorphin and Leu-enkephalin; \ and prepronocipeptin (gene PNOC), whose processing produces nociceptin\ (orphanin FQ) and two other potential neuropeptides.\

The primary structure of rat preproenkephalin \ is highly similar to those of bovine and human preproenkephalins, and contains four copies of Met-enkephalin, one of Leu-enkephalin, one of Met-enkephalin-Arg6-Gly7-Leu8, and one of Met-enkephalin-Arg6-Phe7 [MEDLINE:85054887], [MEDLINE:85063850].

\ \ \N \N neuropeptide signaling pathway ; GO:0007218 19418 IPR000698 Arrestin (retinal S-antigen) is a major protein of the retinal rod outer segments. It interacts with photo-activated phosphorylated rhodopsin, inhibiting or 'arresting' its ability to interact with transducin\ PUB00001029. The protein binds calcium, and shows similarity in its C-terminus to

-transducin and\ other purine nucleotide-binding proteins. In mammals, arrestin is associated with autoimmune uveitis.\ Arrestins comprise a family of closely-related proteins that includes

-arrestin-1 and -2, which regulate\ the function of

-adrenergic receptors by binding to their phosphorylated forms, impairing their capacity\ to activate G(S) proteins; Cone photoreceptors C-arrestin (arrestin-X) PUB00001029, which could bind to\ phosphorylated red/green opsins; and Drosophila phosrestins I and II, which undergo light-induced\ phosphorylation, and probably play a role in photoreceptor transduction [MEDLINE:93199955], [MEDLINE:92388146],\ [MEDLINE:90232360].\ \ \N \N sensory perception ; GO:0007600 19423 IPR000702

\ \ \

L6 is a protein from the large (50S) subunit. In E.coli, it is located in the aminoacyl-tRNA binding\ site of the peptidyltransferase centre, and is known to bind directly to 23S rRNA. It belongs\ to a family of ribosomal proteins, including L6 from bacteria, cyanelles (structures that\ perform similar functions to chloroplasts, but have structural and biochemical characteristics\ of Cyanobacteria) and mitochondria; and L9 from mammals, Drosophila , plants and yeast. L6\ comprises 2 almost identical folds, suggesting that is was derived by the duplication of an\ ancient RNA-binding protein gene. Analysis reveals several sites on the protein surface where\ interactions with other ribosome components may occur, the N-terminus being involved in \ protein-protein interactions and the C-terminus containing possible RNA-binding sites [MEDLINE:94085364].

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 19422 IPR000701 Succinate dehydrogenase (SDH) is a membrane-bound complex of two main components: a membrane-extrinsic component composed of an FAD-binding flavoprotein and an iron-sulfur protein, and a hydrophobic \ component composed of a cytochrome b and a membrane anchor protein. \

The cytochrome b component is a \ mono heme transmembrane protein [MEDLINE:93077541], [MEDLINE:94203185], [MEDLINE:95341681] belonging to a family that includes cytochrome \ b-556 from bacterial SDH (gene sdhC); cytochrome b560 from the mammalian mitochondrial SDH complex and \ that encoded in the mitochondrial genome of some algae and in the plant Marchantia polymorpha; cytochrome \ b from yeast mitochondrial SDH complex (gene SDH3 or CYB3); and protein cyt-1 from Caenorhabditis. These \ cytochromes are proteins of about 130 residues that comprise three transmembrane regions. There are two \ conserved histidines which may be involved in binding the heme group.

\ \ succinate dehydrogenase activity ; GO:0000104 membrane ; GO:0016020 electron transport ; GO:0006118 19419 IPR000698 Arrestin (retinal S-antigen) is a major protein of the retinal rod outer segments. It interacts with photo-activated phosphorylated rhodopsin, inhibiting or 'arresting' its ability to interact with transducin\ PUB00001029. The protein binds calcium, and shows similarity in its C-terminus to

-transducin and\ other purine nucleotide-binding proteins. In mammals, arrestin is associated with autoimmune uveitis.\ Arrestins comprise a family of closely-related proteins that includes

-arrestin-1 and -2, which regulate\ the function of

Ryanodine and Inositol 1,4,5-trisphosphate (IP3) receptors are intracellular Ca²⁺-release channels. They become activated upon binding of their respective ligands, Ca²⁺ and IP3, opening an intrgral Ca²⁺ channel. Ryanodine receptor activation is a key component of muscular contraction, their activation allowing release of Ca²⁺ from the sarcoplasmic reticulum. Mutations in the ryanodine receptor lead to malignant hyperthermia susceptibility the and central core disease of muscle.

\ calcium channel activity ; GO:0005262 membrane ; GO:0016020 calcium ion transport ; GO:0006816 19421 IPR000700

The PAS domain [MEDLINE:98044337], [MEDLINE:97446881] is an approximately 300 amino-acid segment of sequence similarity which is conserved between the Drosophila protein period clock (PER), the Ah receptor nuclear translocator (ARNT) and the Drosophila single- minded (SIM). It is composed of two or more imperfect repeats (PAS-1, PAS-2). In addition, some proteins have another similar region of 40-45 amino acids situated carboxy-terminal to any PAS repeat and which contributes to the PAS structural domain: the PAC motif. The PAS family can be divided in two groups; the proteins that have the PAS motif followed by a PAC motif, and those that don't. Within the bHLH/PAS proteins, the PAS domain is involved in protein dimerization with another protein of the family. It has also been associated with light reception, light regulation and circadian rhythm regulators (clock).

In bacteria, the PAS domain is usually associated with the input domain of a histidine kinase, or a sensor protein that regulates a histidine kinase.

\ \ two-component sensor molecule activity ; GO:0000155 \N two-component signal transduction system (phosphorelay) ; GO:0000160 19417 IPR000697

The EVH1 (RanBP1-WASP) domain is found in multi-domain proteins implicated in a diverse range of signaling, nuclear transport and cytoskeletal events. This domain of around 115 amino acids is present in species ranging from yeast to mammals. Many EVH1-containing proteins associate with actin-based structures and play a role incytoskeletal organisation. EVH1 domains recognise and bind the proline-rich motif FPPPP with low-affinity, further interactions then form between flanking residues [MEDLINE:21909373]\ \ \ [MEDLINE:97459929]

WASP family proteins contain a EVH1 (WH1) in their N-terminals which bind proline-rich sequences in the WASP interacting protein. Proteins of the RanBP1 family contain a WH1 domain in their N terminal region,\ which seems to bind a different sequence motif present in the C terminal\ part of RanGTP protein [MEDLINE:99098349],[MEDLINE:95241496].

Tertiary structure of the WH1 domain of the Mena protein revealed structure similarities with the pleckstrin homology (PH) domain. The overall fold consists of a compact parallel -sandwich, closed along one edge by a long -helix. A highlyconserved cluster of three surface-exposed aromatic side-chains forms the recognition site for the molecules target ligands. [MEDLINE:99268533].

\ \ \N \N \N 19414 IPR000694 Keratinocytes from the skin epidermis are functionally specialised to protect against the damagingeffects of external agents, including ultraviolet (UV) light [MEDLINE:88261298]. The presence of damage\ somewhere in genomic DNA activates a signal transduction cascade, which results in the expression\ of a number of genes, including the gene for small proline-rich proteins [MEDLINE:90356372]. These proteins\ are rich in Pro, Cys and Gln and are either structural proteins or metal-binding proteins. They can\ also bind DNA, however, since they contain many Lys, Ser and Thr residues, which are known to mediate\ DNA-binding in repressor proteins [MEDLINE:88261298]. Small proline-rich proteins are also found in higher\ concentrations during normal keratinocyte differentiation, although the reason for this is unclear\ [MEDLINE:90356372].\

Note: No protein matches are shown due to the low specificity of this rule.

\ \ \N \N \N 19415 IPR000695 H⁺-Transporting ATPases (proton pumps) are the main ion pumps in the plasma membrane and play acentral role PUB00004574 in the physiology and bioenergetics of plant cells. They are the primary\ active transporters of the plasma membrane and are responsible for generating the membrane potential\ that drives translocation of cations, amino-acids, sugars, and hormones, whilst also contributing to\ the maintenance of intracellular and extracellular pH and cell turgor PUB00004574. Proton pumps are\ members of the P-type (or E1-E2-type) cation-transporting ATPase superfamily, which has evolved from\ a common ancestral gene [MEDLINE:94202222]. The sequences are believed to contain 8-10 transmembrane helices,\ some of which are well conserved throughout the superfamily. They may thus all operate via a similar\ mechanism, with an aspartylphosphoryl enzyme intermediate [MEDLINE:87033715] being formed during the catalytic\ cycle.\ \ \ P-type ATPase activity ; GO:0015662 membrane ; GO:0016020 proton transport ; GO:0015992 19416 IPR000696

Aspartic proteases have a catalytic aspartate residue at their active site.A number of families (denoted by the letter A followed by a number) have\ been identified, most of which (including pepsin, retropepsin and\ cauliflower mosaic virus peptidase) have been grouped into a single clan\ (AA), as they are all thought to share a common ancestry. Families A6 and\ A21 belong to the AB clan. The remaining families have not yet received\ clan assignments [MEDLINE:95405261], [MEDLINE:93176119], see Protease Database http://merops.sanger.ac.uk/merops.htm].

\ \

Nodavirus coat precusor endopeptidases belong to the A6 family of aspartic\ proteases [MEDLINE:90339486]. At the moment, it is not clear whether they share a common\ ancestry with other aspartic proteases. Nodaviruses are small, icosahedral\ viruses, pathogenic to insects and mammals. A virus particle consists of a\ single virion, within which is packaged two RNA stands, RNA1 and RNA2.

\ \

Nodavirus coat precursor endopeptidase (also known as protein ) is the\ only protein encoded by RNA2. During the process of virion assembly, this\ precursor is cleaved into coat proteins and gamma. RNA1 encodes two\ proteins, at least one of which is involved in RNA replication. The\ relatively uncomplicated nature of their structural protein and RNA\ constituents make the nodaviruses a good virus model [MEDLINE:90339486].

\ \

The 3D structure of the capsid protein has been determined by X-ray\ crystallography to 2.8A resolution [MEDLINE:90339486]. The structure contains a -barrel\ domain, with a prominent protrusion composed largely of -sheet. This\ protrusion, together with similar protrusions from neighbouring subunits,\ forms a prominent trigonal pyramid with quasi-3-fold symmetry [MEDLINE:90339486]. Two -helices extend toward the interior of the particle [MEDLINE:90339486].

\ \ aspartic-type endopeptidase activity ; GO:0004190 \N proteolysis and peptidolysis ; GO:0006508 19411 IPR000691 The Streptomyces family of bacteria produce a number of protease inhibitors, which are characterised bytheir strong activity towards subtilisin. They are collectively known as Streptomyces subtilisin inhibitors\ (SSI). Some SSI also inhibit trypsin and chymotrypsin. Mutation of the active site residue can influence\ inhibition specificity [MEDLINE:91349173]. SSI is a homodimer, each monomer containing 2 anti-parallel

-sheets\ and 2 short

-helices. Protease binding induces the widening of a channel-like structure, in which\ hydrophobic side-chains are sandwiched between 2 lobes [MEDLINE:85033707]. Loss of the C-terminal tetrapeptide\ VFAF drastically reduces the inhibitory effect of the proteins when there is less than one molecule of\ inhibitor present per molecule of enzyme. This implies that the tetrapeptide is neccessary to maintain the\ correct 3D fold [MEDLINE:80227614]. Structural similarities between the primary and secondary contact loops of SSI,\ and the ovomucoid and pancreatic secretory trypsin inhibitor family suggest evolution of the 2 families from\ a common ancestor [MEDLINE:85033707].\ \ serine protease inhibitor activity ; GO:0004867 \N \N 19412 IPR000692 Fibrillarin is a component of a nucleolar small nuclear ribonucleoprotein (SnRNP), functioning in vivoin ribosomal RNA processing [MEDLINE:91225069], [MEDLINE:93261822]. It is associated with U3, U8 and U13 small nuclear\ RNAs in mammals [MEDLINE:91225069] and is similar to the yeast NOP1 protein [MEDLINE:90076121]. Fibrillarin has a\ well conserved sequence of around 320 amino acids, and contains 3 domains, an N-terminal Gly/Arg-rich\ region; a central domain resembling other RNA-binding proteins and containing an RNP-2-like consensus\ sequence; and a C-terminal

-helical domain. An evolutionarily related pre-rRNA processing protein,\ which lacks the Gly/Arg-rich domain, has been found in various archaebacteria.\ \ RNA binding activity ; GO:0003723 nucleus ; GO:0005634 rRNA processing ; GO:0006364 19413 IPR000693 Sea anemones produce many different neurotoxins with related structure and function. Proteinsbelonging to this family include the neurotoxins, of which there are several, including calitoxin and anthopleurin.\ The neurotoxins bind specifically to the sodium channel, thereby delaying its inactivation during\ signal transduction, resulting in strong stimulation of mammalian cardiac muscle contraction. Calitoxin\ 1 has been found in neuromuscular prearations of crustaceans, where it increases transmitter release,\ causing firing of the axons. Three disulfide bonds are present in this protein.\ \ toxin activity ; GO:0015070 \N \N 19408 IPR000688 Bacterial membrane-bound nickel-dependent hydrogenases requires a number of accessory proteinswhich are involved in their maturation. The exact role of these proteins is not yet clear, but some seem\ to be required for the incorporation of the nickel ions [MEDLINE:94137733]. One of these proteins is generally\ known as hypA. It is a protein of about 12 to 14 kD that contains, in its C-terminal region, four conserved\ cysteines that form a zinc-finger like motif. E. coli has two proteins that belong to this family, hypA and\ hybF. A homolog, MJ0214, has also been found in the genome of the archaebacteria Methanococcus jannaschii.\ \ nickel ion binding activity ; GO:0016151 \N protein modification ; GO:0006464 19409 IPR000689 Several proteins were found to be evolutionary related, including E. coli ubiH, which is involved inubiquinone biosynthesis and which catalyzes the convertion of 2-octaprenyl-6-methoxyphenol to \ 2-octaprenyl-6-methoxy-1,4-benzoquinone; yeast COQ6, a ubiquinone biosynthesis monooxygenase;\ C. elegans hypothetical protein K07B1.2; E. coli proteins visC and yleB; and Synechocystis strain\ PCC 6803 hypothetical protein slr1300. UbiH and COQ6 are monooxygenases that require FAD as a\ cofactor.\ \ monooxygenase activity ; GO:0004497 \N \N 19410 IPR000690

A specific C2H2 Zn-finger is conserved in matrin and several RNA-binding proteins. The Zn-finger follows\ the general pattern C-x2-C-x(12,16)-H-x5-H, and is different from the 'classical' DNA-binding C2H2 Zn-finger.

\ \ nucleic acid binding activity ; GO:0003676 nucleus ; GO:0005634 \N 19406 IPR000686 Fanconi anaemia (FA) [MEDLINE:93258346], [MEDLINE:95015009], [MEDLINE:92244337] is a recessive inherited disease characterisedby defective DNA repair. FA cells are sensitive to DNA cross-linking agents that cause chromosomal instability\ and cell death. The disease is manifested clinically by progressive pancytopenia, variable physical anomalies,\ and predisposition to malignancy. Four complementation groups have been identified, designated A to D. The\ gene for group C (FACC) has been cloned. Expression of the FACC cDNA corrects the phenotypic defect of FA(C)\ cells, resulting in normalized cell growth in the presence of DNA cross-linking agents such as mitomycin C\ (MMC). Gene transfer of the FACC gene should provide a survival advantage to transduced hematopoietic cells,\ suggesting that FA might be an ideal candidate for gene therapy [MEDLINE:95015009]. The function of the FACC gene\ is not known. Immunofluorescence and sub-cellular fractionation studies of human cell lines, and COS-7 cells\ transiently expressing human FACC, showed the protein to be located primarily in the cytoplasm. Yet, placement\ of a nuclear localisation signal at the N-terminus of FACC directed the hybrid protein to the nuclei of\ transfected COS-7 cells. Such findings suggest an indirect role for FACC in regulating DNA repair in this\ group of Fanconi anaemia [MEDLINE:94336670].\ \ \N \N DNA repair ; GO:0006281 19407 IPR000687 Several uncharacterized proteins were found to be evolutionary related, including yeast protein RIO1;C. elegans hypothetical protein ZK632.3; Methanococcus jannaschii hypothetical protein MJ0444;\ and Thermoplasma acidophilum hypothetical protein in rpoA2 3'region. The eukaryotic members of this\ family are proteins of about 55 to 60 kD, while the archebacterial ones are half that size. The central part\ of these proteins is highly conserved.\ \ molecular_function unknown ; GO:0005554 \N \N 19401 IPR000682 Protein-L-isoaspartate(D-aspartate) O-methyltransferase (EC: 2.1.1.77) (PCMT) [MEDLINE:97397023] (which is also known as L-isoaspartyl protein carboxyl methyltransferase)\ is an enzyme that catalyzes the transfer of a methyl group from S-\ adenosylmethionine to the free carboxyl groups of D-aspartyl or L-isoaspartyl\ residues in a variety of peptides and proteins. The enzyme does not act on\ normal L-aspartyl residues L-isoaspartyl and D-aspartyl are the products of\ the spontaneous deamidation and/or isomerization of normal L-aspartyl and L-\ asparaginyl residues in proteins. PCMT plays a role in the repair and/or\ degradation of these damaged proteins; the enzymatic methyl esterification of\ the abnormal residues can lead to their conversion to normal L-aspartyl\ residues. The SAM domain from IPR000051 is present in most of these proteins.\ \ protein-L-isoaspartate (D-aspartate) O-methyltransferase activity ; GO:0004719 \N protein modification ; GO:0006464 19402 IPR000683

This family of enzymes utilise NADP or NAD, and is known as the GFO/IDH/MOCA family in Swiss-Prot.GFO is a glucose--fructose oxidoreductase, which converts D-glucose and D-fructose into\ D-gluconolactone and D-glucitol in the sorbitol-gluconate pathway. MOCA is a rhizopine catabolism\ protein which may catalyze the NADH-dependent dehydrogenase reaction involved in rhizopine catabolism.\ Other proteins belonging to this family include Gal80, a negative regulator for the expression of lactose and\ galactose metabolic genes; and several hypothetical proteins from yeast, E. coli and Bacillus.

The oxidoreductase, N-terminal domain is almost always associated with the oxidoreductase, C-terminal domain (see IPR004104).

\ \ oxidoreductase activity ; GO:0016491 \N metabolism ; GO:0008152 19403 IPR000684 RNA polymerase II (EC: 2.7.7.6) [MEDLINE:91354042], [MEDLINE:91048805] is one of the three forms of RNA polymerase thatexist in eukaryotic nuclei. The C-terminal region of the largest subunit of this oligomeric enzyme consists\ of the tandem repeat of a conserved heptapeptide [MEDLINE:91068296]. The number of repeats varies according to\ the species (for example there are 17 in Plasmodium, 26 in yeast, 44 in Drosophila, and 52 in mammals). The\ region containing these repeats is essential for the function of polymerase II. This repeated heptapeptide\ (called CT7n or CTD) is rich in hydroxyl groups. It probably projects out of the globular catalytic domain\ and may interact with the acidic activator domains of transcriptional regulatory proteins. It is also known\ to bind by intercalation to DNA. RNA polymerase II is activated by phosphorylation. The serine and threonine\ residues in the CT7n repeats are the target of such phosphorylation.\ \ DNA binding activity ; GO:0003677 DNA-directed RNA polymerase II, core complex ; GO:0005665 transcription from Pol II promoter ; GO:0006366 19404 IPR000685 Ribulose bisphosphate carboxylase (EC: 4.1.1.39) (RuBisCO) [MEDLINE:83307243], PUB00005318 catalyzes theinitial step in Calvin's reductive pentose phosphate cycle in plants as well as purple and green bacteria.\ It consists of a large catalytic unit and a small subunit of undetermined function. In plants, the large\ subunit is coded by the chloroplastic genome while the small subunit is encoded in the nuclear genome.\ Molecular activation of RuBisCO by CO₂ involves the formation of a carbamate with the epsilon-amino group\ of a conserved lysine residue. This carbamate is stabilized by a magnesium ion. One of the ligands of\ the magnesium ion is an aspartic acid residue close to the active site lysine PUB00005318.\ \ ribulose-bisphosphate carboxylase activity ; GO:0016984 ribulose bisphosphate carboxylase complex ; GO:0009573 carbon utilization by fixation of carbon dioxide ; GO:0015977 19405 IPR000685 Ribulose bisphosphate carboxylase (EC: 4.1.1.39) (RuBisCO) [MEDLINE:83307243], PUB00005318 catalyzes theinitial step in Calvin's reductive pentose phosphate cycle in plants as well as purple and green bacteria.\ It consists of a large catalytic unit and a small subunit of undetermined function. In plants, the large\ subunit is coded by the chloroplastic genome while the small subunit is encoded in the nuclear genome.\ Molecular activation of RuBisCO by CO₂ involves the formation of a carbamate with the epsilon-amino group\ of a conserved lysine residue. This carbamate is stabilized by a magnesium ion. One of the ligands of\ the magnesium ion is an aspartic acid residue close to the active site lysine PUB00005318.\ \ ribulose-bisphosphate carboxylase activity ; GO:0016984 ribulose bisphosphate carboxylase complex ; GO:0009573 carbon utilization by fixation of carbon dioxide ; GO:0015977 19399 IPR000680 This family of lipoproteins is found in Borrelia spirochetes. The function of these proteins isuncertain, but it may serve to avoid the host immune response by changing from one surface\ exposed variable major outer membrane lipoprotein to another.\ \ \N membrane ; GO:0016020 \N 19400 IPR000681

Beta-3 receptors have limited distribution. They are found in low levels\ in adipose tissue and the gastrointestinal tract, where they stimulate\ lipolysis and increased gut motility . They appear to coexist with -2\ receptors in skeletal muscle, where the latter predominate. Beta-3 receptors\ activate adenylyl cyclase through Gs PUB00005869.

\ \ beta-adrenergic receptor activity ; GO:0004939 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19396 IPR000677 All legume seeds contain storage globulins, a family of proteins of different size and structural organisationthat share several properties (including similar amino acid composition, salting-in solubility, etc.). The\ globulins are generally classified with respect to their molecular mass as 2S, 7S (vicilin) or 11S (legumin).\ Narbonin belongs to the smaller, 2S globulins. It is a monomer of 290 amino acid residues and consists of a\ single polypeptide chain. Narbonin folds as an

-protein, with strands and helices alternating to\ form an 8-stranded parallel

-barrel surrounded by a ring of 7 helices PUB00006082,\ PUB00006082, the familiar topology of triose phosphate isomerase and many other enzymes. To date, attempts to\ identify an enzymatic activity for this protein, however, have failed PUB00006082.\ \ nutrient reservoir activity ; GO:0045735 \N \N 19397 IPR000678 In mammals, the second stage of spermatogenesis is characterized by the conversion of nucleosomalchromatin to the compact, nonnucleosomal and transcriptionally inactive form found in the sperm nucleus.\ This condensation is associated with a double-protein transition. The first transition corresponds to the\ replacement of histones by several spermatid-specific proteins, also called transition proteins, which are\ themselves replaced by protamines during the second transition. Nuclear transition protein 2 (TP2) is one\ of those spermatid-specific proteins. TP2 is a basic, zinc-binding protein [MEDLINE:92028893] of 116 to 137\ amino-acid residues. \

Structurally, TP2 consists of three distinct parts, a conserved serine-rich N-terminal\ domain of about 25 residues, a variable central domain of 20 to 50 residues which contains cysteine residues,\ and a conserved C-terminal domain of about 70 residues rich in lysines and arginines.

\ \ DNA binding activity ; GO:0003677 nucleus ; GO:0005634 spermatogenesis ; GO:0007283 19398 IPR000679 A number of transcription factors (including erythroid-specific transcription factor and nitrogen regulatoryproteins), specifically bind the DNA sequence (A/T)GATA(A/G) [MEDLINE:91065513] in the regulatory regions of genes.\ They are consequently termed GATA-binding transcription factors. The interactions occur via highly-conserved\ zinc finger domains in which the zinc ion is coordinated by 4 cysteine residues [MEDLINE:89376538], [MEDLINE:93324913].\ NMR studies have shown the core of the zinc finger to comprise 2 irregular anti-parallel

-sheets and an

-helix, followed by a long loop to the C-terminal end of the finger. The N-terminal part, which includes\ the helix, is similar in structure, but not sequence, to the N-terminal zinc module of the glucocorticoid\ receptor DNA-binding domain. The helix and the loop connecting the 2

-sheets interact with the major\ groove of the DNA, while the C-terminal tail wraps around into the minor groove. It is this tail that is the\ essential determinant of specific binding. Interactions between the zinc finger and DNA are mainly hydrophobic,\ explaining the preponderance of thymines in the binding site; a large number of interactions with the\ phosphate backbone have also been observed [MEDLINE:93324913].Two GATA zinc fingers are found in the GATA\ transcription factors. However there are several proteins which only contains a single copy of the domain.\ \ transcription factor activity ; GO:0003700 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 19394 IPR000674 Aldehyde oxidase (EC: 1.2.3.1) catalyzes the conversion of an aldehyde in the presence of oxygen and waterto an acid and hydrogen peroxide. The enzyme is a homodimer, and requires FAD, molybdenum and two\ 2FE-2S clusters as cofactors. Xanthine dehydrogenase (EC: 1.1.1.204) catalyzes the hydrogenation of xanthine\ to urate, and also requires FAD, molybdenum and two 2FE-2S clusters as cofactors. This activity is often\ found in a bifunctional enzyme with xanthine oxidase (EC: 1.1.3.22) activity too. The enzyme can be converted\ from the dehydrogenase form to the oxidase form irreversibly by proteolysis or reversibly through oxidation\ of sulfhydryl groups.\ \ \ oxidoreductase activity ; GO:0016491 \N electron transport ; GO:0006118 19395 IPR000675

Aerial plant organs are protected by a cuticle composed of an insoluble polymeric structural compound,cutin, which is a polyester composed of hydroxy and hydroxyepoxy fatty acids PUB00000292. Plant pathogenic\ fungi produce extracellular degradative enzymes PUB00000292 that play an important role in pathogenesis.\ They include cutinase, which hydrolyses cutin, facilitating fungus penetration through the cuticle. Inhibition\ of the enzyme can prevent fungal infection through intact cuticles. Cutin monomers released from the cuticle\ by small amounts of cutinase on fungal spore surfaces can greatly increase the amount of cutinase secreted by\ the spore, the mechanism for which process is as yet unknown PUB00000292, PUB00000292.

Cutinase is a serine esterase containing the classical Ser, His, Asp triad of serine hydrolases PUB00000292.\ The protein belongs to the - class, with a central -sheet of 5 parallel strands covered by 5\ helices on either side of the sheet. The active site cleft is partly covered by 2 thin bridges formed by amino\ acid side chains, by contrast with the hydrophobic lid possessed by other lipases PUB00000292. The protein \ also contains 2 disulphide bridges, which are essential for activity, their cleavage resulting in complete \ loss of enzymatic activity PUB00000292. Two cutinase-like proteins (MtCY39.35 and MtCY339.08c) have been \ found in the genome of the bacteria Mycobacterium tuberculosis.

\ \ \N \N \N 19392 IPR000673 CheB methylesterase is responsible for removing the methyl group from the gamma-glutamyl methylester residues in the methyl-accepting chemotaxis proteins (MCP). The enzyme catalyzes the reaction:\ protein L-glutamate O-methyl ester and water is converted to protein L-glutamate and methanol. CheB\ is regulated through phosphorylation by CheA. The N-terminal region of the protein is similar to that\ of other regulatory components of sensory transduction systems. The Myxococcus FrzG protein also\ belongs to this family, and is required for the normal aggregation of cells during fruiting body\ formation.\ \ signal transducer activity ; GO:0004871 \N signal transduction ; GO:0007165 19393 IPR000674 Aldehyde oxidase (EC: 1.2.3.1) catalyzes the conversion of an aldehyde in the presence of oxygen and waterto an acid and hydrogen peroxide. The enzyme is a homodimer, and requires FAD, molybdenum and two\ 2FE-2S clusters as cofactors. Xanthine dehydrogenase (EC: 1.1.1.204) catalyzes the hydrogenation of xanthine\ to urate, and also requires FAD, molybdenum and two 2FE-2S clusters as cofactors. This activity is often\ found in a bifunctional enzyme with xanthine oxidase (EC: 1.1.3.22) activity too. The enzyme can be converted\ from the dehydrogenase form to the oxidase form irreversibly by proteolysis or reversibly through oxidation\ of sulfhydryl groups.\ \ \ oxidoreductase activity ; GO:0016491 \N electron transport ; GO:0006118 19390 IPR000672 Enzymes that participate in the transfer of one-carbon units require the coenzyme tetrahydrofolate (THF).Various reactions generate one-carbon derivatives of THF, which can be interconverted between different\ oxidation states by methylene-THF dehydrogenase (EC: 1.5.1.5), methenyl-THF cyclohydrolase (EC: 3.5.4.9)\ and formyl-THF synthetase (EC: 6.3.4.3) [MEDLINE:89247401], [MEDLINE:93250056]. The dehydrogenase and cyclohydrolase\ activities are expressed by a variety of multifunctional enzymes, including the tri-functional eukaryotic\ C1-tetrahydrofolate synthase [MEDLINE:89247401]; a bifunctional eukaryotic mitochondrial protein; and the\ bifunctional E.coli folD protein [MEDLINE:89247401], [MEDLINE:93250056]. Methylene-tetrahydrofolate dehydrogenase and\ methenyltetrahydrofolate cyclo-hydrolase share an overlapping active site [MEDLINE:89247401], and as such are\ usually located together in proteins, acting in tandem on the carbon-nitrogen bonds of substrates other\ than peptide bonds.\ \ enzyme activity ; GO:0003824 \N folic acid and derivative biosynthesis ; GO:0009396 19391 IPR000672 Enzymes that participate in the transfer of one-carbon units require the coenzyme tetrahydrofolate (THF).Various reactions generate one-carbon derivatives of THF, which can be interconverted between different\ oxidation states by methylene-THF dehydrogenase (EC: 1.5.1.5), methenyl-THF cyclohydrolase (EC: 3.5.4.9)\ and formyl-THF synthetase (EC: 6.3.4.3) [MEDLINE:89247401], [MEDLINE:93250056]. The dehydrogenase and cyclohydrolase\ activities are expressed by a variety of multifunctional enzymes, including the tri-functional eukaryotic\ C1-tetrahydrofolate synthase [MEDLINE:89247401]; a bifunctional eukaryotic mitochondrial protein; and the\ bifunctional E.coli folD protein [MEDLINE:89247401], [MEDLINE:93250056]. Methylene-tetrahydrofolate dehydrogenase and\ methenyltetrahydrofolate cyclo-hydrolase share an overlapping active site [MEDLINE:89247401], and as such are\ usually located together in proteins, acting in tandem on the carbon-nitrogen bonds of substrates other\ than peptide bonds.\ \ enzyme activity ; GO:0003824 \N folic acid and derivative biosynthesis ; GO:0009396 19389 IPR000671 The hydrogenase-specific gene (hup and hyp) products of R.capsulatus show [MEDLINE:93268090] a high degree ofsimilarity to hydrogenase gene products from E.coli (hyaD) [MEDLINE:90202716], R.leguminosarum (hupD) [MEDLINE:91355885],\ A.vinelandii (hoxM) [MEDLINE:92325046] and A.eutrophus (hoxM) [MEDLINE:93015670], which together are designated the hupD/\ hyaD family. The hup and hox gene products are absolutely required for hydrogenase activity, hoxM mediating\ the attachment of hydrogenase to the bacterial membrane, which is essential for enzymatic activity. The function\ of hyaD is unknown, but with hyaE could form a complex involved in processing of the hydrogenase 1 structural\ operon.\ \ hydrogenase activity ; GO:0008901 hydrogenase complex ; GO:0009375 \N 19388 IPR000670

Urotensin II is a vasoactive 'somatostatin-like' peptide, first identified in fish spinal cord but later found in humans and other mammals [MEDLINE:99427933]. A cyclic hexapeptide region of the molecule is responsible for the biological activity and is absolutely conserved between species [MEDLINE:20476544]. Urotensin II is the most potent mammalian vasoconstrictor identified to date and causes contraction of arterial blood vessels, including the thoracic aorta [MEDLINE:99427933], [MEDLINE:20476544]. The urotensin II receptor was originally isolated as an orphan receptor, expressed in neural and sensory tissues and named GPR14, or sensory epithelial neuropeptide-like receptor (SENR) [MEDLINE:95251679]. The receptor has been found to be expressed in the CNS (cerebellum and spinal cord), skeletal muscle, pancreas, heart, endothelium and vascular smooth muscle [MEDLINE:21180329]. It is likely to be involved in the pathophysiological control of cardiovascular function and may also influence CNS and endocrine functions [MEDLINE:99427933], [MEDLINE:21180329]. Binding of urotensin II to the receptor leads to activation of phospholipase C, through coupling to Gq/11 family proteins. The resulting increase in intracellular calcium may cause the contraction of vascular smooth muscle [MEDLINE:20476544].

\ \ urotensin II receptor activity ; GO:0001604 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19387 IPR000669 Mannitol-1-phosphate 5-dehydrogenase catalyzes the NAD-dependent reduction of mannitol-1-phosphateto fructose-6-phosphate [MEDLINE:91267934] as part of the phosphoenolpyruvate-dependent phosphotransferase\ system (PTS). The PTS facilitates the vectorial translocation of metabolisable carbohydrates to form\ the corresponding sugar phosphates, which are then converted to glycolytic intermediates [MEDLINE:92348013].\ Mannitol 2-dehydrogenase catalyzes the NAD-dependent reduction of mannitol to fructose [MEDLINE:94075966].\ Several dehydrogenases have been shown [MEDLINE:94075966] to be evolutionary related, including \ mannitol-1-phosphate 5-dehydrogenase (EC: 1.1.1.17) (gene mtlD), mannitol 2-dehydrogenase (EC: 1.1.1.67) (gene mtlK);\ mannonate oxidoreductase (EC: 1.1.1.57) (fructuronate reductase) (gene uxuB); E. coli hypothetical\ proteins ydfI and yeiQ; and yeast hypothetical protein YEL070w.\ \ enzyme activity ; GO:0003824 \N metabolism ; GO:0008152 19386 IPR000668

Cysteine protease can be divided into several families, including C1, C2 and C10, which are looselytermed papain-like. The best known example of cysteine proteases is the papain (C1) family. The papain\ family has a wide variety of activities, including broad-range (papain) and narrow-range endo-peptidases,\ aminopeptidases, dipeptidyl peptidases and enzymes with both exo- and endo-peptidase activity\ [MEDLINE:95147707]. Members of the papain family are widespread, found in baculovirus [MEDLINE:93176119],\ eubacteria, yeast, and practically all protozoa, plants and mammals [MEDLINE:95147707]. The proteins are typically\ lysosomal or secreted, and proteolytic cleavage of the propeptide is required for enzyme activation, although\ bleomycin hydrolase is cytosolic in fungi and mammals [MEDLINE:88024931].

The catalytic residues of papain are Cys-25 and His-159, other important residues being Gln-19, which\ helps form the 'oxyanion hole', and Asn-175, which orientates the imidazole ring of His-159.

\ \ cysteine-type peptidase activity ; GO:0008234 \N proteolysis and peptidolysis ; GO:0006508 19385 IPR000667

D-Ala-D-Ala carboxypeptidase (clan SE) is involved in the metabolism of\ cell components [MEDLINE:92074811]; it is synthesised with a leader peptide to target it\ to the cell membrane [MEDLINE:95147689]. After cleavage of the leader peptide, the enzyme\ is retained in the membrane by a C-terminal anchor [MEDLINE:95147689]. There are three\ families of serine-type D-Ala-D-Ala peptidase (designated S11, S12 and S13),\ which are also known as low molecular weight penicillin-binding proteins [MEDLINE:95147689].\ Family S13 comprises D-Ala-D-Ala peptidases that have sufficient sequence\ similarity around their active sites to assume a distant evolutionary\ relationship to other clan members; members of the S13 family also bind\ penicilin and have D-amino-peptidase activity. Proteases of family S11 have\ exclusive D-Ala-D-Ala peptidase activity, while some members of S12 are\ C -lactamases [MEDLINE:95147689].

\ \ \ serine carboxypeptidase activity ; GO:0004185 \N proteolysis and peptidolysis ; GO:0006508 19382 IPR000663 Atrial natriuretic peptides (ANPs) are vertebrate hormones that play an important role in the control ofcardiovascular homeostatis, and sodium and water balance in general [MEDLINE:91354028], [MEDLINE:89123413], PUB00005323.\ There are different NPs that vary in length but share a common core. All are processed from a single precursor.\ A disulphide bond resident in the C-terminal section is required for full activity of atriopeptins. The family\ of NPs includes structurally-related peptides that elicit similar pharmacological spectra. Amongst these are\ brain natriuretic peptide (BNP); C-type natriuretic peptide (CNP); ventricular natriuretic peptide (VNP)\ PUB00005323; and green mamba natriuretic peptide (DNP) [MEDLINE:92332489].\ \ hormone activity ; GO:0005179 extracellular ; GO:0005576 \N 19383 IPR000664 The lethal(2)giant larvae tumour-suppressor gene of Drosophila controls cell proliferation and/ordifferentiation in the optic centres of the brain and the imaginal discs. The structure of the l(2)gl genes,\ determined by sequencing genomic and cDNA clones, indicates the use of alternative splicing, either in\ the 5' untranslated or 3' coding exons. The gene thus encodes two putative proteins, p127 and p78,\ differing at their C-termini. A 3'-truncated l(2)gl transposon that leaves the coding sequence of p78 intact,\ but deletes 141 residues of p127, was capable of suppressing tumour formation in l(2)gl-deficient animals\ \ \ \ [MEDLINE:87244337]. Mutations in the Drosophila l(2)gl gene cause malignant transformation of the optic centres of\ the larval brain and imaginal discs. The l(2)gl gene from Drosophila pseudoobscura shows a high degree of\ conservation with the corresponding protein-coding domain from D.melanogaster\ \ \ \ [MEDLINE:93275648]. These proteins seem to all contain the WD repeats from IPR001680.\ \ \N \N \N 19384 IPR000665 Hemagglutinin is responsible for attaching viruses to cell receptors and for initiating infection. Neuroaminidase activity helps the efficient spread of the virus by dissociating the mature virions from the neuraminic acid-containing glycoproteins. Hemagglutinin-neuramidase is external, and anchored to the envelope by its N-terminal hydrophobic sequence. Proteins belonging to this family are from ssRNA negative-strand viruses.\ exo-alpha-sialidase activity ; GO:0004308 \N viral infectious cycle ; GO:0019058 19381 IPR000662 Proteins belonging to this family include coat protein VP1 from polyomaviruses, which are dsDNA viruses with no RNA stage in their life cycle. The virus capsid is composed of 72 icosahedral units, each of which is composed of five copies of VP1. The virus attaches to the cell surface by recognition of oligosaccharides terminating in

(2,3)-linked sialic acid.\ \N \N \N 19380 IPR000659 Pyridoxamine 5'-phosphate oxidase (EC: 1.4.3.5) is a FMN flavoprotein involved in the de novo synthesis\ of pyridoxine (vitamin B6) and pyridoxal phosphate. It oxidizes pyridoxamine-5-P (PMP) and pyridoxine-5-P\ (PNP) to pyridoxal-5-P. The sequences of the enzyme from bacterial (genes pdxH or fprA) [MEDLINE:93015640] and\ fungal (gene PDX3) [MEDLINE:95204349] sources show that this protein has been highly conserved throughout\ evolution. PdxH is evolutionary related [MEDLINE:96102876] to one of the enzymes in the phenazine biosynthesis\ protein pathway, phzD (also known as phzG).\ \ \ pyridoxamine-phosphate oxidase activity ; GO:0004733 \N pyridoxine biosynthesis ; GO:0008615 19379 IPR000657

Geminiviruses are characterised by a genome of circular single-strandedDNA encapsidated in twinned (geminate) quasi-isometric particles, from which the group derives its name \ PUB00001145. Most geminiviruses can be divided into 2 subgroups\ on the basis of host range and/or insect vector. The genomes of the whitefly-transmitted \ cassava latent (CLV), \ tomato golden mosaic (TGMV) and \ bean golden mosaic (BGMV) viruses possess a bipartite genome. \ By contrast, only a single DNA component has been identified for the leafhopper-transmitted \ maize streak (MSV) and \ wheat dwarf (WDV) viruses PUB00001145, [MEDLINE:88124198]. \ Beet curly top (BCTV), bean summer death and \ tobacco yellow dwarf viruses belong to a third possible subgroup. \ Sequence comparison of the whitefly-transmitted squash leaf curl\ \ \ \ [MEDLINE:91082449] and \ tomato yellow leaf curl viruses [MEDLINE:92107660], [MEDLINE:92024070] \ with the genomic components of \ TGMV and \ BGMV reveals a close evolutionary relationship [MEDLINE:91082449]. \ Amino acid sequence alignments of potato yellow mosaic viral (PYMV) \ proteins with those encoded by other geminiviruses show that \ PYMV is closely related to geminiviruses \ isolated from the New World, especially in the putative coat protein gene regions [MEDLINE:91311403].\

Geminiviruses contain three ORFs (designated AL1, AL2, and AL3) that \ overlap and are specified by multiple polycistronic mRNAs. The AL3 protein comprises approximately 0.05% \ of the cellular proteins and is present in the soluble and organelle fractions [MEDLINE:94303163]. \ AL3 may form oligomers [MEDLINE:96386567]. Immunoprecipitation of AL3 in a \ baculovirus expression system extracts expressing both AL1 and AL3 showed \ that the two proteins also complex with each other. The AL3 protein is involved in viral replication. \

\ \ \N \N \N 19378 IPR000655 The Cro family comprises a set of small, single-domain DNA binding proteins that regulate phage transcriptionby binding to DNA in a sequence-specific manner using a characteristic helix-turn-helix (HTH) motif\ [MEDLINE:86250772]. The motif occurs between residues 16-35. It consists of 2

-helices joined by a short turn\ that contains a critically conserved glycine (position 9 in the motif). The second helix binds to DNA via a\ number of hydrogen bonds and hydrophobic interactions, which occur between specific side chains and the\ exposed bases and thymine methyl groups within the major groove of the DNA [MEDLINE:86227496]. The first helix\ helps to stabilise the structure [MEDLINE:82220161]. This motif is very similar in sequence and structure to the\ N-terminal region of the lamda [MEDLINE:84036178] and other repressor proteins, and has also been identified in\ many other DNA-binding proteins on the basis of sequence and structure similarity [MEDLINE:86250772].\ \ transcription factor activity ; GO:0003700 \N regulation of transcription, DNA-dependent ; GO:0006355 19375 IPR000652 Triosephosphate isomerase (EC: 5.3.1.1) (TIM) [MEDLINE:90373768] is the glycolytic enzyme that catalyzes thereversible interconversion of glyceraldehyde 3-phosphate and dihydroxyacetone phosphate. TIM plays an\ important role in several metabolic pathways and is essential for efficient energy production. It is a\ dimer of identical subunits, each of which is made up of about 250 amino-acid residues. A glutamic acid\ residue is involved in the catalytic mechanism [MEDLINE:91172292]. The sequence around the active site residue\ is perfectly conserved in all known TIM's.\ \ triose-phosphate isomerase activity ; GO:0004807 \N metabolism ; GO:0008152 19376 IPR000653 The members of this family are probably all pyridoxal-phosphate-dependent aminotransferase enzymes with a variety of molecular functions. The family includes StsA P72454.\ \N \N \N 19377 IPR000654

Guanine nucleotide binding proteins (G-proteins) are a family of membrane-associated proteins that couple extracellularly-activated integral-membrane receptors to intracellular effectors, such as ion channels and enzymes that vary the concentration of second messenger molecules ([MEDLINE:91354032], [MEDLINE:91227903]). G-proteins are composed of 3 subunits (, and gamma) which, in the resting state, associate as a trimer at the inner face of the plasma membrane. The subunit has a molecule of guanosine diphosphate (GDP) bound to it. Stimulation of the G-protein by an activated receptor leads to its exchange for GTP (guanosine triphosphate). This results in the separation of the from the and gamma subunits, which always remain tightly associated as a dimer. Both the and -gamma subunits are then able to interact with effectors, either individually or in a cooperative manner. The intrinsic GTPase activity of the subunit hydrolyses he bound GTP to GDP. This returns the subunit to its inactive conformation and allows it to reassociate with the -gamma subunit, thus restoring the system to its resting state.

G-protein subunits are 350-400 amino acids in length and have molecular weights in the range 40-45 kD. Seventeen distinct types of subunit have been identified in mammals. These fall into 4 main groups on the basis of both sequence similarity and function: -s, -q, -i and -12 ([MEDLINE:91227903]). The G-protein -q (G -q) class are widely expressed, toxin insensitive proteins that couple receptors, such as the m1 acetylcholine receptor, to the effector enzyme phospholipase C (PLC), causing subsequent InsP3- mediated release of calcium from internal stores. Alpha-q subunits found in squid and Drosophila are believed to be involved in signal transduction, which is thought to be an InsP3-mediated process in invertebrates.

\ GTP binding activity ; GO:0005525 \N G-protein coupled receptor protein signaling pathway ; GO:0007186 19374 IPR000651 This domain is found in several guanine nucleotide exchange factors for Ras-like small GTPases, and liesN-terminal to the RasGef (Cdc25-like) domain. Proteins belonging to this family include guanine nucleotide\ dissociation stimulator, which stimulates the dissociation of GDP from the Ras-related RalA and RalB\ GTPases and allows GTP binding and activation of the GTPases; GTPase-activating protein (GAP) for Rho1\ and Rho2, which is involved in the control of cellular morphogenesis; and the yeast cell division control\ protein, which promotes the exchange of Ras-bound GDP by GTP and controls the level of cAMP when\ the cell division cycle is triggered. Also included is the son of sevenless protein, which promotes the\ exchange of Ras-bound GDP by GTP during neuronal development.\ \ guanyl-nucleotide exchange factor activity ; GO:0005085 \N small GTPase mediated signal transduction ; GO:0007264 19372 IPR000649 Initiation factor 2 binds to Met-tRNA, GTP and the small ribosomal subunit. The eukaryotic translationinitiation factor EIF-2B is a complex made up of five different subunits,

, gamma, delta and epsilon,\ and catalyzes the exchange of EIF-2-bound GDP for GTP. This family includes initiation factor 2B

and delta subunits from eukaryotes; related proteins from archaebacteria and IF-2 from prokaryotes.\ \ GTP binding activity ; GO:0005525 eukaryotic translation initiation factor 2B complex ; GO:0005851 translational initiation ; GO:0006413 19373 IPR000650 Geminiviruses are characterised by a genome of circular single-stranded DNA encapsidated in twinned (geminate)quasi-isometric particles, from which the group derives its name PUB00001145. Most geminiviruses can be\ divided into 2 subgroups on the basis of host range and/or insect vector: i.e. those that infect\ dicotyledenous plants and are transmitted by the same whitefly species, and those that infect \ mono-cotyledenous plants and are transmitted by different leafhopper vectors. The genomes of the whitefly-transmitted\ cassava latent (CLV), tomato golden mosaic (TGMV) and bean golden mosaic (BGMV) viruses possess a bipartite\ genome. By contrast, only a single DNA component has been identified for the leafhopper-transmitted maize\ streak (MSV) and wheat dwarf (WDV) viruses PUB00001145, [MEDLINE:88124198]. Beet curly top (BCTV), bean summer death\ and tobacco yellow dwarf viruses belong to a third possible subgroup. Like MSV and WDV, BCTV is transmitted by\ a specific leafhopper species, yet like the whitefly-transmitted gemini-viruses it has a host range confined to\ dicotyledenous plants. Sequence comparison of the whitefly-transmitted squash leaf curl\ \ \ \ [MEDLINE:91082449] and tomato\ yellow leaf curl viruses [MEDLINE:92107660], [MEDLINE:92024070] with the genomic components of TGMV and BGMV reveals a close\ evolutionary relationship [MEDLINE:91082449]. Amino acid sequence alignments of potato yellow mosaic viral (PYMV)\ proteins with those encoded by other geminiviruses show that PYMV is closely related to geminiviruses isolated\ from the New World, especially in the putative coat protein gene regions [MEDLINE:91311403].\ \ structural molecule activity ; GO:0005198 viral capsid ; GO:0019028 \N 19371 IPR000648 A number of eukaryotic proteins that seem to be involved with sterol synthesis and/or its regulation havebeen found [MEDLINE:94287711] to be evolutionary related. These include mammalian oxysterol-binding protein\ (OSBP), a protein of about 800 amino-acid residues that binds a variety of oxysterols (oxygenated derivatives\ of cholesterol); yeast OSH1, a protein of 859 residues that also plays a role in ergosterol synthesis; yeast\ proteins HES1 and KES1, highly related proteins of 434 residues that seem to play a role in ergosterol synthesis;\ and yeast hypothetical proteins YHR001w, YHR073w and YKR003w.\ \ \N \N steroid metabolism ; GO:0008202 19369 IPR000646 This family includes hexon-associated proteins from adenoviruses. Adenoviruses are responsible for diseases such as pneumonia, cystitis, conjunctivitis and diarrhoea, all of which can be fatal to patients who are immunocompromised [MEDLINE:95219386].\ \ \N \N \N 19368 IPR000645 The secretion pathway (GSP) for the export of proteins (also called the type II pathway) [MEDLINE:93174466]requires a number of protein components. One of them is known as the 'N' protein and has been sequenced\ in a variety of bacteria such as Aeromonas hydrophila (gene exeN); Erwinia carotovora (gene outN); Klebsiella pneumoniae (gene\ pulN); or Vibrio cholerae (gene epsN). The size of the 'N' protein is around 250 amino acids. It apparently\ contains a single transmembrane domain located in the N-terminal section. The short N-terminal domain is\ predicted to be cytoplasmic and the large C-terminal domain periplasmic.\ \ protein transporter activity ; GO:0008565 type II protein secretion system complex ; GO:0015627 type II protein (Sec) secretion system ; GO:0015628 19370 IPR000647 Nuclear factor I (NF-I) or CCAAT box-binding transcription factor (CTF) [MEDLINE:89354548], [MEDLINE:90251434] (alsoknown as TGGCA-binding proteins) are a family of vertebrate nuclear proteins which recognize and bind, as\ dimers, the palindromic DNA sequence 5'-TGGCANNNTGCCA-3'. CTF/NF-I binding sites are present in viral and\ cellular promoters and in the origin of DNA replication of Adenovirus type 2. The CTF/NF-I proteins were\ first identified as nuclear factor I, a collection of proteins that activate the replication of several\ Adenovirus serotypes (together with NF-II and NF-III) [MEDLINE:83065188]. The family of proteins was also\ identified as the CTF transcription factors, before the NFI and CTF families were found to be identical\ [MEDLINE:88288392]. The CTF/NF-I proteins are individually capable of activating transcription and DNA replication.\ In a given species, there are a large number of different CTF/NF-I proteins, generated both by alternative\ splicing and by the occurrence of four different genes. CTF/NF-1 proteins contain 400 to 600 amino acids.\ The N-terminal 200 amino-acid sequence, almost perfectly conserved in all species and genes sequenced,\ mediates site-specific DNA recognition, protein dimerization and Adenovirus DNA replication. The C-terminal\ 100 amino acids contain the transcriptional activation domain. This activation domain is the target of gene\ expression regulatory pathways ellicited by growth factors and it interacts with basal transcription factors\ and with histone H3 [MEDLINE:96127902].\ \ transcription factor activity ; GO:0003700 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 19366 IPR000643 Iodothyronine deiodinase (EC: 3.8.1.4) (DI) PUB00006081, PUB00006081 is the vertebrate enzyme responsible for the deiodination ofthe prohormone thyroxine (T4 or 3,5,3',5'-tetraiodothyronine) into the biologically active hormone T3\ (3,5,3'-triiodothyronine) and of T3 into the inactive metabolite T2 (3,3'-diiodothyronine). All known DI are\ proteins of about 250 residues that contain a selenocysteine at their active site. Three types of DI are\ known, type II is essential for providing the brain with the appropriate levels of T3 during the critical\ period of development, and type III is essential for the regulation of thyroid hormone inactivation during\ embryological development.\ \ thyroxine deiodinase activity ; GO:0004800 \N \N 19367 IPR000644

CBS domains are small intracellular modules mostly found in 2 or four copies within a protein. The exact function of these domains is unknown, however it isthought that they bind to some as yet unidentified small molecule (perhaps with an adenosyl moiety) and regulate the activity of attached enzymatic or other domains.

\ \

CBS domains are found in enzymes such as cystathionine--synthase (CBS) where mutations lead to homocystinuria. Two CBS domains are found in inosine-monophosphate dehydrogenase (IMPDH) from all species, however the CBS domains are not needed for activity. The CBS domains are found inserted within a loop of the TIM barrel structure of the IMPDH enzymatic domain. Pairs of CBS domains associate to form a single compact structure. A family of polyA polymerases also contain CBS domains.

\ \

CBS domains are found in the intracellular regions of a number of different integral membrane proteins. Two CBS domains are found in intracellular loops of several voltage gated chloride channels. A family of magnesium transporters also contain CBS domains.

\ \ \N \N \N 19363 IPR000640 This family includes the carboxyl terminal regions of elongation factor G, elongation factor 2 and sometetracycline resistance proteins. It is always found associated with IPR000795, which contains the signatures\ for the N-terminus of the proteins. The elongation factors promote the GTP-dependent translocation of the\ nascent protein chain from the A-site to the P-site of the ribosome. Phosphorylation by EF-2 kinase\ completely inactivates EF-2.\ \ GTP binding activity ; GO:0005525 \N translational elongation ; GO:0006414 19364 IPR000641 The Cfx genes in Alcaligenes eutrophus encode a number of Calvin cycle enzymes. The observed sizes of twoof the gene products, CfxX and CfxY, are 35 kD and 27 kD respectively [MEDLINE:93054349]. No functions could\ be assigned to CfxX and CfxY, but CfxQ is required for the expression of rubisco. These proteins show a\ high degree of similarity to the B. subtilis stage V sporulation protein K [MEDLINE:92157863].\ \ ATP binding activity ; GO:0005524 \N \N 19365 IPR000642

Metalloproteases can be split into five clans, and futher sub-divided into families, on the basis of their metal binding residues.

The peptidase M41 family belongs to a larger family of zinc metalloproteases. This family\ includes the cell division protein FtsH, and the yeast mitochondrial respiratory chain complexes\ assembly protein, which is a putative ATP-dependent protease required for assembly of the\ mitochondrial respiratory chain and ATPase complexes. FtsH is an integral membrane protein,\ which seems to act as an ATP-dependent zinc metallopeptidase that binds one zinc ion.

\ \ ATP binding activity ; GO:0005524 \N proteolysis and peptidolysis ; GO:0006508 19361 IPR000638 Gas vesicles are small, hollow, gas filled protein structures found in several cyanobacterial and archaebacterialmicroorganisms [MEDLINE:90104301]. They allow the positioning of the bacteria at the favourable depth for growth.\ Gas vesicles are hollow cylindrical tubes, closed by a hollow, conical cap at each end. Both the conical end\ caps and central cylinder are made up of 4-5 nm wide ribs that run at right angles to the long axis of the\ structure. Gas vesicles seem to be constituted of two different protein components, GVPa and GVPc. GVPa, a\ small protein of about 70 amino acid residues, is the main constituent of gas vesicles and form the essential\ core of the structure. The sequence of GVPa is extremely well conserved. GvpJ and gvpM, two proteins encoded\ in the cluster of genes required for gas vesicle synthesis in the archaebacteria Halobacterium halobium and\ Haloferax mediterranei, have been found [MEDLINE:91323716] to be evolutionary related to GVPa. The exact function\ of these two proteins is not known, although they could be important for determining the shape determination\ gas vesicles. The N-terminal domain of Aphanizomenon flos-aquae protein gvpA/J is also related to GVPa.\ \ \N \N \N 19362 IPR000639 The

hydrolase fold is common to a number of hydrolytic enzymes of widely differing phylogeneticorigin and catalytic function. The core of each enzyme is an

-sheet (rather than a barrel), containing\ 8 strands connected by helices [MEDLINE:93028317]. The enzymes are believed to have diverged from a common ancestor,\ preserving the arrangement of the catalytic residues. All have a catalytic triad, the elements of which are borne\ on loops, which are the best conserved structural features of the fold. The epoxide hydrolases (EH) add water to\ epoxides, forming the corresponding diol. On the basis of sequence similarity, it has been proposed that the\ mammalian soluble EHs contain 2 evolutionarily distinct domains, the N-terminal domain is similar to bacterial\ haloacid dehalogenase, while the C-terminal domain is similar to soluble plant EH, microsomal EH, and bacterial\ haloalkane dehalogenase (HLD) [MEDLINE:95134356]. The mechanism of HLD, established by X-ray crystallographic analysis\ of an HDL-substrate intermediate [MEDLINE:93295480], involves nucleophilic attack of Asp-124 on the halogen-substituted\ terminal carbon of the substrate, forming a covalently-bound ester intermediate. The Asp-260/His-289 pair\ activate a water molecule that hydrolyses the ester intermediate to release the product. The similarity of EH to\ HLD is important for deducing a catalytic mechanism for EH. Mutagenesis experiments on murine soluble EH\ confirmed the crucial role of nucleophile Asp-333 and His-523 in the catalytic mechanism and the importance of\ conserved His-263 and His-332 [MEDLINE:95229605].\ \ enzyme activity ; GO:0003824 \N \N 19359 IPR000635 Although the overall picture of HCMV DNA synthesis appears typical of the herpesviruses, some novel features are emerging. Six herpesvirus-group-common genes encode proteins that likely constitute the replication fork machinery, including a two-subunit DNA polymerase, a helicas-primase complex and a single-stranded DNA-binding protein [MEDLINE:97276294]. \

The herpes simplex virus type-1 single-strand DNA-binding protein ICP8 is a 128-kDa zinc metalloprotein. Photoaffinity labeling has shown that the region encompassing residues 368-902 contains the single-strand DNA-binding site of ICP8 [MEDLINE:20001947]. The herpes simplex virus type-1 UL5, UL8, and UL52 genes encode an essential heterotrimeric DNA helicase-primase that is responsible for concomitant DNA unwinding and primer synthesis at the viral DNA\ replication fork. ICP8 may stimulate DNA unwinding and enable bypass of cisplatin damaged DNA by recruiting the helicase-primase to the DNA [MEDLINE:98256308].

\ \ single-stranded DNA binding activity ; GO:0003697 host cell nucleus ; GO:0042025 DNA replication ; GO:0006260 19360 IPR000637 High mobility group (HMG) proteins are a family of relatively low molecular weight non-histone components\ in chromatin. HMG-I and HMG-Y are proteins of about 100 amino acid residues which are produced by the\ alternative splicing of a single gene. HMG-I proteins bind preferentially to the minor groove of AT-rich\ regions in double-stranded DNA [MEDLINE:90256776], [MEDLINE:94021372]. It is suggested that these proteins could function\ in nucleosome phasing and in the 3' end processing of mRNA transcripts. They are also involved in the\ transcription regulation of genes containing, or in close proximity to, AT-rich regions. DNA-binding of these,\ and several related, proteins is effected by an 11-residue domain known as an AT-hook. Within known HMG-I\ proteins are found three highly conserved regions, closely related to the consensus sequence TPKRPRGRPKK. A\ synthetic oligopeptide with this sequence specifically binds to substrate DNA in a manner reminiscent of\ intact HMG-I proteins. Structure predictions suggest that the peptide has a secondary structure similar to\ the anti-tumour and anti-viral drugs netropsin and distamycin, and to the dye Hoechst 33258. These ligands,\ which also preferentially bind to AT-rich DNA, effectively compete with both the synthetic peptide and the\ HMG-I proteins for DNA binding. The peptide also contains novel structural features such as a predicted Asx\ bend, or 'hook', at its N-terminus, and laterally-projecting cationic Arg/Lys 'bristles', which may play a\ role in the binding of HMG-I proteins. The predicted peptide structure, the AT-hook, is a previously\ undescribed DNA-binding motif [MEDLINE:90256776].\ \ \ DNA binding activity ; GO:0003677 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 19357 IPR000633 Vinculin is a eukaryotic protein that appears to be involved in the attachment of actin-based microfilaments tothe plasma membrane [MEDLINE:90284037]. It also interacts with other structural proteins, such as talin [MEDLINE:90078327]\ and

-actinin. The protein is located on the cytoplasmic side of focal contacts or adhesion plaques. Vinculin\ is a large protein (~1000 residues) that contains an acidic N-terminal domain, separated from a smaller, basic\ C-terminal domain by a 50-residue proline-rich region [MEDLINE:92021009]. The central part of the N-terminal domain\ consists of a variable number of repeats of a 110-residue domain, one of which is lacking in nematode vinculin\ [MEDLINE:90332642].\ \ \N \N \N 19358 IPR000634 Serine and threonine dehydratases [MEDLINE:89380167], [MEDLINE:87092415] are functionally and structurally relatedpyridoxal-phosphate dependent enzymes. L-serine dehydratase (EC: 4.3.1.17) and D-serine dehydratase\ (EC: 4.3.1.18) catalyze the dehydratation of L-serine (respectively D-serine) into ammonia and pyruvate.\ Threonine dehydratase (EC: 4.3.1.19) (TDH) catalyzes the dehydratation of threonine into

-ketobutarate\ and ammonia. In Escherichia coli and other microorganisms, two classes of TDH are known to exist. One is involved\ in the biosynthesis of isoleucine, the other in hydroxamino acid catabolism. Threonine synthase (EC: 4.2.3.1)\ is also a pyridoxal-phosphate enzyme, it catalyzes the transformation of homoserine-phosphate into threonine.\ It has been shown [MEDLINE:87080286] that threonine synthase is distantly related to the serine/threonine\ dehydratases. In all these enzymes, the pyridoxal-phosphate group is attached to a lysine residue.\ \ \N \N amino acid metabolism ; GO:0006520 19356 IPR000632 The product of the S.cerevisiae gene MRS6 (Mrs6p) [MEDLINE:95188267] shows significantsimilarity both to the mammalian GDP dissociation inhibitor (GDI) of Rab-type small G proteins [MEDLINE:96062207],\ [MEDLINE:95045420] and to the human choroideraemia protein (component A of Rab-specific GGTase II) [MEDLINE:95072565].\ Disruption of the MRS6 gene is lethal to haploid yeast cells. This is consistent with the notion that Mrs6p\ interacts with Rab proteins, which are known to have essential functions in vesicular transport. Mrs6p has\ also been shown to affect mitochondrial functions [MEDLINE:95188267].\ \ RAB escort protein activity ; GO:0005084 \N intracellular protein transport ; GO:0006886 19355 IPR000631 Several uncharacterized proteins have been shown to share regions of similarities, including yeast chromosomeXI hypothetical protein YKL151c; C. elegans hypothetical protein R107.2; E. coli hypothetical protein yjeF;\ Bacillus subtilis hypothetical protein yxkO; Helicobacter pylori hypothetical protein HP1363; Mycobacterium\ tuberculosis hypothetical protein MtCY77.05c; Mycobacterium leprae hypothetical protein B229_C2_201;\ Synechocystis strain PCC 6803 hypothetical protein sll1433; and Methanococcus jannaschii hypothetical protein\ MJ1586. These are proteins of about 30 to 40 kD whose central region is well conserved.\ \ molecular_function unknown ; GO:0005554 \N \N 19354 IPR000630

\ \ \

Ribosomal protein S8 is one of the proteins from the small ribosomal subunit. In E. coli, S8 is known to bind\ directly to 16S ribosomal RNA. It belongs to a family of ribosomal proteins which, on the basis of sequence\ similarities PUB00005070, groups eubacterial, algal and plant chloroplast, cyanelle, archaebacterial and\ Marchantia polymorpha mitochondrial S8; mammalian and plant S15A; and yeast S22 (S24) ribosomal proteins.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 19352 IPR000628

Vasopressin and oxytocin are members of the neurohypophyseal hormone family\ found in all mammalian species . They are present in high levels in the\ posterior pituitary. Vasopressin has an essential role in the control of\ the water content of the body, acting in the kidney to increase water and\ sodium absorption . In higher concentrations, vasopressin stimulates\ contraction of vascular smooth muscle, stimulates glycogen breakdown in the\ liver, induces platelet activation, and evokes release of corticotrophin\ from the anterior pituitary . Vasopressin and its analogues are used\ clinically to treat diabetes insipidus PUB00005908.

In the periphery, the V1A receptor is found in high levels in vascular\ smooth muscle, myometrium and the bladder where it mediates contraction .\ V1B receptors can be distinguished from V1A receptors by the low affinity of\ certain antagonists at the former. The receptors stimulate phosphoinositide\ metabolism and are found in the anterior pituitary PUB00005908.

\ \ vasopressin receptor activity ; GO:0005000 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19353 IPR000629 A number of eukaryotic and prokaryotic proteins involved in ATP-dependent, nucleic-acid unwinding havebeen characterized [MEDLINE:92203994], [MEDLINE:89097246], [MEDLINE:91125473] on the basis of their structural similarity. All\ these proteins share a number of conserved sequence motifs. Some of them are specific to this family while\ others are shared by other ATP-binding proteins or by proteins belonging to the helicases 'superfamily'\ PUB00004025. One of these motifs, called the 'D-E-A-D-box', represents a special version of the\ B motif of ATP-binding proteins. Proteins currently known to belong to this family include eukaryotic\ initiation factor eIF-4A; yeast PRP5, PRP28 and MSS116 splicing proteins, and proteins DHH1, DRS1, MAK5 and\ ROK1; mouse Pl10, C.elegans helicase glh-1; Drosophila Rm62 (p62), Me31B and Vasa; and E. coli putative RNA\ helicases dbpA, deaD, rhlB and rhlE.\ \ ATP dependent helicase activity ; GO:0008026 \N \N 19351 IPR000627 Dioxygenases catalyze the incorporation of both atoms of molecular oxygen into substrates. Cleavage of aromaticrings is one of the most important functions of dioxygenases. The substrates of ring-cleavage dioxygenases can be\ classified into two groups according to the mode of scission of the aromatic ring. Intradiol enzymes cleave the\ aromatic ring between two hydroxyl groups, whereas extradiol enzymes cleave the aromatic ring between a\ hydroxylated carbon and another adjacent nonhydroxylated carbon [MEDLINE:89359362]. Intradiol dioxygenases require a\ nonheme ferric ion as a cofactor. The enzymes that belong to this family are protocatechuate 3,4-dioxygenase\ (EC: 1.13.11.3) (3,4-PCD), an oligomeric enzyme complex which consists of 12 copies each of an

and a

subunits; catechol 1,2-dioxygenase (EC: 1.13.11.1) (gene catA or clcA); and chlorocatechol 1,2-dioxygenase\ (EC: 1.13.11.1) (gene tfdC).\ \ ferric iron binding activity ; GO:0008199 \N aromatic compound metabolism ; GO:0006725 19350 IPR000626

Ubiquitin [MEDLINE:91274342], PUB00000768, PUB00000768 is a protein of seventy six amino acid residues, found in alleukaryotic cells and whose sequence is extremely well conserved from protozoan to vertebrates. It is widely known as a post-translational tag used to signal a protein's hydrolytic destruction. Other functions for ubiquitin, depend on its differential internal isopeptide linkages. In addition, several ubiquitin-like proteins have\ been discovered from genome-sequencing efforts, other structural studies, and genetic screens. These new data show that proteins with the ubiquitin domain are\ adaptable, transposable genetic elements, which have been appended to other genes and utilized for many different cellular functions, depending on the ubiquitin-like\ protein's identity, subcellular location, and method of covalent attachment. The post-translational ligation of proteins to members of the ubiquitin superfamily can\ signal many different fates for the target protein [Larsen and Wang (2002) J. Proteome Res. 1, 411-419.]

Ubiquitin is a globular protein, the last four C-terminal residues (Leu-Arg-Gly-Gly) extending from the compact\ structure to form a 'tail' important for its function. The latter is mediated by the covalent conjugation of\ ubiquitin to target proteins, by an isopeptide linkage between the C-terminal glycine and the epsilon amino\ group of lysine residues in the target proteins.

In most species, there are many genes coding for ubiquitin. However they can be classified into two classes. The\ first class produces polyubiquitin molecules consisting of exact head to tail repeats of ubiquitin. The number of\ repeats is variable. In the majority of polyubiquitin precursors, there is a final amino-acid after the last repeat. The \ second class of genes produces precursor proteins consisting of a single copy of ubiquitin fused to a C-terminal \ extension protein (CEP). There are two types of CEP proteins and both seem to be ribosomal proteins. There are a \ number of proteins which are evolutionary related to ubiquitin, including ubiquitin-like proteins from baculoviruses; \ mammalian proteins GDX, FAU and RAD23-related proteins; human spliceosome associated protein 114, proteins \ BAT3 and CKAP1/TFCB, and ubiquitin-like proteins SMT3A, SMT3C and SMT3B; yeast proteins RAD23, DK2 and\ SMT3; and C. elegans SMT3 and ubl-1 proteins.

\ \ \N \N \N 19348 IPR000623 Shikimate kinase (EC: 2.7.1.71) catalyzes the fifth step in the biosynthesis of aromatic amino acids from chorismate(the so-called shikimate pathway) [MEDLINE:95337427]. The enzyme catalyzes the following reaction:\

\
ATP + shikimate = ADP + shikimate-3-phosphate\

\ The protein is found in bacteria (gene aroK or aroL), plants and fungi (where\ it is part of a multifunctional enzyme that catalyses five consecutive steps in this pathway). In 1994, the 3D\ structure of shikimate kinase was predicted to be very close to that of adenylate kinase, suggesting a functional\ similarity as well as an evolutionary relationship [MEDLINE:95218635]. This prediction has since been confirmed\ experimentally. The protein is reported to possess an

fold, consisting of a central sheet of five\ parallel

-strands flanked by

-helices. Such a topology is very similar to that of adenylate kinase\ [MEDLINE:98263262].\ \ ATP binding activity ; GO:0005524 \N amino acid biosynthesis ; GO:0008652 19349 IPR000625 REV is a viral anti-repression trans-activator protein, which appears to act post-transcriptionally to relieve negativerepression of GAG and ENV production. It is a phosphoprotein whose state of phosphorylation is mediated by a\ specific serine kinase activity present in the nucleus. REV accumulates in the nucleoli.\ \ transcription factor activity ; GO:0003700 host cell nucleus ; GO:0042025 regulation of transcription, DNA-dependent ; GO:0006355 19345 IPR000620 This domain is found in proteins including the Erwinia chrysanthemi PecM protein, which is involved in pectinase, cellulase and blue pigment regulation; and the Salmonella typhimurium PagO protein, the function of which is unknown. The family also includesmany hypothetical membrane proteins of unknown function. Many of the proteins contain two copies of\ the aligned region.\ \ \N membrane ; GO:0016020 \N 19346 IPR000621

Adrenocorticotrophin (ACTH), melanocyte-stimulating hormones (MSH) and -endorphin are peptide products of pituitary pro-opiomelanocortin.\ ACTH regulates synthesis and release of glucocorticoids and aldosterone\ in the adrenal cortex; it also has a trophic action on these cells PUB00005891.\ ACTH and -endorphin are synthesised and released in response to\ corticotrophin-releasing factor at times of stress (heat, cold, infections,\ etc.) - their release leads to increased metabolism and analgesia res..\ MSH has a trophic action on melanocytes, and regulates pigment production\ in fish and amphibia. The ACTH receptor is found in high levels in\ the adrenal cortex - binding sites are present in lower levels in the\ CNS. The MSH receptor is expressed in high levels in melanocytes,\ melanomas and their derived cell lines PUB00005891. Receptors are found in low\ levels in the CNS. MSH regulates temperature control in the septal region\ of the brain and releases prolactin from the pituitary.

A further gene, which encodes a melanocortin receptor that is functionally\ distinct from the ACTH and MSH receptors, has also been characterised [MEDLINE:93216807], [MEDLINE:94226597], [MEDLINE:94022273], [MEDLINE:94234987], [MEDLINE:94241974].\ The protein contains ~300 amino acids, with calculated molecular mass of\ ~36 KDa, and potential N-linked glycosylation and phosphorylation sites\ [MEDLINE:94226597]. The melanocortin 5 receptor (MC5-R) mediates increase in cAMP\ accumulation with a characteristic pharmacology [MEDLINE:94234987]. Very low expression\ levels have been detected in brain, while high levels are found in adrenals,\ stomach, lung and spleen [MEDLINE:94234987]. In situ hybridisation studies have also shown\ the MC5 receptor to be expressed in the three layers of the adrenal cortex,\ predominantly in the aldosterone-producing zona glomerulosa cells [MEDLINE:94234987].\ Structure-activity studies have indicated that N- and C-terminal portions\ of -MSH appear to be key determinants in the activation of mouse\ MC5R, while the melanocortin core heptapeptide sequence is devoid of\ pharmacological activity [MEDLINE:94241974].

\ \ \ melanocortin receptor activity ; GO:0004977 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19347 IPR000622

The K-Cl co-transporter (KCC) mediates the coupled movement of K⁺ and Cl^-ions across the plasma membrane of many animal cells. This transport is\ involved in the regulatory volume decrease in response to cell swelling in\ red blood cells, and has been proposed to play a role in the vectorial\ movement of Cl^- across kidney epithelia. The transport process involves one\ for one electroneutral movement of K⁺ together with Cl^-, and, in all\ known mammalian cells, the net movement is outward [MEDLINE:96279170].

\ \

In neurones, it appears to play a unique role in maintaining low\ intracellular Cl^-concentration, which is required for the functioning of Cl^-\ dependent fast synaptic inhibition, mediated by certain neurotransmitters,\ such as gamma-aminobutyric acid (GABA) and glycine.

\ \

Two isoforms of the K-Cl co-transporter have been described, termed KCC1 and\ KCC2, containing 1085 and 1116 amino acids, respectively. They are both\ predicted to have 12 transmembrane (TM) regions in a central hydrophobic\ domain, together with hydrophilic N- and C-termini that are likely\ cytoplasmic. Comparison of their sequences with those of other\ ion-tranporting membrane proteins reveals that they are part of a new\ superfamily of cation-chloride co-transporters, which includes the Na-Cl and\ Na-K-2Cl co-transporters. KCC1 is widely expressed in human tissues, while\ KCC2 is expressed only in brain neurones, making it likely that this is the\ isoform responsible for maintaining low Cl^- concentration in neurones [MEDLINE:96279171], [MEDLINE:99127889].

\ \

KCC1 is widely expressed in human tissues, and when heterologously expressed,\ possesses the functional characteristics of the well-studied red blood cell\ K-Cl co-transporter, including stimulation by both swelling and\ N-ethylmaleimide. Several splice variants have also been identified.

\ \ transporter activity ; GO:0005215 membrane ; GO:0016020 ion transport ; GO:0006811 19344 IPR000618

Insect cuticle is composed of proteins and chitin. The cuticular proteins seem to be specific to the type ofcuticle (flexible or stiff) that occur at stages of the insect development. The proteins found in the flexible\ cuticle of larva and pupa of different insects share a conserved C-terminal section [MEDLINE:89068693] such a\ region is also found in the soft endocuticle of adults insects [MEDLINE:91146588] as well as in other cuticular\ proteins including in arachnids [MEDLINE:97166616]. In addition, cuticular proteins share hydrophobic regions\ dominated by tetrapeptide repeats (A-A-P-A/V), which are presumed to be functionally important [MEDLINE:91146588],\ [MEDLINE:97218698]. Many insect cuticle proteins also include a 35-36 amino acid motif known as the R and R consensus. An extended form of this motif has been shown [MEDLINE:21411895] to bind chitin. It has no sequence similiarity to the cysteine-containing chitin-binding domain of chitinases and some peritrophic membrane proteins, suggesting that arthropods have two distinct classes of chitin-binding proteins, those with the chitin-binding domains found in lectins, chitinases and peritrophic membranes (cysCBD), and those with the type of chitin-binding domains found in cuticular proteins (non-cysCBD) [MEDLINE:21411895].

The cuticle protein signature has been found in locust cuticle proteins 7 (LM-7), 8 (LM-8), 19\ (LM-19) and endocuticle structural glycoprotein ABD-4; Hyalophora cecropia cuticle proteins 12 and 66;\ Drosophila melanogaster larval cuticles proteins I, II, III and IV (LCP1 to LCP4); drosophila pupal cuticle proteins PCP,\ EDG-78E and EDG-84E; Manduca sexta cuticle protein LCP-14; Tenebrio molitor cuticle proteins ACP-20, A1A, A2B\ and A3A; and Araneus diadematus (spider) cuticle proteins ACP 11.9, ACP 12.4, ACP 12.6, ACP 15.5 and ACP 15.7.

\ \ \N \N \N 19340 IPR000612 Several proteins have been shown [MEDLINE:98248213] to be evolutionary related. These are small proteins of from 52 to140 amino-acid resiudes that contains two transmembrane domains.\ \ molecular_function unknown ; GO:0005554 integral to membrane ; GO:0016021 \N 19341 IPR000614 Several uncharacterized proteins have been shown to be evolutionary related, and contain in the their centralsection a well conserved region. These proteins include the E. coli hypothetical protein yebR; Bacillus subtilis\ hypothetical protein ytsP; Zymomonas mobilis hypothetical 17.7 kD protein in lpd 3'region (orf6); and yeast\ hypothetical protein YKL069W. These are small proteins of 9 to 20 kD.\ \ molecular_function unknown ; GO:0005554 \N \N 19342 IPR000615 This family of proteins, family 8, was first described for Caenorhabditis elegans\ \ \ [MEDLINE:98086477]. The products of these genes are possibly transmembrane proteins of unknown function. Homologs have been found in Mus musculus (Mouse), Drosophila melanogaster (fruit fly), Homo sapiens (human) and Sus scrofa (Pig). The human gene, VMD2 encodes Bestrophin. Mutations in this gene cause juvenile-onset vitelliform macular dystrophy (Best's disease) [MEDLINE:98367043], [MEDLINE:98324772].\ \ molecular_function unknown ; GO:0005554 \N \N 19343 IPR000617 Napins are low-molecular weight, basic storage proteins synthesised in rape-seed embryos during seedmaturation [MEDLINE:87033665], [MEDLINE:84113267]. Sequence comparisons have revealed that napin belongs to a diverse\ protein family, which includes major allergens, trypsin inhibitors and natural anti-fungal proteins. Napin\ comprises 2 polypeptide chains (MW 9000 and 4000) held together by disulphide bonds. The protein is\ initially synthesised as a precursor of 178 residues, which is proteolytically cleaved to generate mature\ napin chains, with 86 and 29 residues respectively.\ \

The allergens in this family include allergens with the following designations: Bra j 1.

\ \ nutrient reservoir activity ; GO:0045735 \N \N 19339 IPR000611

\ \ \ neuropeptide Y receptor activity ; GO:0004983 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19338 IPR000610

5HT1-like receptors were originally classified according to their nanomolar affinity for 5HT, susceptibility to antagonism by methiothepin and/or\ methysegide, resistance to antagonism by 5HT2 and 5HT3 antagonists, and\ high affinity for the agonist 5-carboxamidotryptamine . Five subtypes\ of 5HT1-like receptors have now been identified - these do not fit all the\ above criteria, and 5HT1C has been reclassified 5HT2C PUB00005889. All are linked\ to the inhibition of adenylyl cyclase, share a high degree of sequence\ similarity, and have overlapping pharmacological specificities.

The 5HT1A receptor is found pre- and post-synaptically in neurons in the\ CNS, and in the periphery . It is also abundant in foetal lymphatic\ tissue. Clinically, 5HT1A receptor ligands represent potential anxiolytic\ and hypertensive agents PUB00005889. Several potent and selective 5HT1A receptor\ agonists have been described; there are no selective antagonists.

\ \ \N integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19336 IPR000608 Ubiquitin-conjugating enzymes (EC: 6.3.2.19) (UBC or E2 enzymes) [MEDLINE:91274342], [MEDLINE:90296400], [MEDLINE:92023523]catalyze the covalent attachment of ubiquitin to target proteins. An activated ubiquitin moiety is transferred\ from an ubiquitin-activating enzyme (E1) to E2 which later ligates ubiquitin directly to substrate proteins with\ or without the assistance of 'N-end' recognizing proteins (E3). A cysteine residue is required for \ ubiquitin-thiolester formation. There is a single conserved cysteine in UBC's and the region around that residue is\ conserved in the sequence of known UBC isozymes. There are, however, exceptions, TSG101 is one of several\ UBC homologues that lacks this active site cysteine [MEDLINE:97397670], [MEDLINE:97385231]. In most species there are many\ forms of UBC (at least 9 in yeast) which are implicated in diverse cellular functions.\ \ ubiquitin conjugating enzyme activity ; GO:0004840 \N ubiquitin cycle ; GO:0006512 19337 IPR000609 Animals recognise a wide variety of chemicals using their senses of taste and smell. The nematode C.eleganshas only 14 types of chemosensory neuron, yet is able to respond to dozens of chemicals because each\ neuron detects several stimuli. More than 40 highly divergent transmembrane proteins that could contribute\ to this functional diversity have been described. Most of the candidate receptor genes are in clusters of\ similar genes; 11 of these appear to be expressed in small subsets of chemosensory neurons. A single type of\ neuron can potentially express at least 4 different receptor genes. Some of these might encode receptors for\ water-soluble attractants, repellents and pheromones, which may be divergent members of the \ G-protein-coupled receptor family [MEDLINE:96028095]. Sequences of the srg family of C.elegans receptor-like proteins contain\ 7 hydrophobic, putative transmembrane, regions. These can be distinguished from other 7TM proteins (especially\ those known to couple G-proteins) by their own characteristic TM signatures.\ \ transmembrane receptor activity ; GO:0004888 membrane ; GO:0016020 signal transduction ; GO:0007165 19331 IPR000603 The 3A protein is found in bromoviruses and Cucumoviruses, whose genomes contain 3 RNA segments.The third segment (RNA 3) contains two proteins, the coat protein and the 3A protein. The function of the\ 3A protein is uncertain but has been shown to be involved in movement of the virus from the initially infected\ cells to adjacent cells [MEDLINE:98022951].\ \ DNA binding activity ; GO:0003677 \N \N 19333 IPR000605 This family includes RNA helicases thought to be involved in duplex unwinding during viral RNA replication.Members of this family are found in a variety of single stranded RNA viruses.\ \ RNA helicase activity ; GO:0003724 \N \N 19334 IPR000606 This family includes RNA helicases thought to be involved in duplex unwinding during viral RNA replication.Members of this family are found in positive-strand single stranded RNA viruses from superfamily 1.\ \ RNA-directed RNA polymerase activity ; GO:0003968 \N viral genome replication ; GO:0019079 19335 IPR000607 Double-stranded RNA-specific adenosine deaminase (EC: 3.5.-"/.-) converts multiple adenosines to inosinesand creates I/U mismatched base pairs in double-helical RNA substrates without apparent sequence\ specificity. DRADA has been found to modify adenosines in AU-rich regions more frequently, probably\ due to the relative ease of melting A/U base pairs compared to G/C base pairs. The protein functions to\ modify viral RNA genomes, and may be responsible for hypermutation of certain negative-stranded viruses.\ DRADA edits the mRNAs for the glutamate receptor subunits by site-selective adenosine deamination. The\ DRADA repeat is also found in viral E3 proteins, which contain a double-stranded RNA-binding domain.\ \ double-stranded RNA adenosine deaminase activity ; GO:0003726 \N adenosine deaminase reaction ; GO:0006155 19332 IPR000604 The major outer membrane protein of Chlamydia contains four symmetrically spaced variable domains (VDs Ito IV). This protein maintains the structural rigidity of the outer membrane and facilitates porin formation,\ permitting diffusion of solutes through the intracellular reticulate body membrane. It is believed to play a role\ in pathogenesis and possibly adhesion. Along with the lipopolysaccharide, the major out membrane protein\ (MOMP) makes up the surface of the elementary body cell. Disulfide bond interactions within and between\ MOMP molecules and other components form high molecular weight oligomers. The MOMP is the protein used\ to determine the different serotypes.\ \ porin activity ; GO:0015288 external outer membrane (sensu Gram-negative Bacteria) ; GO:0009279 \N 19328 IPR000600 A family of bacterial proteins has been described which groups transcriptional repressors, sugar kinases andyet uncharacterized open reading frames [MEDLINE:95039896]. This family, known as ROK (Repressor, ORF, Kinase)\ includes the xylose operon repressor, xylR, from Bacillus subtilis, Lactobacillus pentosus and Staphylococcus\ xylosus; N-acetylglucosamine repressor, nagC, from Escherichia coli; glucokinase (EC: 2.7.1.2) from Streptomyces\ coelicolor; fructokinase (EC: 2.7.1.4) from Pediococcus pentosaceus, Streptococcus mutans and Zymomonas mobilis;\ allokinase (EC: 2.7.1.55) and mlc from E. coli; and E. coli hypothetical proteins yajF and yhcI and the\ corresponding Haemophilus influenzae proteins. The repressor proteins (xylR and nagC) from this family possess\ an N-terminal region not present in the sugar kinases and which contains an helix-turn-helix DNA-binding motif.\ \ \N \N \N 19329 IPR000601 The PKD domain was first identified in the Polycystic kidney disease protein PKD1, and contains an Ig-like fold. PKD1 is involved in adhesive protein-protein and protein-carbohydrate interactions, however it is not clear if the PKD domains mediate any of these interactions. Most of these domains are present in the extracellular parts of proteins involved ininteractions with other proteins. The domain is most often found in proteins \ archaebacteria and some vertebrates.\ \ \N \N \N 19330 IPR000602

Glycoside hydrolase family 38 CAZY:GH_38).

\ \

Lysosomal -mannosidase is necessary for the catabolism of N-linked carbohydrates released during glycoprotein turnover. The enzyme\ catalyzes the hydrolysis of terminal, non-reducing -D-mannose residues in -D-mannosides, and can\ cleave all known types of -mannosidic linkages. Defects in the gene cause lysosomal -mannosidosis\ (AM), a lysosomal storage disease characterized by the accumulation of unbranched oligo-saccharide chains.

\ \ alpha-mannosidase activity ; GO:0004559 \N carbohydrate metabolism ; GO:0005975 19327 IPR000599

Several 7TM receptors have been cloned but their endogenous ligands are\ unknown; these have been termed orphan receptors. GPR12 was isolated from\ a rat pituitary library and is found in discrete regions of the brain,\ pituitary and testis, but is absent in other tissues [MEDLINE:92070499].

\ \ G-protein coupled receptor activity, unknown ligand ; GO:0016526 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19326 IPR000597

\ \ \

Ribosomal protein L3 is one of the proteins from the large ribosomal subunit. In Escherichia coli, L3 is known to\ bind to the 23S rRNA and may participate in the formation of the peptidyltransferase center of the ribosome. It\ belongs to a family of ribosomal proteins which, on the basis of sequence similarities includes bacterial, red algal, cyanelle, \ mammalian, yeast and Arabidopsis thaliana L3 proteins; archaeal Haloarcula marismortui\ HmaL3 (HL1), and yeast mitochondrial YmL9 [MEDLINE:92283262], [MEDLINE:92362624], [MEDLINE:90153945], PUB00005071.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 19323 IPR000594 Ubiquitin-activating enzyme (E1 enzyme) [MEDLINE:91274342], [MEDLINE:92023523] activates ubiquitin by firstadenylating with ATP its C-terminal glycine residue and thereafter linking\ this residue to the side chain of a cysteine residue in E1, yielding an\ ubiquitin-E1 thiolester and free AMP. Later the ubiquitin moiety is\ transferred to a cysteine residue on one of the many forms of ubiquitin-\ conjugating enzymes (E2).\

The family of ubiquitin-activating enzymes shares in its catalytic domain significant similarity with a large\ family of NAD/FAD-binding proteins. This domain is based on the common NAD/FAD-binding fold and\ finds members of several families, including UBA ubiquitin activating enzymes; the hesA/moeB/thiF family;\ NADH peroxidases; the LDH family; sarcosin oxidase; phytoene dehydrogenases; alanine dehydrogenases;\ hydroxyacyl-CoA dehydrogenases and many other NAD/FAD dependent dehydrogenases and oxidases.

\ \ enzyme activity ; GO:0003824 \N \N 19324 IPR000595 Proteins that bind cyclic nucleotides (cAMP or cGMP) share a structural domain of about 120 residues [MEDLINE:89375346],[MEDLINE:92210523], [MEDLINE:91263261]. The best studied of these proteins is the prokaryotic catabolite gene activator (also\ known as the cAMP receptor protein) (gene crp) where such a domain is known to be composed of three

-helices and\ a distinctive eight-stranded, antiparallel

-barrel structure. There are six invariant amino acids in this domain,\ three of which are glycine residues that are thought to be essential for maintenance of the structural integrity of\ the

-barrel. cAMP- and cGMP-dependent protein kinases (cAPK and cGPK) contain two tandem copies of the cyclic\ nucleotide-binding domain. The cAPK's are composed of two different subunits, a catalytic chain and a regulatory chain,\ which contains both copies of the domain. The cGPK's are single chain enzymes that include the two copies of the domain\ in their N-terminal section. Vertebrate cyclic nucleotide-gated ion-channels also contain this domain. Two such\ cations channels have been fully characterized, one is found in rod cells where it plays a role in visual signal\ transduction.\ \ \N \N \N 19325 IPR000596

Cholecystokinins (CCKs) and gastrins are naturally-occurring peptides that share a common C-terminal sequence, GWMDF; full biological activity resides in this region. In the periphery, the principal physiological actions of CCK include gall bladder contraction, pancreatic enzyme secretion and regulation of secretion/absorption in the gastrointestinal tract. In the CNS, CCK induces analgesia, satiety and a decrease in exploratory behaviour. In mesolimbic and\ mesocortical neurons, CCK coexists with dopamine. It is found throughout the digestive tract, with high concentrations in the duodenum and jejunum. It is also found in peripheral nerves to other smooth muscles and to secretory glands, and is one of the most abundant peptides in the brain. The highest levels of the CCKA receptor are found in peripheral tissues, notably the pancreas, stomach, intestine and gall bladder PUB00005877. It has only a limited distribution in the brain. The receptor has been implicated in the pathogenesis of schizophrenia, Parkinson's disease, drug addiction and feeding disorders.

\ \ cholecystokinin receptor activity ; GO:0004951 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19319 IPR000590 Hydroxymethylglutaryl-coenzyme A synthase (EC: 4.1.3.5) (HMG-CoA synthase) catalyzes the condensation ofacetyl-CoA with acetoacetyl-CoA to produce HMG-CoA and CoA [MEDLINE:94304197]. A cysteine is known to act as the catalytic\ nucleophile in the first step of the reaction, the acetylation of the enzyme by acetyl-CoA. In vertebrates there are\ two isozymes located in different subcellular compartments, a cytosolic form which is the starting point of the\ mevalonate pathway which leads to cholesterol and other sterolic and isoprenoid compounds, and a mitochondrial form\ responsible for ketone body biosynthesis. HMG-CoA is also found in other eukaryotes such as insects, plants and fungi.\ \ hydroxymethylglutaryl-CoA synthase activity ; GO:0004421 \N acetyl-CoA metabolism ; GO:0006084 19320 IPR000591 This is a domain of unknown function present in signaling proteins including dishevelled, Egl-10, and Pleckstrinproteins. Segment polarity dishevelled protein is required to establish coherent arrays of polarized cells and\ segments in embryos, and plays a role in wingless signaling. Egl-10 regulates G-protein signaling in the central\ nervous system. Mammalian regulators of G-protein signaling also contain these domains, and regulate signal\ transduction by increasing the GTPase activity of G-protein

subunits, thereby driving them into their\ inactive GDP-bound form.\ \ \N \N intracellular signaling cascade ; GO:0007242 19321 IPR000592

\ \ \

A number of eukaryotic and archaeal ribosomal proteins can be grouped on the basis of sequence\ similarities. One of these families include mammalian, yeast, Chlamydomonas reinhardtii and Entamoeba histolytica\ S27, and Methanococcus jannaschii MJ0250 [MEDLINE:93181260]. These proteins have from 62 to 87 amino acids. They\ contain, in their central section, a putative zinc-finger region of the type C-x(2)-C-x(14)-C-x(2)-C.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 19322 IPR000593 Ras GTPase-activating protein (rasGAP) is a major contributor to the downregulation of ras by facilitating GTP hydrolysis of activated ras. In addition, GAP participates in the down-stream effector system of the ras signaling pathway. Abnormal signal transduction involving activated ras genes plays a major role in the development of a variety of tumors. Depending on the precise genetic alteration, its location within the gene and the effects it exerts on protein function, rasGAP can theoretically function as either an oncogene or as a tumor suppressor gene [MEDLINE:96344293].\ RAS GTPase activator activity ; GO:0005099 \N small GTPase mediated signal transduction ; GO:0007264 19317 IPR000588 Cauliflower mosaic viruses belong to a group of plant viruses known as pararetroviruses, which have a double-stranded DNA genome. The genome includes an open reading frame (ORF V) that shows similarities to the pol\ gene of retroviruses. This ORF codes for a polyprotein that includes a reverse transcriptase, which, on the basis\ of a DTG triplet near the N-terminus, was suggested to include an aspartic protease. The presence of an aspartic\ protease has been confirmed by mutational studies, implicating Asp-45 in catalysis. The protease releases itself\ from the polyprotein and is involved in reactions required to process the ORF IV polyprotein, which includes the\ viral coat protein gene [MEDLINE:95405254].\ \ aspartic-type endopeptidase activity ; GO:0004190 \N proteolysis and peptidolysis ; GO:0006508 19318 IPR000589

\ \ \

Ribosomal protein S15 is one of the proteins from the small ribosomal subunit. In Escherichia coli, this protein binds\ to 16S ribosomal RNA and functions at early steps in ribosome assembly. It belongs to a family of ribosomal proteins\ which, on the basis of sequence similarities [MEDLINE:91088262], PUB00005070, groups bacterial and plant chloroplast S15;\ archaeal Haloarcula marismortui HmaS15 (HS11); yeast mitochondrial S28; and mammalian, yeast, Brugia pahangi\ and Wuchereria bancrofti S13. S15 is a protein of 80 to 250 amino-acid residues.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 19316 IPR000587 Creatinase or creatine amidinohydrolase (EC: 3.5.3.3) catalyzes the conversion of creatine and water to sarcosineand urea. The enzyme works as a homodimer, and is induced by choline chloride. Each monomer of creatinase\ has two clearly defined domains, a small N-terminal domain, and a large C-terminal domain. Each of the two active\ sites is made by residues of the large domain of one monomer and some residues of the small domain of the other\ monomer.\ \ \ creatinase activity ; GO:0016980 \N creatine metabolism ; GO:0006600 19315 IPR000586

\ \ \ somatostatin receptor activity ; GO:0004994 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19314 IPR000585 Hemopexin (EC: 3.2.1.35) is a serum glycoprotein that binds heme and transports it to the liver for breakdown andiron recovery, after which the free hemopexin returns to the circulation. Structurally hemopexin consists of two\ similar halves of approximately two hundred amino acid residues connected by a histidine-rich hinge region. Each\ half is itself formed by the repetition of a basic unit of some 35 to 45 residues. Hemopexin-like repeats have been\ found in two other types of proteins, vitronectin, a cell adhesion and spreading factor found in plasma and tissues,\ and matrixins MMP-1, MMP-2, MMP-3, MMP-9, MMP-10, MMP-11, MMP-12, MMP-14, MMP-15 and MMP-16, members of the matrix\ metalloproteinases family [MEDLINE:86192819], [MEDLINE:88190048]. These zinc endoproteases have a single hemopexin-like domain in\ their C-terminal section. It is suggested that the hemopexin domain facilitates binding to a variety of molecules\ and proteins, for example the HX repeats of some matrixins bind tissue inhibitor of metallopeptidases (TIMPs).\ \ \N \N \N 19313 IPR000584

\ \

\ \ voltage-gated calcium channel activity ; GO:0005245 \N calcium ion transport ; GO:0006816 19311 IPR000582

Acyl-CoA-binding protein (ACBP) is a small (10 Kd) protein that binds medium- and long-chain acyl-CoA esterswith high affinity, and may act as an intra-cellular carrier of acyl-CoA esters. ACBP has a number of important\ physiological and biochemical functions: it is known as a diazepam binding inhibitor, as a putative neurotransmitter,\ as a regulator of insulin release from pancreatic cells, and as a mediator in corticotropin-dependent adrenal\ steroidogenesis [MEDLINE:86278003], [MEDLINE:92389322]. It is possible that the protein acts as a neuropeptide that takes part\ in the modulation of gamma-aminobutyric acid-ergic transmission [MEDLINE:86278003]. The structure of ACBP has been deduced\ by NMR spectroscopy and has been shown to be a mainly- protein, consisting of 5 short -helices and 3\ connecting -strands [MEDLINE:92389322].

\ \

ACBP is a highly conserved protein of about 90 residues that has been so far found in vertebrates, insects, plants\ and yeast. Other proteins belonging to the ACBP family include mouse endozepine-like peptide (ELP) (gene DBIL5) \ [MEDLINE:97053970]; mammalian MA-DBI, a transmembrane protein of unknown function which has been found in mammals; and \ human DRS-1 [MEDLINE:99284489], a protein of unknown function that contains a N-terminal ACBP-like domain and a C-terminal \ enoyl-CoA isomerase/hydratase domain.

\ \ acyl-CoA binding activity ; GO:0000062 \N \N 19309 IPR000580 Several eukaryotic proteins are evolutionary related and are thought to be involved in transcriptional regulation.These proteins are highly similar in a region of about 50 residues that include a conserved leucine-zipper domain\ most probably involved in homo- or hetero-dimerization. Proteins containing this signature include the vertebrate\ protein TSC-22 [MEDLINE:97175009], a transcriptional regulator which seems to act on C-type natriuretic peptide (CNP)\ promoter; mammalian protein DIP (DSIP-immunoreactive peptide) [MEDLINE:97136879], a protein whose function is not yet\ known; Drosophila protein bunched [MEDLINE:96038094] (gene bun) (also known as shortsighted), a probable transcription\ factor required for peripheral nervous system morphogenesis, eye development and oogenesis; and the C. elegans\ hypothetical protein T18D3.7.\ \ transcription factor activity ; GO:0003700 \N regulation of transcription, DNA-dependent ; GO:0006355 19307 IPR000577 It has been shown [MEDLINE:92065803] that four different type of carbohydrate kinases seem to be evolutionary related.These enzymes include L-fucolokinase (EC: 2.7.1.51) (gene fucK); gluconokinase (EC: 2.7.1.12) (gene gntK); glycerol\ kinase (EC: 2.7.1.30) (gene glpK); xylulokinase (EC: 2.7.1.17) (gene xylB); and L-xylulose kinase (EC: 2.7.1.53)\ (gene lyxK). These enzymes are proteins of from 480 to 520 amino acid residues.\ \ \N \N carbohydrate metabolism ; GO:0005975 19308 IPR000579

Proteins that transport heavy metals in micro-organisms and mammals share similarities in their sequences and structures. Some of these proteins are involved in bacterial resistance to toxic metals, such as lead and cadmium, \ while others are involved in inherited human syndromes, such as Wilson and Menkes diseases [MEDLINE:94378325].

Cation-transporting P-type ATPase from Mycobacterium leprae is a member of this group. It is an integral membrane protein, with 12 predicted transmembrane (TM) domains. The protein,\ which contains a single copy of the HMA domain, catalyses the reaction:

\ \

 ATP + H(2)O = ADP + orthophosphate

\ \ P-type ATPase activity ; GO:0015662 membrane ; GO:0016020 cation transport ; GO:0006812 19312 IPR000583 A large group of biosynthetic enzymes are able to catalyze the removal of the ammonia group from glutamine andthen to transfer this group to a substrate to form a new carbon-nitrogen group. This catalytic activity is known as\ glutamine amidotransferase (GATase) (EC: 2.4.2.-) [MEDLINE:74014736]. The GATase domain exists either as a separate polypeptidic\ subunit or as part of a larger polypeptide fused in different ways to a synthase domain. On the basis of sequence\ similarities two classes of GATase domains have been identified [MEDLINE:87250264], [MEDLINE:84264639], class-I (also known as\ trpG-type) and class-II (also known as purF-type). Enzymes containing Class-II GATase domains include amido\ phosphoribosyltransferase (glutamine phosphoribosylpyrophosphate amidotransferase) (EC: 2.4.2.14), which catalyzes the\ first step in purine biosynthesis (gene purF in bacteria, ADE4 in yeast); glucosamine--fructose-6-phosphate aminotransferase\ (EC: 2.6.1.16), which catalyzes the formation of glucosamine 6-phosphate from fructose 6-phosphate and glutamine\ (gene glmS in Escherichia coli, nodM in Rhizobium, GFA1 in yeast); and asparagine synthetase (glutamine-hydrolyzing)\ (EC: 6.3.5.4), which is responsible for the synthesis of asparagine from aspartate and glutamine. A cysteine is present at\ the N-terminal extremity of the mature form of all these enzymes.\ \ \N \N metabolism ; GO:0008152 19310 IPR000581 Two dehydratases, dihydroxy-acid dehydratase (EC: 4.2.1.9) (gene ilvD or ILV3) and 6-phosphogluconatedehydratase (EC: 4.2.1.12) (gene edd) have been shown to be evolutionary related [MEDLINE:92325055]. Dihydroxy-acid\ dehydratase catalyzes the fourth step in the biosynthesis of isoleucine and valine, the dehydratation of\ 2,3-dihydroxy-isovaleic acid into

-ketoisovaleric acid. 6-Phosphogluconate dehydratase catalyzes the\ first step in the Entner-Doudoroff pathway, the dehydratation of 6-phospho-D-gluconate into \ 6-phospho-2-dehydro-3-deoxy-D-gluconate. Another protein containing this signature is the E. coli hypothetical protein\ yjhG. The N-terminal part of the proteins contains a cysteine that could be involved in the binding of a\ 2Fe-2S iron-sulfur cluster [MEDLINE:94131281].\ \ enzyme activity ; GO:0003824 \N metabolism ; GO:0008152 19304 IPR000574 This signature is found in coat proteins from the related tymoviruses. The coat protein is also known as the virionprotein. The virus coat is composed of 180 copies of the coat protein arranged in an icosahedral shell.\ \ structural molecule activity ; GO:0005198 viral capsid ; GO:0019028 \N 19305 IPR000576 In bacteria there are a number of families of transport proteins, including symporters and antiporters, thatmediate the intake of a variety of sugars with the concomitant uptake of hydrogen ions (proton symporters)\ [MEDLINE:93174460]. The lacY family of E.coli and Klebsiella pneumoniae are proton/

-galactoside symporters,\ which, like most sugar transporters, are integral membrane proteins with 12 predicted transmembrane (TM) regions.\ Also similar to the lacY family are the rafinose (rafB) and sucrose (cscB) permeases from E.coli\ \ \ \ [MEDLINE:93062804].\ \ hydrogen:sugar symporter-transporter activity ; GO:0005403 membrane ; GO:0016020 transport ; GO:0006810 19306 IPR000577 It has been shown [MEDLINE:92065803] that four different type of carbohydrate kinases seem to be evolutionary related.These enzymes include L-fucolokinase (EC: 2.7.1.51) (gene fucK); gluconokinase (EC: 2.7.1.12) (gene gntK); glycerol\ kinase (EC: 2.7.1.30) (gene glpK); xylulokinase (EC: 2.7.1.17) (gene xylB); and L-xylulose kinase (EC: 2.7.1.53)\ (gene lyxK). These enzymes are proteins of from 480 to 520 amino acid residues.\ \ \N \N carbohydrate metabolism ; GO:0005975 19302 IPR000572

A number of different eukaryotic oxidoreductases that require and bind a molybdopterin cofactor have been shown [MEDLINE:91198061] to share a few regions of sequence similarity. These enzymes include xanthine dehydrogenase (EC: 1.1.1.204), \ aldehyde oxidase (EC: 1.2.3.1), nitrate reductase (EC: 1.7.1.1), and sulfite oxidase (EC: 1.8.3.1). The multidomain redox \ enzyme NAD(P)H:nitrate reductase (NR) catalyzes the reduction of nitrate to nitrite in a single polypeptide electron \ transport chain with electron flow from NAD(P)H-FAD-cytochrome b5-molybdopterin-NO(3). Three forms of NR are known, an \ NADH-specific enzyme found in higher plants and algae (EC: 1.7.1.1); an NAD(P)H-bispecific enzyme found in higher plants, \ algae and fungi (EC: 1.7.1.2); and an NADPH-specific enzyme found only in fungi (EC: 1.7.1.3) [MEDLINE:90371632]. The \ mitochondrial enzyme sulphite oxidase (sulphite:ferricytochrome c oxidoreductase; EC 1.8.2.1) catalyses oxidation of \ sulphite to sulphate, using cytochrome c as the physiological electron acceptor. Sulphite oxidase consists of 2 \ structure/function domains, an N-terminal heme domain, similar to cytochrome b5; and a C-terminal molybdopterin domain \ [MEDLINE:90078175].

\ Despite functional parallels, members of the family show no sequence similarity to the C-terminal molybdopterin \ domain of xanthine dehydrogenase, although xanthine dehydrogenase, nitrate reductases and sulphite oxidase all \ contain the eukaryotic molybdopterin oxidoreductases signature. Sequence comparison suggests that only a single Cys residue (Cys186 in chicken \ sulphite oxidase), is invariant in all these enzymes, indicating that it may play a role in binding molybdopterin to the \ protein [MEDLINE:91065892], [MEDLINE:95204456].

\ \ \N \N electron transport ; GO:0006118 19303 IPR000573 Synonym(s): Citrate hydro-lyase, Aconitase

Aconitate hydratase (EC: 4.2.1.3) is the enzyme from the\ tricarboxylic acid cycle that catalyzes the reversible, stereo-specific,\ isomerization of citrate to isocitrate via cis-aconitate in the tricarboxylic acid\ cycle, a non-redox active process [MEDLINE:90092136], [MEDLINE:97172692]. Aconitase, in\ its active form, contains a 4Fe-4S iron-sulfur cluster; three cysteine residues have\ been shown to be ligands of the 4Fe-4S cluster [MEDLINE:89264479]. Unlike the majority of\ iron-sulphur proteins that function as electron carriers, the Fe-S cluster of\ aconitase reacts directly with an enzyme substrate [MEDLINE:94202210].

The aconitate hydratase, C-terminal domain is almost always fouund along with the aconitate hydratase, N-terminal domain IPR001030.

\ \ hydro-lyase activity ; GO:0016836 \N metabolism ; GO:0008152 19300 IPR000569 The name HECT comes from 'Homologous to the E6-AP Carboxyl Terminus' [MEDLINE:95223981]. Proteins containing this domain at the C-terminus includeubiquitin-protein ligase, which regulates ubiquitination of CDC25. Ubiquitin-protein ligase accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester, and then directly transfers the ubiquitin to targeted substrates. A cysteine residue is required for ubiquitin-thiolester formation. Human thyroid receptor interacting\ protein 12, which also contains this domain, is a component of an ATP-dependent multisubunit protein that interacts with the ligand binding domain of the thyroid hormone receptor. It could be an E3 ubiquitin-protein ligase. Human ubiquitin-protein ligase E3A interacts with the E6 protein of the cancer-associated human papillomavirus types 16 and 18. The E6/E6-AP complex binds to and targets the P53 tumor-suppressor protein for ubiquitin-mediated\ proteolysis.\ \ ubiquitin-protein ligase activity ; GO:0004842 intracellular ; GO:0005622 ubiquitin cycle ; GO:0006512 19301 IPR000571 Zinc finger domains are thought to be involved in DNA-binding, and exist as different types, depending on thepositions of the cysteine residues. Proteins containing zinc finger domains of the C-x8-C-x5-C-x3-H type include zinc\ finger proteins from eukaryotes involved in cell cycle or growth phase-related regulation, e.g. human TIS11B\ (butyrate response factor 1), a probable regulatory protein involved in regulating the response to growth factors,\ and the mouse TTP growth factor-inducible nuclear protein, which has the same function. The mouse TTP protein\ is induced by growth factors. Another protein containing this domain is the human splicing factor U2AF 35 kD\ subunit, which plays a critical role in both constitutive and enhancer-dependent splicing by mediating essential\ protein-protein interactions and protein-RNA interactions required for 3' splice site selection. It has been\ shown that different CCCH zinc finger proteins interact with the 3'\ untranslated region of various mRNA [MEDLINE:98369176], [MEDLINE:99263003]. This type of zinc finger is very often present in two\ copies.\ \ nucleic acid binding activity ; GO:0003676 \N \N 19299 IPR000568

\ \

\ \ \ \ \ \ \ \

The CF(0) A subunit is a highly hydrophobic protein and has been predicted to contain 8 transmembrane (TM)\ regions [MEDLINE:90285184]. It is a key component of the proton channel, possibly playing a direct role in the translocation\ of protons across the membrane. Sequence comparison of A subunits reveals that the overall level of similarity is quite\ low, but the degree of conservation is relatively high in putative TM domain 5, which contains a conserved arginine.\ Mutagenesis experiments have shown that the Arg residue is required for proton translocation, its replacement\ resulting in loss of ATPase activity [MEDLINE:89123453].

\ \ hydrogen-transporting two-sector ATPase activity ; GO:0003936 membrane ; GO:0016020 proton transport ; GO:0015992 19298 IPR000566 Proteins which transport small hydrophobic molecules such as steroids, bilins, retinoids, and lipids share limitedregions of sequence homology and a common tertiary structure architecture [MEDLINE:87305323], [MEDLINE:92302245], [MEDLINE:91017498],\ [MEDLINE:93264947], [MEDLINE:89187941]. This is an eight stranded antiparallel

-barrel with a repeated + 1 topology enclosing\ a internal ligand binding site [MEDLINE:93264947], [MEDLINE:91017498]. The name 'lipocalin' has been proposed [MEDLINE:87305323] for\ this protein family, but cytosolic fatty-acid binding proteins are also included. The sequences of most members of the family, the core or kernal lipocalins, are characterized by\ three short conserved stretches of residues, while others, the outlier lipocalin group, share only one or two of these\ [MEDLINE:92028985], [MEDLINE:93264947]. Proteins known to belong to this family include

-1-microglobulin (protein HC);

-1-acid glycoprotein (orosomucoid) [MEDLINE:89113403]; aphrodisin; apolipoprotein D;

The allergens in this family include allergens with the following designations: Bla g 4, Bos d 2, Bos d 5, Can f 1, Can f 2, Equ c 1 and Equ c 2.

\ \ transporter activity ; GO:0005215 \N transport ; GO:0006810 19295 IPR000562 Fibronectin is a multi-domain glycoprotein, found in a soluble form in plasma, and in an insoluble form in looseconnective tissue and basement membranes, that binds cell surfaces and various compounds including collagen,\ fibrin, heparin, DNA, and actin. Fibronectins are involved in a number of important functions e.g., wound\ healing; cell adhesion; blood coagulation; cell differentiation and migration; maintenance of the cellular\ cytoskeleton; and tumour metastasis [MEDLINE:87175578]. The major part of the sequence of fibronectin consists of the\ repetition of three types of domains, which are called type I, II, and III [MEDLINE:87054047]. Type II domain is\ approximately forty residues long, contains four conserved cysteines involved in disulfide bonds and is part of\ the collagen-binding region of fibronectin. In fibronectin the type II domain is duplicated. Type II domains have\ also been found in a range of proteins including blood coagulation factor XII; bovine seminal plasma proteins\ PDC-109 (BSP-A1/A2) and BSP-A3 [MEDLINE:87270621]; cation-independent mannose-6-phosphate receptor [MEDLINE:92359495];\ mannose receptor of macrophages [MEDLINE:90324192]; 180 Kd secretory phospholipase A2 receptor [MEDLINE:94124484]. DEC-205\ receptor [MEDLINE:95272679]; 72 Kd and 92 Kd type IV collagenase (EC: 3.4.24.24) [MEDLINE:88198218]; and hepatocyte\ growth factor activator [MEDLINE:93252878].\ \ \N \N \N 19296 IPR000563 Many flagellar proteins are exported by a flagellum-specific export pathway. Attempts have been made to characterisethe apparatus responsible for this process, by designing assays to screen for mutants with export defects.\ Experiments involving filament removal from temperature-sensitive flagellar mutants of Salmonella typhimurium have\ shown that, while most mutants were able to regrow filaments, flhA, fliH, fliI and fliN mutants showed no or greatly\ reduced regrowth. This suggests that the corresponding gene products are involved in the process of flagellum-specific export [MEDLINE:91258342]. The sequence of fliH has been deduced and shown to encode a protein of molecular mass\ of 25,782 Da.\ \ motor activity ; GO:0003774 flagellum (sensu Bacteria) ; GO:0009288 ciliary/flagellar motility ; GO:0001539 19293 IPR000559

Formate--tetrahydrofolate ligase (EC: 6.3.4.3) (formyltetrahydrofolate synthetase) (FTHFS) is one of the enzymesparticipating in the transfer of one-carbon units, an essential element of various biosynthetic pathways. In many of\ these processes the transfers of one-carbon units are mediated by the coenzyme tetrahydrofolate (THF). In eukaryotes\ the FTHFS activity is expressed by a multifunctional enzyme, C-1-tetrahydrofolate synthase (C1-THF synthase), which\ also catalyzes the dehydrogenase and cyclohydrolase activities. Two forms of C1-THF synthases are known [MEDLINE:88227973],\ one is located in the mitochondrial matrix, while the second one is cytoplasmic. In both forms the FTHFS domain\ consists of about 600 amino acid residues and is located in the C-terminal section of C1-THF synthase. In prokaryotes\ FTHFS activity is expressed by a monofunctional homotetrameric enzyme of about 560 amino acid residues [MEDLINE:90344789].

The crystal structure of N(10)-formyltetrahydrofolate synthetase from Moorella thermoacetica shows that the subunit is composed of three domains organized around three mixed -sheets. There are two cavities between adjacent domains. One of them was identified as the nucleotide binding site by\ homology modeling. The large domain contains a seven-stranded -sheet surrounded by helices on both sides. The second domain contains a five-stranded -sheet with two -helices packed on one side while the other two are a wall of the active site cavity. The\ third domain contains a four-stranded -sheet forming a half-barrel. The concave side is\ covered by two helices while the convex side is another wall of the large cavity. Arg 97 is likely\ involved in formyl phosphate binding. The tetrameric molecule is relatively flat with the shape of\ the letter X, and the active sites are located at the end of the subunits far from the subunit interface [MEDLINE:20213239].

\ \ ATP binding activity ; GO:0005524 \N folic acid and derivative biosynthesis ; GO:0009396 19297 IPR000565

\ \

Eukaryotic topoisomerase II exists as a homodimer; in bacteriophage T4 it \ consists of three heterologous subunits; in prokaryotes it exists as a tetramer\ of two subunits (two each of gyrA and gyrB); and in E.coli, a second type II\ topoisomerase, involved in chromosome segregation (topoisomerase IV),\ consists of two subunits (parC and parE). GyrB, parE, and the product of \ bacteriophage T4 gene 39, are all similar to the eukaryotic proteins.

\ \

The crystal structure of an N-terminal fragment of the Escherichia coli DNA\ gyrase B in complex with a non-hydrolysable ATP analogue, has been\ determined to 2.5A resolution [MEDLINE:91270367]. The fold comprises two domains, both of\ which exhibit novel topologies. The fragment forms a dimer, whose N-terminal\ domains are responsible for ATP binding and hydrolysis. The C-terminal\ domains form the sides of a 20A hole through the protein dimer, which may\ play a role in DNA strand passage during the supercoiling reaction [MEDLINE:91270367].

\ \ ATP binding activity ; GO:0005524 \N DNA topological change ; GO:0006265 19294 IPR000560 Acid phosphatases (EC: 3.1.3.2) are a heterogeneous group of proteins that hydrolyze phosphate esters, optimally atlow pH. It has been shown [MEDLINE:91115848] that a number of acid phosphatases, from both prokaryotes and eukaryotes,\ share two regions of sequence similarity, each centered around a conserved histidine residue. These two histidines\ seem to be involved in the enzymes' catalytic mechanism [MEDLINE:93327749], [MEDLINE:93054596]. The first histidine is located\ in the N-terminal section and forms a phosphohistidine intermediate while the second is located in the C-terminal\ section and possibly acts as proton donor. Enzymes belonging to this family are called 'histidine acid phosphatases'\ and include the E. coli pH 2.5 acid phosphatase (gene appA) and glucose-1-phosphatase (EC: 3.1.3.10) (gene agp); yeast\ constitutive and repressible acid phosphatases (genes PHO3 and PHO5); fission yeast acid phosphatase (gene pho1);\ aspergillus phytases A and B (EC: 3.1.3.8) (gene phyA and phyB); mammalian lysosomal and prostatic acid phosphatase;\ and several C. elegans hypothetical proteins.\ \ acid phosphatase activity ; GO:0003993 \N \N 19291 IPR000557 Calponin [MEDLINE:94176338], [MEDLINE:94193769] is a thin filament-associated protein that is implicated in the regulationand modulation of smooth muscle contraction. It is capable of binding to actin, calmodulin, troponin C and\ tropomyosin. The interaction of calponin with actin inhibits the actomyosin MgATPase activity. Calponin is a\ basic protein of approximately 34 Kd. Multiple isoforms are found in smooth muscles. Calponin contains three\ repeats of a well conserved 26 amino acid domain. Such a domain is also found in vertebrate smooth muscle protein\ (SM22 or transgelin), and a number of other proteins whose physiological role is not yet established, including\ Drosophila synchronous flight muscle protein SM20, C.elegans unc-87 protein [MEDLINE:95014721], rat neuronal protein NP25\ [MEDLINE:94285742], and an Onchocerca volvulus antigen [MEDLINE:95021519].\ \ \N \N \N 19292 IPR000558 Histone H2B is one of the four histones, along with H2A, H3 and H4, which forms the eukaryotic nucleosome core.Histone H2B is a small, highly conserved nuclear protein that, together with 2 molecules each of histones H2A, H3\ and H4, forms the eukaryotic nucleosome core [MEDLINE:91252337]; the nucleosome octamer winds ~146 DNA base-pairs.\ \ DNA binding activity ; GO:0003677 nucleus ; GO:0005634 chromosome organization and biogenesis (sensu Eukarya) ; GO:0007001 19288 IPR000554

\ \ \

A number of eukaryotic ribosomal proteins can be grouped on the basis of sequence similarities [MEDLINE:93382795].\ One of these families consists of Xenopus S8, and mammalian, insect and yeast S7. These proteins have about\ 200 amino acids.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 19289 IPR000555 Mov34 proteins act as the regulatory subunit of the 26 proteasome, which is involved in the ATP-dependent degradation of ubiquitinated proteins. The function of this domain is unclear, but it is found in the N-terminus of the proteasome regulatory subunits, eukaryotic initiation factor 3 (eIF3) subunits and regulators of transcription factors.\ \ \N \N \N 19290 IPR000556

Glycoside hydrolase family 48 CAZY:GH_48).

\ \

The largest cellulase gene sequenced to\ date is one of the cellulases (celA) from the genome of the thermophilic anaerobic bacterium Caldocellum\ saccharolyticum. The celA gene product is a polypeptide of 1751 amino acids; this has a multidomain structure\ comprising two catalytic domains and two cellulose-binding domains, linked by Pro-Thr-rich regions. The\ N-terminal domain encodes an endoglucanase activity on carboxymethylcellulose, consistent with its similarity\ to several endo-1, 4--D-glucanase sequences. The C-terminal domain shows similarity to a cellulase from\ Clostridium thermocellum (CelS), which acts synergistically with a second component to hydrolyse crystalline\ cellulose [MEDLINE:95336703].

\ \ hydrolase activity, hydrolyzing O-glycosyl compounds ; GO:0004553 \N carbohydrate metabolism ; GO:0005975 19287 IPR000552

\ \ \

A number of eukaryotic and archaeal ribosomal proteins can be grouped on the basis of sequence\ similarities. One of these families consists of mammalian [MEDLINE:88283346], Trypanosoma brucei,\ Caenorhabditis elegans and fungal L44, and Haloarcula marismortui LA [MEDLINE:93277953].

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 19286 IPR000551 The many bacterial transcription regulation proteins which bind DNA through a 'helix-turn-helix' motifcan be classified into subfamilies on the basis of sequence similarities. One of these is the MerR subfamily.\ MerR, which is found in many bacterial species mediates the mercuric-dependent induction of the mercury\ resistance operon. In the absence of mercury merR represses transcription by binding tightly, as a dimer,\ to the 'mer' operator region; when mercury is present the dimeric complex binds a single ion and becomes\ a potent transcriptional activator, while remaining bound to the mer site. Members of the family include the\ mercuric resistance operon regulatory protein merR; \ Bacillus subtilis bltR and bmrR; Bacillus glnR;\ Streptomyces coelicolor hspR; Bradyrhizobium japonicum nolA; E. coli superoxide response regulator soxR;\ and Streptomyces lividans transcriptional activator tipA [MEDLINE:93345463], [MEDLINE:89123021], [MEDLINE:95332191],\ [MEDLINE:91324301], [MEDLINE:91110583], [MEDLINE:90161989]. \ Other members include hypothetical proteins from E. coli, B. subtilis\ and Haemophilus influenzae. Within this family, the HTH motif is situated towards the N-terminus.\ \ transcription factor activity ; GO:0003700 intracellular ; GO:0005622 regulation of transcription, DNA-dependent ; GO:0006355 19285 IPR000550 All organisms require reduced folate cofactors for the synthesis of a variety of metabolites. Most microorganisms must synthesize folate de novo because they lack the active transport system of higher vertebrate cells which allows these organisms to use dietary folates. Enzymes involved in folatebiosynthesis are therefore targets for a variety of antimicrobial agents such as trimethoprim or sulfonamides. 7,8-dihydro-6-hydroxymethylpterin-pyrophosphokinase (EC: 2.7.6.3) (HPPK) catalyzes the attachment of pyrophosphate to 6-hydroxymethyl-7,8-dihydropterin to form 6-hydroxymethyl-7,8-dihydropteridine pyrophosphate. This is the first step in a three-step pathway leading to 7,8 dihydrofolate. Bacterial HPPK (gene folK or sulD) [MEDLINE:92394901] is a protein of 160 to 270 amino acids. In the lower eukaryote Pneumocystis carinii, HPPK is the central domain of a multifunctional folate synthesis enzyme (gene fas) [MEDLINE:92210001].\ \ \ 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase activity ; GO:0003848\ \N \N folic acid and derivative biosynthesis ; GO:0009396 19282 IPR000547 Clathrin is the major protein of the polyhedral coat of coated pits and vesicles. Two different adaptor protein complexes link the clathrin lattice either to the plasma membrane or to the trans golgi network.Clathrin triskelions, composed of 3 heavy chains and 3 light chains, are the basic subunits of the clathrin coat. In the presence of light chains, hub assembly is influenced by both the pH and the concentration of calcium. The heavy chains each contain 7 repeats in the arm region. Other eukaryotic proteins, for example vacuolar membrane proteins, may contain one or two repeats.\ \ \N \N \N 19283 IPR000548 The myelin sheath is a multi-layered membrane, unique to the nervous system, that functions as an insulator to greatly increase the velocity of axonal impulse conduction [MEDLINE:87166035]. Myelin basic protein (MBP) [MEDLINE:91249486], [MEDLINE:91251156] is a hydrophilic protein that may function to maintain the correct structure of myelin, interacting with the lipids in the myelin membrane by electrostatic and hydrophobic interactions. In mammals various forms of MBP exist which are produced by the alternative splicing of a single gene; these forms differ by the presence or the absence of short (10 to 20 residues) peptides in various internal locations in the sequence. The major form of MBP is generally a protein of about 18.5 Kd (170 residues). MBP is the target of many post-translational modifications: it is N-terminally acetylated, methylated on an arginine residue, phosphorylated by various serine/threonine protein-kinases, and deamidated on some glutamine residues.\ \N \N \N 19281 IPR000545 Alpha-lactalbumin comprises 15 percent of the total human milk protein and is essential for lactose production [MEDLINE:87065037]. It is a globular calcium-binding metalloprotein secreted in the lactating mammary gland [MEDLINE:92015247], the calcium being bound in a novel binding loop that is superficially similar to the classic EF-hand motif. Lactalbumin attaches to

-galactosyltransferase on the luminal surface of the Golgi apparatus, creating the lactose synthetase complex [MEDLINE:87065037], which catalyses the addition of galactose to glucose, forming lactose. It has been claimed that calcium controls the release of lactalbumin from the golgi membrane and that the pattern of ion binding may also affect the catalytic properties of the lactose synthetase complex. The lactalbumin gene also contains a novel upstream regulatory sequence called the 'milk box' [MEDLINE:89025693], which is also found in genes of other milk proteins, and may be involved in either hormone regulation or tissue-specific expression in the lactating mammary gland.Alpha-lactalbumin is similar to C-type lysozyme in terms of primary sequence and structure [MEDLINE:84185596], and has probably evolved from a common ancestral protein. There is, however, no similarity in function.\ \ calcium ion binding activity ; GO:0005509 \N lactose biosynthesis ; GO:0005989 19284 IPR000549 Photosystem I (PSI) [MEDLINE:89076908] is an integral membrane protein complex that uses light energy to mediate electron transfer from plastocyanin to ferredoxin. It is found in the chloroplasts of plants and cyanobacteria. PSI is composed of at least 14 different subunits, two of which, PSI-G (gene psaG) and PSI-K (gene psaK), are small hydrophobic proteins of about 7 to 9 Kd and evolutionary related [MEDLINE:93366808]. Both seem to contain two transmembrane regions. Cyanobacteria contain only PSI-K.\ \N membrane ; GO:0016020 photosynthesis ; GO:0015979 19279 IPR000542 A number of eukaryotic acetyltransferases can, on the basis of sequence similarities, be grouped together into a family. These enzymes include choline o-acetyltransferase (EC: 2.3.1.6), an enzyme that catalyzes the biosynthesis of the neurotransmitter acetylcholine [MEDLINE:88097472]; carnitine o-acetyltransferase (EC: 2.3.1.7) [MEDLINE:93131929]; peroxisomal carnitine octanoyltransferase (EC: 2.3.1.-), a fatty acid

-oxidation pathway enzyme which is involved in the transport of medium-chain acyl-coenzyme A's from peroxisome to mitochondria [MEDLINE:89166509]; mitochondrial carnitine palmitoyltransferases I and II (EC: 2.3.1.21) (CPT), enzymes involved in fatty acid metabolism and transport [MEDLINE:93194885]; and Mycoplasma pneumoniae putative acetyltransferase C09_orf600.\ acyltransferase activity ; GO:0008415 \N \N 19280 IPR000544 Lipoate-protein ligase B [MEDLINE:95095954] (gene lipB) is the bacterial enzyme that creates an amide linkage that joins the free carboxyl group of lipoic acid to the epsilon-amino group of a specific lysine residue in lipoate-dependent enzymes. Such an enzyme has also be found in fungi [MEDLINE:97411912], where it is located in the mitochondria. It also seems to exist in plants and is encoded in the chloroplast genome of the red alga Cyanidium caldarium.\ \N \N lipoate biosynthesis ; GO:0009107 19276 IPR000539 The frizzled (fz) locus of Drosophila coordinates the cytoskeletons of epidermal cells, producing a parallel array of cuticular hairs and bristles [MEDLINE:91060073], [MEDLINE:89159415]. In fz mutants, the orientation of individual hairs with respect both to their neighbours and to the organism as a whole is altered. In the wild-type wing, all hairs point towards the distal tip [MEDLINE:89159415]. In the developing wing, fz has 2 functions: it is required for the proximal-distal transmission of an intracellular polarity signal; and it is required for cells to respond to the polarity signal. Fz produces an mRNA that encodes an integral membrane protein with 7 putative transmembrane (TM) domains. This protein should contain both extracellular and cytoplasmic domains, which could function in the transmission and interpretation of polarity information [MEDLINE:89159415]. This signature is usually found downstream of the Fz domain (IPR000024)\ frizzled receptor activity ; GO:0004928 membrane ; GO:0016020 \N 19277 IPR000540 The bacterial protein motA [MEDLINE:96298011] is required for the rotation of the flagellar motor. This protein probably forms a transmembrane proton channel used to energize the flagellar rotary motor. The motA protein is an integral membrane protein that contains four transmembrane domains.\ motor activity ; GO:0003774 membrane ; GO:0016020 chemotaxis ; GO:0006935 19275 IPR000538 The link domain [MEDLINE:93305086] is a hyaluronan(HA)-binding region found in proteins of vertebrates that are involved in the assembly of extracellular matrix, cell adhesion, and migration. The structure has been shown [MEDLINE:96390850] to consist of two

helices and two antiparallel

sheets arranged around a large hydrophobic core similar to that of C-typelectin. This domain contains four conserved cysteines involved in two disulfide bonds. The link domain has also been termed HABM [MEDLINE:93305086] (HA binding module) and PTR [MEDLINE:96275534] (proteoglycan tandem repeat). Proteins with such a domain include the proteoglycans aggrecan, brevican, neurocan and versican, which are expressed in the CNS; the cartilage link protein (LP), a proteoglycan that together with HA and aggrecan forms multimolecular aggregates; Tumor necrosis factor-inducible protein TSG-6, which may be involved in cell-cell and cell-matrix interactions during inflammation and tumorgenesis; and CD44 antigen, the main cell surface receptor for HA.\ \ hyaluronic acid binding activity ; GO:0005540 \N cell adhesion ; GO:0007155 19278 IPR000541 The following uncharacterized proteins have been shown to share regions of similarities, yeast chromosome VII hypothetical protein YGL211w; Dictyostelium discoideum protein veg136; and Methanococcus jannaschii hypothetical proteins MJ1157 and MJ1478.\ molecular_function unknown ; GO:0005554 \N \N 19269 IPR000533 Tropomyosins [MEDLINE:87270655], PUB00005316 are a family of closely related proteins present in muscle and non-muscle cells. In striated muscle, tropomyosin mediate the interactions between the troponin complex and actin so as to regulate muscle contraction. The role of tropomyosin in smooth muscle and non-muscle tissues is not clear. Tropomyosin is an

-helical protein that forms a coiled-coil structure of 2 parallel helices containing 2 sets of 7 alternating actin binding sites PUB00005316. There are multiple cell-specific isoforms, created by differential splicing of the messenger RNA from one gene, but the proportions of the isoforms vary between different cell types. Muscle isoforms of tropomyosin are characterized by having 284 amino acid residues and a highly conserved N-terminal region, whereas non-muscle forms are generally smaller and are heterogeneous in their N-terminal region.\

The allergens in this family include allergens with the following designations: Met e 1.

\ \ \N \N \N 19270 IPR000534 The semialdehyde dehydrogenase signature is found in N-acetyl-glutamine semialdehyde dehydrogenase (AgrC), which is involved in arginine biosynthesis, and aspartate-semialdehyde dehydrogenase, an enzyme involved in the biosynthesis of various amino acids from aspartate. The signature is also found in yeast and fungal Arg5,6 protein, which is cleaved into the enzymes N-acety-gamma-glutamyl-phosphate reductase and acetylglutamate kinase. These are also involved in arginine biosynthesis.\ \N \N amino acid metabolism ; GO:0006520 19271 IPR000534 The semialdehyde dehydrogenase signature is found in N-acetyl-glutamine semialdehyde dehydrogenase (AgrC), which is involved in arginine biosynthesis, and aspartate-semialdehyde dehydrogenase, an enzyme involved in the biosynthesis of various amino acids from aspartate. The signature is also found in yeast and fungal Arg5,6 protein, which is cleaved into the enzymes N-acety-gamma-glutamyl-phosphate reductase and acetylglutamate kinase. These are also involved in arginine biosynthesis.\ \N \N amino acid metabolism ; GO:0006520 19272 IPR000535 Major sperm proteins are central components in molecular interactions underlying sperm motility. These proteins oligomerise to form an extensive filament system that extends from sperm villipoda, along the leading edge of the pseudopod. About 30 MSP isoforms may exist in C. elegans.\ structural molecule activity ; GO:0005198 \N cell motility ; GO:0006928 19273 IPR000536 The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. In the absence of ligand, steroid hormone receptors are thought to be weakly associated with nuclear components. Hormone binding greatly increases receptor affinity. The hormone-receptor complex appears to recognize discrete DNA sequences upstream of transcriptional start sites.\ steroid hormone receptor activity ; GO:0003707 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 19274 IPR000537 The COX10/ctaB/cyoE signature is found in prenyltransferases including bacterial 4-hydroxybenzoate octaprenyltransferase (gene ubiA); yeast mitochondrial para-hydroxybenzoate--polyprenyltransferase (gene COQ2); and protoheme IX farnesyltransferase (heme O synthase) from yeast and mammals(gene COX10), and from bacteria (genes cyoE or ctaB) [MEDLINE:94207029], [MEDLINE:95191390]. These are integral membrane proteins, which probably contain seven transmembrane segments. The signature is also found in cytochrome C oxidase assembly factor. The complexity of cytochrome C oxidase requires assistance in building the complex, and this is carried out by the cytochrome C oxidase assembly factor.\ \N membrane ; GO:0016020 \N 19267 IPR000531 In Escherichia coli the TonB protein interacts with outer membrane receptor proteins that carry out high-affinity binding and energy-dependent uptake of specific substrates into the periplasmic space. These substrates are either poorly permeable through the porin channels or are encountered at very low concentrations. In the absence of tonB these receptors bind their substrates but do not carry out active transport. The tonB protein also interacts with some colicins. The proteins that are currently known or presumed to interact with tonB include btuB, cirA, fatA, fcuT, fecA, fhuE, fptA, hemR, irgA, iutA, pfeA, pupA and tbp1. Most of these proteins contain a short conserved region at their N-terminus.\ transporter activity ; GO:0005215 membrane ; GO:0016020 transport ; GO:0006810 19268 IPR000532 A number of polypeptidic hormones, mainly expressed in the intestine or the pancreas, belong to a group of structurally related peptides [MEDLINE:88267732], [MEDLINE:88267738]. Once such hormone, glucagon is widely distributed and produced in the

-cells of pancreatic islets [MEDLINE:86083105]. It affects glucose metabolism in the liver [MEDLINE:83299996] by inhibiting glycogen synthesis, stimulating glycogenolysis and enchancing gluconeogenesis. It also increases mobilisation of glucose, free fatty acids and ketone bodies, which are metabolites produced in excess in diabetes mellitus. Glucagon is produced, like other peptide hormones, as part of a larger precursor (preproglucagon), which is cleaved to produce glucagon, glucagon-like protein I and glucagon-like protein II [MEDLINE:88257102]. The structure of glucagon itself is fully conserved in all known mammalian species [MEDLINE:86083105]. Other members of the structurally similar group include glicentin precursor, secretin, gastric inhibitory protein, vasoactive intestinal peptide (VIP), prealbumin, peptide HI-27 and growth hormone releasing factor.\ hormone activity ; GO:0005179 extracellular ; GO:0005576 \N 19266 IPR000530

\ \ \

A number of eukaryotic ribosomal proteins can be grouped on the basis of sequence similarities. The small ribosomal subunit protein S12 contains 130-150 amino acid residues, and is thought to be involved in the translation initiation step. This family consists of eukaryotic S12 ribosomal proteins, including those from vertebrates [MEDLINE:88007693], Trypanosoma brucei\ \ \ \ [MEDLINE:93165083], Caenorhabditis elegans, Drosophila and yeast.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 19265 IPR000529

\ \ \

Ribosomal protein S6 is one of the proteins from the small ribosomal subunit. In Escherichia coli, S6 is known to bind together with S18 to 16S ribosomal RNA. It belongs to a family of ribosomal proteins which, on the basis of sequence similarities, groups bacterial, red algal chloroplast and cyanelle S6 ribosomal proteins.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 19264 IPR000528

Plant cells contain proteins, called lipid transfer proteins (LTP) [MEDLINE:91354044], [MEDLINE:91182807], [MEDLINE:90299003], which transfer phospholipids, glycolipids, fatty acids and sterols from liposomes or microsomes to mitochondria [MEDLINE:94344962]. These proteins, whose subcellular location is not yet known, could play a major role in membrane biogenesis by conveying phospholipids such as waxes or cutin from their site of biosynthesis to membranes unable to form these lipids. PLTPs exist in animal and plant tissues, including rat liver cytosol, potato tuber, castor bean, maize seedlings, spinach, barley and wheat. While there is no sequence similarity between animal and plant PTLPs, similarity between the plant proteins is high. Plant LTP's are proteins of about 9 Kd (90 amino acids), containing eight conserved cysteine residues which form 4 disulphide bridges. Plant PTLPs are also similar to -amylase inhibitor I2 from the seeds of ragi, Indian finger millet and amylase/protease inhibitors from rice and barley.

The allergens in this family include allergens with the following designations: Par j 1 and Par j 2.

\ \ lipid binding activity ; GO:0008289 \N lipid transport ; GO:0006869 19261 IPR000525 RepB is an initiator of plasmid replication, and possesses nicking-closing- (topoisomerase I) like activity. The protein is also able to perform a strand transfer reaction on ssDNA that contains its target.\ DNA-directed DNA polymerase activity ; GO:0003887 extrachromosomal circular DNA ; GO:0005727 DNA replication initiation ; GO:0006270 19262 IPR000526 Auxin binding protein is located in the lumen of the endoplasmic reticulum (ER). The primary structure contains an N-terminal hydrophobic leader sequence of 30-40 amino acids, which could represent a signal for translocation of the protein to the ER [MEDLINE:90060001], [MEDLINE:92338848]. The mature protein comprises around 165 residues, and contains a number of potential N-glycosylation sites. In vitro transport studies have demonstrated co-translational glycosylation [MEDLINE:92338848]. Retention within the lumen of the ER correlates withan additional signal located at the C terminus, represented by the sequence Lys-Asp-Glu-Leu, known to be responsible for preventing secretion of proteins from the lumen of the ER in eucaryotic cells [MEDLINE:90060001], [MEDLINE:92338848].\ \ receptor activity ; GO:0004872 endoplasmic reticulum lumen ; GO:0005788 \N 19263 IPR000527 The flgH, flgI and fliF genes of Salmonella typhimurium encode the major proteins for the L, P and M rings of the flagellar basal body [MEDLINE:89291739]. In fact, the basal body consists of four rings (L,P,S and M) surrounding the flagellar rod, which is believed to transmit motor rotation to the filament [MEDLINE:90172414]. The M ring is integral to the inner membrane of the cell, and may be connected to the rod via the S (supramembrane) ring, which lies just distal to it. The L and P rings reside in the outer membrane and periplasmic space, respectively. FlgH and FlgI, which are exported across the cell membrane to their destinations in the outer membrane and periplasmic space, have typical N-terminal cleaved signal-peptide sequences. FlgH is predicted to have an extensive

-sheet structure, in keeping with other outer membrane proteins [MEDLINE:89291739].\ motor activity ; GO:0003774 flagellar basal body, distal rod, L ring (sensu Bacteria) ; GO:0009427 ciliary/flagellar motility ; GO:0001539 19260 IPR000524 The many bacterial transcription regulation proteins which bind DNA through a 'helix-turn-helix' motif can be classified into subfamilies on the basis of sequence similarities. One such family groups together a range of proteins, including gntR, hutC, korA, ntaR, and E.coli proteins A, P30, fadR, exuR, farR, dgoR and phnF [MEDLINE:89350876], [MEDLINE:91285375], [MEDLINE:92065803]. Within this family, the HTH motif is situated towards the N-terminus.\ transcription factor activity ; GO:0003700 intracellular ; GO:0005622 regulation of transcription, DNA-dependent ; GO:0006355 19259 IPR000523 Magnesium-chelatase is a three-component enzyme that catalyses the insertion of Mg²⁺ into protoporphyrin IX. This is the first unique step in the synthesis of (bacterio)chlorophyll. As a result, it is thought that Mg-chelatase has an important role in channeling intermediates into the (bacterio)chlorophyll branch in response to conditions suitable for photosynthetic growth. ChlI and BchD have molecular weights between 38-42 kDa.\ magnesium chelatase activity ; GO:0016851 \N chlorophyll biosynthesis ; GO:0015995 19258 IPR000522 This is a sub-family of bacterial binding-protein-dependent transport systems family, and includes transport system permease proteins involved in the transport across the membrane of several compounds. This Pfam entry contains the inner components of this multicomponent transport system.\ \ \ transporter activity ; GO:0005215 membrane ; GO:0016020 transport ; GO:0006810 19257 IPR000519 A cysteine-rich domain of approximately forty five amino-acid residues has been found in some extracellular eukaryotic proteins [MEDLINE:95120477], [MEDLINE:97330915], [MEDLINE:93299378], [MEDLINE:94025035]. It is known as either the 'P', 'trefoil' or 'TFF' domain, and contains six cysteines linked by three disulfide bonds with connectivity 1-5, 2-4, 3-6. The domain has been found in a variety of extracellular eukaryotic proteins [MEDLINE:95120477], [MEDLINE:93299378], [MEDLINE:94025035], including protein pS2 (TFF1), a protein secreted by the stomach mucosa; spasmolytic polypeptide (SP) (TFF2), a protein of about 115 residues that inhibits gastrointestinal motility and gastric acid secretion; intestinal trefoil factor (ITF) (TFF3); Xenopus stomach proteins xP1 and xP4; Xenopus integumentary mucins A.1 (FIM-A.1 or preprospasmolysin) and C.1 (FIM-C.1), proteins which may be involved in defense against microbial infections by protecting the epithelia from the external environment; Xenopus skin protein xp2 (or APEG); Zona pellucida sperm-binding protein B (ZP-B); intestinal sucrase-isomaltase (EC: 3.2.1.48 / EC: 3.2.1.10), a vertebrate membrane bound, multifunctional enzyme complex which hydrolyzes sucrose, maltose and isomaltose; and lysosomal

-glucosidase (EC: 3.2.1.20).\ \N \N \N 19256 IPR000518

Metallothioneins (MT) are small proteins that bind heavy metals, such as zinc, copper, cadmium and nickel. They have a high content of cysteine residues that bind the metal ions through clusters of thiolate bonds [MEDLINE:89118264], PUB00001490, PUB00001490. An empirical classification into three classes was proposed by Kojima [MEDLINE:92140139], with class III MTs including atypical polypeptides composed of gamma-glutamylcysteinyl units. Class I and class II MTs (the proteinaceous sequences) have now been grouped into families of phylogenetically-related and thus alignable sequences. The MT superfamily is subdivided into families, subfamilies, subgroups, and isolated isoforms and alleles. The metallothionein superfamily comprises all polypeptides that resemble equine renal metallothionein in several respects [MEDLINE:88029881], e.g., low molecular weight; high metal content; amino acid composition with high Cys and low aromatic residue content; unique sequence with characteristic distribution of cysteines, and spectroscopic manifestations indicative of metal thiolate clusters. A MT family subsumes MTs that share particular sequence-specific features and are thought to be evolutionarily related. Fifteen MT families have been characterised, each family being identified by its number and its taxonomic range.

Family 14 consists of prokaryota MTs. Its members are recognised by the sequence pattern K-C-A-C-x(2)-C-L-C.The taxonomic range of the members extends to cyanobacteria. Known characteristics are: 53 to 56 AAs; 9 conserved Cys; one conserved tyrosine residue; one conserved histidine residue; contain other unusual residues.

\ \ heavy metal binding activity ; GO:0005505 \N \N 19254 IPR000516 Bacterial membrane-bound nickel-dependent hydrogenases [MEDLINE:92267032], [MEDLINE:92283771], [MEDLINE:92167818] seem to be associated with a b-type cytochrome involved in electron transfer from hydrogen to oxygen. This cytochrome is a protein of about 28 kDa that seems to have four transmembrane regions, which include several histidine residues that may be involved in coordination of the haem iron group. The gene coding for this cytochrome is adjacent to that coding for the large subunit of the hydrogenase. It has been assigned a variety of names in different species: hupC, hyaC, hydC or hoxZ.\ oxidoreductase activity ; GO:0016491 membrane ; GO:0016020 electron transport ; GO:0006118 19255 IPR000517

\ \ \

Ribosomal protein L30 is one of the proteins from the large ribosomal subunit. L30 belongs to a family of ribosomal proteins which, on the basis of sequence similarities [MEDLINE:92195798], groups bacteria and archaea L30, yeast mitochondrial L33, and Drosophila , slime mould, fungal and mammalian L7 ribosomal proteins. L30 from bacteria are small proteins of about 60 residues, those from archaea are proteins of about 150 residues, and eukaryotic L7 are proteins of about 250 to 270 residues.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 19250 IPR000512 Diphtheria toxin (EC: 2.4.2.36) is a 58 kDa protein secreted by lysogenic strains of Corynebacterium diphtheriae. The toxin causes the disease diphtheria in humans by gaining entry into the cell cytoplasm and inhibiting protein synthesis [MEDLINE:96155972]. The mechanism of inhibition involves transfer of the ADP-ribose group of NAD to elongation factor-2 (EF-2), rendering EF-2 inactive. The catalysed reaction is as follows:

\
NAD⁺ + peptide diphthamide = nicotinamide + peptide N-(ADP-D-ribosyl)diphthamide\

\ The crystal structure of the diphtheria toxin homodimer has been determined to 2.5A resolution [MEDLINE:92269934]. The structure reveals a Y-shaped molecule of 3 domains, a catalytic domain (fragment A), whose fold is of the

type; a transmembrane (TM) domain, which consists of 9

-helices, 2 pairs of which may participate in pH-triggered membrane insertion and translocation; and a receptor-binding domain, which forms a flattened

-barrel with a jelly-roll-like topology [MEDLINE:92269934]. The TM- and receptor binding-domains together constitute fragment B.\ \ toxin activity ; GO:0015070 extracellular ; GO:0005576 pathogenesis ; GO:0009405 19251 IPR000513 The N-terminal and internal 5'3'-exonuclease domains are commonly found together, and are most often associated with 5' to 3' nuclease activities. The XPG protein signatures (PDOC00658 DNA-repair proteins with 600 to 700 amino acids between the 53_EXO domains also carry the XPG protein signatures.

In several proteins from herpesviridae, the two 53EXO domains are separated by 50 to 120 amino acids. These proteins are implicated in the inhibition of the expression of the host genes.

\ \ nuclease activity ; GO:0004518 \N \N 19252 IPR000514

Glycoside hydrolase family 39 CAZY:GH_39).

\ \ \

The most highly conserved regions in these enzymes are located in their N-terminal\ sections. These contain a glutamic acid residue which, on the basis of\ similarities with other families of glycosyl hydrolases [MEDLINE:95350217], probably acts as\ the proton donor in their catalytic mechanism.

\ \ hydrolase activity, hydrolyzing O-glycosyl compounds ; GO:0004553 \N carbohydrate metabolism ; GO:0005975 19253 IPR000515

\ transporter activity ; GO:0005215 membrane ; GO:0016020 transport ; GO:0006810 19247 IPR000511 Cytochrome c heme-lyase (CCHL) (EC: 4.4.1.17) and cytochrome Cc1 heme-lyase (CC1HL) [MEDLINE:92362611] are mitochondrial enzymes that catalyze the covalent attachment of a heme group on two cysteine residues of cytochrome c and c1. These two enzymes are functionally and evolutionary related. There are two conserved regions, the first is located in the central section and the second in the C-terminal section. Both patterns contain conserved histidine, tryptophan and acidic residues which could be important for the interaction of the enzymes with the apoproteins and/or the heme group.\ holocytochrome c synthase activity ; GO:0004408 mitochondrion ; GO:0005739 \N 19248 IPR000512 Diphtheria toxin (EC: 2.4.2.36) is a 58 kDa protein secreted by lysogenic strains of Corynebacterium diphtheriae. The toxin causes the disease diphtheria in humans by gaining entry into the cell cytoplasm and inhibiting protein synthesis [MEDLINE:96155972]. The mechanism of inhibition involves transfer of the ADP-ribose group of NAD to elongation factor-2 (EF-2), rendering EF-2 inactive. The catalysed reaction is as follows:

\
NAD⁺ + peptide diphthamide = nicotinamide + peptide N-(ADP-D-ribosyl)diphthamide\

type; a transmembrane (TM) domain, which consists of 9

-helices, 2 pairs of which may participate in pH-triggered membrane insertion and translocation; and a receptor-binding domain, which forms a flattened

-barrel with a jelly-roll-like topology [MEDLINE:92269934]. The TM- and receptor binding-domains together constitute fragment B.\ \ toxin activity ; GO:0015070 extracellular ; GO:0005576 pathogenesis ; GO:0009405 19249 IPR000512 Diphtheria toxin (EC: 2.4.2.36) is a 58 kDa protein secreted by lysogenic strains of Corynebacterium diphtheriae. The toxin causes the disease diphtheria in humans by gaining entry into the cell cytoplasm and inhibiting protein synthesis [MEDLINE:96155972]. The mechanism of inhibition involves transfer of the ADP-ribose group of NAD to elongation factor-2 (EF-2), rendering EF-2 inactive. The catalysed reaction is as follows:

\
NAD⁺ + peptide diphthamide = nicotinamide + peptide N-(ADP-D-ribosyl)diphthamide\

type; a transmembrane (TM) domain, which consists of 9

-helices, 2 pairs of which may participate in pH-triggered membrane insertion and translocation; and a receptor-binding domain, which forms a flattened

-barrel with a jelly-roll-like topology [MEDLINE:92269934]. The TM- and receptor binding-domains together constitute fragment B.\ \ toxin activity ; GO:0015070 extracellular ; GO:0005576 pathogenesis ; GO:0009405 19246 IPR000510 Enzymes belonging to this family include cofactor-requiring nitrogenases and protochlorophyllide reductase. The key enzymatic reactions in nitrogen fixation are catalyzed by the nitrogenase complex, which has two components, the iron protein (component 2), and a component (component 1) which is either a molybdenum-iron, vanadium-iron or iron-iron protein. The enzyme (EC: 1.18.6.1) forms a hexamer of two

, two

and two delta chains. Protochlorophyllide reductase (EC: 1.3.1.33) is involved in the light-dependent accumulation of chlorophyll, probably at the step of reduction of protochlorophyllide to chlorophyllide.\ oxidoreductase activity ; GO:0016491 \N electron transport ; GO:0006118 19245 IPR000509

\ \ \

A number of eukaryotic ribosomal proteins can be grouped on the basis of sequence similarities. The L36E ribosomal family consists of mammalian, Caenorhabditis elegans and Drosophila L36, Candida albicans L39, and yeast YL39 ribosomal proteins [MEDLINE:93249466].

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 19242 IPR000506 Acetohydroxy acid isomeroreductase catalyses the conversion of acetohydroxy acids into dihydroxy valerates. This reaction is the second in the synthetic pathway of the essential branched side chainamino acids valine and isoleucine [MEDLINE:97361822]. The enzyme forms a tetramer of similar but non-identical chains, and requires magnesium as a cofactor.\ \ \ ketol-acid reductoisomerase activity ; GO:0004455 \N branched chain family amino acid biosynthesis ; GO:0009082 19243 IPR000507

Beta-1 and -2 receptors often coexist, but one subtype normally\ predominates. Beta-1 receptors are the predominant subtype in cardiac\ tissue (where they mediate positive inotropic and chronotropic effects) and\ in the kidney (where they enhance renin release) . The receptor activates\ adenylyl cyclase through Gs PUB00005869.

\ \ beta1-adrenergic receptor activity ; GO:0004940 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19244 IPR000508

Signal peptidases (SPases) [MEDLINE:93088402] (also known as leader peptidases) remove the signal peptides from secretory proteins. In prokaryotes three types of SPases are known: type I (gene lepB) which is responsible for the processing of the majority of exported pre-proteins; type II (gene lsp) which only process lipoproteins, and a third type involved in the processing of pili subunits.

SPase I (EC: 3.4.21.89) is an integral membrane protein that is anchored in the cytoplasmic membrane by one or two N-terminal transmembrane domains, with the main part of the protein protuding in the periplasmic space. SPase I can process nonlipoprotein\ substrates that are exported by the SecYEG pathway or the twin arginine translocation (Tat) pathway. SPase I is evolutionary related to the yeast mitochondrial inner membrane protease subunit 1 and 2 (genes IMP1 and IMP2) [MEDLINE:94090338]. In eukaryotes the removal of signal peptides is effected by an oligomeric enzymatic complex composed of at least five subunits: the signal peptidase complex (SPC). The SPC is located in the endoplasmic reticulum membrane. Two components of mammalian SPC, the 18 Kd (SPC18) and the 21 Kd (SPC21) subunits as well as the yeast SEC11 subunit have been shown [MEDLINE:92347314] to share regions of sequence similarity with prokaryotic SPases I and yeast IMP1/IMP2.

The proteolytic region of bacterial SPase I has a novel protein fold, comprised of two large antiparallel -sheet domains [MEDLINE:22363347]. One of the -sheet domains contains all of the conserved regions in the SPase I family; the other -sheet domain, which varies in\ size with the different SPases, does not contain any of the conserved sequence motifs in the SPase family. The catalytic domain also contains an extended -ribbon\ that protrudes from the conserved -sheet domain. There is a disulfide bond between Cys residues in the non-conserved -sheet domain.

\ \ peptidase activity ; GO:0008233 membrane ; GO:0016020 proteolysis and peptidolysis ; GO:0006508 19241 IPR000505

Human 5HT1D and 5HT1B receptors share virtually identical pharmacological\ profiles, and no selective ligands have been described . 5HT1D receptors\ are found in neurons in the CNS, and in vascular smooth muscles in the\ periphery. 5HT1D/5HT1B receptors may be the therapeutic substrate of the\ anti-migraine drug, sumatriptan; these sites are also implicated in feeding\ behaviour, anxiety, depression, cardiac function and movement PUB00005889.

\ \ \N integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19240 IPR000504 Many eukaryotic proteins that are known or supposed to bind single-stranded RNA contain one or more copies of a putative RNA-binding domain of about 90 amino acids. This is known as the eukaryotic putative RNA-binding region RNP-1 signature [MEDLINE:89252819], [MEDLINE:89223025], or RNA recognition motif (RRM). RRMs are found in a variety of RNA binding proteins, including heterogeneous nuclear ribonucleoproteins (hnRNPs), proteins implicated in regulation of alternative splicing, and protein components of small nuclear ribonucleoproteins (snRNPs). The motif also appears in a few single stranded DNA binding proteins. The RRM structure consists of four strands and two helices arranged in an

sandwich, with a third helix present during RNA binding in some cases [MEDLINE:94119674]. Two individual models were built which identify subtypes of this domain, but there is no functional difference between the subtypes.\ nucleic acid binding activity ; GO:0003676 \N \N 19237 IPR000501 The members of this family are associated with capsid intermediates during packaging of dsDNA viruses with no RNA stage in their replication cycle [MEDLINE:98362148]. The protein may affect translocation of the virus glycoproteins to membranes, and is involved in capsid maturation.\ \N \N \N 19238 IPR000502

M5 mRNA has been found in the CNS, but a translation product has not been\ identified . It is thought that this receptor subtype may be important\ during development, or may serve a unique function relative to the other\ receptor subtypes . No selective agonist has been described PUB00005867.

\ \ muscarinic acetylcholine receptor activity ; GO:0004981 membrane ; GO:0016020 \N 19239 IPR000503

Histamine is distributed within mast cells in all peripheral tissues and\ is a well-characterised mediator of inflammation and allergy . It also\ regulates release of gastric acid from parietal cells in the gastric\ mucosa. H2 receptors are found in high levels in the stomach and heart,\ and have limited distribution in smooth muscle and cells of the immune\ system. H2 antagonists are used clinically in the treatment of peptic\ ulceration PUB00005888.

\ \ histamine receptor activity ; GO:0004969 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19236 IPR000500

\ \

\ \ \ connexon channel activity ; GO:0015285 connexon complex ; GO:0005922 cell communication ; GO:0007154 19234 IPR000498 The ompA-like transmembrane domain is present in a number of different outer membrane proteins of several Gram-negative bacteria. Many of the proteins having this domain in the N-terminal also have the conserved bacterial outer membrane protein domain IPR006664. \

OmpA consists of a regular, extended eight-stranded -barrel and appears to be constructed like an inverse micelle with large water-filled cavities, but does not form a pore. The cavities seem to be highly conserved during evolution. The structure corroborates the concept that all outer membrane proteins consist of -barrels [MEDLINE:99023200]. The -barrel membrane anchor appears to be the outer membrane equivalent of the single-chain -helix anchor of the inner membrane.

\ \ \N external outer membrane (sensu Gram-negative Bacteria) ; GO:0009279 \N 19235 IPR000499

\ \ endothelin receptor activity ; GO:0004962 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19233 IPR000497

D1 receptors are found in greatest abundance in the caudate-putamen,\ nucleus accumbens and olfactory tubercle, with lower levels in the frontal\ cortex, habenula, amygdala, hypothalamus and thalamus. In the periphery,\ binding sites are found in the kidney, heart, liver and parathyroid gland\ . The receptors stimulate adenylyl cyclase through Gs; they may also\ be able to stimulate phosphoinositide metabolism PUB00005878.

\ \ dopamine receptor activity ; GO:0004952 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19231 IPR000494 The type-1 insulin-like growth-factor receptor (IGF-1R) and insulin receptor (IR) are closely related members of the tyrosine-kinase receptor superfamily IPR000719. IR is essential for glucose homeostasis, whereas IGF-1R is involved in both normal growth and development and malignant transformation. Homologues of these receptors are found in animals as simple as cnidarians. The epidermal growth-factor receptor (EGFR) family is closely related to the IR family and has\ significant sequence identity to the first three domains of the extracellular portion of IGF-IR (L1-Cys-rich-L2). \

The L domains each consist of a single-stranded right-handed -helix. The Cys-rich region is composed of eight disulphide-bonded modules, seven of which form a rod-shaped domain with modules associated in an unusual manner. The three domains surround a central space of sufficient size to accommodate a ligand molecule. Although the fragment (residues 1-462) does not bind ligand, many of the determinants responsible for hormone binding and ligand specificity map to this central site. This structure therefore shows how the IR subfamily might interact with their ligands[MEDLINE:98352788].

A number of receptor systems have been implicated to play an important role in the\ development and progression of many human cancers. The epidermal growth\ factor (EGF) receptor tyrosine kinase family has been found to consistently play a\ leading role in tumor progression [MEDLINE:20047800].

\ \ epidermal growth factor receptor activity ; GO:0005006 membrane ; GO:0016020 \N 19232 IPR000496

\ \ \ bradykinin receptor activity ; GO:0004947 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19230 IPR000493

Inositol 1,4,5-trisphosphate (InsP3) is an intracellular second messengerthat transduces growth factor and neurotransmitter signals. InsP3 mediates\ the release of Ca²⁺ from intracellular stores by binding to specific Ca²⁺\ channel-coupled receptors. One such receptor contains a C-terminal Ca²⁺\ channel with 8 possible transmembrane (TM) regions, while its N-terminal\ cytoplasmic region houses ligand-binding and modulatory sites [MEDLINE:92007769], [MEDLINE:90324264]. Ca²⁺\ appears to inhibit ligand binding, possibly by interacting with a Ca²⁺-binding protein that itself inhibits the receptor.

The InsP3 receptor is an integral membrane protein located in the\ endoplasmic reticulum. It is a homotetramer. The protein shows some\ similiarity to the ryanodine receptor, which functions as a Ca²⁺-release\ channel in the sarcoplasmic reticulum of cardiac and skeletal muscle [MEDLINE:91250425].

\ \ \ inositol 1,4,5-triphosphate-sensitive calcium-release channel activity ; GO:0005220 membrane ; GO:0016020 calcium ion transport ; GO:0006816 19229 IPR000492 Protamines P1 and P2 form a family of small basic peptides that represent the major sperm proteins in placental mammals. In human and mouse protamine P2 is one of the most abundant sperm proteins.Protamine 2 (PRM2) is a low molecular weight arginine-rich protein which is present in haploid spermatogenic cells of human, mouse and other primates. The protamine P2 gene codes for a P2 precursor, pro-P2 which is later processed by proteolytic cleavages in its N-terminal region to form the mature P2 protamines [MEDLINE:93292525].\

Protamines substitute for histones in the chromatin of sperm during the haploid phase of spermatogenesis. They compact sperm DNA into a highly condensed, stable and inactive complex.

\ \ DNA binding activity ; GO:0003677 nucleus ; GO:0005634 spermatogenesis ; GO:0007283 19228 IPR000491

Inhibin has two isoforms, A and B, with the same subunit but different subunits. Inhibin A is a dimer of and A subunits, inhibin B is a dimer of and B subunits.

Activin A is a dimer of A subunits, activin AB is a dimer of A and B chains.

Genes coding for mouse activin C and E are closely linked and exhibit a liver-specific expression pattern in adult tissues.

\ \ hormone activity ; GO:0005179 extracellular ; GO:0005576 cell growth and/or maintenance ; GO:0008151 19227 IPR000490

Glycoside hydrolase family 17 CAZY:GH_17). Currently these enzymes have only been found in plants and in fungi.

\ \ hydrolase activity, hydrolyzing O-glycosyl compounds ; GO:0004553 \N carbohydrate metabolism ; GO:0005975 19225 IPR000488 The death domain [MEDLINE:95277834], [MEDLINE:96013161], [MEDLINE:96005604] (FAS/TNF cytosolic interaction domain) has firstbeen described as a region in the cytoplasmic tail of the 75 Kd TNF receptor\ (TNFR-1) (see PDOC00561) which is involved in TNF-mediated cell death\ signaling. A corresponding region is found in the cytoplasmic tail of FAS/APO1\ another surface receptor inducing apoptotic cell death. This region mediates\ self-association of these receptors, thus giving the signal to downstream\ events leading to apoptosis.\ Subsequently, a number of other proteins have been found to interact with the\ cytoplasmic part of either FAS or the TNF receptor in the region of the death\ domain. Overexpression of these proteins usually leads to cell death. By\ profile analysis, it has been shown that a number of other proteins contain\ regions with significant similarity to the death domain. Interestingly,\ several of these proteins also work in the context of cell death signaling.\ In most of these proteins, the death domain is located at the extreme C-\ terminus. Exceptions are ankyrin, MyD88 and pelle, all protein probably not\ directly involved in cell death signaling. In the case of ankyrin, the isoform\ 2.1 is a splice variant which has the death domain located at the C-terminus.\ \ \N \N signal transduction ; GO:0007165 19226 IPR000489

All organisms require reduced folate cofactors for the synthesis of a varietyof metabolites. Most microorganisms must synthesize folate de novo because\ they lack the active transport system of higher vertebrate cells which allows\ these organisms to use dietary folates. Proteins containing this domain include dihydropteroate synthase (EC: 2.5.1.15) as well as a group of methyltransferase enzymes including\ methyltetrahydrofolate, corrinoid iron-sulfur protein methyltransferase (MeTr) Q46389 that catalyzes a key step\ in the Wood-Ljungdahl pathway of carbon dioxide fixation.

\ \

Dihydropteroate synthase (EC: 2.5.1.15) (DHPS) catalyzes the condensation of\ 6-hydroxymethyl-7,8-dihydropteridine pyrophosphate to para-aminobenzoic acid\ to form 7,8-dihydropteroate. This is the second step in the three steps\ pathway leading from 6-hydroxymethyl-7,8-dihydropterin to 7,8-dihydrofolate.\ DHPS is the target of sulfonamides which are substrates analog that compete\ with para-aminobenzoic acid.\ Bacterial DHPS (gene sul or folP) [MEDLINE:91072277] is a protein of about 275 to 315 amino\ acid residues which is either chromosomally encoded or found on various\ antibiotic resistance plasmids. In the lower eukaryote Pneumocystis carinii,\ DHPS is the C-terminal domain of a multifunctional folate synthesis enzyme\ (gene fas) [MEDLINE:92210001].

\ \ dihydropteroate synthase activity ; GO:0004156 \N folic acid and derivative biosynthesis ; GO:0009396 19224 IPR000487 Flaviviruses encode a single polyprotein. This is cleaved intothree structural and seven non-structural proteins. All, but two,\ are cleaved by the NS2B-NS3 protease complex [MEDLINE:98139110], [MEDLINE:95190967].\ \ \N \N \N 19222 IPR000485 The many bacterial transcription regulation proteins which bind DNA through a'helix-turn-helix' motif can be classified into subfamilies on the basis of\ sequence similarities. One such family is the AsnC subfamily [MEDLINE:95288779]. \ The 'helix-turn-helix' DNA-binding motif of these proteins is located in the\ N-terminal part of the sequences.\ \ transcription factor activity ; GO:0003700 intracellular ; GO:0005622 regulation of transcription, DNA-dependent ; GO:0006355 19223 IPR000486 Dioxygenases catalyze the incorporation of both atoms of molecular oxygen intosubstrates. Cleavage of aromatic rings is one of the most important function\ of dioxygenases. The substrates of ring-cleavage dioxygenases can be\ classified into two groups according to the mode of scission of the aromatic\ ring. Intradiol enzymes cleave the aromatic ring between two hydroxyl groups,\ whereas extradiol enzymes cleave the aromatic ring between a hydroxylated\ carbon and another adjacent nonhydroxylated carbon. Extradiol dioxygenases are\ usually homomultimeric, bind one atom of ferrous ion per subunit and have a\ subunit size of about 33 Kd. It has been shown [MEDLINE:89359362], [MEDLINE:94171820] that the known extradiol\ dioxygenases are evolutionary related. The conserved glutamate has been shown [MEDLINE:96069815],\ in bphC, to be implicated in the binding of the ferrous iron atom.\ \ ferrous iron binding activity ; GO:0008198 \N aromatic compound metabolism ; GO:0006725 19221 IPR000484

Purple bacteria have a diverse metabolism, which enables them to growphotosynthetically under anaerobic conditions by virtue of using a\ photosynthetic reaction centre (PRC) [MEDLINE:84259352]. Most reaction centres from these\ bacteria comprise 3 elements (the light (L), medium (M) and heavy (H)\ chains), although some contain a tightly-bound cytochrome molecule PUB00001143. \ Several other factors, such as carotenoid, bacteriochlorophyll pigments,\ quinones and other light-harvesting co-factors are also required PUB00001143, all\ of which are associated with the L and M chains [MEDLINE:88227960].

The complete complex\ is intimately involved in the transformation of light energy into chemical\ energy [MEDLINE:88227960], with an adjacent oxidoreductase complex using the reduced\ quinones to produce a membrane potential [MEDLINE:84259352]. Many of these processes are\ similar to corresponding processes in the thylakoid membranes of higher\ plant chloroplasts, which contain photosystem II, a complex similar to the\ bacterial PRC [MEDLINE:84259352].\ The L and M chains are similar polypeptides, which span the membrane and\ are required for pigment binding PUB00001143, PUB00001143. \ They have been shown to be photo-\ chemically active in the absence of the H chain PUB00001143. \ In the photosystem II of\ eukaryotic chloroplasts two other related proteins are also involved: the D1 (psbA) and\ D2 proteins (psbD). These four types of protein probably evolved from a\ common ancestor [see PUB00001143, PUB00005326 for recent reviews].\ In L and M chains, the first histidine is a ligand of the magnesium\ ion of the special pair bacteriochlorophyll, the second is a ligand of a\ ferrous non-heme iron atom. In photosystem II these two histidines are thought\ to play a similar role. \ The PRC is one of the few transmembrane (TM) complexes for which there is a known structure: it \ has been shown that both the L and M chains have 5 TM helices of between\ 24-30 amino acids, which are tilted up to 38 degrees to the membrane PUB00005326.\ A difference in the number and type of charged residues on either side of\ the membrane sets up an electrical dipole, which may affect the direction\ and speed of the light-driven electron transport effected by the PRC PUB00001143.\ Although the sequences of the TM regions are not well conserved, L and M\ chains contain small clusters of conserved amino acids that correspond to\ binding sites for bacteriochlorophyll, iron and quinone PUB00001143.

\ \ \N \N photosynthesis ; GO:0015979 19220 IPR000483

Leucine Rich RepeatsIPR001611 are short sequence motifspresent in a number of proteins with diverse functions and\ cellular locations [MEDLINE:95117131]. Leucine Rich Repeats are often flanked\ by cysteine rich domains. This domain is often found at the\ C-terminus of tandem leucine rich repeats.

\ \

Some platelet glycoproteins belong to this group. The CD42a-d-complex serves as receptor for von Willebrand factor (vWf) and thrombin. The actual binding site for vWf and thrombin lies on CD42b (GPIb ). The complex mediates adhesion of platelets to subendothelial matrices (exposed upon damage to the\ endothelium) at high shear rates and amplifies the platelet response to thrombin during platelet activation where thrombin is involved. CD42a is the platelet glycoprotein IX (GPIX), CD42b is the platelet glycoprotein Ib chain (GPIba) also called GPIbalpha or glycocalicin, CD42c is the platelet glycoprotein Ib chain (GPIBb or GPIb-) and CD42d is the platelet glycoprotein V (GPV). These proteins contain the leucine-rich repeat (IPR001611/>) and the two cysteine-rich flanking regions: N-terminal (IPR000372) and C-terminal, described in the current entry.

\ \

CD molecules are leucocyte antigens on cell surfaces. CD antigens nomenclature is updated at http://www.ncbi.nlm.nih.gov/PROW/guide/45277084.htm \

\ \ \ \N \N \N 19219 IPR000482

5-Hydroxytryptamine (or serotonin) is ubiquitous in plants and animals. It is an important neurotransmitter and local hormone in the CNS and instestine, and is implicated in a vast array of physiological and patho- physiological pathways PUB00005667. In the periphery, 5HT contracts a number of smooth muscles, and induces endothelium-dependent vasodilation through the formation of NO PUB00005667. It is a mediator of peristalsis, and may be involved in platelet aggregation and homeostasis. In the CNS, 5HT is believed to be involved in a wide range of functions, including the control of appetite, mood, anxiety, hallucinations, sleep, vomiting and pain perception PUB00005667. 5HT receptor ligands are of clinical use in the treatment of depression, migraine and post-operative vomiting. Numerous receptor subtypes have been classified according to their antagonist susceptibilities and their affinities for 5HT. Five 5HT1 subtypes and at least three 5HT2 subtypes have now been identified, in addition to subtypes 5HT3-7 PUB00005667. All share a high degree of sequence similarity, and have overlapping pharmacological specificities. The 5HT2 receptor was originally classified according to its ability to display micromolar affinity for 5HT, to be labelled with [³H]spiperone, and by its susceptibility to 5HT antagonists PUB00005667. At least 3 members of the family exist (including the re-classified 5HT1C receptor), all of which share a high degree of sequence similarity and stimulate the phosphoinositide pathway.

\ \ \N integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19216 IPR000479 The cation-independent mannose-6-phosphate receptor is a type I membrane protein responsible for transport of phosphorylated lysosomal enzymes from the golgi complex and the cell surface to lysosomes. Lysosomal enzymes bearing phosphomannosyl residues bind specifically to mannose-6-phosphate receptors in the golgi apparatus and the resulting receptor-ligand complex is transported to an acidic prelysosomal compartment where the low pH mediates the dissociation of the complex. This receptor also binds insulin growth factor. It contains15 copies of a repeat.\ \ transporter activity ; GO:0005215 membrane ; GO:0016020 transport ; GO:0006810 19217 IPR000480 Glutelins are major storage proteins that aggregate in protein bodies in the endosperm of maize\ \ \ \ PUB00004575, PUB00004575. They comprise the second largest protein \ fraction in maize endosperm [MEDLINE:85215560] (zeins being the largest), and show \ sequence similarities to other cereal storage proteins, such as gliadins, \ glutenins, hordeins, etc.. Glutelins have a well-defined structure, \ including an N-terminal region containing varying numbers of repeats of \ the sequence PPPHVL PUB00004575; a Gln rich region that can be separated into 2 \ domains; and a Cys rich C-terminal domain that shows some regions of \ internal similarity. Glutelins have been shown PUB00004575 to exhibit structural \ similarity to other cereal storage proteins, including a

-reverse \ turn region which forms a loose helix-like domain.\ \ nutrient reservoir activity ; GO:0045735 \N \N 19215 IPR000477 The use of an RNA template to produce DNA, for integration into the host genome and exploitation of a host cell, is a strategy employed in the replication of retroid elements, such as the retroviruses and bacterial retrons. The enzyme catalysing polymerisation is an RNA-directed DNA-polymerase, or reverse trancriptase (RT) (EC: 2.7.7.49). Reverse transcriptase occurs in a variety of mobile elements, including retrotransposons, retroviruses, group II introns, bacterial msDNAs, hepadnaviruses, and caulimoviruses.

Retroviral reverse transcriptase is synthesised as part of the POL polyprotein that contains; an aspartyl protease, a reverse transcriptase, RNase H and integrase. POL polyprotein undergoes specific enzymatic cleavage to yield the mature proteins. The discovery of retroelements in the prokaryotes raises intriguing questions concerning their roles in bacteria and the origin and evolution of reverse transcriptases and whether the bacterial reverse transcriptases are older than eukaryotic reverse transcriptases [MEDLINE:96425795].

\ \ RNA-directed DNA polymerase activity ; GO:0003964 \N RNA dependent DNA replication ; GO:0006278 19218 IPR000481

The multiallelic mating type locus B -1 of S.commune encodes\ a pheromone receptor and putative pheromone genes [MEDLINE:97132648]. Analysis of this\ locus has provided evidence that pheromones and pheromone receptors govern\ recognition of self versus non-self, and sexual development in this homobasidiomycetous fungus\ \ \ \ [MEDLINE:96080162].

\ \ \ mating-type alpha-factor pheromone receptor activity ; GO:0004934 membrane ; GO:0016020 \N 19213 IPR000475 The virion infectivity factor (vif) of human immunodeficiency virustype 1(HIV-1) affects the infectivity of virus particles [MEDLINE:87292118] to \ T lymphocytes and macrophages (in some cases\ increasing the infectivity of HIV-1 particles by 100- to 1000-fold), \ but has no direct effect on transcription, translation or virus release.\ Vif antibodies are found in the sera of patients at all levels of HIV-1\ infection, indicating that vif is expressed in natural infections in vivo.\ Other lentiviruses, including simian immunodeficiency virus, visna virus,\ and feline immunodeficiency virus, have vif open reading frames, suggesting\ vif plays an essential role during natural infections [MEDLINE:93021374].\ The expression of vif in BHK-21 cells has been shown to be linked to a\ modification of the C-terminus of gp41env, which modification is\ inhibited by trans-epoxysuccinyl-L-leucylamido-(4-guanidio)butane (E64),\ a specific inhibitor of cysteine proteases [MEDLINE:91140723]. Coupled with sequence\ analysis and the effects of point mutations in vif, it has been suggested\ that vif could be a cysteine protease. Virions \ produced in the absence of Vif have abnormal core morphology and \ those produced in primary T cells carry immature core proteins \ and low levels of mature capsid.\ \ \N \N viral infectious cycle ; GO:0019058 19214 IPR000476 Glycoprotein hormones [MEDLINE:81280516], [MEDLINE:93075015] (or gonadotropins) are a family of proteins which include the mammalian hormones follitropin (FSH), lutropin (LSH), thyrotropin(TSH)placental chorionic gonadotrophins hCG and eCG [MEDLINE:84041490] and chorionic \ gonadotropin (CG), as well as at least two forms of fish\ gonadotropins. These hormones are central to the \ complex endocrine system that regulates normal growth, sexual development, \ and reproductive function [MEDLINE:82214055]. The hormones LH, FSH and TSH are secreted\ by the anterior pituitary gland, while hCG and eCG are secreted by the \ placenta [MEDLINE:91321740]. \ All these hormones consist of two glycosylated chains (

and

). The

subunit is common to each protein dimer (well conserved within species, \ but differing between them [MEDLINE:82214055]), and a unique

subunit, which \ confers biological specificity [MEDLINE:84041490].\ The

chains are highly conserved proteins of about 100 amino acid\ residues which contain ten conserved cysteines all involved in disulfide\ bonds [MEDLINE:94261179], as shown in the following schematic representation.\

\
                        +---------------------------+\
            +----------+|             +-------------|--+\
            |          ||             |             |  |\
        xxxxCxCxxxxxxCxCCxxxxxxxxxxxxxCCxxxxxxxxxxCxCxxCx\
              |      |                 |          |\
              +------|-----------------+          |\
                     |                            |\
                     +----------------------------+\
\
\
'C': conserved cysteine involved in a disulfide bond.\

\ Intracellular levels of free

subunits are greater than those of the\ mature glycoprotein, implying that hormone assembly is limited by the\ appearance of the specific

subunits, and hence that synthesis of

and

is independently regulated [MEDLINE:84041490].\ \ hormone activity ; GO:0005179 extracellular ; GO:0005576 \N 19209 IPR000470 The Cfx genes in Alcaligenes eutrophus encode a number of Calvin cycleenzymes [MEDLINE:93054349]. The observed sizes of two of the gene products, CfxX and CfxY,\ are 35 kDa and 27 kDa respectively [MEDLINE:93054349]. No functions could be assigned to\ CfxX and CfxY. These proteins show a high degree of similarity to the\ B.subtilis stage V sporulation protein K [MEDLINE:92157863].\ \ ATP binding activity ; GO:0005524 \N \N 19210 IPR000471 Interferons [MEDLINE:87053170] are proteins which produce antiviral and antiproliferativeresponses in cells. On the basis of their sequence interferons are classified\ into five groups:

-II (or omega),

, delta (or trophoblast).\ The sequence differences may possibly cause different responses to various inducers, or \ result in the recognition of different target cell types [MEDLINE:82060261]. The main\ conserved structural feature of interferons is a disulphide bond that, \ except in mouse

interferon, occurs in all

and omega\ sequences.\ \ hematopoietin/interferon-class (D200-domain) cytokine receptor ligand activity ; GO:0005126 extracellular ; GO:0005576 defense response ; GO:0006952 19211 IPR000472 Transforming growth factor-

(TGF-

) forms a family with othergrowth factors described in PDOC00223. The receptors for most of the \ members of this growth factor family are related. These proteins are\ receptor-type kinases of Ser/Thr type PDOC00223/>), which have a single\ transmembrane domain and a specific hydrophilic Cys-rich ligand-binding domain [MEDLINE:97175397], [MEDLINE:94322910], [MEDLINE:97066313]. The C-terminal part of the extracellular\ domain is conserved. Some of the receptors of this family contain subclass-specific\ N-terminal extensions of this homology domain. The type I receptors also possess 7 extracellular residues\ preceding the cysteine box.\ \ transforming growth factor-beta receptor activity ; GO:0005024 membrane ; GO:0016020 \N 19206 IPR000467 The D111/G-patch domain [MEDLINE:99400969] is a short conserved region of about 40 amino acidswhich occurs in a number of putative RNA-binding proteins, including tumor \ suppressor and DNA-damage-repair proteins, suggesting that this\ domain may have an RNA binding function. This domain\ has seven highly conserved glycines.\ A multiple alignment of a small subset of D111/G-patch domains is shown in Fig. 2b\ of [MEDLINE:99280069] .\ \ nucleic acid binding activity ; GO:0003676 intracellular ; GO:0005622 \N 19212 IPR000473

\ \ \

Ribosomal protein L36 is the smallest protein from the large subunit of the\ prokaryotic ribosome. It belongs to a family of ribosomal proteins which, on\ the basis of sequence similarities PUB00005070 can be grouped into: bacterial L36; algal and plant chloroplast L36; Cyanelle L36. L36 is a small basic and cysteine-rich protein of 37 amino-acid residues.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 19207 IPR000468 Barnase is the extracellular ribonuclease IPR001887.\ ribonuclease inhibitor activity ; GO:0008428 intracellular ; GO:0005622 \N 19208 IPR000469 Guanine nucleotide binding proteins (G-proteins) are a family of membrane-associated proteins that couple extracellularly-activated integral-membrane\ receptors to intracellular effectors, such as ion channels and enzymes that\ vary the concentration of second messenger molecules [MEDLINE:91354032], [MEDLINE:91227903] ]. G-proteins are\ composed of 3 subunits (

and gamma) which, in the resting state,\ associate as a trimer at the inner face of the plasma membrane. The

subunit has a molecule of guanosine diphosphate (GDP) bound to it:\ stimulation of the G-protein by an activated receptor leads to its exchange\ for GTP (guanosine triphosphate). This results in the separation of the

from the

and gamma subunits, which always remain tightly\ associated as a dimer. Both the

and

-gamma subunits are then able\ to interact with effectors, either individually or in a cooperative manner.\ The intrinsic GTPase activity of the

subunit hydrolyses the bound GTP\ to GDP. This returns the

subunit to its inactive conformation and\ allows it to reassociate with the

-gamma subunit, thus restoring the\ system to its resting state.\ G-protein

subunits are 350-400 amino acids in length and have\ molecular weights in the range 40-45 kDa. Seventeen distinct types of

subunit have been identified in mammals. These fall into 4 main groups on\ the basis of both sequence similarity and function:

-S,

-Q,

-I and

-12 [MEDLINE:91227903]. Many

subunits are substrates for\ ADP-ribosylation by cholera or pertussis toxins. They are often N-terminally\ acylated, usually with myristate and/or palmitoylate, and these fatty acid\ modifications are probably important for membrane association and high-\ affinity interactions with other proteins. The atomic structure of the

subunit of the G-protein involved in mammalian vision, transducin,\ has been elucidated in both GTP- and GDB-bound forms, and shows considerable\ similarity in both primary and tertiary structure in the nucleotide-binding\ regions to other G-proteins, such as p21-ras and EF-Tu.\ The

-12 group of G-proteins includes G12 and G13 proteins. An

-12-like protein has also been found in Drosophila. The functions of\ these proteins are unknown.\ \ \ GTP binding activity ; GO:0005525 \N G-protein coupled receptor protein signaling pathway ; GO:0007186 19204 IPR000465 Xeroderma pigmentosum (XP) [MEDLINE:94212451] is a human autosomal recessive disease,characterized by a high incidence of sunlight-induced skin cancer. People's\ skin cells with this condition are hypersensitive to ultraviolet light, due\ to defects in the incision step of DNA excision repair. There are a minimum of\ seven genetic complementation groups involved in this pathway: XP-A to XP-G.\ XP-A is the most severe form of the disease and is due to defects in a 30 Kd\ nuclear protein called XPA (or XPAC) [MEDLINE:92011785].\ The sequence of the XPA protein is conserved from higher eukaryotes\ \ \ \ [MEDLINE:92109732] to\ yeast (gene RAD14) [MEDLINE:92158051]. XPA is a hydrophilic protein of 247 to 296 amino-acid\ residues which has a C4-type zinc finger motif in its central section.\ \ damaged DNA binding activity ; GO:0003684 nucleus ; GO:0005634 nucleotide-excision repair ; GO:0006289 19205 IPR000466

In addition to their role in energy metabolism, purines (especially\ adenosine and adenine nucleotides) produce a wide range of pharmacological\ effects mediated by activation of cell surface receptors . Distinct\ receptors exist for adenosine. In the periphery, the main effects of\ adenosine include vasodilation, bronchoconstriction, immunosuppresion,\ inhibition of platelet aggregation, cardiac depression, stimulation of\ nociceptive afferents, inhibition of neurotransmitter release and\ inhibition of the release of other factors, e.g. hormones PUB00005868. In the CNS,\ adenosine exerts a pre- and post-synaptic depressant action, reducing motor\ activity, depressing respiration, inducing sleep and relieving anxiety. The\ physiological role of adenosine is thought to be to adjust energy demands\ in line with oxygen supply. Many of the clinical actions of methylxanthines\ are thought to be mediated through antagonism of adenosine receptors. Four\ subtypes of receptor have been identified, designated A1, A2A, A2B and A3.

\ \

A3 receptors are found in high levels in the testis, and in lower levels in\ the lung, kidney and heart . They are also found in low levels in regions\ of the CNS (including the cerebral cortex, striatum and olfactory bulb). The\ presence in high levels in the testis has led to the suggestion that it may\ play a role in reproduction PUB00005868. The A3 receptor inhibits adenylyl cyclase\ through a pertussis-toxin-sensitive G-protein, probably belonging to the\ Gi/Go class.

\ \ A3 adenosine receptor activity, G-protein coupled ; GO:0001613 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19203 IPR000465 Xeroderma pigmentosum (XP) [MEDLINE:94212451] is a human autosomal recessive disease,characterized by a high incidence of sunlight-induced skin cancer. People's\ skin cells with this condition are hypersensitive to ultraviolet light, due\ to defects in the incision step of DNA excision repair. There are a minimum of\ seven genetic complementation groups involved in this pathway: XP-A to XP-G.\ XP-A is the most severe form of the disease and is due to defects in a 30 Kd\ nuclear protein called XPA (or XPAC) [MEDLINE:92011785].\ The sequence of the XPA protein is conserved from higher eukaryotes\ \ \ \ [MEDLINE:92109732] to\ yeast (gene RAD14) [MEDLINE:92158051]. XPA is a hydrophilic protein of 247 to 296 amino-acid\ residues which has a C4-type zinc finger motif in its central section.\ \ damaged DNA binding activity ; GO:0003684 nucleus ; GO:0005634 nucleotide-excision repair ; GO:0006289 19201 IPR000462 A number of phosphatidyltransferases, which are all involved in phospholipidbiosynthesis and that share the property of catalyzing the displacement of CMP\ from a CDP-alcohol by a second alcohol with formation of a phosphodiester bond\ and concomitant breaking of a phosphoride anhydride bond share a conserved\ sequence region [MEDLINE:87165905], [MEDLINE:91161601].\ These enzymes are proteins of from 200 to 400 amino acid residues. The\ conserved region contains three aspartic acid residues and is located in the\ N-terminal section of the sequences.\ \ \N \N phospholipid biosynthesis ; GO:0008654 19202 IPR000463 The Fatty Acid-Binding Proteins (FABPs) are a family of proteins that areprincipally located in the cytosol and are characterised by the ability to\ bind to hydrophobic ligands, such as fatty acids, retinol, retinoic acid, \ bile salts and pigments [MEDLINE:88193123], [MEDLINE:91094810]. Recently, a number of family members have\ been identified that are secreted, such as gastrotropin and mammary-derived\ growth inhibitor. The family is implicated in general lipid metabolism,\ acting as intracellular transporters of hydrophobic metabolic intermediates\ and as carriers of lipids between membranes [MEDLINE:88193123], [MEDLINE:91094810], [MEDLINE:91094808]. \ The FABPs exhibit a high degree both of sequence and structural similarity.\ They are small, 12-18 kDa, soluble proteins composed of 110-160 residues. \ Their crystal structures show them to be 10-stranded anti-parallel

-\ barrels with a +1,+1 topology, which wrap around an internal cavity to \ form a ligand binding site [MEDLINE:91094810], [MEDLINE:91094808]. The anti-parallel

-barrel fold is also\ exploited by the lipocalins, which function similarly by binding small\ hydrophobic molecules. Similarity at the sequence level, however, is less\ obvious, being confined to a single short N-terminal motif.\ \ lipid binding activity ; GO:0008289 \N transport ; GO:0006810 19199 IPR000458 This family of trypanosomal proteins resemble vertebrate mucins.The protein consists of three regions. The N and C terminii are\ conserved between all members of the family, whereas the central\ region is not well conserved and contains a large number of\ threonine residues which can be glycosylated [MEDLINE:96025798].\ Indirect evidence suggested that these genes might encode the core\ protein of parasite mucins, glycoproteins that were proposed to be\ involved in the interaction with, and invasion of, mammalian host\ cells.\ \ \N \N \N 19200 IPR000460

Neuroligins constitute a family of brain neurone-specific membrane proteinswhose structural and biochemical characteristics are indicative of a role in\ heterotypic cell adhesion [MEDLINE:97467410]. Functionally, they bind to the extracellular\ domains of a subset of -neurexins in a Ca²⁺-dependent manner. They have\ been localised to the postsynaptic membranes of excitatory synapses [MEDLINE:99128369].\ This, together with the fact that their C-termini likely bind to PSD-95 (a\ PDZ-domain protein enriched in postsynaptic densities), suggests that they\ may be involved in the recruitment of proteins (such as receptors, ion\ channels and signal-transduction molecules) to synaptic sites of cell\ adhesion.

To date, three neuroligins have been reported, designated neuroligin 1-3 [MEDLINE:96162010].\ Multiple sequence alignment has revealed them to be highly similar, sharing\ overall ~52% identity. The similarity is distributed over the whole protein\ sequence, with the extracellular and transmembrane (TM) domains being more\ conserved than the cytoplasmic regions. They are composed of five domains:\ an N-terminal cleaved signal sequence; a large extracellular region \ homologous to esterases; a linker between the TM domain and the esterase \ homology domain that may be O-glycosylated; a single TM domain; and a\ cytoplasmic C-terminal tail. Further sequence comparisons place the\ neuroligins into the large family of esterase homology domain proteins, \ which includes thyroglobulin, acetylcholinesterase, and gliotactin,\ although the neuroligins are themselves catalytically inactive.

\ \ \N membrane ; GO:0016020 cell adhesion ; GO:0007155 19198 IPR000456

\ \ \

Ribosomal protein L17 is one of the proteins from the large ribosomal subunit. Bacterial L17 is a protein of 120 to 130 amino-acid residues while yeast YmL8 is\ twice as large (238 residues). The N-terminal half of YmL8 is colinear\ with the sequence of L17 from Escherichia coli.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 19197 IPR000455

\ \ \N integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19195 IPR000453 Chorismate synthase (EC: 4.2.3.5) catalyzes the last of the seven steps in the\ shikimate pathway which is used in prokaryotes, fungi and plants for the\ biosynthesis of aromatic amino acids. It catalyzes the 1,4-trans elimination\ of the phosphate group from 5-enolpyruvylshikimate-3-phosphate (EPSP) to form\ chorismate which can then be used in phenylalanine, tyrosine or tryptophan\ biosynthesis. Chorismate synthase requires the presence of a reduced flavin\ mononucleotide (FMNH2 or FADH2) for its activity.\ Chorismate synthase from various sources shows [MEDLINE:92042037],\ [MEDLINE:92114793] a high degree of sequence\ conservation. It is a protein of about 360 to 400 amino-acid residues.\ \ chorismate synthase activity ; GO:0004107 \N aromatic amino acid family biosynthesis ; GO:0009073 19196 IPR000454

\ \

\ \ \ \ \ \ \

\ \ \ hydrogen-transporting two-sector ATPase activity ; GO:0003936 membrane ; GO:0016020 proton transport ; GO:0015992 19193 IPR000451

Various studies (reviewed in [MEDLINE:94339489], [MEDLINE:92263472], PUB00001009, PUB00001009, [MEDLINE:90367115]) have allowed the characterization of afamily of eukaryotic transcription factors with basic impact on oncogenesis,\ embryonic development and differentiation including immune response and acute\ phase reaction. Members of this family include p50, p52, \ p65, c-Rel, v-Rrel, RelB, and the Drosophila proteins, Dorsal and Dif. \ Most of these transcription factors bind as homo- and heterodimers to the\ consensus a DNA sequence motif termed kappa-B according the\ first described factor-binding sequence motif located in the immunoglobulin\ kappa light chain enhancer region.

Proteins of this family appear to be regulated, at least in part, by\ subcellular localization whereby the inactive cytoplasmic forms become active\ transcriptional control proteins by translocation to the nucleus. Members of\ the Rel family share a highly conserved 300 amino acids domain termed Rel\ homology domain (RHD) located towards the amino terminus.\ For several proteins it has been demonstrated ([MEDLINE:94339489] and references therein)\ that the Rel homology domain includes:\

a DNA-binding domain, which binds to the consensus DNA sequence motif\ 5'-GGGRNNYYCC-3' (except for dorsal, which recognizes the related motif\ 5'-GRGAAAANCC-3');
a dimerization domain, which is located in the C-terminal part of the\ RHD;
a PKA phosphorylation site (seePDOC00004) (except in RelB);
a nuclear localization signal (NLS), which consists of a stretch of four\ or five basic residues.

DNA binding requires the entire RHD, by contrast with\ other eukaryotic and prokaryotic transcription factors, where much\ smaller DNA-binding domains confer full specificity and binding\ affinity for the target [MEDLINE:95132005]. The N-terminal \ region of the RHD includes a conserved cysteine that seems to be essential for DNA-binding in p50 [MEDLINE:94333807]. The unique C-terminal(not found in p50 or p52) is thought to be involved in gene activation and cytoplasmic anchoring functions.

The structure of the transcription factor NF-kB p50 homodimer bound to\ a palindromic kB site shows the RHD to fold into 2 distinct domains,\ similar to the -sandwich structure of the immunoglobulins [MEDLINE:95132005]. The \ p50 dimer envelops an undistorted B-DNA helix, making specific contacts\ along the 10bp kB recognition site, mainly through loops connecting\ secondary structure elements in both domains. The C-terminal domains\ form a dimerisation interface between -sheets using residues that\ are strongly conserved in the Rel family.

\ \ transcription factor activity ; GO:0003700 \N regulation of transcription, DNA-dependent ; GO:0006355 19194 IPR000452

The term opioid refers to a class of substance that produces its effects\ via the major classes of opioid receptor, termed mu, delta and kappa .\ In the CNS, the kappa opioid receptor is found in the cerebral cortex,\ substantia nigra, interpeduncular nucleus, striatum and hippocampus. In\ the periphery, it is found in the myenteric plexus of the guinea pig ileum,\ and it is also in certain smooth muscles, e.g. rabbit vas deferens PUB00005896.\ K-opioid receptors are believed to mediate analgesia, sedation, miosis and\ diuresis. Dynorphin is the most potent endogenous ligand.

\ \ kappa-opioid receptor activity ; GO:0004987 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19192 IPR000450

5HT1-like receptors were originally classified according to their nanomolar affinity for 5HT, susceptibility to antagonism by methiothepin and/or\ methysegide, resistance to antagonism by 5HT2 and 5HT3 antagonists, and\ high affinity for the agonist 5-carboxamidotryptamine . Five subtypes\ of 5HT1-like receptors have now been identified - these do not fit all the\ above criteria, and 5HT1C has been reclassified 5HT2C PUB00005889. All are linked\ to the inhibition of adenylyl cyclase, share a high degree of sequence\ similarity, and have overlapping pharmacological specificities.

The 5HT1F receptor has limited distribution in peripheral tissues and has\ been detected only in the uterus and mesentary. In the CNS, mRNA is\ present in the cerebral cortex, hippocampus, raphe and spinal cord.\ Elucidation of its physiological role will require development of selective\ ligands . There are no selective antagonists or agonists - the 5HT1D\ agonist sumatriptan has reasonable affinity PUB00005889.

\ \ \N integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19191 IPR000449

UBA domains are a commonly occurring sequence motif of approximately 45 amino acid residues that are found in diverse proteins involved in the ubiquitin/proteasome pathway, DNA excision-repair, and cell signaling via protein kinases [MEDLINE:97025177]. The human homologue of\ yeast Rad23A is one example of a nucleotide excision-repair protein that contains both an internal and a C-terminal UBA\ domain.

The solution structure of human Rad23A UBA(2) showed that the domain forms a compact three-helix bundle [MEDLINE:99061330]. Comparison of the structures of UBA(1) and UBA(2) reveals that both form\ very similar folds and have a conserved large hydrophobic surface patch which may be a common protein-interacting surface present in diverse UBA domains. Evidence that ubiquitin binds to UBA domains leads to the prediction that the hydrophobic surface patch of UBA domains interacts\ with the hydrophobic surface on the five-stranded -sheet of ubiquitin [MEDLINE:22075341].

\ \ \ \ \ \N \N \N 19190 IPR000448 The Nucleocapsid (N) Protein is said to have a 'tight' structure.The carboxyl end of the N-terminal domain possesses an RNA binding domain.\ Sequence alignments show 2 regions of reasonable conservation, \ approx. 64-103 and 201-329 [MEDLINE:98264477]. A whole functional protein is required \ for encapsidation to take place [MEDLINE:98162573].\ \ \N \N \N 19188 IPR000446 Lantibiotics are heavily-modified bacteriocin-like peptides from Gram-positive bacteria. They contain

-unsaturated amino acids\ (dehydroalanine and dehydrobutyrine) and lanthionine or 3-methyllanthionine\ rings (collectively known as thioether rings). There are 2 types of\ lantibiotic: type A (which include nisin, subtilin, epidermin, gallidermin\ and Pep5) are strongly cationic and bactericidal - nisin, subtilin and Pep5\ inhibit the growth of Gram-positive bacteria, probably by voltage-dependent\ pore formation in the cytoplasmic membrane, resulting in cellular efflux of\ electrolytes, amino acids and ATP; type B lantibiotics possess at most one\ positive charge and are not bactericidal. Nisin, subtilin, epidermin and\ gallidermin are believed to have evolved from a common ancestor [MEDLINE:89034093].\ The sequences of lantibiotics do not adopt regular secondary structures \ (i.e.,

-helices and

-strands) because of their constituent\ thioether rings (5 are found in nisin). Nevertheless, the rings may be\ important in providing rigid local structures, which could be essential\ for pore formation in membranes [MEDLINE:93077518]. Solution NMR indicates nisin to\ have a screw-shaped structure, which undergoes only limited change in\ passing to a membrane-mimicking environment.\ \ Gram-positive antibacterial peptide activity ; GO:0008224 \N defense response ; GO:0006952 19189 IPR000447 FAD-dependent glycerol-3-phosphate dehydrogenase (G3PDH; EC: 1.1.99.5) catalyzesthe conversion of glycerol-3-phosphate into dihydroxyacetone phosphate:\

\
 sn-glycerol-3-phosphate + acceptor = glycerone phosphate + reduced acceptor\

\ Insulin exposure often stimulates G3PDH\ activity [MEDLINE:95160670], [MEDLINE:97124854], and thus is key to reducing the effects of the disease\ diabetes. In obese people, where insulin resistance has been demonstrated,\ the amount of G3PDH has been shown to be correspondingly lower than\ that in normal weight people [MEDLINE:95160670].\ In bacteria [MEDLINE:91100269] it is associated with the utilization of glycerol coupled to\ respiration. In E.coli and H.influenzae , two isozymes are known: one expressed under\ anaerobic conditions (gene glpA) and one in aerobic conditions (gene glpD). In\ eukaryotes, a mitochondrial form of GPD participates in the glycerol phosphate\ shuttle in conjunction with an NAD-dependent cytoplasmic GPD (EC: 1.1.1.8) [MEDLINE:94078674] ,[MEDLINE:94237837]. This mechanism is responsible for\ the preservation of a redox balance [MEDLINE:96332489], [MEDLINE:98220299]. In this environment, the enzyme\ has been recorded to increase activity in the presence of calcium [MEDLINE:96154250].\ These enzymes are proteins of about 60 to 70 Kd which contain a probable\ FAD-binding domain in their N-terminal extremity. The mammalian enzyme differs\ from the bacterial or yeast proteins by having an EF-hand calcium-binding\ region (SeePDOC00018) in its C-terminal extremity.\ \ glycerol-3-phosphate dehydrogenase activity ; GO:0004368 glycerol-3-phosphate dehydrogenase complex ; GO:0009331 glycerol-3-phosphate metabolism ; GO:0006072 19184 IPR000440 This family contains chain 3 of the NADH-ubiquinone / plastoquinone oxidoreductaseEC: 1.6.5.3, which catalyses the following reactions:\

\
NADH + ubiquinone = NAD⁺ + ubiquinol\

\ \ \ \

\
NADH + plastoquinone = NAD⁺ + plastoquinol\

\ \ NADH dehydrogenase (ubiquinone) activity ; GO:0008137 \N oxidative phosphorylation, NADH to ubiquinone ; GO:0006120 19185 IPR000442 Group II introns use intron-encoded reverse transcriptase,maturase and DNA endonuclease activities for site-specific\ insertion into DNA [MEDLINE:98031910]. Although this type of intron is\ self splicing in vitro they require a maturase protein for\ splicing in vivo. It has been shown that a specific region\ of the aI2 intron is needed for the maturase function [MEDLINE:94301788].\ This region was found to be conserved in group II introns\ and called domain X [MEDLINE:94077696].\ \ \N \N RNA splicing ; GO:0008380 19186 IPR000443 Islet amyloid polypeptide (IAPP) (also known as diabetes-associated peptideor amylin) is a pancreatic islet hormone that is stored with insulin in

cell granules [MEDLINE:90290487]. IAPP has a propensity to form islet cell-disrupting \ amyloid deposits, and opposes the action of insulin in peripheral tissues; \ the peptide may therefore have a significant role in the development of Type\ 2 diabetes mellitus [MEDLINE:90290487]. It is thought that an intrinsic structural motif of\ IAPP, which only occurs in species that develop age-associated or Type 2 \ diabetes (e.g., humans and cats), is linked to its amyloidogenicity [MEDLINE:90290487].\ IAPP is a short, 37-residue peptide. The hormone selectively inhibits \ insulin-stimulated glucose utilisation and glycogen deposition in muscle,\ but does not affect adipocyte glucose metabolism. The sequences of amylin\ and the calcitonin gene-related peptides (CGRPs) show strong similarity:\ both peptides have a conserved N-terminal intramolecular disulphide bridge,\ and both have a C-terminal glycine, which suggests that the C-terminal\ residue of amylin, like that of CGRP, is amidated [MEDLINE:90099324].\ Near- and far-UV CD spectra of human

CGRP, analogues and fragments of\ CGRP, and amylin have been recorded in aqueous solution and in trifluoro-\ ethanol/water mixtures [MEDLINE:91248117]. The peptides were shown to contain significant\ amounts of

-helix in aqueous solution, this amount increasing upon \ addition of TFE. Amylin appears to contain less helix than CGRP [MEDLINE:91248117].\ \ hormone activity ; GO:0005179 extracellular ; GO:0005576 \N 19187 IPR000445 The HhH motif is an around 20 amino acids domain present in prokaryotic andeukaryotic non-sequence-specific DNA binding proteins [MEDLINE:95393988], [MEDLINE:99141217], [MEDLINE:99141601]. \ The HhH motif is similar to, but distinct from, the HtH motif. Both of these\ motifs have two helices connected by a short turn. In the HtH motif the second\ helix binds to DNA with the helix in the major groove. This allow the contact\ between specific base and residues throughout the protein. In the HhH motif\ the second helix does not protrude from the surface of the protein and\ therefore cannot lie in the major groove of the DNA. Crystallographic studies\ suggest that the interaction of the HhH domain with DNA is mediated by amino\ acids located in the strongly conserved loop (L-P-G-V) and at the N-terminal\ end of the second helix [MEDLINE:95393988]. This interaction could involve the formation of\ hydrogen bonds between protein backbone nitrogens and DNA phosphate groups\ [MEDLINE:96292250]. \ The structural difference between the HtH and HhH domains is reflected at the\ functional level: whereas the HtH domain, found primarily in gene regulatory\ proteins, binds DNA in a sequence specific manner, the HhH domain is rather\ found in proteins involved in enzymatic activities and binds DNA with no\ sequence specificity [MEDLINE:96292250].\ \ DNA binding activity ; GO:0003677 \N \N 19182 IPR000438 Fatty acid synthesis involves a set of reactions, commencing with carboxylation of acetyl-CoA to malonyl-CoA. This is an irreversible\ reaction, catalysed by the acetyl-CoA carboxylase complex (EC: 6.4.1.2); a\ heterohexamer of biotin carboxyl carrier protein, biotin carboxylase and two\ non-identical carboxyl transferase subunits (

and

) in a 2:2\ association [MEDLINE:92380982]. \ The reaction involves two steps: \

 Biotin carrier protein + ATP + HCO₃^- =  Carboxybiotin carrier protein + ADP + P_i

 Carboxybiotin carrier protein + Acetyl-CoA = Malonyl-CoA + Biotin carrier protein

\ In the first step, biotin carboxylase catalyses the carboxylation of the\ carrier protein to form an intermediate. Next, the transcarboxylase complex\ transfers the carboxyl group from the intermediate to acetyl-CoA forming\ malonyl-CoA.\ \ acetyl-CoA carboxylase activity ; GO:0003989 acetyl-CoA carboxylase complex ; GO:0009317 fatty acid biosynthesis ; GO:0006633 19183 IPR000439

\ \ \

A number of eukaryotic and archaebacterial ribosomal proteins can be grouped\ on the basis of sequence similarities [MEDLINE:95251669]. One of these families consists of:

\ \

Mammalian L15.

Insect L15.

Plant L15.

Yeast YL10 (L13) (Rp15r).

Archaebacterial L15e.

\ \

These proteins have about 200 amino acid residues.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 19181 IPR000437 In prokaryotes, membrane lipoproteins are synthesized with a precursor signalpeptide, which is cleaved by a specific lipoprotein signal peptidase (signal\ peptidase II). The peptidase recognizes a conserved sequence and cuts upstream\ of a cysteine residue to which a glyceride-fatty acid lipid is attached [MEDLINE:90361710]. The first archaebacterial protein known to be modified in such a fashion is halocyanin from Natrobacterium pharaonis\ \ \ \ [MEDLINE:94253046], a membrane associated copper-binding protein.\ \ \N \N \N 19180 IPR000436

Sushi domains are also known as Complement control protein (CCP) modules, or short consensus repeats (SCR), exist in a widevariety of complement and adhesion proteins. \ The structure is known for this domain,\ it is based on a -sandwich arrangement; one\ face made up of three -strands hydrogen-bonded to form a triple-stranded region at its\ centre and the other face formed from two separate -strands [MEDLINE:91278097].

\ \

CD21 (also called C3d receptor, CR2, Epstein Barr virus receptor or EBV-R) is the receptor for EBV and for C3d, C3dg and iC3b. Complement components may activate B cells through CD21. CD21 is part of a large signal-transduction complex that also involves CD19, CD81, and Leu13.

\ \

Some of the proteins in this group are responsible for the molecular basis of the blood group antigens, surface markers on the outside of the red blood cell membrane. Most of these markers are proteins, but some are carbohydrates attached to lipids or proteins [Reid M.E., Lomas-Francis C. The Blood Group Antigen FactsBook Academic Press, London / San Diego, (1997)]. Complement decay-accelerating factor (Antigen CD55) belongs to the Cromer blood group system and is associated with Cr(a), Dr(a), Es(a), Tc(a/b/c), Wd(a), WES(a/b), IFC and UMC antigens. Complement receptor type 1 (C3b/C4b receptor) (Antigen CD35) belongs to the Knops blood group system and is associated with Kn(a/b), McC(a), Sl(a) and Yk(a) antigens.

\ \ \

CD molecules are leucocyte antigens on cell surfaces. CD antigens nomenclature is updated at http://www.ncbi.nlm.nih.gov/PROW/guide/45277084.htm \

\ \ \ \N \N \N 19177 IPR000433 Skeletal muscle dystrophin is a 427 kDa protein thought to act as a link between the actin cytoskeleton and the extracellular matrix. Perturbations of the dystrophin-associated complex, for example, between dystrophin and the transmembrane glycoprotein

-dystroglycan, may lead to muscular dystrophy.\ Previously, the cysteine-rich region and first half of the carboxy-terminal domain of dystrophin were shown to interact with

-dystroglycan through a stretch of fifteen amino acids at the carboxy-terminus of

-dystroglycan. This region of dystrophin implicated in binding

-dystroglycan contains four modular protein domains: a WW domain, two putative Ca2+-binding EF-hand motifs, and a putative zinc finger ZZ domain [MEDLINE:96402609], [MEDLINE:99281760].\ \ \N \N \N 19178 IPR000434 Polycystin-1 is a large protein containing a variety of extracellular domains.Polycystic kidney diseases (PKD) are disorders characterised by large\ numbers of cysts distributed throughout grossly-enlarged kidneys. Cyst\ development is associated with impairment of kidney function, and\ ultimately kidney failure and death. \ PKD1 is the major locus of autosomal dominant polycystic kidney disease 1\ [MEDLINE:96202312]. PKD1 mRNA is widely expressed in adult tissue, with high levels in\ brain and moderate signal in kidney. The principal role of the PKD1\ protein, polycystin-1, is in maintaining renal epithelial differentiation\ and organisation from early foetal life. Polycystin-1 expression appears\ higher in epithelia, indicating that the disease does not result from\ complete loss of the protein [MEDLINE:96202312].\ \ \N \N \N 19179 IPR000435 Tektin heteropolymers form unique protofilaments of flagellar microtubules[MEDLINE:96180023]. The proteins are predicted to form extended rods composed of 2

-\ helical segments (~180 residues long) capable of forming coiled coils,\ interrupted by non-helical linkers [MEDLINE:96180023]. The 2 segments are similar in \ sequence, indicating a gene duplication event. Along each tektin rod, \ cysteine residues occur with a periodicity of ~8nm, coincident with the\ axial repeat of tubulin dimers in microtubules [MEDLINE:96180023]. It is proposed that\ the assembly of tektin heteropolymers produces filaments with repeats of\ 8, 16, 24, 32, 40, 48 and 96nm, generating the basis for the complex\ spatial arrangements of axonemal components [MEDLINE:96180023].\ \ \N microtubule ; GO:0005874 microtubule cytoskeleton organization and biogenesis ; GO:0000226 19174 IPR000430 Casein kinase II (CK-2) is a protein serine/threonine kinase whose activity isindependent of cyclic nucleotides and calcium. CK-2 phosphorylates many\ different proteins. The substrate specificity [MEDLINE:91002687] of this enzyme can be summarized as follows:\

Under comparable conditions Ser is favored over Thr.
An acidic residue (either Asp or Glu) must be present three residues from the C-terminal of the phosphate acceptor site.
Additional acidic residues in positions +1, +2, +4, and +5 increase the phosphorylation rate. Most physiological substrates have at least one acidic residue in these positions.
Asp is preferred to Glu as the provider of acidic determinants.
A basic residue at the N-terminal of the acceptor site decreases the phosphorylation rate, while an acidic one will increase it.

Note: No protein matches are shown due to the low specificity of this rule.

\ \ \N \N \N 19175 IPR000431

5-Hydroxytryptamine (or serotonin) is ubiquitous in plants and animals. It is an important neurotransmitter and local hormone in the CNS and instestine, and is implicated in a vast array of physiological and patho- physiological pathways PUB00005667. In the periphery, 5HT contracts a number of smooth muscles, and induces endothelium-dependent vasodilation through the formation of NO PUB00005667. It is a mediator of peristalsis, and may be involved in platelet aggregation and homeostasis. In the CNS, 5HT is believed to be involved in a wide range of functions, including the control of appetite, mood, anxiety, hallucinations, sleep, vomiting and pain perception PUB00005667. 5HT receptor ligands are of clinical use in the treatment of depression, migraine and post-operative vomiting. Numerous receptor subtypes have been classified according to their antagonist susceptibilities and their affinities for 5HT. Five 5HT1 subtypes and at least three 5HT2 subtypes have now been identified, in addition to subtypes 5HT3-7 PUB00005667. All share a high degree of sequence similarity, and have overlapping pharmacological specificities. The 5HT5 receptor has a similar pharmacology to the 5HT1D receptor. In the CNS, its mRNA is found in the cerebral cortex, hippocampus, habenula, olfactory bulb and granular layer of the cerbellum PUB00005667. There are no selective agonists, and the receptor does not appear to be linked to the adenylyl cyclase or phosphoinositide pathways PUB00005667.

\ \ \N integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19176 IPR000432

This is the C-terminal domain of proteins in the mutS family of DNA mismatch repair proteins and is found associated with MutS III domain (IPR007696).Yeast MSH3, bacterial proteins involved in DNA mismatch repair and the predicted protein product of the Rep-3 gene of mouse share extensive sequence similarity. \ This family of proteins is named after the Salmonella typhimurium MutS protein that is involved in replication repair and plays a role in preventing recombination between non-identical sequences [MEDLINE:93288013]. \ Human MSH has been implicated in non-polyposis colorectal carcinoma (HNPCC) and is a mismatch binding protein.\ Mismatch repair contributes to the overall fidelity of DNA replication [MEDLINE:87297443]. It\ involves the correction of mismatched base pairs that have been missed by the\ proofreading element of the DNA polymerase complex. The sequence of some\ proteins involved in mismatch repair in different organisms have been found to\ be evolutionary related [MEDLINE:91330898], [MEDLINE:93288013]. \ A region rich in glycine and negatively charged residues is found\ in the C-terminal section of these protein about 80 residues to the C-\ terminal of an ATP-binding site IPR007696/>.

\ \ ATP binding activity ; GO:0005524 \N mismatch repair ; GO:0006298 19173 IPR000429 Hirudin is a potent thrombin inhibitor secreted by the salivary glands ofthe medicinal leech, Hirudo medicinalis\ \ \ \ [MEDLINE:86149219]. It forms a stable non-covalent\ complex with

-thrombin, thereby abolishing its ability to cleave\ fibrinogen. The protein belongs to the hirudin family.\ The structure of hirudin has been solved by NMR [MEDLINE:89274194], and the structure \ of a recombinant hirudin-thrombin complex has been determined by X-ray\ crystallography to 2.3A [MEDLINE:90327074]. Hirudin consists of an N-terminal globular\ domain and an extended C-terminal domain. Residues 1-3 form a parallel

-\ strand with residues 214-217 of thrombin, the nitrogen atom of residue 1\ making a hydrogen bond with the Ser195 O gamma atom of the catalytic site.\ The C-terminal domain makes numerous electrostatic interactions with an\ anion-binding exosite of thrombin, while the last five residues are in\ a helical loop that forms many hydrophobic contacts [MEDLINE:90327074].\ \ serine protease inhibitor activity ; GO:0004867 \N \N 19170 IPR000426 The proteasome (or macropain) (EC: 3.4.25.1) [MEDLINE:93228587], [MEDLINE:89104406], [MEDLINE:92278429], [MEDLINE:95211199], [MEDLINE:97036935] is a eukaryotic andarchaebacterial multicatalytic proteinase complex that seems to be involved in\ an ATP/ubiquitin-dependent nonlysosomal proteolytic pathway. In eukaryotes the\ proteasome is composed of about 28 distinct subunits which form a highly\ ordered ring-shaped structure (20S ring) of about 700 Kd.\ Most proteasome subunits can be classified, on the basis on sequence\ similarities into two groups, A and B. Subunits that belong to the A-type\ group are proteins of from 210 to 290 amino acids that share a number of\ conserved sequence regions.\ \ \ 20S core proteasome complex ; GO:0005839\ proteasome endopeptidase activity ; GO:0004299 \N ubiquitin-dependent protein catabolism ; GO:0006511 19171 IPR000427

E2 is an early regulatory protein found in the dsDNA papillomaviruses. The viral genome is a 7.9-kb circular DNA that codes for at least eight early and two late (capsid) proteins. The products of the early genes E6 and E7 are oncoproteins that destabilize thecellular tumor suppressors p53 and pRB. The product of the E1 gene is a helicase necessary for viral DNA replication. The products\ of the E2 gene play key roles in the regulation of viral gene transcription and DNA replication. During early stages of viral infection, the\ E2 protein represses the transcription of the oncogenes E6 and E7, reintroduction of E2 into cervical cancer cell-lines leads to repression of E6/E7 transcription, stabilization of the tumor suppressor p53, and\ cell-cycle arrest at the G1 phase of the cell cycle. E2 can also induce apoptosis by a p53-independent mechanism.

E2 proteins from all papillomavirus strains bind a consensus palindromic sequence ACCgNNNNcGGT present in multiple copies in the regulatory region. It can either activate or repress transcription, depending on E2RE's position with regard to proximal promoter elements. Repression occurs by sterically hindering the assembly of the transcription initiation complex. \ The E2 protein is composed of a C-terminal DNA-binding\ domain and an N-terminal trans-activation domain. E2 exists in solution and binds to DNA as a dimer The E2-DNA binding domain forms a dimeric �-barrel, with each subunit contributing an\ anti-parallel 4-stranded �-sheet "half-barrel" [MEDLINE:93024918], PUB00010655. The topology of each subunit is �1-1-�2-�3-2-�4. Helix 1 is the recognition helix housing all of\ the amino acid residues involved in direct DNA sequence specification. Upon dimerization, strands �2 and �4 at the edges of each subunit participate in a\ continuous hydrogen-bonding network, which results in an 8-stranded �-barrel. The dimer interface is extensive, made up of hydrogen bonds\ between subunits and a substantial hydrophobic �-barrel core.

\ \ transcription factor activity ; GO:0003700 host cell nucleus ; GO:0042025 regulation of transcription, DNA-dependent ; GO:0006355 19172 IPR000428 Proteins that transport heavy metals in micro-organisms and mammals sharesimilarities in their sequences and structures. These proteins provide an\ important focus for research, some being involved in bacterial resistance\ to toxic metals, such as lead and cadmium, while others are involved in\ inherited human syndromes, such as Wilson and Menkes diseases [MEDLINE:94378325].\ A conserved 30-residue domain has been found in a number of these heavy\ metal transport or detoxification proteins [MEDLINE:94378325]. The domain, which has been\ termed Heavy-Metal-Associated (HMA), contains two conserved cysteines that\ are probably involved in metal binding. \ The HMA domain has been identified in the N-terminal regions of a variety\ of cation transporting ATPases, and in other ATPases such as fixI from \ Rhizobium meliloti; pacS from Synechococcus strain PCC 7942; Mycobacterium \ leprae ctpA and ctpB; and Escherichia coli hypothetical protein yhhO. In\ addition, the domain has been found in bacterial mercuric reductase; the\ copP copper-binding protein of Helicobacter pylori; and in bacterial\ mercuric transport proteins.\ The structure of the mercuric ion-binding protein MerP from Shigella\ flexneri has been determined. The fold has been classed as a ferredoxin-like

sandwich, having a

architecture,\ with the two

-helices overlaying a four-stranded anti-parallel

-\ sheet [MEDLINE:97332449]. Structural differences between the reduced and mercury-bound \ forms of merP are localised to the metal-binding loop containing the \ consensus sequence GMTCXXC, the two cysteines of which are involved in\ bi-coordination of Hg²⁺ [MEDLINE:97332449].\ \ copper ion binding activity ; GO:0005507 \N copper ion transport ; GO:0006825 19169 IPR000425

A number of transmembrane (TM) channel proteins can be grouped togetheron the basis of sequence similarities [MEDLINE:93314267], 2, [MEDLINE:91194556], [MEDLINE:91352825], [MEDLINE:95117132].

These include:\

Mammalian major intrinsic protein (MIP). MIP is the major component of lens fiber gap junctions.
Mammalian aquaporins [MEDLINE:95117132]. These proteins form water-specific channels that provide the plasma membranes of red cells and kidney proximal and collecting tubules with high permeability to water, thereby permitting water to move in the direction of an osmotic gradient.
Soybean nodulin-26, a major component of the peribacteroid membrane induced during nodulation in legume roots after Rhizobium infection.
Plants tonoplast intrinsic proteins (TIP). There are various isoforms of TIP: (seed), gamma, Rt (root), and Wsi (water-stress induced). These proteins may allow the diffusion of water, amino acids and/or peptides from the tonoplast interior to the cytoplasm..
Bacterial glycerol facilitator protein (gene glpF), which facilitates the movement of glycerol across the cytoplasmic membrane.
Salmonella typhimurium propanediol diffusion facilitator (gene pduF).
Yeast FPS1, a glycerol uptake/efflux facilitator protein.
Drosophila neurogenic protein 'big brain' (bib). This protein may mediate intercellular communication; it may functions by allowing the transport of certain molecules(s) and thereby sending a signal for an exodermal cell to become an epidermoblast instead of a neuroblast.
Yeast hypothetical protein YFL054c.
A hypothetical protein from the pepX region of Lactococcus lactis.

MIP family proteins are thought to contain 6 TM domains. Sequence analysis\ suggests that the proteins may have arisen through tandem, intragenic\ duplication from an ancestral protein that contained 3 TM domains [MEDLINE:91352825].

\ \ transporter activity ; GO:0005215 membrane ; GO:0016020 transport ; GO:0006810 19167 IPR000423 The flgH, flgI and fliF genes of Salmonella typhimurium encode the majorproteins for the L, P and M rings of the flagellar basal body [MEDLINE:89291739]. The\ sequences of these and of the flgJ gene have been determined, and the amino\ acid sequences of their products deduced [MEDLINE:89291739]. \ The flgJ gene, lies immediately adjacent to flgI and is the last gene of the\ flgB operon. It encodes a flagellar protein involved in hydrolysis\ of peptidoglycan [MEDLINE:99175455], whose\ deduced sequence is hydrophilic, and may correspond to a cytoplasmic \ protein [MEDLINE:89291739]. Several aspects of the DNA sequence of these genes and their\ surrounds suggest complex regulation of the flagellar gene system [MEDLINE:89291739].\ \ motor activity ; GO:0003774 flagellum (sensu Bacteria) ; GO:0009288 ciliary/flagellar motility ; GO:0001539 19168 IPR000424 The Escherichia coli single-strand binding protein [MEDLINE:91203755] (gene ssb), also knownas the helix-destabilizing protein, is a protein of 177 amino acids. It\ binds tightly, as a homotetramer, to single-stranded DNA (ss-DNA) and plays an\ important role in DNA replication, recombination and repair.\ Closely related variants of SSB are encoded in the genome of a variety of\ large self-transmissible plasmids. SSB has also been characterized in bacteria\ such as Proteus mirabilis or Serratia marcescens.\ Eukaryotic mitochondrial proteins that bind ss-DNA and are probably involved\ in mitochondrial DNA replication are structurally and evolutionary related to\ prokaryotic SSB.\ \ \N \N \N 19166 IPR000422 3,4-Dihydroxy-2-butanone 4-phosphate is biosynthesizedfrom ribulose 5-phosphate and serves as the biosynthetic\ precursor for the xylene ring of riboflavin [MEDLINE:97355137].\ It is sometimes found as a bifunctional enzyme with GTP cyclohydrolase II that catalyses the first committed step in the biosynthesis of riboflavin (IPR000926).\

No sequences with significant homology to DHBP synthase are found in the metazoa.

\ \ \ 3,4 dihydroxy-2-butanone-4-phosphate synthase activity ; GO:0008686\ \N \N vitamin B2 biosynthesis ; GO:0009231 19165 IPR000421 Blood coagulation factors V and VIII contain a C-terminal, twice repeated,domain of about 150 amino acids, which is called F5/8 type C, FA58C, or C1/C2-\ like domain. In the slime mold cell adhesion protein discoidin, a related\ domain, named discoidin I-like domain, DLD, or DS, has been found which shares\ a common C-terminal region of about 110 amino acids with the FA58C domain, but\ whose N-terminal 40 amino acids are much less conserved. Similar domains have\ been detected in other extracellular and membrane proteins [MEDLINE:86313665], [MEDLINE:93296201], [MEDLINE:96213908]\ In coagulation factors V and VIII the repeated domains compose part of a\ larger functional domain which promotes binding to anionic phospholipids on\ the surface of platelets and endothelial cells [MEDLINE:88150178]. The C-terminal domain of\ the second FA58C repeat (C2) of coagulation factor VIII has been shown to be\ responsible for phosphatidylserine-binding and essential for activity [MEDLINE:90248570], [MEDLINE:94253186].\ It forms an amphipathic

-helix, which binds to the membrane [MEDLINE:95200924].\ FA58C contains two conserved cysteines in most proteins, which link the\ extremities of the domain by a disulfide bond [MEDLINE:93277880], [MEDLINE:95338127], [MEDLINE:97008954]. A further disulfide\ bond is located near the C-terminal of the second FA58C domain in MFGM Q08431\ \ \ \ [MEDLINE:97008954].\

\ +------------------------------------------------------------------------+\ | +-+ |\ | | | |\ CxPLGxxQITASxxxxxRLxxxWxxxxWxxxxxxQGxxxxxxxxxxxxGNxxxxxxxxxxRxPxcxcLRxExGC\ \ 'C': conserved cysteine involved in a disulfide bond.\ 'c': cysteine involved in a disulfide bond in MFGM Q08431/>.\ 'x': any amino acid.\ upper case letters: conserved residues.\

\ \ \N \N cell adhesion ; GO:0007155 19164 IPR000420 A number of yeast cell wall glycoproteins are characterized by the presence oftandem repeats of a region of 18 to 19 residues [MEDLINE:93311116], [MEDLINE:97446433].\ \ \N \N \N 19162 IPR000417 Thiamine pyrophosphate (TPP), a required cofactor for many enzymes in the cell, is synthesised de novo in Salmonella typhimurium\ \ \ \ [MEDLINE:97386431]. Five kinase \ activities have been implicated in TPP synthesis, which involves joining \ a 4-methyl-5-(

-hydroxyethyl)thiazole (THZ) moiety and a 4-amino-5-\ hydroxymethyl-2-methylpyrimidine (HMP) moiety [MEDLINE:97386431], [MEDLINE:95074059]. \ THZ kinase (EC: 2.7.1.50) activity is involved in the salvage synthesis of \ TH-P from the thiazole: \

\
2-methyl-4-amino-5-hydroxymethylpyrimidine diphosphate + 4-4-methyl-5-(2-phosphonooxyethyl)-thiazole = pyrophosphate + thiamin monophosphate\

\ Hydroxyethylthiazole kinase expression is regulated at the mRNA level by\ intracellular thiamin pyrophosphate [MEDLINE:95074059].\ \ hydroxyethylthiazole kinase activity ; GO:0004417 \N thiamin biosynthesis ; GO:0009228 19160 IPR000415

This family is involved in the reduction of nitrogen containing compounds.Members of this family utilise FMN as a cofactor and are\ often found to be homodimers. Possible characteristics include Oxygen-insensitive NAD(P)H nitroreductase (FMN-dependent nitroreductase) (Dihydropteridine reductase) (EC: 1.6.99.7) and NADH dehydrogenase (EC: 1.6.99.3). A number of the proteins are described as oxidoreductases. They are primarily found in bacterial lineages though a number of eukaryotic homologs have been identified: Caenorhabditis elegans P34273, \ Drosophila melanogaster P34273/>\ \ \ \ Q9VTE7. \ There is no protein matches to this domain from phosynthetic eukaryotes.

\ \ \ oxidoreductase activity ; GO:0016491 \N electron transport ; GO:0006118 19161 IPR000416 VP4 is one of the two surface proteins of rotaviruses (the other one being VP7). VP4 is the rotavirus cell attachment protein in vitro and in vivo [MEDLINE:96099463]. The receptor-binding specificity of rotaviruses, via VP4, may be influenced by the associated VP7 protein [MEDLINE:96135238]. Positions 150 and 187 of VP4 play an important role in early rotavirus-cell interactions [MEDLINE:98227922].\ \ \N viral capsid ; GO:0019028 \N 19163 IPR000418

Transcription factors are protein molecules that bind to specific DNAsequences in the genome, resulting in the induction or inhibition of gene\ transcription [MEDLINE:90299137]. The ets oncogene is such a factor, possessing a region \ of 85-90 amino acids known as the ETS (erythroblast transformation specific) domain [MEDLINE:90299137], [MEDLINE:91071573]. This domain is rich in\ positively-charged and aromatic residues, and binds to purine-rich segments\ of DNA. The ETS domain has been identified in other transcription factors\ such as PU.1, human erg, human elf-1, human elk-1, GA binding protein, and\ a number of others [MEDLINE:90299137], [MEDLINE:91071573], [MEDLINE:93145976].\ It is generally localized at the C-terminus of the protein,\ with the exception of ELF-1, ELK-1, ELK-3, ELK-4 and ERF where it is found at\ the N-terminus.

NMR-analysis of the structure of the Ets domains revealed that it contains three -helixes (13)\ and four-stranded -sheets (14) arranged in the order alpha1-beta1-beta2-alpha2-alpha3-beta3-beta4 forming a\ winged helixturnhelix (wHTH) topology [MEDLINE:22448644]. The third -helix is\ responsive to contact to the major groove of the DNA. Different members of the Ets family proteins\ display distinct DNA binding specificities. The Ets domains and the flanking amino acid sequences\ of the proteins influence the binding affinity, and the alteration of a\ single amino acid in the Ets domain can change its DNA binding specificities.

Avian leukemia virus E26 is a replication defective retrovirus that induces a\ mixed erythroid/myeloid leukemia in chickens. E26 virus carries two distinct\ oncogenes, v-myb and v-ets. The ets portion of this oncogene is required for\ the induction of erythroblastosis. V-ets and c-ets-1, its cellular progenitor,\ have been shown [MEDLINE:90335804] to be nuclear DNA-binding proteins. Ets-1 differs slightly\ from v-ets at its carboxy-terminal region. In most species where it has been\ sequenced, c-ets-1 exists in various isoforms generated by alternative\ splicing and differential phosphorylation.

\ \ transcription factor activity ; GO:0003700 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 19159 IPR000413

\ Some

subunits are cleaved post-\ translationally to produce a heavy and a light chain linked by a disulfide\ bond [MEDLINE:87131067], [MEDLINE:90337122] . Integrin

chains share a conserved sequence which is found at\ the beginning of the cytoplasmic domain, just after the end of the\ transmembrane region. Within the N-terminal domain of

subunits, seven sequence repeats, each\ of approximately 60 amino acids, have been found [MEDLINE:88166645]. It has been predicted \ that these repeats assume the

-propeller fold. The domains contain seven \ four-stranded

-sheets arranged in a torus around a pseudosymmetry axis\ [MEDLINE:97144395]. Integrin ligands and a putative Mg²⁺ ion are predicted to bind to the\ upper face of the propeller, in a manner analogous to the way in which the\ trimeric G-protein

subunit (G

) (which also has a

-propeller\ fold) binds the G protein

subunit [MEDLINE:97144395].\ \ cell adhesion receptor activity ; GO:0004895 integrin complex ; GO:0008305 cell-matrix adhesion ; GO:0007160 19157 IPR000412

\ A number of bacterial transport systems have been found to contain integral\ membrane components that have similar sequences PUB00009997: these systems fit the\ characteristics of ATP-binding cassette transporters [MEDLINE:92065822]. The\ proteins form homo- or hetero-oligomeric channels, allowing ATP-mediated \ transport. Hydropathy analysis of the proteins has revealed the presence\ of 6 possible transmembrane regions. These proteins belong to family 2 of ABC transporters.\ \ ATP binding activity ; GO:0005524 membrane ; GO:0016020 transport ; GO:0006810 19158 IPR000413

\ Some

subunits are cleaved post-\ translationally to produce a heavy and a light chain linked by a disulfide\ bond [MEDLINE:87131067], [MEDLINE:90337122] . Integrin

chains share a conserved sequence which is found at\ the beginning of the cytoplasmic domain, just after the end of the\ transmembrane region. Within the N-terminal domain of

subunits, seven sequence repeats, each\ of approximately 60 amino acids, have been found [MEDLINE:88166645]. It has been predicted \ that these repeats assume the

-propeller fold. The domains contain seven \ four-stranded

subunit (G

) (which also has a

-propeller\ fold) binds the G protein

subunit [MEDLINE:97144395].\ \ cell adhesion receptor activity ; GO:0004895 integrin complex ; GO:0008305 cell-matrix adhesion ; GO:0007160 19156 IPR000411

\ \

Eukaryotic topoisomerase II exists as a homodimer; in bacteriophage T4 it \ consists of three heterologous subunits; in prokaryotes it exists as a tetramer\ of two subunits (two each of gyrA and gyrB); and in E.coli, a second type II\ topoisomerase, involved in chromosome segregation (topoisomerase IV),\ consists of two subunits (parC and parE). GyrB, parE, and the product of \ bacteriophage T4 gene 39, are all similar to the eukaryotic proteins.

Investigations have shown that full-length ParC and ParE are required to\ reconstitute Topo IV activity, while truncated ParC and ParE are inactive. Topo IV activity is inhibited by quinolone and coumarin antibiotics, \ but the concentrations required for 50% inhibition of activity are 3-30-fold\ higher than those required to inhibit DNA gyrase [MEDLINE:94043292]. Norfloxacin-induced \ DNA cleavage patterns of Topo IV and DNA gyrase are distinct, but over-\ lapping. The native forms of ParC and ParE are respectively a dimer and a\ monomer, while the active form of Topo IV is a heterotetramer, ParC2ParE2. \ It is thought that the inactivity of truncated forms of ParC and ParE might\ be attributed to their failure to form the heterotetramer [MEDLINE:94043292].

\ \ ATP binding activity ; GO:0005524 \N DNA unwinding ; GO:0006268 19152 IPR000406 The GDP dissociation inhibitor for rho proteins, rho GDI, regulates GDP/GTPexchange. The protein contains 204 amino acids, with a calculated Mr value\ of 23,421. Hydropathy analysis shows it to be largely hydrophilic, with a\ single hydrophobic region. Results of database searches suggest rho GDI is\ a novel protein, currently with no known homologue. \ The protein plays an important role in the activation of the superoxide\ (O2-)-generating NADPH oxidase of phagocytes. This process requires the\ interaction of membrane-associated cytochrome b559 with 3 cytosolic\ components: p47-phox, p67-phox and a heterodimer of the small G-protein\ p21rac1 and rho GDI [MEDLINE:94039069]. The association of p21rac and GDI inhibits\ dissociation of GDP from p21rac, thereby maintaining it in an inactive form.\ The proteins are attached via a lipid tail on p21rac that binds to the\ hydrophobic region of GDI [MEDLINE:96389574]. Dissociation of these proteins might be\ mediated by the release of lipids (e.g., arachidonate and phosphatidate)\ from membranes through the action of phospholipases [MEDLINE:96389574]. The lipids may then\ compete with the lipid tail on p21rac for the hydrophobic pocket on GDI.\ \ Rho GDP-dissociation inhibitor activity ; GO:0005094 cytoplasm ; GO:0005737 \N 19153 IPR000407

A number of nucleoside diphosphate and triphosphate hydrolases as well as someyet uncharacterized proteins have been found to belong to the same family [MEDLINE:96158985], [MEDLINE:96355615]. The uncharacterized proteins all seem to be membrane-bound.

\ \

CD molecules are leucocyte antigens on cell surfaces. CD antigens nomenclature is updated at http://www.ncbi.nlm.nih.gov/PROW/guide/45277084.htm \

\ \ \ \ \N \N \N 19154 IPR000408

The regulator of chromosome condensation (RCC1) [MEDLINE:93242659] is a eukaryotic proteinwhich binds to chromatin and interacts with ran, a nuclear GTP-binding\ protein IPR002041, to promote the loss of bound GDP and the uptake of\ fresh GTP, thus acting as a guanine-nucleotide dissociation stimulator (GDS).\ The interaction of RCC1 with ran probably plays an important role in the\ regulation of gene expression.

\ \

RCC1, known as PRP20 or SRM1 in yeast, pim1 in fission yeast and BJ1 in\ Drosophila, is a protein that contains seven tandem repeats of a domain of\ about 50 to 60 amino acids. As shown in the following schematic\ representation, the repeats make up the major part of the length of the\ protein. Outside the repeat region, there is just a small N-terminal domain of\ about 40 to 50 residues and, in the Drosophila protein only, a C-terminal\ domain of about 130 residues.

\
+----+-------+-------+-------+-------+-------+-------+-------+-------------+\
|N-t.|Rpt. 1 |Rpt. 2 |Rpt. 3 |Rpt. 4 |Rpt. 5 |Rpt. 6 |Rpt. 7 | C-terminal  |\
+----+-------+-------+-------+-------+-------+-------+-------+-------------+\

\ The RCC1-type of repeat is also found in the X-linked retinitis pigmentosa\ GTPase regulator [MEDLINE:96414315]. The RCC repeats form a

-propeller\ structure.\ \ \N \N \N 19155 IPR000409

The "beige" mouse is established as an animal model of Chediak-HigashiSyndrome (CHS) [MEDLINE:97051925]. The BEACH domain was described in the BEIGE protein\ (D1035670) and in the highly homologous CHS protein Q99698. It is also\ found in distantly related proteins like, for example, Q99698/>\ and Q92636 which are factor associated with neutral\ sphingomyelinase activation [MEDLINE:98281981].

\ \

The BEACH domain is usually followed by a serie of WD repeats (Q92636/>). The function of the BEACH domain is\ unknown.

\ \ \N \N \N 19148 IPR000402 The sodium pump (Na⁺,K⁺ ATPase), located in the plasma membrane of all animalcells [MEDLINE:91254051], is an heterotrimer of a catalytic subunit (

chain), a\ glycoprotein subunit of about 34 Kd (

chain) and a small hydrophobic\ protein of about 6 Kd. The

subunit seems [MEDLINE:90201633] to regulate, through the\ assembly of

heterodimers, the number of sodium pumps transported\ to the plasma membrane.\ Structurally the

subunit is composed of a charged cytoplasmic domain of\ about 35 residues, followed by a transmembrane region, and a large\ extracellular domain that contains three disulfide bonds and glycosylation\ sites. This structure is schematically represented in the figure below.\

\
                                +----+ +--+       +-----------+\
                                |    | |  |       |           |                                \
        xxxxxxxxxxxxxxxxxxxxxxxxCxxxxCxCxxCxxxxxxxCxxxxxxxxxxxCxxxx\
        |-Cyt-||TM||------------Extracellular---------------------|\
\
'C': conserved cysteine involved in a disulfide bond.\

\ \ sodium/potassium-exchanging ATPase activity ; GO:0005391 membrane ; GO:0016020 sodium ion transport ; GO:0006814 19150 IPR000404 Flaviviruses encode a single polyprotein. This is cleaved intothree structural and seven non-structural proteins. The NS4A\ protein is small and poorly conserved among the Flaviviruses.\ NS4A contains multiple hydrophobic potential membrane spanning\ regions [MEDLINE:91069238]. NS4A has only been found in cells infected by Kunjin\ virus\ \ \ \ [MEDLINE:89243193].\ \ \N \N \N 19151 IPR000405

The distribution of galanin receptors in the CNS corresponds to that of\ galanin, with high levels in locus coeruleus, spinal cord, hypothalamus,\ ventral hippocampus and striatum. In the periphery, galanin receptors are\ found in smooth muscle and in pancreas. They are also expressed in some\ hypothalamic tumours. Inhibition of adenylyl cyclase and Ca²⁺ channels,\ and activation of K⁺ channels is effected via a pertussis-toxin-sensitive\ G-protein, probably of the Gi/Go class PUB00005882.

\ \ galanin receptor activity ; GO:0004966 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19149 IPR000403

Phosphatidylinositol 3-kinase (PI3-kinase) (EC: 2.7.1.137) [MEDLINE:92354059] is an enzymethat phosphorylates phosphoinositides on the 3-hydroxyl group of the inositol\ ring. The three products of PI3-kinase - PI-3-P,\ PI-3,4-P(2) and PI-3,4,5-P(3) function as secondary messengers in cell signalling.\ Phosphatidylinositol 4-kinase (PI4-kinase) (EC: 2.7.1.67) [MEDLINE:94252322] is an enzyme\ that acts on phosphatidylinositol (PI) in the first committed step in the\ production of the secondary messenger inositol-1,4,5,-trisphosphate.

The PI3- and PI4-kinases share a well conserved domain at their C-terminal\ section; this domain seems to be distantly related to the catalytic domain of\ protein kinases [MEDLINE:93258821], [MEDLINE:22147077]. The catalytic domain of PI3K has the typical bilobal structure that is seen in other ATP-dependent\ kinases, with a small N-terminal lobe and a large C-terminal lobe. The core of this domain is the most conserved region of the PI3Ks.\ The ATP cofactor binds in the crevice formed by the N-and C-terminal lobes, a loop between two strands provides\ a hydrophobic pocket for binding of the adenine moiety, and a lysine residue interacts\ with the -phosphate. In contrast to protein kinases, the PI3K loop which interacts with the\ phosphates of the ATP and is known as the glycine-rich or P-loop, contains no glycine residues.\ Instead, contact with the ATP -phosphate is maintained through the side chain of a conserved serine\ residue.

\ \ \ inositol/phosphatidylinositol kinase activity ; GO:0004428 \N \N 19147 IPR000401

The recently-identified BRS-4 bombesin receptor subtype is found only in\ the brain, primarily in the cortex and forebrain, and at low levels in the\ midbrain. The relative rank potency of bombesin-like peptides for this\ receptor is [Phe13]bombesin > [Leu13]bombesin > GRP > neuromedin B PUB00005871.

\ \ bombesin receptor activity ; GO:0004946 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19141 IPR000397 Hsp33 is a molecular chaperone, distinguished from allother known chaperones by its mode of functional regulation.\ Its activity is redox regulated. Hsp33 is a cytoplasmically\ localized protein with highly reactive cysteines that\ respond quickly to changes in the redox environment.\ Oxidizing conditions like H₂O₂ cause disulfide bonds\ to form in Hsp33, a process that leads to the activation\ of its chaperone function [MEDLINE:99148267].\ \ \N \N \N 19142 IPR000398 Thymidylate synthase (EC: 2.1.1.45) [MEDLINE:80264003], [MEDLINE:90358505]catalyzes the reductive methylation\ of dUMP to dTMP with concomitant conversion of 5,10-methylenetetrahydrofolate\ to dihydrofolate:\

\
5,10-methylenetetrahydrofolate + dUMP = dihydrofolate + dTMP\

\ This provides the sole de novo pathway for \ production of dTMP and is the only enzyme in folate metabolism in which the\ 5,10-methylenetetrahydrofolate is oxidised during one-carbon transfer [MEDLINE:87094223].\ The enzyme is essential for regulating the balanced supply of the 4 DNA\ precursors in normal DNA replication: defects in the enzyme activity\ affecting the regulation process cause various biological and genetic\ abnormalities, such as thymineless death [MEDLINE:91056070]. The enzyme is an important target for certain chemotherapeutic drugs. \ Thymidylate synthase is an enzyme of about 30 to 35 Kd in most species except\ in protozoan and plants where it exists as a bifunctional enzyme that includes\ a dihydrofolate reductase domain [MEDLINE:87094223].\ A cysteine residue is involved in the catalytic mechanism (it covalently binds\ the 5,6-dihydro-dUMP intermediate). The sequence around the active site of\ this enzyme is conserved from phages to vertebrates.\ \ thymidylate synthase activity ; GO:0004799 \N dTMP biosynthesis ; GO:0006231 19143 IPR000399 A number of enzymes require thiamine pyrophosphate (TPP) (vitamin B1) as acofactor. It has been shown [MEDLINE:89211377] that some of these enzymes are structurally\ related.\ \ \N \N \N 19144 IPR000399 A number of enzymes require thiamine pyrophosphate (TPP) (vitamin B1) as acofactor. It has been shown [MEDLINE:89211377] that some of these enzymes are structurally\ related.\ \ \N \N \N 19145 IPR000399 A number of enzymes require thiamine pyrophosphate (TPP) (vitamin B1) as acofactor. It has been shown [MEDLINE:89211377] that some of these enzymes are structurally\ related.\ \ \N \N \N 19146 IPR000400

Glycoside hydrolase family 46 CAZY:GH_46).

\ \

Chitosanase enzymes catalyse the endohydrolysis\ of -1,4-linkages between N-acetyl-D-glucosamine and D-glucosamine\ residues in a partly acetylated chitosan.

\ \ chitosanase activity ; GO:0016977 extracellular ; GO:0005576 carbohydrate metabolism ; GO:0005975 19139 IPR000395 There are seven antigenically distinct forms of botulinum neurotoxin, designated A, B, C1, D, E, F and G. The seven neurotoxins are potent\ protein toxins that inhibit neurotransmitter release from peripheral\ cholinergic synapses [MEDLINE:90264400]. On binding to the neuronal synapses, the\ molecules are internalised and move by retrograde transport up the axon\ into the spinal cord, where they can move between post- and presynaptic\ neurons. The toxin inhibits neurotransmitter release by acting as a zinc\ endopeptidase that cleaves synaptic proteins\ such as synaptobrevins, syntaxin and SNAP-25 [MEDLINE:97052807].\ The protein toxins exist as disulphide-linked heterodimers of light and \ heavy chains. The light chain has the pharmacological activity, while the\ N- and C-termini of the heavy chain mediate channel formation and toxin\ binding [MEDLINE:90264400]. The light chain exhibits a high level of sequence similarity\ to tetanus toxin (TeTx). Alignment of all characterised neurotoxin sequences\ reveals the presence of highly conserved amino acid domains interspersed\ with amino acid tracts with little overall similarity. The most divergent\ region corresponds to the C-terminal extremity of each toxin, which may\ reflect differences in specificity of binding to neurone acceptor sites [MEDLINE:92174922].\ \ toxin activity ; GO:0015070 \N pathogenesis ; GO:0009405 19140 IPR000396 Cyclic-AMP phosphodiesterase (EC: 3.1.4.17) (PDE) catalyses the hydrolysis of cAMP to thecorresponding nucleoside 5' monophosphate. On the basis of sequence\ similarity, most PDEs can be grouped together [MEDLINE:90239855], but 2 enzymes lie apart\ from the main family and represent a second distinct class [MEDLINE:88065501]: this\ includes PDEs from Dictyostelium and yeast. \ There is, in the central part of these enzymes, a highly conserved region\ which contains three histidines.\ \ cAMP-specific phosphodiesterase activity ; GO:0004115 \N cAMP catabolism ; GO:0006198 19138 IPR000394 Sigma factors [MEDLINE:89024591] are bacterial transcription initiation factors that promotethe attachment of the core RNA polymerase to specific initiation sites and are\ then released. They alter the specificity of promoter recognition. Most\ bacteria express a multiplicity of sigma factors. Two of these factors, sigma-\ 70 (gene rpoD), generally known as the major or primary sigma factor, and\ sigma-54 (gene rpoN or ntrA) direct the transcription of a wide variety of\ genes. The other sigma factors, known as alternative sigma factors, are\ required for the transcription of specific subsets of genes.\ With regard to sequence similarity, sigma factors can be grouped into two\ classes: the sigma-54 and sigma-70 families. The sigma-70 family has many\ different sigma factors (see the relevant entry IPR000943). The sigma-54\ family consists exclusively of sigma-54 factor [MEDLINE:90198529], [MEDLINE:95020576] required for the\ transcription of promoters that have a characteristic -24 and -12 consensus\ recognition element but which are devoid of the typical -10,-35 sequences\ recognized by the major sigma factors. The sigma-54 factor is also\ characterized by its interaction with ATP-dependent positive regulatory\ proteins that bind to upstream activating sequences.\ Structurally sigma-54 factors consist of three distinct regions:\

A relatively well conserved N-terminal glutamine-rich region of about 50 residues that contains a potential leucine zipper motif.
A region of variable length which is not well conserved.
A well conserved C-terminal region of about 350 residues that contains a second potential leucine zipper, a potential DNA-binding 'helix-turn-helix' motif and a perfectly conserved octapeptide whose function is not known.

\ \ sigma factor activity ; GO:0016987 \N regulation of transcription, DNA-dependent ; GO:0006355 19137 IPR000393

Several pharmacologically distinct neuropeptide Y receptors have been\ characterised, designated NPY Y1-Y6. The Y5 receptor is a 456-residue\ protein with less than 35% overall identity to known Y-type receptors PUB00005893.\ The messenger RNA is found primarily in the central nervous system,\ including the paraventricular nucleus of the hypothalamus [MEDLINE:96317589]. Y5 receptors\ have been postulated to be the 'feeding' receptors, and may provide new\ approaches for the study and treatment of obesity and eating disorders [MEDLINE:96317589].

\ \ neuropeptide Y receptor activity ; GO:0004983 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19136 IPR000392 Nitrogen fixing bacteria possess a nitrogenase enzyme complex (EC: 1.18.6.1) [MEDLINE:89369712] thatcomprises 2 components, which catalyse the reduction of molecular nitrogen\ to ammonia [MEDLINE:84212258], PUB00003113: component I (nitrogenase MoFe protein or dinitrogenase)\ contains 2 molecules each of 2 non-identical subunits; component II \ (nitrogenase Fe protein or dinitrogenase reductase) is a homodimer, the\ monomer being coded for by the nifH gene PUB00003113. Component II has 2 ATP-binding\ domains and one 4Fe-4S cluster per homodimer: it supplies energy by ATP \ hydrolysis, and transfers electrons from reduced ferredoxin or flavodoxin\ to component I for the reduction of molecular nitrogen to ammonia [MEDLINE:91370837].\ There are a number of conserved regions in the sequence of these proteins: in\ the N-terminal section there is an ATP-binding site motif 'A' (P-loop) IPR001687 and in\ the central section there are two conserved cysteines which have been shown,\ in nifH, to be the ligands of the 4Fe-4S cluster.\ \ oxidoreductase activity ; GO:0016491 \N electron transport ; GO:0006118 19133 IPR000389 A number of small hydrophilic plant seed proteins are structurally related.These proteins contains from 83 to 153 amino acid residues and may play a role\ PUB00004531, PUB00004531 in equipping the seed for survival, maintaining a minimal level of\ hydration in the dry organism and preventing the denaturation of cytoplasmic\ components. They may also play a role during imbibition by controlling water\ uptake.\ \ \N \N \N 19134 IPR000390

Members of this family which have been characterized, belong to the small multidrug resistance (Smr) protein family and are integral membrane proteins. They confer resistance to a wide range of toxic compounds by removing them for the cells. The efflux is coupled to an influx of protons.An example is Escherichia coli mvrC P23895.

\ \ \N integral to membrane ; GO:0016021 \N 19135 IPR000391 The degradation of aromatic compounds by aerobic bacteria frequently begins with the dihydroxylation of the substrate by nonheme iron-containing dioxygenases. These enzymes consist of two or three soluble proteins that interact to form an electron-transport chain that transfers electrons from reduced nucleotides (NADH) via flavin and [2Fe-2S] redox centers to a terminal dioxygenase [MEDLINE:93073713].Aromatic-ring-hydroxylating dioxygenases oxidize aromatic hydrocarbons and related compounds to cis-arene diols. These enzymes utilize a mononuclear non-heme iron center to catalyze the addition of dioxygen to their respective substrates. \

Naphthalene 1,2-dioxygenase (NDO) from Pseudomonas sp has a domain structure and iron coordination of the Rieske domain is very similar to that of the cytochrome bc1 domain. The active-site iron center of one of the subunits is directly connected by hydrogen bonds through a single amino acid, Asp205, to the Rieske [2Fe-2S] center in a neighboring subunit. This may be the main route for electron transfer [MEDLINE:98298434].

\ \ enzyme activity ; GO:0003824 \N aromatic compound metabolism ; GO:0006725 19132 IPR000388

The sulphonylurea receptor (SUR) is a member of the ATP-binding cassette\ superfamily that associates with certain K⁺ channel inward rectifier\ subunits to form ATP-sensitive K⁺ channels (KATP channels) [MEDLINE:95232532], [MEDLINE:96072967].\ These are a family of K⁺ channels that are inhibited by intracellular ATP, which can\ couple metabolic state to cell excitability. Their presence on pancreatic\ islet cells allows the cells to function as metabolic sensors,\ regulating insulin release in relation to glucose metabolism. Furthermore,\ SUR is the site of action for the sulphonylurea oral hypoglycaemic agents\ that are used widely for the treatment of non-insulin dependent diabetes\ mellitus. When these agents bind to the sulphonlyurea receptor, they reduce\ KATP channel activity, stimulating insulin release.

\ \

As mentioned, SUR is a member of the ATP-binding cassette superfamily. This raises the possibility\ that SUR may transport some endogenous substance, as yet unidentified.\ Two closely related genes have been found to encode the sulphonylurea\ receptors, SUR1 and SUR2, there being three splice variants of the second\ form [MEDLINE:98346877]. They are thought to contain 13-17 transmembrane (TM) domains,\ with two potential nucleotide binding folds, and a large number of possible\ protein kinase A, or C phosphorylation sites. Comparison of the properties\ of cloned and wild-type KATP channels suggests that SUR1 may associate with\ the inward rectifier subunit Kir6.2 to form the pancreatic cell KATP\ channel. Splice variants of SUR2 (termed SUR2A and SUR2B) may form the\ cardiac and smooth muscle isoforms, respectively, again when combined with\ Kir 6.2. This co-assembly likely occurs with an obligate 4:4 stoichiometry,\ giving rise to an octameric channel.

\ \

Mutations in SUR genes have been characterised; these can result in\ truncations of the second predicted nucleotide binding fold, leading to\ persistent hyperinsulinemic hypoglycaemia of infancy, a rare familial\ disorder characterised by excessive, unregulated insulin secretion.

\ \ \ sulfonylurea receptor activity ; GO:0008281 membrane ; GO:0016020 potassium ion transport ; GO:0006813 19130 IPR000386 The haemagglutinin (HA) glycoprotein of influenza virus is a trimer containing three structurally distinct regions: a globular head of anti-parallel

-helical stalk; and a globular foot of\ anti-parallel

-sheet [MEDLINE:88232903], [MEDLINE:85012744], [MEDLINE:81123029], [MEDLINE:81123030]. \

\ \ \N \N viral infectious cycle ; GO:0019058 19131 IPR000387

This family includes two subfamilies: Ser/Thr (EC: 3.1.3.16) and Tyr dual specificity protein phosphatase and tyrosine specific protein phosphatase (EC: 3.1.3.48).

Ser/Thr and Tyr dual specificity phosphatases are a group of enzymes with both Ser/Thr (EC: 3.1.3.16) and tyrosine specific protein\ phosphatase (EC: 3.1.3.48) activity able to remove both the serine/threonine or tyrosine-bound phosphate group from a wide\ range of phosphoproteins, including a number of enzymes which have been phosphorylated\ under the action of a kinase.\ Dual specificity protein phosphatases (DSPs) regulate mitogenic signal transduction and control\ the cell cycle. Tyrosine specific protein phosphatases catalyze the removal of a phosphate group attached to a tyrosine residue. They are also very important in the control of cell growth, proliferation, differentiation and\ transformation.

\ \ \ protein phosphatase activity ; GO:0004721 \N protein amino acid dephosphorylation ; GO:0006470 19129 IPR000385 A number of proteins involved in the biosynthesis of metallo cofactors havebeen shown [MEDLINE:96172783], [MEDLINE:95197640] to be evolutionary related.\ Members of this family share, in their N-terminal region, a conserved domain that\ contains three cysteines. In moaA, these cysteines have been shown [MEDLINE:96172783] to be\ important for the biological activity. They could be involved in the binding of\ an iron-sulfur cluster.\ \ enzyme activity ; GO:0003824 \N \N 19128 IPR000383

Lactococcus X-Pro dipeptidyl-peptidase proteins belong to the S15 family of\ the carboxypeptidase (SC) clan [MEDLINE:95147689], See Protease Database http://merops.sanger.ac.uk/merops.htm, Merops id=S15.001]. These proteins, which have similar\ specificity to mammalian dipeptidyl-peptidase IV, cleave Xaa-Pro-releasing\ N-terminal dipeptides. The penultimate residue must be proline.\ In Lactococcus, the proteins exist as cytoplasmic homodimers [MEDLINE:95147689].

\ \ Xaa-Pro aminopeptidase activity ; GO:0008451 \N proteolysis and peptidolysis ; GO:0006508 19127 IPR000382 The nucleotide sequence for the RNA of potato leafroll luteovirus (PLRV) hasbeen determined [MEDLINE:89279282], [MEDLINE:89171329]. The sequence contains six large open reading frames\ (ORFs). The 5' coding region encodes two polypeptides of 28K and 70K, which \ overlap in different reading frames; it is suggested that the third ORF in \ the 5' block is translated by frameshift readthrough near the end of the 70K \ protein, yielding a 118K polypeptide [MEDLINE:89279282]. Segments of the predicted amino\ acid sequences of these ORFs resemble those of known viral RNA polymerases, \ ATP-binding proteins and viral genome-linked proteins.\ The nucleotide sequence of the genomic RNA of beet western yellow virus\ (BWYV) has been determined [MEDLINE:89057523]. The sequence contains six long ORFs. A \ cluster of three of these ORFs, including the coat protein cistron, display\ extensive amino acid sequence similarity to corresponding ORFs of a second\ luteovirus, the PAV isolate of barley yellow dwarf virus (BYDV)\ \ \ \ [MEDLINE:89057523].\ \ \N \N \N 19126 IPR000381

Inhibin has two isoforms, A and B, with the same subunit but different subunits. Inhibin A is a dimer of and A subunits, inhibin B is a dimer of and B subunits.

Activin A is a dimer of A subunits, activin AB is a dimer of A and B chains.

Genes coding for mouse activin C and E are closely linked and exhibit a liver-specific expression pattern in adult tissues.

\ \ hormone activity ; GO:0005179 extracellular ; GO:0005576 cell growth and/or maintenance ; GO:0008151 19123 IPR000379 This profile covers the active site serine of a wide variety of enzymes including esterases, lipases, pepitdases etc. Proteolytic enzymes that exploit serine in their catalytic activity are ubiquitous, being found in viruses, bacteria and eukaryotes.\ enzyme activity ; GO:0003824 \N \N 19124 IPR000380 Prokaryotic topoisomerase I (EC: 5.99.1.2) [MEDLINE:95292060], PUB00001074, PUB00001074, otherwise known as relaxing enzyme, untwisting enzyme or swivelase, catalyses the ATP-independent breakage of single-\ stranded DNA, followed by passage and rejoining of another single-stranded \ DNA region [MEDLINE:94159070]. This reaction brings about the conversion of one topological\ isomer of DNA into another: e.g., relaxation of superhelical turns; \ interconversion of simple and knotted rings of single-stranded DNA; and\ intertwisting of single-stranded rings of complementary sequences [MEDLINE:94159070], [MEDLINE:90036864].\ Prokaryotic topoisomerase I folds in an unusual way to give 4 distinct\ domains, enclosing a hole large enough to accommodate a double-stranded DNA\ segment [MEDLINE:94159070]. A tyrosine at the active site, which lies at the interface of\ 2 domains, is involved in transient breakage of a DNA strand, and formation\ of a covalent protein-DNA intermediate [MEDLINE:94159070]. The structure reveals a\ plausible mechanism by which this and related enzymes could catalyse the \ passage of one DNA strand through a transient break in another strand [MEDLINE:94159070].\ Escherichia coli contains 2 type I topoisomerases: topoisomerases I and III [MEDLINE:90036864].\ Topoisomerase III can be purified as a potent concatenase, but its role in\ DNA metabolism is still unclear [MEDLINE:90036864]. Yeast, a eukaryote, also contains a\ topoisomerase, which is similar in sequence and function to the prokaryotic\ type I topoisomerases [MEDLINE:89324087].\ \ DNA topoisomerase type I activity ; GO:0003917 \N DNA unwinding ; GO:0006268 19125 IPR000380 Prokaryotic topoisomerase I (EC: 5.99.1.2) [MEDLINE:95292060], PUB00001074, PUB00001074, otherwise known as relaxing enzyme, untwisting enzyme or swivelase, catalyses the ATP-independent breakage of single-\ stranded DNA, followed by passage and rejoining of another single-stranded \ DNA region [MEDLINE:94159070]. This reaction brings about the conversion of one topological\ isomer of DNA into another: e.g., relaxation of superhelical turns; \ interconversion of simple and knotted rings of single-stranded DNA; and\ intertwisting of single-stranded rings of complementary sequences [MEDLINE:94159070], [MEDLINE:90036864].\ Prokaryotic topoisomerase I folds in an unusual way to give 4 distinct\ domains, enclosing a hole large enough to accommodate a double-stranded DNA\ segment [MEDLINE:94159070]. A tyrosine at the active site, which lies at the interface of\ 2 domains, is involved in transient breakage of a DNA strand, and formation\ of a covalent protein-DNA intermediate [MEDLINE:94159070]. The structure reveals a\ plausible mechanism by which this and related enzymes could catalyse the \ passage of one DNA strand through a transient break in another strand [MEDLINE:94159070].\ Escherichia coli contains 2 type I topoisomerases: topoisomerases I and III [MEDLINE:90036864].\ Topoisomerase III can be purified as a potent concatenase, but its role in\ DNA metabolism is still unclear [MEDLINE:90036864]. Yeast, a eukaryote, also contains a\ topoisomerase, which is similar in sequence and function to the prokaryotic\ type I topoisomerases [MEDLINE:89324087].\ \ DNA topoisomerase type I activity ; GO:0003917 \N DNA unwinding ; GO:0006268 19122 IPR000378

Opsins are the photoreceptors of animal retinas. Vertebrate rhodopsinis found in rod cells and mediates scotopic vision; red, green and blue\ opsins are found in cone cells and mediate photopic vision. Red-sensitive\ opsin has an absorption maximum at 560nm; its deficiency results in\ protanopia colour blindness. Green-sensitive opsin has an absorption\ maximum at 530nm; its deficiency results in deuteranopia colour blindness.\ The ratio of green and red cones to rods is ~1:30 PUB00005667.

\ \ rhodopsin-like receptor activity ; GO:0001584 integral to membrane ; GO:0016021 phototransduction ; GO:0007602 19121 IPR000377

\ \ \N integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19117 IPR000372

The leucine-rich repeat (see IPR001611) is a recently characterized structural motif used in molecular recognition processes as diverse as signal transduction, cell adhesion, cell\ development, DNA repair and RNA processing. All proteins containing these repeats are\ thought to be involved in protein-protein interactions [MEDLINE:95117131], [MEDLINE:95183144]. Leucine-rich repeats are often flanked\ by cysteine rich domains, the N-terminal domain (this one) and the C-terminal domain IPR001611/>.

\ \

CD molecules are leucocyte antigens on cell surfaces. CD antigens nomenclature is updated at http://www.ncbi.nlm.nih.gov/PROW/guide/45277084.htm \

\ \ \ \N \N \N 19118 IPR000374 Phosphatidate cytidylyltransferase (EC: 2.7.7.41) [MEDLINE:86008269], [MEDLINE:96132809], [MEDLINE:97238893] (also known as CDP-diacylglycerol synthase) (CDS) is the enzyme that catalyzes the synthesis of\ CDP-diacylglycerol from CTP and phosphatidate (PA):\

\
CTP + phosphatidate = diphosphate + CDP-diacylglycerol\

\ CDP-diacylglycerol is an\ important branch point intermediate in both prokaryotic and eukaryotic\ organisms. CDS is a membrane-bound enzyme.\ \ phosphatidate cytidylyltransferase activity ; GO:0004605 membrane ; GO:0016020 phospholipid biosynthesis ; GO:0008654 19119 IPR000375 Dynamin is a microtubule-associated force-producing protein of 100 Kdwhich is involved in the production of microtubule bundles. At the N terminus of\ dynamin is a GTPase domain (see IPR001401),\ and at the C-terminus is a PH domain (see IPR001401/>).\ Between these two domains lies a central region of unknown function.\ \ GTP binding activity ; GO:0005525 \N \N 19120 IPR000376

DP receptors have a limited distribution. They mediate relaxation in\ vascular, gastrointestinal and uterine smooth muscle in human and some\ other species; they inhibit platelet activation, and modify release of\ hypothalamic and pituitary hormones. The receptors activate adenylyl\ cyclase through Gs PUB00005901.

\ \ prostaglandin D receptor activity ; GO:0004956 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19115 IPR000370

IP receptors induce relaxation in a range of smooth muscles, including\ blood vessels, and potently inhibit platelet activation. The receptors\ activate adenylyl cyclase through G-proteins PUB00005901.

\ \ prostaglandin I receptor activity ; GO:0004959 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19116 IPR000371

In addition to their role in energy metabolism, purines (especially\ adenosine and adenine nucleotides) produce a wide range of pharmacological\ effects mediated by activation of cell surface receptors . ATP is a\ co-transmitter in sympathetic nerves in the autonomic nervous system,\ where it exerts an important physiological role in the regulation of\ smooth muscle activity, stimulating relaxation of intestinal smooth muscle\ and contraction of the bladder. Receptors for adenine nucleotides are\ involved in a number of other physiological pathways, including stimulation\ of platelet activation by ADP, which is released from the vascular\ endothelium following injury. ATP has excitatory effects in the CNS .\ Distinct receptors exist for adenosine. The main effects of adenosine in\ the periphery include vasodilation, bronchoconstriction, immunosuppression,\ inhibition of platelet aggregation, cardiac depression, stimulation of\ nociceptive afferents, inhibition of neurotransmitter release, and\ inhibition of the release of hormones . In the CNS, adenosine exerts a\ pre- and post-synaptic depressant action, reducing motor activity,\ depressing respiration, inducing sleep and relieving anxiety. The\ physiological role of adenosine is believed to be to adjust energy demands\ in line with oxygen supply PUB00005868.

Purinoceptors have been classified as P1 or P2, depending on their\ preference for adenosine or adenine nucleotides respectively. Adenosine\ receptors (P1 purinoceptors) are characterised by their affinity for\ adenosine and by the ability of methylxanthines to act as antagonists PUB00005868.\ Adenosine has very low affinity for P2 purinoceptors.

\ \

P2Y3 is a protein of 328 amino acids that has been confirmed to be a\ member of the metabotropic purinoceptor family PUB00005868. When expressed in\ the human T cell line Jurkat, P2Y3 mediates transient increases in intracellular Ca²⁺ in response to various nucleotides. The receptor transcript\ is expressed in brain, spinal cord, kidney and lung, and is highly abundant\ in the spleen but not in other peripheral tissues [MEDLINE:96319774]. P2Y3 is thus a\ previously unknown P2 purinoceptor subtype with a preference for nucleoside\ diphosphates [MEDLINE:96319774].

\
UDP-glucose + D-fructose = UDP + sucrose\

\ This family includes the bulk of the sucrose synthase\ protein. However the carboxyl terminal region of the\ sucrose synthases belongs to the glycosyl transferase\ family IPR001296. This enzyme is found mainly in plants\ but also appears in bacteria.\ \ \N \N sucrose metabolism ; GO:0005985 19114 IPR000369

\ \

Ion channels exhibit a high degree of diversity, varying both in their\ electrophysiological and pharmacological properties PUB00009384, [MEDLINE:92042148]. The slow\ voltage-gated potassium channels (Isk) are membrane proteins that induce\ selective potassium permeation by membrane depolarisation. It is thought\ that they may act as discrete potassium-conducting ion channels, or\ alternatively that they may subserve as a modularity protein that activates\ endogenous potassium channels.

The Isk channel protein is considerably smaller than the sodium, potassium\ or calcium channel proteins, and contains only a single putative transmembrane domain. The potassium current elicited by this protein is also\ unusually slow in activation and deactivation after electrical polarisation.\ Such characteristics differ from those of conventional ion channels,\ resembling more those of simple channel-forming peptide ionophores and\ synthetic amphiphilic peptides [MEDLINE:89058617], [MEDLINE:92042148].

\ \ \ voltage-gated potassium channel activity ; GO:0005249 membrane ; GO:0016020 ion transport ; GO:0006811 19111 IPR000366

\ \ \ mating-type factor pheromone receptor activity ; GO:0004932 membrane ; GO:0016020 \N 19112 IPR000367

Guanine nucleotide binding proteins (G-proteins) are a family of membrane-associated proteins that couple extracellularly-activated integral-membrane\ receptors to intracellular effectors, such as ion channels and enzymes that\ vary the concentration of second messenger molecules [MEDLINE:92366949], [MEDLINE:91354032], [MEDLINE:91227903]. G-proteins are\ composed of 3 subunits (, and gamma) which, in the resting state,\ associate as a trimer at the inner face of the plasma membrane. The subunit has a molecule of guanosine diphosphate (GDP) bound to it:\ stimulation of the G-protein by an activated receptor leads to its exchange\ for GTP (guanosine triphosphate). This results in the separation of the from the and gamma subunits, which always remain tightly\ associated as a dimer. Both the and -gamma subunits are then able\ to interact with effectors, either individually or in a cooperative manner.\ The intrinsic GTPase activity of the subunit hydrolyses the bound GTP\ to GDP. This returns the subunit to its inactive conformation and\ allows it to reassociate with the -gamma subunit, thus restoring the\ system to its resting state.

G-protein subunits are 350-400 amino acids in length and have\ molecular weights in the range 40-45 kDa. Seventeen distinct types of subunit have been identified in mammals. These fall into 4 main \ groups on the basis of both sequence similarity and function: -S, -Q, -I and -12 [MEDLINE:91227903]. Many subunits are substrates for\ ADP-ribosylation by cholera or pertussis toxins. They are often N-terminally\ acylated, usually with myristate and/or palmitoylate, and these fatty acid\ modifications are probably important for membrane association and high-\ affinity interactions with other proteins. The atomic structure of the subunit of the G-protein involved in mammalian vision, transducin,\ has been elucidated in both GTP- and GDB-bound forms, and shows considerable\ similarity in both primary and tertiary structure in the nucleotide-binding\ regions to other G-proteins, such as p21-ras and EF-Tu.\ The G-protein -S class couple receptors, such as the -adrenergic\ receptor, to the effector enzyme adenylyl cyclase, which produces the\ intracellular second messenger cyclic adenosine monophosphate (cAMP).\ Alpha-S is found in a variety of tissues in 4 different splice forms (1-4),\ the difference caused by the inclusion or deletion of 15 or 16 residues\ after the 71st amino acid - the only observed functional change is a higher\ rate of GDP dissociation in the longer variants. Alpha-olf is a specialised\ form of -S expressed in olfactory neuroepithelial cells, brain and\ pancreas. In addition to its interaction with adenylyl cyclase, -S\ also activates ion channels, such as atrial voltage gated sodium channels\ and dihydropyridine-sensitive calcium channels in skeletal muscle.

\ \ GTP binding activity ; GO:0005525 \N G-protein coupled receptor protein signaling pathway ; GO:0007186 19110 IPR000363

The pharmacological profile of the -1A receptor closely resembles that\ of the -1D receptor . It appears to be widely distributed in the rat,\ with high levels in peripheral tissues (e.g., vas deferens) and in the CNS\ (e.g., hippocampus, cerebral cortex and brainstem). The receptor is coupled\ to the phosphoinositide pathway through a pertussis-toxin-insensitive\ G-protein, probably of the Gq/G11 class. It is thought to stimulate\ direct entry of extracellular calcium PUB00005869.

\ \ alpha1-adrenergic receptor activity ; GO:0004937 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19108 IPR000361

This family includes HesB which may be involved in nitrogen fixation; the hesB gene is expressed only under nitrogen fixation conditions [MEDLINE:99231861]. Other members of this family include various hypothetical proteins that also contain the NifU-like domain (IPR001075.

\ molecular_function unknown ; GO:0005554 \N \N 19109 IPR000362

A number of enzymes, belonging to the lyase class, for which fumarate is asubstrate, have been shown \ to share a short conserved sequence around a\ methionine which is probably involved in the catalytic activity of this type\ of enzymes [MEDLINE:88193096], PUB00001722. The following are examples of members of this family:

\ \ \

P32427 (PCAB_PSEPU): 3-carboxymuconate lactonizing enzyme, EC: 5.5.1.2 (3-carboxy-cis,cis-muconate cycloisomerase), an enzyme involved in aromatic acids catabolism PUB00001722.

\ \

P24057 (CRD1_ANAPL): Delta-crystallin shares around 90% sequence identity with arginosuccinate lyase,\ showing that it is an example of a 'hijacked' enzyme - accumulated mutations have, however, rendered the\ protein enzymatically inactive.

\ \

P05042 (FUMC_ECOLI): Class I Fumarase enzyme, EC: 4.2.1.2 (fumarate hydratase), which catalyzes the\ reversible hydration of fumarate to L-malate. Class I enzymes are thermolabile dimeric enzymes (as for\ example: Escherichia coli fumC).

\ \

P04424 (ARLY_HUMAN): Arginosuccinase, EC: 4.3.2.1 (argininosuccinate lyase), which catalyzes the\ formation of arginine and fumarate from argininosuccinate, the last step in the biosynthesis of arginine.

\ \

P04422 (ASPA_ECOLI): Aspartate ammonia-lyase, EC: 4.3.1.1 (aspartase), which catalyzes the reversible\ conversion of aspartate to fumarate and ammonia. This reaction is analogous to that catalyzed by fumarase,\ except that ammonia rather than water is involved in the trans-elimination reaction.

\ \

P00923 (FUMA_ECOLI): class II Fumarase enzyme, EC: 4.2.1.2, are thermostable and tetrameric and are\ found in prokaryotes (as for example: Escherichia coli fumA and fumB) as well as in eukaryotes. The\ sequence of the two classes of fumarases are not closely related.

\ \

P25739 (PUR8_ECOLI): Adenylosuccinase, EC: 4.3.2.2 (adenylosuccinate lyase) [MEDLINE:92245079], which catalyzes the\ eighth step in the de novo biosynthesis of purines, the formation of\ 5'-phosphoribosyl-5-amino-4-imidazolecarboxamide and fumarate from 1-(5-\ phosphoribosyl)-4-(N-succino-carboxamide). That enzyme can also catalyze the formation of fumarate and\ AMP from adenylosuccinate.

\ \ enzyme activity ; GO:0003824 \N \N 19107 IPR000358

Ribonucleotide reductase (EC: 1.17.4.1) [MEDLINE:88225729], [MEDLINE:93289354] catalyzes the reductive synthesisof deoxyribonucleotides from their corresponding ribonucleotides:\

\
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H₂O = ribonucleoside diphosphate + reduced thioredoxin\

\ It provides the precursors necessary for DNA synthesis. RNRs divide into three classes on the basis of their metallocofactor usage. Class I RNRs, found in eukaryotes, bacteria, bacteriophage and viruses, use a\ diiron-tyrosyl radical, Class II RNRs, found in bacteria,\ bacteriophage, algae and archaea, use coenzyme B12\ (adenosylcobalamin, AdoCbl). Class III RNRs, found in\ anaerobic bacteria and bacteriophage, use an FeS cluster and\ S-adenosylmethionine to generate a glycyl radical. Many\ organisms have more than one class of RNR present in their\ genomes.

Ribonucleotide reductase is an\ oligomeric enzyme composed of a large subunit (700 to 1000 residues) and a\ small subunit (300 to 400 residues) - class II RNRs are less complex,\ using the small molecule B12 in place of the small chain [MEDLINE:21912423].\ The small chain binds two iron atoms [MEDLINE:90272001] (three Glu, one Asp, and two His are\ involved in metal binding) and contains an active site tyrosine radical. The\ regions of the sequence that contain the metal-binding residues and the active\ site tyrosine are conserved in ribonucleotide reductase small chain from\ prokaryotes, eukaryotes and viruses.\ We have selected one of these regions as a signature pattern. It contains the\ active site residue as well as a glutamate and a histidine involved in the\ binding of iron.

\ \ ribonucleoside-diphosphate reductase activity ; GO:0004748 \N deoxyribonucleoside diphosphate metabolism ; GO:0009186 19105 IPR000356

ATP and UTP stimulate phophoinositide metabolism in some tissues via a\ novel receptor, termed a nucleotide receptor or P2U receptor.

\ \ purinergic nucleotide receptor activity, G-protein coupled ; GO:0045028 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19106 IPR000357

The HEAT repeat is a tandemly repeated, 37-47 amino acid long moduleoccurring in a number of cytoplasmic proteins, including the four\ name-giving proteins huntingtin, elongation factor 3 (EF3), the 65 Kd regulatory subunit of protein phosphatase 2A (PP2A) and the\ yeast PI3-kinase TOR1 [MEDLINE:96024640]. Arrays of HEAT repeats consists of 3 to 36\ units forming a rod-like helical structure and appear to function as \ protein-protein interaction surfaces. It has been noted that many\ HEAT repeat-containing proteins are involved in intracellular \ transport processes.

\ \

In the crystal structure of PP2A PR65/A [MEDLINE:99142607], the HEAT repeats consist\ of pairs of antiparallel helices, as predicted in [MEDLINE:96024640].

\ \ \N \N \N 19104 IPR000355

\ \ \ C-C chemokine receptor activity ; GO:0016493 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19101 IPR000352 Peptide chain release factors (RFs) are required for the termination ofprotein biosynthesis [MEDLINE:96418479]. At present two classes of RFs can be distinguished.\ Class I RFs bind to ribosomes that have encountered a stop codon at their\ decoding site and induce release of the nascent polypeptide. Class II RFs are\ GTP-binding proteins that interact with class I RFs and enhance class I RF\ activity.\ In prokaryotes there are two class I RFs that act in a codon specific manner\ [MEDLINE:91014685]: RF-1 (gene prfA) mediates UAA and UAG-dependent termination while RF-2\ (gene prfB) mediates UAA and UGA-dependent termination. RF-1 and RF-2 are\ structurally and evolutionary related proteins which have been shown [MEDLINE:93027135] to\ be part of a larger family.\ \ translation release factor activity ; GO:0003747 \N translational termination ; GO:0006415 19102 IPR000353 Describes the

domain of the

chain of class II major histocompatibility complex (MHC) proteins. The majorhistocompatibility complex molecules are made of two chains. In class II PUB00002017,\ both the

IPR001003 and the

chains are composed of two extracellular\ domains: an Ig domain and this domain, a transmembrane region and a cytoplasmic tail.\ \ \N membrane ; GO:0016020 immune response ; GO:0006955 19103 IPR000354

Involucrin [MEDLINE:93061995], [MEDLINE:94104476] is a protein present in keratinocytes of epidermis and otherstratified squamous epithelia. Involucrin first appears in the cell cytosol,\ but ultimately becomes cross-linked to membrane proteins by transglutaminase\ thus helping in the formation of an insoluble envelope beneath the plasma\ membrane.

\ \

\ \ \N \N \N 19099 IPR000349 This family contains the major surface antigens of the hepatitus viruses (Hepadnaviridae). The protein is most likely required for an early step of the life cycle involving entry or uncoating of virus particles.\ \N \N viral life cycle ; GO:0016032 19100 IPR000351

Several pharmacologically distinct neuropeptide Y receptors have been\ characterised, designated NPY Y1-Y6. The Y1 receptor is present in smooth\ muscle (e.g., intestine and blood vessels), and has also been described\ in cell lines. The receptors are believed to have a predominantly postsynaptic location, and are involved in the inhibition of adenylyl\ cyclase through a pertussis-toxin-sensitive G-protein, probably of the\ G0/Gi class. There is also evidence that NPY can stimulate an increase\ in intracellular calcium independently of the phosphoinositide pathway PUB00005893.

\ \ neuropeptide Y receptor activity ; GO:0004983 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19098 IPR000348

p24 proteins are major membrane components of COPI- and COPII-coated vesicles and are implicated in cargo selectivity of ER to Golgi transport [MEDLINE:98139537]\ \ \ [MEDLINE:97103176].\ \ Multiple members of the p24 family are found in all eukaryotes, from yeast to mammals. \ Members of the p24 family are type I membrane proteins with a signal peptide at the amino terminus, a lumenal coiled-coil (extracytosolic) domain, a single transmembrane domain with conserved amino acids, and a short cytoplasmic tail. They may be grouped into at least three subfamilies based on primary sequence [MEDLINE:96291865]. One subfamily comprises yeast Emp24p and mammalian p24A. Another subfamily comprises yeast Erv25p and mammalian Tmp21, and the third subfamily comprises mammalian gp25L proteins.

\ \ \ protein carrier activity ; GO:0008320 membrane ; GO:0016020 intracellular protein transport ; GO:0006886 19097 IPR000347 Members of this family are metallothioneins. Theseproteins are cysteine rich proteins that bind to heavy\ metals. Members of this family appear to be closest to\ Class II metallothioneins.\ \ heavy metal binding activity ; GO:0005505 \N \N 19095 IPR000345 In proteins belonging to cytochrome c family [MEDLINE:85113965], the heme group is covalentlyattached by thioether bonds to two conserved cysteine residues. The consensus\ sequence for this site is Cys-X-X-Cys-His and the histidine residue is one of\ the two axial ligands of the heme iron. This arrangement is shared by all\ proteins known to belong to cytochrome c family, which presently includes\ cytochromes c, c', c1 to c6, c550 to c556, cc3/Hmc, cytochrome f and reaction\ center cytochrome c.\

Caution: the prosite signature PS00190 gives a very large number of false positive hits.

\ \ electron transporter activity ; GO:0005489 \N electron transport ; GO:0006118 19096 IPR000346

Hyperglycemic hormone, which controls blood sugar levels, is an abundant\ peptide in the sinus glands of isopods and decapods [MEDLINE:93170291]. The peptide is a potent secretagogue, releasing digestive enzymes\ from the hepatopancreas. It may act as a stress hormone. Homarus americanus (American lobster) molt-inhibiting\ hormone also shows hyper-glycemic hormone activity [MEDLINE:90386659].

\ \ neuropeptide hormone activity ; GO:0005184 extracellular ; GO:0005576 \N 19094 IPR000344 Animals recognise a wide variety of chemicals using their senses of tasteand smell. The nematode Caenorhabditis elegans has only 14 types of chemosensory neuron,\ yet is able to respond to dozens of chemicals because each neuron detects\ several stimuli. More than 40 highly divergent transmembrane proteins that\ could contribute to this functional diversity have been described [MEDLINE:96028095]. Most\ of the candidate receptor genes are in clusters of similar genes; 11 of \ these appear to be expressed in small subsets of chemosensory neurons. A\ single type of neuron can potentially express at least 4 different receptor\ genes [MEDLINE:96028095]. Some of these might encode receptors for water-soluble\ attractants, repellents and pheromones, which may be divergent members\ of the G-protein-coupled receptor family [MEDLINE:96028095].\ Sequences of the sra family of C.elegans receptor-like proteins contain\ 6-7 hydrophobic, putative transmembrane, regions. These can be\ distinguished from other 7TM proteins (especially those known to couple\ G-proteins) by their own characteristic TM signatures.\ \ transmembrane receptor activity ; GO:0004888 integral to membrane ; GO:0016021 chemosensory perception ; GO:0007606 19093 IPR000343

Delta-aminolevulinic acid (ALA) is the obligatory precursor for the synthesisof all tetrapyrroles including porphyrin derivatives such as chlorophyll and\ heme. ALA can be synthesized via two different pathways: the Shemin (or C4)\ pathway which involves the single step condensation of succinyl-CoA and\ glycine and which is catalyzed by ALA synthase (EC: 2.3.1.37) and via the C5\ pathway from the five-carbon skeleton of glutamate. The C5 pathway operates\ in the chloroplast of plants and algae, in cyanobacteria, in some eubacteria\ and in archaebacteria.

\ The initial step in the C5 pathway is carried out by members of this family, glutamyl-tRNA reductases\ (GluTR) [MEDLINE:92367216] which catalyzes the Mg²⁺/NADPH-dependent conversion of glutamate-\ tRNA(Glu) to glutamate-1-semialdehyde (GSA) with the concomitant release of\ tRNA(Glu) which can then be recharged with glutamate by glutamyl-tRNA\ synthetase. GSA is converted to ALA by GSA aminotransferase. This example of an aminoacyl-tRNA being used in any reaction\ other \ than peptide bond formation is highly unusual.

\ GluTR is a protein of about 50 Kd (467 to 550 residues) which contains a few\ conserved region. The best conserved region is located in positions 99 to 122\ in the sequence of known GluTR. This region seems important for the activity\ of the enzyme.

\ \ glutamyl tRNA reductase activity ; GO:0008883 \N porphyrin biosynthesis ; GO:0006779 19092 IPR000343

\ \ glutamyl tRNA reductase activity ; GO:0008883 \N porphyrin biosynthesis ; GO:0006779 19091 IPR000343

\ \ glutamyl tRNA reductase activity ; GO:0008883 \N porphyrin biosynthesis ; GO:0006779 19090 IPR000342 Regulator of G Protein Signaling (RGS) proteins function as GTPase-activating proteins (GAPs) that stimulate the inactivation of heterotrimeric G proteins and are responsible for the rapid turnoff of G protein-coupled receptor signaling pathways. RGS proteins may be regulated on a posttranslational level but the mechanisms controlling the GAP activity of RGS proteins are still poorly understood [MEDLINE:20428734]. There are indications that specific RGS proteins regulate specific G protein-coupled receptor pathways [MEDLINE:20295842].

The RGS domain is present in a number of different proteins that include: G protein-coupled receptor kinase, G- interacting protein and others.

\ \ signal transducer activity ; GO:0004871 \N \N 19089 IPR000341

Phosphatidylinositol 3-kinase (PI3K) (EC: 2.7.1.137) is an enzyme that phosphorylates phosphoinositides on the 3-hydroxyl group of the inositol ring. A subset of PI3Ks has the capacity to bind and be activated by the GTP-bound small GTPase p21Ras\ (Ras). PI3Ks are recognized as one of the principal effectors of Ras\ signalling to the cell-cycle control machinery.

In the structure of the RasPI3K gamma complex, contacts between the two molecules are made\ primarily via the so-called switch I region of Ras and the PI3K RBD. The RBD fold comprises a five-stranded mixed -sheet,\ flanked by two -helices. Interaction between Ras and the PI3K RBD is primarily polar in character and, as characterized by\ kinetic measurements, is reversible and transient [MEDLINE:22147077].

\ \ These regions show some similarity (although not highly \ significant similarity) to Ras-binding IPR000159 domains (unpublished observation).

\ \ \ 1-phosphatidylinositol 3-kinase complex ; GO:0005942\ phosphatidylinositol 3-kinase activity ; GO:0016303 \N \N 19088 IPR000340

Ser/Thr and Tyr dual specificity phosphatases are a group of enzymes with both Ser/Thr (EC: 3.1.3.16) and tyrosine specific proteinphosphatase (EC: 3.1.3.48) activity able to remove both the serine/threonine or tyrosine-bound phosphate group from a wide\ range of phosphoproteins, including a number of enzymes which have been phosphorylated\ under the action of a kinase.\ \ Dual specificity protein phosphatases (DSPs) regulate mitogenic signal transduction and control the cell cycle. The\ crystal structure of a human DSP, vaccinia H1-related phosphatase (or VHR), has been determined at 2.1 angstrom resolution [MEDLINE:96243129]. A shallow active site pocket in VHR allows for the hydrolysis of phosphorylated serine, threonine, or tyrosine protein\ residues, whereas the deeper active site of protein tyrosine phosphatases (PTPs) restricts substrate specificity to only\ phosphotyrosine. Positively charged crevices near the active site may explain the enzyme's preference for substrates with\ two phosphorylated residues. The VHR structure defines a conserved structural scaffold for both DSPs and PTPs. A\ "recognition region" connecting helix alpha1 to strand beta1, may determine differences in substrate specificity between\ VHR, the PTPs, and other DSPs.

\ \ \ \ \ protein tyrosine/serine/threonine phosphatase activity ; GO:0008138 \N protein amino acid dephosphorylation ; GO:0006470 19087 IPR000338 An appreciable number of eukaryotic proteins are acylated by the covalentaddition of myristate (a C14-saturated fatty acid) to their N-terminal residue\ via an amide linkage [MEDLINE:89024587], [MEDLINE:89273388].\ The sequence specificity of the enzyme responsible\ for this modification, myristoyl CoA:protein N-myristoyl transferase (NMT),\ has been derived from the sequence of known N-myristoylated proteins and from\ studies using synthetic peptides. It seems to be the following:\

The N-terminal residue must be glycine.
In position 2, uncharged residues are allowed. Charged residues, proline and large hydrophobic residues are not allowed.
In positions 3 and 4, most, if not all, residues are allowed.
In position 5, small uncharged residues are allowed (Ala, Ser, Thr, Cys, Asn and Gly). Serine is favored.
In position 6, proline is not allowed.

Note: No protein matches are shown due to the low specificity of this rule.

\ \ \N \N \N 19086 IPR000337

\ \ metabotropic glutamate, GABA-B-like receptor activity ; GO:0008067 membrane ; GO:0016020 \N 19083 IPR000335 Bleomycin (Blm) is a glycopeptide antibiotic produced naturally by actinomycetes. It is a strong DNA-cutting agent and thus finds use as \ a potent anti-cancer drug. The DNA-cutting mechanism is complex, \ involving concomitant oxidation of FeII and reduction of oxygen. In\ addition to iron, Blm binds other transition metals: cobalt, nickel, \ copper and zinc. Actinomycetes have developed a defence mechanism \ against this lethal compound, producing a protein that confers \ resistance to Blm through drug sequestering.\ The crystal structure of the bleomycin resistance protein reveals 2\ identically-folded halves, each having an

fold but showing no\ sequence similarity [MEDLINE:94283372]. Each half comprises a 4-stranded

-sheet and\ a short

-helix (3 turns). The sheets within each half lie roughly at\ right-angles and are related by an approximate 2-fold axis. The crystal\ packing shows compact dimers that have a hydrophobic interface and are\ involved in mutual chain exchange.\ \ defense/immunity protein activity ; GO:0003793 \N \N 19084 IPR000336 Flaviviruses are small enveloped viruses with virions comprised of 3 proteins called CIPR001122 , M and E.\ The envelope is composed of protein M IPR001122/> and glycoprotein E. This family corresponds to\ the E protein. The structure is known for a member of this family [MEDLINE:95272700].\ \ structural molecule activity ; GO:0005198 viral envelope ; GO:0019031 \N 19085 IPR000336 Flaviviruses are small enveloped viruses with virions comprised of 3 proteins called CIPR001122 , M and E.\ The envelope is composed of protein M IPR001122/> and glycoprotein E. This family corresponds to\ the E protein. The structure is known for a member of this family [MEDLINE:95272700].\ \ structural molecule activity ; GO:0005198 viral envelope ; GO:0019031 \N 19081 IPR000333 Activin type II receptors are proteins of around 500 residues that sharea high degree of similarity (human and mouse sequences are 99% identical).\ The receptor, which is involved in transmembrane signalling, consists of\ an extracellular domain that specifically binds activin A, a single\ membrane-spanning domain, and an intracellular kinase domain (IPR000719) with\ predicted serine/threonine specificity [MEDLINE:92231944].\ \ ATP binding activity ; GO:0005524 membrane ; GO:0016020 transmembrane receptor protein serine/threonine kinase signaling pathway ; GO:0007178 19082 IPR000334

Glycoside hydrolase family 45 CAZY:GH_45).

\ \

The microbial degradation of cellulose and xylans requires several types of\ enzymes such as endoglucanases, cellobiohydrolases (EC: 3.2.1.91)\ (exoglucanases), or xylanases (EC: 3.2.1.8) [MEDLINE:91069220], [MEDLINE:91359927].\ Fungi and bacteria produce\ a spectrum of cellulolytic enzymes (cellulases) and xylanases which, on the\ basis of sequence similarities, can be classified into families. One of these\ families is known as the cellulase family K or as the glycosyl hydrolases\ family 45 [MEDLINE:93356744].\ The best conserved regions in these enzymes is located in the N-terminal\ section. It contains an aspartic acid residue which has been shown [MEDLINE:93390621] to act\ as a nucleophile in the catalytic mechanism.\ This also has several cysteines that are involved in forming disulphide bridges.

\ \ cellulase activity ; GO:0008810 \N carbohydrate metabolism ; GO:0005975 19080 IPR000332

Beta-1 and -2 receptors often coexist, but one subtype normally\ predominates. Beta-2 receptors mediate relaxation of smooth muscle\ (including vascular beds, bronchus, intestine and uterus); they mediate\ glycogenlysis and glucogenesis in the liver and regulate cell metabolism in\ skeletal muscle; they inhibit the activity of leukocytes and other blood\ cells; and they are found in the heart, but their physiological role here\ is unclear. The receptors are located presynaptically in nerves, where\ they facilitate neurotransmitter release, and in the brain, where they\ regulate a variety of physiological processes. Beta-2 receptors activate\ adenylyl cyclase through Gs PUB00005869.

\ \ beta2-adrenergic receptor activity ; GO:0004941 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19079 IPR000331

The Rap/ran-GAP domain is found in the GTPase activating protein (GAP) responsible for the activation of nuclear Ras-related regulatory proteins Rap1, Rsr1 and Ran in vitro converting it to the putatively inactive GDP-bound state [MEDLINE:91256304], [MEDLINE:95098034]. Ran is an evolutionary conserved member of the Ras superfamily that regulates all receptor-mediated transport between the nucleus and the cytoplasm. RanGAP is a leucine rich repeat containing protein which forms a highly curved crescent. Each LRR forms a short -strand and a longer -helix that results in a - hairpin motif [MEDLINE:22014335].

The domain is also present in tuberin (a tuberous sclerosis homolog protein) that specifically stimulates the intrinsic GTPase activity of Ras-related protein Rap1A suggesting a possible mechanism for its role in the regulation of cellular growth.

\ \ \N \N \N 19077 IPR000329 Uteroglobin [MEDLINE:89199637] is a protein that seems specific to lagomorphes (rabbit, hare,and pica) and which binds progesterone specifically and with high affinity. It\ may regulate progesterone concentrations reaching the blastocyst. Uteroglobin\ is also a potent inhibitor of phospholipase A2. It is a protein of 70 amino\ acids that form antiparallel disulfide-linked dimers. The progesterone-\ binding site is formed by a cavity between the monomeric subunits. A schematic\ representation of the location of the two disulfide bonds in the antiparallel\ dimer is shown below:\

\ NH2-xxCxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxCx-COOH\ | | \ COOH-xCxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxCxx-NH2\

\ \ The precise role of uteroglobin has still to be elucidated [MEDLINE:95288292].\ \ \N \N \N 19078 IPR000330 This domain is found in proteins involved in a variety ofprocesses including transcription regulation (e.g., SNF2, STH1,\ brahma, MOT1) , DNA repair (e.g., ERCC6, RAD16, RAD5), DNA\ recombination (e.g., RAD54), and chromatin unwinding (e.g., ISWI)\ as well as a variety of other proteins with little functional\ information (e.g., lodestar, ETL1).\

Proteins that contain this domain appear to be distantly related to the\ DEAX box helicases IPR001410, however\ no helicase activity has ever been demonstrated for these proteins.

\ \ ATP binding activity ; GO:0005524 \N \N 19076 IPR000328 The gp41 subunit of the envelope protein complex from human immunodeficiency virus (HIV)and simian immunodeficiency viruses (SIV) mediates\ membrane fusion during viral entry [MEDLINE:98356123].\ \ structural molecule activity ; GO:0005198 viral envelope ; GO:0019031 \N 19074 IPR000326 This family of enzymes includes phosphatidylglycerophosphatase B EC: 3.1.3.27 from Escherichia coli and other bacteria, type 2 phosphatidic acidphosphatase EC: 3.1.3.4 (PAP2) as well as other phosphoesterases.\

Other proteins that contain this domain include a bacitracin transport permease from Bacillus licheniformis and a glucose-6-phosphatase from rat.

\ \ \N \N \N 19075 IPR000327 The 'POU' (named after Pit, Oct, Unc and pronounced 'pow') domain is a 70 to 75 amino-acid regionfound upstream of a homeobox domain in some \ eukaryotic transcription factors.\ Such proteins\ bind to specific DNA sequences to cause temporal and spatial regulation of \ the expression of genes, many of which are involved in the regulation of \ neuronal development in the central nervous system of mammals [MEDLINE:90136944]. Some \ other genes are also regulated, including those for immunoglobulin light \ and heavy chains (Oct-2) [MEDLINE:90138945], and trophic hormone genes, such as those for \ prolactin and growth hormone (Pit-1). Both elements of the POU-domain are \ required for high affinity sequence-specific DNA-binding. The domain may \ also be involved in protein-protein interactions [MEDLINE:92331607]. The 3-D structure \ structure of the POU-domain has been determined by multidimensional\ NMR [MEDLINE:93214991] and X-ray crystallography to 3.0 A resolution [MEDLINE:94208057].\ \ transcription factor activity ; GO:0003700 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 19073 IPR000324 Steroid or nuclear hormone receptors (NRs) constitute an important super- family of transcription regulators that are involved in widely diverse \ physiological functions, including control of embryonic development, cell\ differentiation and homeostasis. Members of the superfamily include the\ steroid hormone receptors and receptors for thyroid hormone, retinoids, \ 1,25-dihydroxy-vitamin D3 and a variety of other ligands. The proteins \ function as dimeric molecules in nuclei to regulate the transcription of \ target genes in a ligand-responsive manner [MEDLINE:95206940], [MEDLINE:94218237]. In addition to C-terminal\ ligand-binding domains, these nuclear receptors contain a highly-conserved,\ N-terminal zinc-finger that mediates specific binding to target DNA \ sequences, termed ligand-responsive elements. In the absence of ligand,\ steroid hormone receptors are thought to be weakly associated with nuclear\ components; hormone binding greatly increases receptor affinity.\ \

The vitamin D receptor (VDR) mediates the signal of 1-a,25-dihydroxyvitamin \ D3 by binding to vitamin D responsive elements - it functions either as a \ homodimer, or as a heterodimer of vitamin D and retinoid X receptor\ subunits. Deficiency of VDR causes type IIA rickets [MEDLINE:95206940]. \

\ \ ligand-dependent nuclear receptor activity ; GO:0004879 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 19071 IPR000323 Copper type II, ascorbate-dependent monooxygenases [MEDLINE:90005947] are a class of enzymesthat requires copper as a cofactor and which uses ascorbate as an electron\ donor. This family contains two related enzymes, Dopamine-

-monooxygenase (EC: 1.14.17.1)\ and Peptidyl-glycine

-amidating monooxygenase (EC: 1.14.17.3).\ There are a few regions of sequence similarities between these two enzymes,\ two of these regions contain clusters of conserved histidine residues which\ are most probably involved in binding copper.\ \ copper ion binding activity ; GO:0005507 \N \N 19072 IPR000323 Copper type II, ascorbate-dependent monooxygenases [MEDLINE:90005947] are a class of enzymesthat requires copper as a cofactor and which uses ascorbate as an electron\ donor. This family contains two related enzymes, Dopamine-

-monooxygenase (EC: 1.14.17.1)\ and Peptidyl-glycine

Glycoside hydrolase family 31 CAZY:GH_31).

Glycoside hydrolase family 31 groups a number of glycosyl hydrolases on the basis of sequence\ similarities [MEDLINE:92082464], [MEDLINE:92104191], [MEDLINE:92077121]\ An aspartic acid has been implicated [MEDLINE:91310614] in the catalytic activity of sucrase,\ isomaltase, and lysosomal -glucosidase.

\ \ hydrolase activity, hydrolyzing O-glycosyl compounds ; GO:0004553 \N carbohydrate metabolism ; GO:0005975 19069 IPR000321

The term opioid refers to a class of substance that produces its effects\ via the major classes of opioid receptor, termed mu, delta and kappa PUB00005896.\ The delta opioid receptor has a more discrete distribution in the CNS\ relative to the mu and kappa opioid receptors: it is found in the cerebral\ cortex, amygdala, nucleus accumbens, olfactory tubercle and pontine\ nucleus. It is also found in certain smooth muscles, e.g. hamster vas\ deferens, and in cell lines PUB00005896. Delta-receptors mediate analgesia.

\ \ delta-opioid receptor activity ; GO:0004986 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19067 IPR000319 Aspartate-semialdehyde dehydrogenase (EC: 1.2.1.11) (ASD) catalyzes the secondstep in the common biosynthetic pathway leading from Asp to diaminopimelate\ and Lys, to Met, and to Thr; the NADP-dependent reductive dephosphorylation of\ L-aspartyl phosphate to L-aspartate-semialdehyde.\

\
L-4-aspartyl phosphate + NADPH = L-aspartate-4-semialdehyde + P_i + NADP⁺\

\ In bacteria and fungi, ASD\ is a protein of about 40 Kd (340 to 370 residues) whose sequence is not\ extremely well conserved [MEDLINE:92211328]. A conserved cysteine residue has been implicated\ as important for the catalytic activity [MEDLINE:92287957].\ \ aspartate-semialdehyde dehydrogenase activity ; GO:0004073 \N amino acid metabolism ; GO:0006520 19068 IPR000320

Hedgehog is a family of secreted signal molecules requiredfor embryonic cell differentiation. members of this family are\ composed of two domains. These proteins are autocatalytically cleaved by the\ C terminal domain IPR001767. This family\ is the N terminal domain that is responsible for both local and long-range\ signalling activities.

\ \

The structure of this domain is known [MEDLINE:96069744] and reveals a tetrahedrally\ coordinated zinc ion that appears to be structurally\ analogous to the zinc coordination sites of zinc hydrolases, such as\ thermolysin and carboxypeptidase A. This putative catalytic site\ represents a distinct activity from the autoprocessing activity that\ resides in the carboxy-terminal domain.

\ \ \N \N development ; GO:0007275 19066 IPR000318 Nitrogenase (EC: 1.18.6.1) [MEDLINE:89369712] is the enzyme system responsible for biological nitrogen fixation. Nitrogenase is an oligomeric complex which consists of two components: component 2 is an homodimer of an iron-sulfur protein, while component 1 which contains the active site for the reduction of nitrogen to ammonia exists in three different forms: the molybdenum-iron containing protein (MoFe) is a hetero-tetramer consisting of two pairs of

(nifD) and

(nifK) subunits; the vanadium-iron containing protein (VFe) is a hexamer of two pairs each of

(vnfD),

(vnfK), and delta (vnfG) subunits; the third form seems to only contain iron and is a hexamer composed of

(anfD),

(anfK), and delta (anfG) subunits.The

and

chains of the three types of component 1 are evolutionary related and they are also related to proteins nifE and nifN, which are most probably involved in the iron-molybdenum cofactor biosynthesis [MEDLINE:91094779].\ \ nitrogenase activity ; GO:0016163 \N nitrogen fixation ; GO:0009399 19065 IPR000317

Cysteine protease activity is dependent on an active dyad of cysteine andhistidine, the order and spacing of these residues varying in the 20 or so\ known families. Cysteine proteases have been grouped into two clans (CA and\ CB). Families C1, C2 and C10 are loosely termed papain-like and belong\ to clan CA; five cysteine proteases belong to clan CB; other families have\ not been assigned to clans. Nearly half of all cysteine proteases are found\ exclusively in viruses. The order of catalytic cysteine and histidine\ residues within the primary structure differs between the families and is\ an indication of convergent evolution [MEDLINE:95147707], [MEDLINE:93176119].

\ \

Caliciviruses are positive-stranded ssRNA viruses that cause gastroenteritis. The calicivirus genome contains two open reading frames, ORF1 and ORF2.\ ORF1 encodes a non-structural polypeptide, which has RNA helicase, cysteine\ protease and RNA polymerase activity. The regions of the polyprotein in\ which these activities lie are similar to proteins produced by the picorna-viruses.\ ORF2 encodes a structural protein [MEDLINE:97048080]. Two different families of\ caliciviruses can be distinguished on the basis of sequence similarity,\ namely those classified as small round structured viruses (SRSVs) and those\ classed as non-SRSVs.

\ \

Calicivirus proteases from the non-SRSV group, which are members of the PA\ protease clan, constitute family C24 of the cysteine proteases (proteases\ from SRSVs belong to the C37 family). As mentioned above, the protease\ activity resides within a polyprotein. The enzyme cleaves the polyprotein\ at sites N-terminal to itself, liberating the polyprotein helicase.

\ \ cysteine-type endopeptidase activity ; GO:0004197 \N proteolysis and peptidolysis ; GO:0006508 19063 IPR000315 The B-box zinc finger is an around 40 amino acids domain. One or two copies ofthis motif are generally associated with a ring finger and a coiled coil motif\ to form the so-called tripartite motif. It is found essentially in\ transcription factors, ribonucleoproteins and protooncoproteins, but no\ function is clearly assigned to this domain [MEDLINE:99120579]. It has been shown to be\ essential but not sufficient to localize the PML protein in a punctate pattern\ in interphase nuclei [MEDLINE:96202324]. Among the 7 possible ligands for the zinc atom\ contained in a B-box, only 4 are used and bind one zinc atom in a Cys2-His2\ tetrahedral arrangement. The NMR analysis reveals that the B-box structure\ comprises two

-strands, two helical turns and three extended loop regions\ different from any other zinc binding motif [MEDLINE:96112809].\ \ zinc ion binding activity ; GO:0008270 intracellular ; GO:0005622 \N 19064 IPR000316

Metallothioneins (MT) are small proteins that bind heavy metals, such as zinc, copper, cadmium, nickel, etc. They have a high content of cysteine residues that bind the metal ions through clusters of thiolate bonds [MEDLINE:92140136], PUB00001490, PUB00001490, [MEDLINE:88029881]. An empirical classification into three classes has been proposed by Fowler and coworkers [MEDLINE:88029881] and Kojima [MEDLINE:92140139]. Members of class I are defined to include polypeptides related in the positions of their cysteines to equine MT-1B, and include mammalian MTs as well as MTs from crustaceans and molluscs. Class II groups MTs from a variety of species, including sea urchins, fungi, insects and cyanobacteria. Class III MTs are atypical polypeptides composed of gamma-glutamylcysteinyl units [MEDLINE:88029881]. This original classification system has been found to be limited, in the sense that it does not allow clear differentiation of patterns of structural similarities, either between or within classes. Consequently, all class I and class II MTs (the proteinaceous sequences) have now been grouped into families of phylogenetically-related and thus alignable sequences . This system subdivides the MT superfamily into families, subfamilies, subgroups, and isolated isoforms and alleles. \ The metallothionein superfamily comprises all polypeptides that resemble equine renal metallothionein in several respects [MEDLINE:88029881]: e.g., low molecular weight; high metal content; amino acid composition with high Cys and low aromatic residue content; unique sequence with characteristic distribution of cysteines, and spectroscopic manifestations indicative of metal thiolate clusters. A MT family subsumes MTs that share particular sequence-specific features and are thought to be evolutionarily related. The inclusion of a MT within a family presupposes that its amino acid sequence is alignable with that of all members. Fifteen MT families have been characterised, each family being identified by its number and its taxonomic range: e.g., Family 1: vertebrate MTs.

Family 15 consists of planta MTs. Its members are recognised by the sequence pattern [YFH]-x(5,25)-C-[SKD]-C-[GA]-[SDPAT]-x(0,1)-C-x-[CYF] which yields all plant sequences, but also MTCU_HELPO and the non-MT ITB3_HUMAN. The taxonomic range of the members extends to planta. Planta MTs are 45-84 residue proteins, containing 17 conserved cysteines that bind 5 zinc ions. Generally, there are two Cys-rich regions (domain 1 and domain 3) separated by a Cys-poor region (domain 2) and only the domain 2 contains unusual residues. It is believed that the proteins may have a role in Zn²⁺ homeostasis during embryogenesis. Family 15 includes the following subfamilies: p1, p2, p2v, p3, pec, p21.

\ \ \ zinc ion binding activity ; GO:0008270 \N \N 19062 IPR000314

Gastrins and cholecystokinins (CCKs) are naturally-occurring peptides that\ share a common C-terminal sequence, GWMDF; full biological activity resides\ in this region. The principal physiological role of gastrin is to\ stimulate acid secretion in the stomach; it also has trophic effects on\ gastric mucosa. Gastrin is produced from a single gene transcript, and\ is found predominantly in the stomach and intestine, but also in vagal\ nerves. The CCKB receptor has a widespread distribution in the CNS and\ has been implicated in the pathogenesis of panic-anxiety attacks caused\ by CCK-related peptides PUB00005877. It has a more limited distribution in the\ periphery, where it is found in smooth muscle and secretory glands.

\ \ \ gastrin receptor activity ; GO:0015054 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19061 IPR000313 Upon characterization of WHSC1, a gene mapping to the Wolf-Hirschhornsyndrome critical region and at its C-terminus similar to the Drosophila melanogaster ASH1/trithorax group proteins, a novel protein domain designated PWWP domain was identified [MEDLINE:98282232]. The PWWP domain is named after a conserved Pro-Trp-Trp-Pro motif. It is present in proteins of nuclear origin and plays a role in cell growth and differentiation. Due to its position, the composition of amino acids close to the PWWP motif and the pattern of other domains present it has been suggested that the domain is involved in protein-protein interactions [MEDLINE:20263716].\ \N \N \N 19060 IPR000312

The glycosyl transferase family includes anthranilate phosphoribosyltransferase (TrpD, EC: 2.4.2.18) and thymidine phosphorylase (EC: 2.4.2.2). All these proteins can transfer a phosphorylated ribose substrate.Thymidine phosphorylase (EC: 2.4.2.2) catalyzes the reversible phosphorolysis\ of thymidine, deoxyuridine and their analogues to their respective bases and\ 2-deoxyribose 1-phosphate. This enzyme regulates the availability of thymidine\ and is therefore essential to nucleic acid metabolism.

\ \ \ \ \ transferase activity, transferring glycosyl groups ; GO:0016757 \N metabolism ; GO:0008152 19057 IPR000310 Pyridoxal-dependent decarboxylases are bacterial proteins acting on ornithine, lysine, arginine and related substrates [MEDLINE:94237165].One of the regions of sequence similarity contains a conserved lysine residue, which is the site of attachment of the pyridoxal-phosphate group.\ \ enzyme activity ; GO:0003824 \N \N 19058 IPR000310 Pyridoxal-dependent decarboxylases are bacterial proteins acting on ornithine, lysine, arginine and related substrates [MEDLINE:94237165].One of the regions of sequence similarity contains a conserved lysine residue, which is the site of attachment of the pyridoxal-phosphate group.\ \ enzyme activity ; GO:0003824 \N \N 19059 IPR000312

\ \ \ \ \ transferase activity, transferring glycosyl groups ; GO:0016757 \N metabolism ; GO:0008152 19056 IPR000308

The 14-3-3 proteins are a large family of approximately 30kDa acidic proteins which exist primarily as homo- and heterodimeric within all eukaryotic cells[MEDLINE:91108808], [MEDLINE:21909374]. There is a high degree of sequence identity and conservation between all the 14-3-3 isotypes, particularly in the regions which form the dimer interface or line the central ligand binding channel of the dimeric molecule. Each 14-3-3 protein sequence can be roughly divided into three sections: a divergent amino terminus, the conserved core region\ and a divergent carboxyl terminus. The conserved middle core region of the 14-3-3s encodes an amphipathic groove that forms the main functional domain, a cradle\ for interacting with client proteins. The monomer consists of nine helices\ organized in an antiparallel manner, forming an L-shaped structure. The interior of the L-structure is composed of four\ helices: H3 and H5, which contain many charged and polar amino acids, and H7 and H9, which contain hydrophobic amino acids.\ These four helices form the concave amphipathic groove that interacts with target peptides.\

\ \

14-3-3 proteins mainly bind proteins containing phosphothreonine or phosphoserine motifs however exceptions to this rule do exist. Extensive investigation of the 14-3-3 binding site of the mammalian serine/threonine kinase\ Raf-1 has produced a consensus sequence for 14-3-3-binding, RSxpSxP (in the single-letter amino-acid code, where x denotes any\ amino acid and p indicates that the next residue is phosphorylated). 14-3-3 proteins appear to effect intracellular signalling in one of three ways - by direct regulation of the catalytic activity of the bound protein, by regulating interactions between the bound protein and other molecules in the cell by sequestration or modification or by controlling the subcellular localisation of the bound ligand.\ Proteins appear to initially bind to a single dominant site and then subsequently to many, much weaker secondary interaction sites. The 14-3-3 dimer is capable of changing the conformation of its bound ligand whilst itself undergoing minimal structural alteration.

\ \ \ protein domain specific binding activity ; GO:0019904 \N \N 19055 IPR000307

\ \ \

Ribosomal protein S16 is one of the proteins from the small ribosomal subunit.\ It belongs to a family of ribosomal proteins which, on the basis of sequence\ similarities PUB00005070, groups:\ \

Eubacterial S16.

Algal and plant chloroplast S16.

Cyanelle S16.

Neurospora crassa mitochondrial S24 (cyt-21).

\ \

S16 proteins have about 100 amino-acid residues.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 19052 IPR000304 Delta 1-pyrroline-5-carboxylate reductase (P5CR) (EC: 1.5.1.2) [MEDLINE:90340278], [MEDLINE:90185238] is the enzyme that catalyzes the terminal step in the biosynthesis of proline from glutamate, the NAD(P) dependent oxidation of 1-pyrroline-5-carboxylate into proline.\ pyrroline 5-carboxylate reductase activity ; GO:0004735 \N proline biosynthesis ; GO:0006561 19053 IPR000305

It is found in the amino terminal region of excinuclease abc subunit c (uvrC), bacteriophage T4 endonucleases segA, segB, segC, segD and segE; it is also found in putative endonucleases encoded by group I introns of fungi and phage.

\ \ nuclease activity ; GO:0004518 intracellular ; GO:0005622 DNA repair ; GO:0006281 19054 IPR000306 The FYVE zinc finger is named after four proteins that it has been found in: Fab1, YOTB/ZK632.12, Vac1, and EEA1. The FYVE finger has been shown to bind two Zn²⁺ ions [MEDLINE:96394535]. The FYVE finger has eight potential zinc coordinating cysteine positions. Many members of this family also include two histidines in a motif R+HHC+XCG, where + represents a charged residue and X any residue.\ zinc ion binding activity ; GO:0008270 \N \N 19049 IPR000299 This domain is found in a number of cytoskeletal-associated proteins that associate with various proteins at the interface between the plasma membrane and the cytoskeleton. It is a conserved N-terminal domain of about 150 residues [MEDLINE:91015390], [MEDLINE:92064635], [MEDLINE:95074267], involved in the linkage of cytoplasmic proteins to the membrane.\ \N cytoskeleton ; GO:0005856 \N 19050 IPR000300 This family contains diverse proteins homologous to inositol monophosphatase [MEDLINE:92077133]. Members of this family are Mg²⁺-dependent/Li⁺-sensitive phosphatases. That catalyse a variety of reactions.\ \ inositol/phosphatidylinositol phosphatase activity ; GO:0004437 \N \N 19051 IPR000301

A number of eukaryotic CD antigens have been shown to be related[MEDLINE:91317825]. CD9 (also called DRAP-27, MRP-1 or p24) upregulates HB-EGF activity as a receptor for diphtheria toxin as well as its juxtacrine activity. CD9 mAbs modulate cell adhesion and migration and trigger platelet activation that is blocked by mAbs directed to the platelet Fc receptor CD32. In mice, CD9 mAb KMC8.8 has been shown to inhibit the production of myeloid cells in vitro and has a costimulatory activity for T cells. CD9 is a type III membrane protein, with four putative transmembrane domains.

CD37 (or gp52-40) is involved in signal transduction and serves as a stable marker for malignancies derived from mature B cells, like B-CLL, HCL, and all types of B-NHL.

CD63 transfection reduced melanoma cell motility on fibronectin, collagen and laminin, and reduced the growth and metastasis of melanoma cells in nude mice [MEDLINE:97240780].\ CD63 has been used as a marker for late endosomes and for primary melanomas.\

\ \

These proteins are all type II membrane proteins: they contain an\ N-terminal transmembrane (TM) domain, which acts both as a signal sequence\ and a membrane anchor, and 3 additional TM regions (hence the name 'TM4').\ The sequences contain a number of conserved cysteine residues.

\ \

CD molecules are leucocyte antigens on cell surfaces. CD antigens nomenclature is updated at http://www.ncbi.nlm.nih.gov/PROW/guide/45277084.htm\

\ \ \ \N \N \N 19047 IPR000297

Recommended name: Peptidylprolyl isomerase

Synonyms for proteins with this domain are: Peptidyl-prolyl cis-trans isomerase, PPIase, rotamase, cyclophilin, FKBP65

\ \

Peptidylprolyl isomerase (EC: 5.2.1.8) is an\ enzyme that accelerates protein folding by catalyzing the cis-trans\ isomerization of proline imidic peptide bonds in oligopeptides [MEDLINE:90248433]. It has been reported in bacteria and eukayotes.

\ \ \N \N \N 19048 IPR000298

Cytochrome c oxidase (EC: 1.9.3.1) is the terminal enzyme of the respiratory chain of mitochondria and many aerobic bacteria. It catalyzes the transfer of electrons from reduced cytochrome c to molecular oxygen:

\
4 cytochrome c⁺² + 4 H⁺ + O₂  -->  4 cytochrome  c⁺³ + 2 H₂O

\ \

This reaction is coupled to the pumping of four additional protons across the mitochondrial or bacterial membrane [MEDLINE:20031507].

\ \

Cytochrome c oxidase is an oligomeric enzymatic complex that is located in the mitochondrial inner membrane of eukaryotes and in the plasma membrane of aerobic prokaryotes. The core structure of prokaryotic and eukaryotic cytochrome c oxidase contains three common subunits, I, II and III. In prokaryotes, subunits I and III can be fused and a fourth subunit is sometimes found, whereas in eukaryotes there are a variable number of additional small polypeptidic subunits [MEDLINE:93194828]. The functional role of subunit III is not yet understood.

\ \

As the bacterial respiratory systems are branched, they have a number of distinct terminal oxidases, rather than the single cytochrome c oxidase present in the eukaryotic mitochondrial systems. Although the cytochrome o oxidases do not catalyze the cytochrome c but the quinol (ubiquinol) oxidation they belong to the same heme-copper oxidase superfamily as cytochrome c oxidases. Members of this family share sequence similarities in all three core subunits: subunit I is the most conserved subunit, whereas subunit II is the least conserved [MEDLINE:92268053], [MEDLINE:90293062], [MEDLINE:94364936].

\ \ cytochrome c oxidase activity ; GO:0004129 membrane ; GO:0016020 electron transport ; GO:0006118 19046 IPR000296 The cation dependent mannose-6-phosphate (man-6-P) receptor is one of two transmembrane proteins involved in the transport of lysosomal enzymes from the Golgi complex and the cell surface to lysosomes [MEDLINE:92291105]. Lysosomal enzymes bearing phosphomannosyl residues bind specifically to man-6-P receptors in the Golgi apparatus and the resulting receptor-ligand complex is transported to an acidic prelyosomal compartment, where the low pH mediates dissociation of the complex. Binding is optimal in the presence of divalent cations.

The amino acid sequence is a single polypeptide chain that contains a putative signal sequence and a transmembrane domain [MEDLINE:87244334]. The cation-dependent mannose 6-phosphate (M6P) receptor (CD-MPR) is present predominantly as a\ stable homodimer in membranes and has a single\ M6P-binding site per polypeptide [MEDLINE:87244334], [MEDLINE:89291904]. The molecule crystallizes as a homodimer\ with approximately 20% of the entire surface area of each monomer\ having contact with another through predominantly hydrophobic\ interactions [MEDLINE:22500058]. Each monomer contains a single -helix near its\ amino terminus followed by nine primarily anti-parallel -strands that form\ two -sheets, which are positioned orthogonally to each other. Extensive\ hydrophobic interactions are formed between the two -sheets, which\ results in each monomer forming a flattened -barrel structure. Six cysteine residues form three intramolecular disulphide bonds that\ are essential for the ligand-binding conformation of the receptor to be\ generated. The structures of the liganded molecules show that the\ carbohydrate-recognition domain of the enzyme lies relatively deep\ inside the protein, so that the terminal M6P residue and the penultimate\ sugar ring of bound pentamannosyl phosphate are mostly buried in the\ receptor. This deep binding pocket facilitates the formation of numerous\ interactions between the CD-MPR and its carbohydrate ligands.

\ \ transporter activity ; GO:0005215 membrane ; GO:0016020 transport ; GO:0006810 19045 IPR000295 Leuserpin 2 is a 5-element fingerprint that provides a signature for heparin cofactor II.Heparin cofactor II (HCII) is a glycoprotein in human plasma that inhibits thrombin rapidly in the presence of dermatan sulphate or heparin [MEDLINE:94190883]. In the presence of these glycosaminoglycans, HCII becomes the predominant thrombin inhibitor in place of antithrombin III (AT). It also inhibits chymotrypsin, but in a glycosaminoglycan-independent manner. Not only does HCII function as a thrombin inhibitor, but limited proteolysis near its N- terminus yields biologically active peptide(s) that might participate in inflammation and in wound healing and tissue repair processes [MEDLINE:91093260].\ The sequence of HCII contains a signal peptide of 19 amino acids and a mature protein of 480 amino acids [MEDLINE:88163663]. The N-terminal portion of HCII contains two acidic repeats (EDDDYLD and EDDDYID) that may bind to anion- binding exosite I of thrombin to facilitate covalent complex formation [MEDLINE:92041850].\ The sequence of HCII shares similarity with anti-thrombin III and other members of the

1-antitrypsin superfamily [MEDLINE:88163663].\ \ serine protease inhibitor activity ; GO:0004867 \N \N 19043 IPR000293

Colicins are plasmid-encoded polypeptide toxins produced by and active against Escherichia coli and closely related bacteria. The channel-forming colicins are transmembrane proteins that depolarize the cytoplasmic membrane, leading to dissipation of cellular energy [MEDLINE:90151911], [MEDLINE:90279493]. Colicins A, B, E1, Ia, Ib, and N belong to that group. The N-terminal part of these colicins is involved in their uptake; the central part is important for binding to outer membrane receptors and the C-terminal part is the channel-forming region.

\ \N \N \N 19044 IPR000294 This domain contains post-translational modifications of many glutamate residues by Vitamin K-dependent carboxylation to form gamma-carboxyglutamate (Gla) [MEDLINE:87191342], [MEDLINE:90226255].The GLA domain is responsible for the high-affinity binding of calcium ions. It starts at the N-terminal extremity of the mature form of proteins and ends with a conserved aromatic residue; a conserved Gla-x(3)-Gla-x-Cys motif [MEDLINE:88068589] is found in the middle of the domain which seems to be important for substrate recognition by the carboxylase.\ \ calcium ion binding activity ; GO:0005509 extracellular ; GO:0005576 \N 19041 IPR000291 D-alanine--D-alanine ligase (EC: 6.3.2.4) is a bacterial enzyme involved in cell-wall biosynthesis.It participates in forming UDP-N-acetylmuramyl pentapeptide, the peptidoglycan precursor.\ These enzymes are proteins of 300 to 360 amino acids containing many conserved regions. The N-terminal Gly-rich region could be involved in ATP-binding [MEDLINE:97207065].\ \ D-alanine-D-alanine ligase activity ; GO:0008716 \N peptidoglycan biosynthesis ; GO:0009252 19042 IPR000292

A number of bacterial and archaebacterial proteins involved in transportingformate or nitrite have been shown [MEDLINE:94293770] to be related:\

focA and focB, from Escherichia coli, transporters involved in the bidirectional transport of formate.
fdhC, from Methanobacterium formicicum and Methanobacterium thermoformicicum, a probable formate transporter.
nirC, from E. coli and Salmonella typhimurium, a probable nitrite transporter.
Bacillus subtilis hypothetical protein yrhG.
B. subtilis hypothetical protein ywcJ (ipa-48R).

These transporters are proteins of about 280 residues and seem to contain six\ transmembrane regions.

\ \ transporter activity ; GO:0005215 membrane ; GO:0016020 transport ; GO:0006810 19040 IPR000290 This family includes bacterial colicin and pyocin immunity proteins [MEDLINE:96270557], [MEDLINE:96302249]. These immunity proteins can bind specifically to the DNase-type colicins and pyocins and inhibit their bactericidal activity. The1.8-angstrom crystal structure of the ImmE7 protein consists of four antiparallel

-helices [MEDLINE:96270557]. Sequence similarities between colicins E2, A and E1 [MEDLINE:86094231] are less striking. The colicin\ E2 (pyocin) immunity protein does not share similarity with either the colicin E3 or\ cloacin DF13 [MEDLINE:81053773] immunity proteins. Pyocin protects a cell that harbours the plasmid\ ColE2 encoding colicin E2 against colicin E2; it is thus essential both for autonomous\ replication and colicin E2 immunity [MEDLINE:85239907].\ \ \N \N \N 19038 IPR000286 Histones can be reversibly acetylated on several lysine residues.Regulation of transcription is caused in part by this\ mechanism. Histone deacetylases catalyse the removal\ of the acetyl group. Histone deacetylases, acetoin utilization proteins and acetylpolyamine amidohydrolases are all members of this ancient protein superfamily [MEDLINE:97426514].\ \ \N \N \N 19039 IPR000289

\ \ \

A number of eukaryotic and archaebacterial ribosomal proteins can be grouped \ on the basis of sequence similarities. Examples are:\ \

Mammalian S28 [MEDLINE:21864036]

Plant S28 [MEDLINE:94105355]

Fungi S33 [MEDLINE:93127729]

Archaebacterial S28e.

\ \

These proteins have from 64 to 78 amino acids and a highly conserved C-terminal extremity region.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 19037 IPR000283 Respiratory-chain NADH dehydrogenase (EC: 1.6.5.3) PUB00001096, PUB00001096 (also known as complexI or NADH-ubiquinone oxidoreductase) is an oligomeric enzymatic complex\ located in the inner mitochondrial membrane which also seems to exist in\ the chloroplast and in cyanobacteria (as a NADH-plastoquinone oxidoreductase).\ Among the 25 to 30 polypeptide subunits of this bioenergetic enzyme complex\ there is one with a molecular weight of 75 kDa (in mammals), which is the\ largest subunit of complex I and is a component of the iron-sulfur (IP)\ fragment of the enzyme. It seems to bind to two 4Fe-4S clusters (called N-3\ and N-4).\ \ NADH dehydrogenase (ubiquinone) activity ; GO:0008137 \N oxidative phosphorylation, NADH to ubiquinone ; GO:0006120 19035 IPR000281 This domain contains a helix-turn-helix motif [MEDLINE:96165253].Every member of this family is N-terminal to a SIS domain IPR001347. Members of this family are probably regulators of genes\ involved in phosphosugar metobolism.\ \ transcription factor activity ; GO:0003700 \N regulation of transcription, DNA-dependent ; GO:0006355 19036 IPR000282 A number of receptors for lymphokines, hematopoeitic growth factors and growthhormone-related molecules share common domains, and can be divided into families. Cytokine receptor class 2 family includes interleukin-10 receptor; interferon-gamma receptor; interferon-

receptor; and tissue factor.\ \ hematopoietin/interferon-class (D200-domain) cytokine receptor activity ; GO:0004896 membrane ; GO:0016020 \N 19034 IPR000280

Cattle diarrhoea virus and hog cholera virus belong to the pestiviruses,\ single-stranded RNA viruses whose genomes encode one large polyprotein [MEDLINE:95147689].\ The p80 endopeptidase resides towards the middle of the polyprotein and is\ responsible for processing all non-structural pestivirus proteins [MEDLINE:95147689], [MEDLINE:91335765].\ The p80 enzyme is similar to other proteases in the SA clan and is predicted\ to have a fold similar to that of chymotrypsin [MEDLINE:95147689], [MEDLINE:89348028]. An HDS catalytic triad\ has been identified [MEDLINE:89348028].

\ \ serine-type endopeptidase activity ; GO:0004252 \N proteolysis and peptidolysis ; GO:0006508 19032 IPR000277 A number of pyridoxal-dependent enzymes involved in the metabolism of cysteine, homocysteine and methionine have been shown [MEDLINE:92250430], [MEDLINE:93289814] to be evolutionary related. These enzymes are proteins of about 400 amino-acid residues. The pyridoxal-P group is attached to a lysine residue located in the central section of these enzymes.\ \N \N amino acid metabolism ; GO:0006520 19033 IPR000278 Lambda phage regulatory protein CIII is a small protein that plays a role in stabilising the CII transcriptional activator, via a mechanism that is not yet fully understood [MEDLINE:91271360], [MEDLINE:87317682]. Stabilised CII activates CI, the gene for the repressor protein that prevents transcription of proteins required for lytic development. The central portion of the protein is well conserved and is both necessary and sufficient for the activity of the protein [MEDLINE:91271360]. Comparative analysis of the CIII sequence in lambda, HK022 and the lambdoid bacteriophage P22 has led to the suggestion that this central region assumes an amphipathic

-helical structure [MEDLINE:91271360].\ transcription co-activator activity ; GO:0003713 \N regulation of transcription, DNA-dependent ; GO:0006355 19029 IPR000274 Adenylate cyclase (EC: 4.6.1.1) is the enzyme responsible for the synthesis of cAMP from ATP. From sequence data, it has been proposed that there are three different classes of adenylate cyclases [MEDLINE:95167157]. Class I cyclases are found in enterobacteria and related Gram-negative bacteria. They are proteins of about 850 residues that consist of two functional domains: a N-terminal catalytic domain and a C-terminal regulatory domain.There are two highly conserved regions, the first one is located in the catalytic domain and the second one in the regulatory domain. The second signature includes a conserved histidine which could be phosphorylated by a PTS system IIA enzyme, thus leading to the activation of the cyclase.\ \ adenylate cyclase activity ; GO:0004016 \N cAMP biosynthesis ; GO:0006171 19030 IPR000275 Coagulogen is a gel-forming protein of hemolymph that hinders the spread of invaders by immobilising them [MEDLINE:86059292], [MEDLINE:84289359]. The protein contains a single 175- residue polypeptide chain; this is cleaved after Arg-18 and Arg-46 by a clotting enzyme contained in the hemocyte and activated by a bacterial endotoxin (lipopolysaccharide). Cleavage releases two chains of coagulin, A and B, linked by two disulphide bonds, together with the peptide C [MEDLINE:86059292], [MEDLINE:84289359]. Gel formation results from interlinking of coagulin molecules. Secondary structure prediction suggests the C peptide forms an

- helix, which is released during the proteolytic conversion of coagulogen to coagulin gel [MEDLINE:86059292]. The

-sheet structure and 16 half-cystines found in the molecule appear to yield a compact protein stable to acid and heat.\ \N \N \N 19031 IPR000276

\ \ rhodopsin-like receptor activity ; GO:0001584 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19028 IPR000272

The FXYD protein family contains at least seven members in mammals [MEDLINE:22427112]. Two other family members that are not obvious orthologs of any identified mammalian FXYD protein\ exist in zebrafish. All these proteins share a signature sequence of six conserved\ amino acids comprising the FXYD motif in the NH2-terminus, and two glycines and\ one serine residue in the transmembrane domain. FXYD proteins are widely distributed in mammalian tissues with prominent expression\ in tissues that perform fluid and solute transport or that are electrically excitable.

Initial functional characterization suggested that FXYD proteins act as channels or as modulators of ion\ channels however studies have revealed that most FXYD proteins\ have another specific function and act as tissue-specific regulatory subunits of the\ Na,K-ATPase. Each of these auxiliary\ subunits produces a distinct functional effect on the transport characteristics of\ the Na,K-ATPase that is adjusted to the specific functional demands of the tissue in\ which the FXYD protein is expressed. FXYD proteins appear to preferentially\ associate with Na,K-ATPase alpha1- isozymes, and affect their function in a way that\ render them operationally complementary or supplementary to coexisting isozymes.

\ \ ion channel activity ; GO:0005216 membrane ; GO:0016020 ion transport ; GO:0006811 19026 IPR000270 The Phox and Bem1p domain, is present in many eukaryotic cytoplasmic signalling proteins. The domain adopts a

-grasp fold, similar tothat found in ubiquitin and Ras-binding domains. A motif, variously termed OPR, PC and AID, represents the most conserved region\ of the majority of PB1 domains, and is necessary for PB1 domain function. This function is the formation of PB1 domain\ heterodimers, although not all PB1 domain pairs associate. \ \ \N \N \N 19027 IPR000271

\ \ \

Ribosomal protein L34 is one of the proteins from the large subunit of the prokaryotic ribosome. It is a small basic protein of 44 to 51 amino-acid residues [MEDLINE:93096601]. L34 belongs to a family of ribosomal proteins which, on the basis of sequence similarities, groups: Eubacterial L34, Red algal chloroplast L34, Cyanelle L34.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 19025 IPR000269 Amine oxidases (AO) are enzymes that catalyze the oxidation of a wide range of biogenic amines including many neurotransmitters, histamine and xenobiotic amines. There are two classes of amine oxidases: flavin-containing (EC: 1.4.3.4) and copper-containing (EC: 1.4.3.6).Copper-containing AO act as a disulphide-linked homodimer. The catalysed reaction,

RCH₂NH₂ + H₂O + O₂ = RCHO + NH₃ + H₂O₂

requires one copper ions per subunit and topaquinone as cofactors [MEDLINE:96164434].\ Copper-containing amine oxidases are found in bacteria, fungi, plants and animals.\ \ amine oxidase (copper-containing) activity ; GO:0008122 \N \N 19024 IPR000269 Amine oxidases (AO) are enzymes that catalyze the oxidation of a wide range of biogenic amines including many neurotransmitters, histamine and xenobiotic amines. There are two classes of amine oxidases: flavin-containing (EC: 1.4.3.4) and copper-containing (EC: 1.4.3.6).Copper-containing AO act as a disulphide-linked homodimer. The catalysed reaction,

RCH₂NH₂ + H₂O + O₂ = RCHO + NH₃ + H₂O₂

requires one copper ions per subunit and topaquinone as cofactors [MEDLINE:96164434].\ Copper-containing amine oxidases are found in bacteria, fungi, plants and animals.\ \ amine oxidase (copper-containing) activity ; GO:0008122 \N \N 19022 IPR000268 In eukaryotes, there are three different forms of DNA-dependent RNA polymerases (EC: 2.7.7.6) transcribing different sets of genes. Each class of RNA polymerase is an assemblage of ten to twelve different polypeptides. In archaebacteria, there is generally a single form of RNA polymerase which also consist of an oligomeric assemblage of 10 to 13 polypeptides.The N-terminal extremity of this family of polymerase subunits contains two cysteines that could play a role in the binding of a metal ion.\ \ DNA-directed RNA polymerase activity ; GO:0003899 \N transcription ; GO:0006350 19023 IPR000269 Amine oxidases (AO) are enzymes that catalyze the oxidation of a wide range of biogenic amines including many neurotransmitters, histamine and xenobiotic amines. There are two classes of amine oxidases: flavin-containing (EC: 1.4.3.4) and copper-containing (EC: 1.4.3.6).Copper-containing AO act as a disulphide-linked homodimer. The catalysed reaction,

RCH₂NH₂ + H₂O + O₂ = RCHO + NH₃ + H₂O₂

\ \ \

The ribosomal proteins catalyse ribosome assembly and stabilise the rRNA, tuning the structure of the ribosome for optimal function. Evidence suggests that, in prokaryotes, the peptidyl transferase reaction is performed by the large subunit 23S rRNA, whereas proteins probably have a greater role in eukaryotic ribosomes. Most of the proteins lie close to, or on the surface of, the 30S subunit, arranged peripherally around the rRNA [MEDLINE:97428328]. The small subunit ribosomal proteins can be categorised as primary binding proteins, which bind directly and independently to 16S rRNA; secondary binding proteins, which display no specific affinity for 16S rRNA, but its assembly is contingent upon the presence of one or more primary binding proteins; and tertiary binding proteins, which require the presence of one or more secondary binding proteins and sometimes other tertiary binding proteins.\ The small ribosomal subunit protein S17 is known to bind specifically to the 5' end of 16S ribosomal RNA in Escherichia coli (primary rRNA binding protein), and is thought to be involved in the recognition of termination codons. Experimental evidence [MEDLINE:98058740] has revealed that S17 has virtually no groups exposed on the ribosomal surface.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 19020 IPR000265

EP3 receptors mediate contraction in a wide range of smooth muscles,\ including gastrointestinal and uterine. They also inhibit neurotransmitter release in central and autonomic nerves through a presynaptic action,\ and inhibit secretion in glandular tissues (e.g., acid secretion from\ gastric mucosa, and sodium and water reabsorption in the kidney). mRNA\ is found in high levels in the kidney and uterus, and in lower levels in\ the brain, thymus, lung, heart, stomach and spleen. The receptors activate\ adenylate cyclase via an uncharacterised G-protein, probably of the Gi/Go\ class PUB00005901.

\ \ prostaglandin E receptor activity ; GO:0004957 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19019 IPR000264 A number of serum transport proteins are known to be evolutionarily related, including albumin,

-fetoprotein, vitamin D-binding protein and afamin [MEDLINE:90112461], [MEDLINE:86216223], [MEDLINE:94299534]. Albumin is the main protein of plasma; it binds water, cations (such as Ca²⁺, Na⁺ and K⁺), fatty acids, hormones, bilirubin and drugs - its main function is to regulate the colloidal osmotic pressure of blood. Alphafeto- protein (

-fetoglobulin) is a foetal plasma protein that binds various cations, fatty acids and bilirubin. Vitamin D-binding protein binds to vitamin D and its metabolites, as well as to fatty acids. The biological role of afamin (

-albumin) has not yet been characterised. The 3D structure of human serum albumin has been determined by X-ray crystallography to a resolution of 2.8A [MEDLINE:92334427]. It comprises three homologous domains that assemble to form a heart-shaped molecule [MEDLINE:92334427]. Each domain is a product of two subdomains that possess common structural motifs [MEDLINE:92334427]. The principal regions of ligand binding to human serum albumin are located in hydrophobic cavities in subdomains IIA and IIIA, which exhibit similar chemistry. Structurally, the serum albumins are similar, each domain containing five or six internal disulphide bonds, as shown schematically below:

\
                    +---+          +----+                        +-----+\
                    |   |          |    |                        |     |\
 xxCxxxxxxxxxxxxxxxxCCxxCxxxxCxxxxxCCxxxCxxxxxxxxxCxxxxxxxxxxxxxxCCxxxxCxxxx\
   |                 |       |     |              |               |\
   +-----------------+       +-----+              +---------------+\

\ \ carrier activity ; GO:0005386 extracellular space ; GO:0005615 transport ; GO:0006810 19018 IPR000263 Geminiviruses are characterised by a genome of circular single-stranded DNA encapsidated in twinned (geminate) quasi-isometric particles, from which the group derives its name PUB00001145. Most geminiviruses can be divided into 2 subgroups on the basis of host range and/or insect vector: i.e. those that infect dicotyledenous plants and are transmitted by the same whitefly species, and those that infect monocotyledenous plants and are transmitted by different leafhopper vectors. It has been shown that the 104 N-terminal amino acids of the maize streak virus coat protein bind DNA non-specifically PUB00001145.\ \ structural molecule activity ; GO:0005198 viral capsid ; GO:0019028 \N 19017 IPR000262 A number of oxidoreductases that act on

-hydroxy acids and which are FMN-containing flavoproteins have been shown [MEDLINE:90216683], [MEDLINE:91104894], [MEDLINE:92041948] to be structurally related.The first step in the reaction mechanism of these enzymes is the abstraction of the proton from the

-carbon of the substrate producing a carbanion which can subsequently attach to the N5 atom of FMN. A conserved histidine has been shown [MEDLINE:89123500] to be involved in the removal of the proton. The region around this active site residue is highly conserved and contains an arginine residue which is involved in substrate binding.\ \ oxidoreductase activity ; GO:0016491 \N electron transport ; GO:0006118 19016 IPR000261

The EH (for Eps15 Homology) domain is a protein-protein interaction module of approximately 95 residues which was originally identified as a repeated sequence present in three copies at the N-terminus of the tyrosine kinase substrates Eps15 and Eps15R [MEDLINE:96003812], [MEDLINE:21909370]. The EH domain was subsequently found in several proteins implicated in endocytosis, vesicle transport and signal transduction in organisms ranging from yeast to mammals. EH domains are present in one to three copies and they may include calcium-binding domains of the EF-hand type [MEDLINE:98060074], [MEDLINE:99147100]. Eps15 is divided into three domains: domain I contains signatures of a regulatory domain, including a candidate tyrosine phosphorylation site and EF-hand-type calcium-binding domains, domain II presents the characteristic heptad repeats of coiled-coil rod-like proteins, and domain III displays a repeated aspartic acid-proline-phenylalanine motif similar to a consensus sequence of several methylases [MEDLINE:93361014].

EH domains have been shown to bind specifically but with moderate affinity to peptides containing short, unmodified motifs through predominantly hydrophobic interactions. The target motifs are divided into three classes: class I consists of the concensus Asn-Pro-Phe (NPF) sequence; class II consists of aromatic and hydrophobic di- and tripeptide motifs, including the Phe-Trp (FW), Trp-Trp (WW), and Ser-Trp-Gly (SWG) motifs; and class III contains the His-(Thr/Ser)-Phe motif (HTF/HSF) [MEDLINE:97447799], [MEDLINE:99043861]. The structure of several EH domains has been solved by NMR spectroscopy. The fold consists of two helix-loop-helix characteristic of EF-hand domains, connected by a short antiparallel -sheet. The target peptide is bound in a hydrophobic pocket between two helices. Sequence analysis and structural data indicate that not all the EF-hands are capable of binding calcium because of substitutions of the calcium-liganding residues in the loop [MEDLINE:98387926], [MEDLINE:20222965], [MEDLINE:21285759].

This domain is often implicated in the regulation of protein transport/sorting and membrane trafficking. Messenger RNA translation initiation and cytoplasmic poly(A) tail shortening require the poly(A)-binding protein (PAB) in yeast. The PAB-dependent poly(A) ribonuclease (PAN) is organized into distinct domains containing repeated sequence elements [MEDLINE:92405166].

\ \ \N \N \N 19014 IPR000259 Members of this family of bacterial proteins are involved in regulation of length and mediation of adhesion of fimbriae. Fimbriae (also called pili), are polar filaments radiating from the surface of the bacterium to a length of 0.5-1.5 micrometers, that enable bacteria to colonize the epithelium of specific host organs. Fimbriae are also responsible to promote virulence [MEDLINE:99185199], [MEDLINE:92022146], [MEDLINE:88038337].\ \N fimbria ; GO:0009289 cell adhesion ; GO:0007155 19015 IPR000260 This domain is found in the NADH ubiquinone oxidoreductase (complex I) (EC: 1.6.5.3) which catalyses the transfer of two electrons from NADH to ubiquinone in a reaction that is associated with proton translocation across the membrane [MEDLINE:93110040]. This signature is found upstream of IPR001750.\ NADH dehydrogenase (ubiquinone) activity ; GO:0008137 mitochondrion ; GO:0005739 oxidative phosphorylation, NADH to ubiquinone ; GO:0006120 19013 IPR000258 Certain Gram-negative bacteria express proteins that enable them to promote nucleation of ice at relatively high temperatures (above -5C) [MEDLINE:91083949], [MEDLINE:94040446]. These proteins are localised at the outer membrane surface and can cause frost damage to many plants. The primary structure of the proteins contains a highly repetitive domain that dominates the sequence. The domain comprises a number of 48-residue repeats, which themselves contain 3 blocks of 16 residues, the first 8 of which are identical. It is thought that the repetitive domain may be responsible for aligning water molecules in the seed crystal.

\
              [.........48.residues.repeated.domain..........]\
             /              / |              | \\              \\\
            AGYGSTxTagxxssli  AGYGSTxTagxxsxlt  AGYGSTxTaqxxsxlt\
            [16.residues...]  [16.residues...]  [16.residues...]\

\ \ \N external outer membrane (sensu Gram-negative Bacteria) ; GO:0009279 \N 19012 IPR000257 Uroporphyrinogen decarboxylase (EC: 4.1.1.37) (URO-D), the fifth enzyme of the heme biosynthetic pathway, catalyzes the sequential decarboxylation of the four acetyl side chains of uroporphyrinogen to yield coproporphyrinogen [MEDLINE:92249304]. URO-D deficiency is responsible for the human genetic diseases familial porphyria cutanea tarda (fPCT) and hepatoerythropoietic porphyria (HEP). The sequence of URO-D has been well conserved throughout evolution. The best conserved region is located in the N-terminal section; it contains a perfectly conserved hexapeptide. There are two arginine residues in this hexapeptide which could be involved in the binding, via salt bridges, to the carboxyl groups of the propionate side chains of the substrate.

The crystal structure of human uroporphyrinogen decarboxylase shows it as comprised of a single domain containing a (/)8-barrel with a deep active site cleft formed by loops at the C-terminal ends of the barrel strands. \ URO-D is a dimer in solution. Dimerisation juxtaposes the active site clefts of the monomers, suggesting a functionally important interaction between the catalytic centers [MEDLINE:98232492].

\ \ uroporphyrinogen decarboxylase activity ; GO:0004853 \N porphyrin biosynthesis ; GO:0006779 19011 IPR000256 NS1 is a homodimeric RNA-binding protein found in influenza virus that is required for viral replication. NS1 binds polyA tails of mRNA keeping them in the nucleus. NS1 inhibits pre-mRNA splicing by tightly binding to a specific stem-bulge of U6 snRNA [MEDLINE:98025053].\ RNA binding activity ; GO:0003723 \N \N 19010 IPR000254 The microbial degradation of cellulose and xylans requires several types of enzymes such as endoglucanases (EC: 3.2.1.4), cellobiohydrolases (EC: 3.2.1.91) (exoglucanases), or xylanases (EC: 3.2.1.8) [MEDLINE:91359927]. Structurally, cellulases and xylanases generally consist of a catalytic domain joined to a cellulose-binding domain (CBD) by a short linker sequence rich in proline and/or hydroxy-amino acids. The CBD of a number of fungal cellulases has been shown to consist of 36 amino acid residues, and it is found either at the N-terminal or at the C-terminal extremity of the enzymes. As it is shown in the following schematic representation, there are four conserved cysteines in this type of CBD domain, all involved in disulfide bonds.

\
                         +----------------+\
                         |          +-----|---------+\
                         |          |     |         |\
                  xxxxxxxCxxxxxxxxxxCxxxxxCxxxxxxxxxCx\

\ \ hydrolase activity, hydrolyzing O-glycosyl compounds ; GO:0004553 extracellular ; GO:0005576 carbohydrate metabolism ; GO:0005975 19008 IPR000252 The function of this family is unknown. The proteins containpredicted transmembrane helices and may be membrane transport proteins.\ Members of this family are found in bacteria and archaea.\ \ molecular_function unknown ; GO:0005554 membrane ; GO:0016020 \N 19009 IPR000253

The forkhead-associated (FHA) domain [MEDLINE:96005606] is a phosphopeptide recognition domain found in many regulatory proteins. It displays specificity for phosphothreonine-contining epitopes but will also recognise phosphotyrosine with relatively high affinity. It spans approximately 80-100 amino acid residues folded into an 11-stranded sandwich, which sometimes contain small helical insertions between the loops connecting the strands [MEDLINE:21909375].

To date, genes encoding FHA-contining proteins have been identified in eubacterial and eukaryotic but not aracheal genomes. The domain is present in a diverse range of proteins, such as kinases, phosphatases, kinesins, transcription factors, RNA-binding proteins and metabolic enzymes which partake in many different cellular processes - DNA repair, signal transduction, vesicular transport and protein degradation are just a few examples.

\ \ \N \N \N 19007 IPR000250

\ \

Scytalidopepsin B is a fungal aspartic protease belonging to the A4 family\ [MEDLINE:95405261], Merops id=A04.001 at http://merops.sanger.ac.uk/merops.htm]. This family of proteases has been assigned to a clan A. The\ proteins are thermostable, pepstatin insensitive and are active at low pH\ ranges [MEDLINE:95405261]. The enzyme has a unique heterodimeric structure, with a\ 39-residue light chain and a 173-residue heavy chain bound to each other\ non-covalently [MEDLINE:92011747].

\ \ aspartic-type endopeptidase activity ; GO:0004190 \N proteolysis and peptidolysis ; GO:0006508 19006 IPR000249 A family of small bacterial proteins has been discovered [MEDLINE:95020600], [MEDLINE:95173114] thatseem to be involved in the formation of specific microcompartments in the\ cell in which the metabolism of potentially toxic by-products takes place.\ These proteins have from 90 to 120 amino acid residues with the exception of\ two Synechococcus hypothetical proteins which contains respectively 275 and\ 297 amino acids and which are made up of two tandem homologous domains.\ \ \N \N \N 19005 IPR000248

Angiotensin II is the principal mediator of the renin-angiotensin system;\ it circulates in the bloodstream, stimulating vasoconstriction and\ retention of salt and water PUB00005870. It also stimulates increased fluid intake\ and regulates the neuroendocrine system. Many of its actions are mediated\ by release of hormones from endocrine glands, e.g. vasopressin, catecholamines, aldosterone, growth-hormone, etc. Molecular cloning studies have\ identifed 2 major receptor subtypes, designated AT1 and AT2.

\ \ \ angiotensin type II receptor activity ; GO:0004945 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 19004 IPR000247 Cucumoviruses are tripartite RNA plant viruses believed to share a closeevolutionary relationship with brome mosaic viruses. The cucumoviruses\ include cucumber mosaic virus\ \ \ \ [MEDLINE:91037954], peanut stunt virus\ \ \ \ [MEDLINE:92024111] and tomato aspermy virus\ \ \ \ [MEDLINE:91116297]. The viral coat proteins show a high degree of sequence\ similarity [MEDLINE:91037954].\ \ structural molecule activity ; GO:0005198 viral capsid ; GO:0019028 \N 19003 IPR000246 Two enzymes have this signature; L-asparaginase (EC: 3.5.1.1) and glycosylasparaginase (EC: 3.5.1.26).

L-asparaginase catalyses the following reaction:

\
L-asparagine + H₂O = L-aspartate + NH₃\

Glycosylasparaginase catalyzes:\

N4-(-N-acetyl-D-glucosaminyl)-L-asparagine + H(2)O =\
                                N-acetyl--glucosaminylamine + L-aspartate

\ cleaving the GlcNAc-Asn bond that links oligosaccharides to asparagine in N-linked glycoproteins. The enzyme is composed of two non-identical

subunits joined by strong non-covalent forces and has one glycosylation site located in the

subunit [MEDLINE:97031448] and plays a major role in the degradation of glycoproteins.

\ \ asparaginase activity ; GO:0004067 \N glycoprotein catabolism ; GO:0006516 19002 IPR000245

\ \

\ \ \ \ \ \ \

\ \

Several vacuolar organelles of eukaryotic cells have acidic interiors\ caused by an electrochemical proton gradient created by vacuolar ATPase \ [MEDLINE:89211433], which continually pumps protons into them. Although the proton\ gradient is not great enough to synthesise ATP (even at low concentrations\ of ATP), it is essential for some organelle functions, including\ accumulation of hormones and neurotransmitters in secretory granules, and\ acidification of lysosomes to create optimal conditions for lysozyme\ hydrolases [MEDLINE:91248182].\ Vacuolar ATPase is distinct from 2 other forms of membrane ATPase (plasma\ membrane and eubacterial), although the structures of all 3 types are\ similar [MEDLINE:88289753]. The protein comprises 2 main domains: a membrane bound domain,\ which contains at least 2 different subunits (20 kDa and 16 kDa); and a\ peripheral domain, which contains an ATP hydrolysis site. The 16 kDa\ subunit of the membrane domain has 4 transmembrane regions, and has been\ implicated in the proton-conducting role of the enzyme. Electron microscopy \ studies have shown that vacuolar ATPase has a 'ball and stalk' structure\ resembling that of the mitochondrial F-ATPase PUB00003103.

\ \ hydrogen-transporting two-sector ATPase activity ; GO:0003936 membrane ; GO:0016020 proton transport ; GO:0015992 19001 IPR000244

\ \ \

Ribosomal protein L9 is one of the proteins from the large ribosomal subunit.\ In Escherichia coli, L9 is known to bind directly to the 23S rRNA. It belongs\ to a family of ribosomal proteins grouped on the basis of sequence similarities\ [MEDLINE:94139664], PUB00005071.

The crystal structure of Bacillus stearothermophilus L9 shows the 149-residue protein comprises two globular domains connected by a rigid linker PUB00005071. Each domain contains an rRNA binding site, and the protein functions as a\ structural protein in the large subunit of the ribosome. The C-terminal domain consists of two loops, an -helix and a three-stranded mixed\ parallel, anti-parallel -sheet packed against the central -helix. The long central -helix is exposed to solvent in the middle and participates in the\ hydrophobic cores of the two domains at both ends.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 18997 IPR000241 This domain is probably a methylase. It is associated with the THUMP domain that also occurs with RNA modification domains [MEDLINE:21192780].\ molecular_function unknown ; GO:0005554 \N \N 18998 IPR000242

\
Protein tyrosine phosphate + H₂O = protein tyrosine + P_i\

\ \ These enzymes are very important in the control of cell growth,\ proliferation, differentiation and transformation. Multiple forms of PTPase\ have been characterized and can be classified into two categories: soluble\ PTPases and transmembrane receptor proteins that contain PTPase domain(s).

\ \

Structurally, all known receptor PTPases, are made up of a variable length\ extracellular domain, followed by a transmembrane region and a C-terminal\ catalytic cytoplasmic domain. Some of the receptor PTPases contain fibronectin\ type III (FN-III) repeats, immunoglobulin-like domains, MAM domains or\ carbonic anhydrase-like domains in their extracellular region. The cytoplasmic\ region generally contains two copies of the PTPAse domain. The first seems to\ have enzymatic activity, while the second is inactive but seems to affect\ substrate specificity of the first. In these domains, the catalytic cysteine\ is generally conserved but some other, presumably important, residues are not.

\ \

PTPase domains consist of about 300 amino acids. There are two conserved\ cysteines, the second one has been shown to be absolutely required for\ activity. Furthermore, a number of conserved residues in its immediate\ vicinity have also been shown to be important.

\ \ protein tyrosine phosphatase activity ; GO:0004725 \N protein amino acid dephosphorylation ; GO:0006470 18999 IPR000243 The proteasome (or macropain) (EC: 3.4.25.1) [MEDLINE:93228587], [MEDLINE:89104406], [MEDLINE:92278429], [MEDLINE:95211199], [MEDLINE:97036935] is a eukaryotic andarchaebacterial multicatalytic proteinase complex that seems to be involved in\ an ATP/ubiquitin-dependent nonlysosomal proteolytic pathway. In eukaryotes the\ proteasome is composed of about 28 distinct subunits which form a highly\ ordered ring-shaped structure (20S ring) of about 700 Kd.\ Most proteasome subunits can be classified, on the basis on sequence\ similarities into two groups, A and B. Subunits that belong to the B-type\ group are proteins of from 190 to 290 amino acids that share a number of\ conserved sequence regions.\ \ \ 20S core proteasome complex ; GO:0005839\ proteasome endopeptidase activity ; GO:0004299 \N ubiquitin-dependent protein catabolism ; GO:0006511 19000 IPR000244

\ \ \

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 18995 IPR000239 Rapid regulation of G-protein-coupled receptors (GPCRs) involves agonist-promoted receptor phosphorylation by GPCR kinases (GRKs) [MEDLINE:97248497]. This process\ is followed by arrestin binding and transient receptor internalisation. \ It has been shown that

-adrenergic receptor kinase (

ARK-1 or GRK2)\ follows a similar pattern of internalisation upon agonist activation of

(2)-adrenergic receptors (

(2)AR) and that

ARK expression\ levels modulate receptor sequestration [MEDLINE:97248497]. Such studies indicate a\ functional relationship between receptor phosphorylation and sequestration,\ showing that

ARK not only translocates from the cytoplasm to the\ plasma membrane in response to receptor occupancy, but also shares\ endocytic mechanisms with the

(2)AR [MEDLINE:97248497]. These results suggest a role\ for

ARK in the sequestration process, or involvement of receptor\ internalisation in the intracellular trafficking of the kinase [MEDLINE:97248497].\ \ ATP binding activity ; GO:0005524 \N signal transduction ; GO:0007165 18996 IPR000240 Maspin is a member of the serpin family of protease inhibitors [MEDLINE:94120413]. Theprotein is expressed in normal mammary epithelial cells but not in most\ mammary carcinoma cell lines. Analysis of human breast cancer specimens\ has revealed that loss of maspin expression occurs most frequently in\ advanced cancers, supporting the hypothesis that maspin functions as a\ tumour suppressor [MEDLINE:94120413].\ \ serine protease inhibitor activity ; GO:0004867 \N \N 18992 IPR000236 The hepatitis B virus (HBV) X gene shares sequences with both the polymerase and precore genes, carries several regulatory signals critical to the replicative cycle, and its product has a transactivating function [MEDLINE:96005033]. The transactivating function is probably associated with a tumorigenic potential of HBx, since x gene sequences, encoding functional HBx, have been repeatedly found integrated into the genome of liver carcinoma cells [MEDLINE:96138896].\ \N \N \N 18993 IPR000237 The GRIP (golgin-97, RanBP2alpha,Imh1p and p230/golgin-245) domain[MEDLINE:99227354], [MEDLINE:99227355], [MEDLINE:99227356]\ is found in many large coiled-coil proteins. It has been shown to\ be sufficient for targeting to the Golgi. The GRIP domain contains\ a completely conserved tyrosine residue.\ \ \N \N \N 18994 IPR000238

\ \ \

Ribosome-binding factor A [MEDLINE:98083058] (gene rbfA) is a bacterial protein that\ associates with free 30S ribosomal subunits. It does not associate with 30S\ subunits that are part of 70S ribosomes or polysomes. It is essential for\ efficient processing of 16S rRNA.\ Ribosome-binding factor A is a protein of from 13 to 15 Kd which is found in\ most prokaryotic organisms. A putative chloroplastic form seems to exist in\ plants.

\ \ \N \N rRNA processing ; GO:0006364 18991 IPR000235

\ \ \

Ribosomal protein S7 is one of the proteins from the small ribosomal subunit.\ In Escherichia coli, S7 is known to bind directly to part of the 3'end of 16S\ ribosomal RNA. It belongs to a family of ribosomal proteins which have been grouped on the\ basis of sequence similarities [MEDLINE:93332645], PUB00005070, PUB00005070. THe structure for S7 is known [MEDLINE:97473002].

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 18989 IPR000233 Cadherins are transmembrane glycoproteins vital in calcium-dependent cell-cell adhesion during tissue differentiation [MEDLINE:89091113]. Cadherins cluster to form foci of homophilic binding units. A key determinant to the strength of the binding that it is mediated by cadherins is the juxtamembrane region of the cadherin. This region induces clustering and also binds to the protein p120ctn [MEDLINE:98234411]. The cytoplasmic region is highly conserved in sequence and has been shown experimentally to regulate the cell-cell binding function of the extracellular domain of E-cadherin, possibly through interaction with the cytoskeleton [MEDLINE:89091113]. This domain is found upstream of the cadherin domain IPR002126.\ \ calcium ion binding activity ; GO:0005509 membrane ; GO:0016020 homophilic cell adhesion ; GO:0007156 18990 IPR000234 This family of proteins are the surface glycoprotein of various herpesviruses.The glycoprotein is anchored to the lipid envelope of the virus by a transmembrane region.\ \ \N \N \N 18988 IPR000232 Heat shock factor (HSF) is a transcriptional activator of heat shock genes[MEDLINE:91077922]: it binds specifically to heat shock promotor elements, which are\ palindromic sequences rich with repetitive purine and pyrimidine motifs [MEDLINE:91077922].\ Under normal conditions, HSF is a homotrimeric cytoplasmic protein, but\ heat shock activation results in relocalisation to the nucleus [MEDLINE:91334376].\ Each HSF monomer contains one C-terminal and three N-terminal leucine zipper\ repeats [MEDLINE:91334377]. Point mutations in these regions result in disruption of\ cellular localisation, rendering the protein constitutively nuclear [MEDLINE:91334376].\ Two sequences flanking the N-terminal zippers fit the consensus of a bi-\ partite nuclear localisation signal (NLS). Interaction between the N- and \ C-terminal zippers may result in a structure that masks the NLS sequences \ : following activation of HSF, these may then be unmasked, resulting in \ relocalisation of the protein to the nucleus [MEDLINE:91334377]. The DNA-binding component\ of HSF lies to the N-terminus of the first NLS region, and is referred to\ as the HSF domain.\ \ transcription factor activity ; GO:0003700 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 18986 IPR000229 Arenaviruses are single stranded RNA viruses. This family represents thenucleocapsid protein that encapsidates the viral ssRNA [MEDLINE:96177154].\ \ \N viral nucleocapsid ; GO:0019013 \N 18987 IPR000231

\ \ \

A number of eukaryotic, bacterial and archaebacterial ribosomal proteins can be grouped\ on the basis of sequence similarities. One of these families consists of:\ \

Mammalian L30 [MEDLINE:86006278]

Leishmania major L30

Yeast YL32 [MEDLINE:88058966].

Bacillus subtilis hypothetical protein ybxF

Thermococcus celer L30 [MEDLINE:92051399]

A probable ribosomal protein (ORF 1) from Methanococcus vannielii [MEDLINE:89362493]

A probable ribosomal protein (ORF 104) from Sulfolobus acidocaldarius [MEDLINE:89315197]

\ \

These proteins, of the L30e family, have 82 to 114 amino-acid residues.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 18985 IPR000228 RNA cyclases are a family of RNA-modifying enzymes that are conserved in eukaryotes, bacteria and archaea.\ RNA 3'-terminal phosphate cyclase (EC: 6.5.1.4) [MEDLINE:97327572], [MEDLINE:90340098] catalyzes the conversion\ of 3'-phosphate to a 2',3'-cyclic phosphodiester at the end of RNA.\

\
ATP + RNA 3'-terminal-phosphate = AMP + diphosphate + RNA terminal-2',3'-cyclic-phosphate\

\ These enzymes might be responsible for production of the cyclic phosphate RNA ends that are known to be required by many RNA ligases in both prokaryotes and eukaryotes.\

RNA cyclase is a protein of from 36 to 42 Kd. The best conserved region is a\ glycine-rich strech of residues located in\ the central part of the sequence and which is reminiscent of various ATP, GTP\ or AMP glycine-rich loops.

The crystal structure of RNA 3'-terminal phosphate cyclase shows that each molecule consists of two domains. The larger domain contains three repeats of a folding unit comprising two parallel helices and a\ four-stranded sheet; this fold was previously identified in translation initiation factor 3 (IF3).\ The large domain is similar to one of the two domains of 5-enolpyruvylshikimate-3-phosphate\ synthase and UDP-N-acetylglucosamine enolpyruvyl transferase. The smaller domain uses a\ similar secondary structure element with different topology, observed in many other proteins such\ as thioredoxin [MEDLINE:20139688]. Although the active site of this enzyme could not be\ unambiguously assigned, it can be mapped to a region surrounding His309, an adenylate\ acceptor, in which a number of amino acids are highly conserved in the enzyme from different\ sources [MEDLINE:20139688].

\ \ RNA-3'-phosphate cyclase activity ; GO:0003963 \N \N 18984 IPR000228 RNA cyclases are a family of RNA-modifying enzymes that are conserved in eukaryotes, bacteria and archaea.\ RNA 3'-terminal phosphate cyclase (EC: 6.5.1.4) [MEDLINE:97327572], [MEDLINE:90340098] catalyzes the conversion\ of 3'-phosphate to a 2',3'-cyclic phosphodiester at the end of RNA.\

\
ATP + RNA 3'-terminal-phosphate = AMP + diphosphate + RNA terminal-2',3'-cyclic-phosphate\

\ These enzymes might be responsible for production of the cyclic phosphate RNA ends that are known to be required by many RNA ligases in both prokaryotes and eukaryotes.\

\ \ RNA-3'-phosphate cyclase activity ; GO:0003963 \N \N 18980 IPR000224 This protein is found in ssRNA negative-strand rhabdoviruses. It isknown as the phosphoprotein or P protein [MEDLINE:98042447],\ [MEDLINE:98001332]. This protein may be part of the RNA\ dependent RNA polymerase complex [MEDLINE:98042447]. The\ phosphorylation states of this protein may regulate the transcription\ and replication complexes [MEDLINE:98001332].\ \ RNA-directed RNA polymerase activity ; GO:0003968 \N \N 18981 IPR000225

The armadillo repeat is an approximately 40 amino acid long tandemlyrepeated sequence motif first identified in the Drosophila melanogaster segment polarity\ gene armadillo. Similar repeats were later found in the mammalian armadillo\ homolog -catenin, the junctional plaque protein plakoglobin, the\ adenomatous polyposis coli (APC) tumor suppressor protein, and a number\ of other proteins [MEDLINE:94170379].

\ \

The 3 dimensional fold of an armadillo repeat is known from the crystal\ structure of -catenin [MEDLINE:98449700]. There, the 12 repeats form a superhelix of -helices, with three helices per unit. The cylindrical structure\ features a positively charged grove which presumably interacts with the\ acidic surfaces of the known interaction partners of -catenin.

\ \ \N \N \N 18982 IPR000226 Interleukin-7 (IL-7) [MEDLINE:89302581] is a cytokine that serves as a growth factor forearly lymphoid cells of both B- and T-cell lineages. Interleukin-9 (IL-9) [MEDLINE:90257340]\ is a cytokine that supports IL-2 independent and IL-4 independent growth of\ helper T-cells.\ Interleukin-7 and -9 seems to be evolutionary related PUB00001026.\ \ growth factor activity ; GO:0008083 extracellular ; GO:0005576 immune response ; GO:0006955 18983 IPR000227 Angiotensinogen [MEDLINE:83169849], is catalytically cleaved by renin to produce angio- tensin I in response to lowered blood pressure. Angiotensin converting\ enzyme (ACE), subsequently removes a dipeptide to produce angiotensin II,\ the physiologically active peptide, which functions in the regulation of\ volume and mineral balance of body fluids. Angiotensinogen is synthesised\ in the liver and secreted in plasma. The protein belongs to the superfamily\ of serine protease inhibitors.\ Angiotensinogen appears to be associated with a predisposition to essential\ hypertension; it is also associated with pregnancy-induced hypertension\ (pih) (preeclampsia), a heterogeneous disorder that complicates 5-7% of all\ pregnancies and remains a leading cause of maternal, foetal and neonatal\ morbidity and mortality [MEDLINE:93291876].\ \ serine protease inhibitor activity ; GO:0004867 \N \N 18976 IPR000220 Protein phosphorylation plays a central role in many biological and biomedical phenomena. Substrates of tyrosine protein kinases are generally characterized by a lysine\ or an arginine seven residues to the N-terminal side of the phosphorylated\ tyrosine [MEDLINE:98315925]. An acidic residue (Asp or Glu) is often found at either three or\ four residues to the N-terminal side of the tyrosine\ [MEDLINE:82174595].\ There are a number of exceptions to this rule such as the tyrosine phosphorylation sites\ of enolase and lipocortin II [MEDLINE:84239729].\

Note: No protein matches are shown due to the low specificity of this rule.

\ \ \N \N \N 18977 IPR000221 Protamines are small, highly basic proteins, that substitute for histones insperm chromatin during the haploid phase of spermatogenesis. They pack\ sperm DNA into a highly condensed, stable and inactive complex. There are\ two different types of mammalian protamine, called P1 and P2. P1 has been\ found in all species studied, while P2 is sometimes absent. There seems to be\ a single type of avian protamine whose sequence is closely related to that of\ mammalian P1 [MEDLINE:90036816].\ \ DNA binding activity ; GO:0003677 nucleus ; GO:0005634 spermatogenesis ; GO:0007283 18978 IPR000222 Protein phosphatase 2C (PP2C) is one of the four major classes of mammalianserine/threonine specific protein phosphatases (EC: 3.1.3.16). PP2C [MEDLINE:92201367] is a\ monomeric enzyme of about 42 Kd which shows broad substrate specificity and\ is dependent on divalent cations (mainly manganese and magnesium) for its\ activity. Its exact physiological role is still unclear. Three isozymes are\ currently known in mammals: PP2C-

, -

and -gamma. In yeast, there are\ at least four PP2C homologs: phosphatase PTC1 [MEDLINE:93360976] which has weak tyrosine\ phosphatase activity in addition to its activity on serines, phosphatases PTC2\ and PTC3, and hypothetical protein YBR125c. Isozymes of PP2C are also known\ from Arabidopsis thaliana (ABI1, PPH1), Caenorhabditis elegans (FEM-2,\ F42G9.1, T23F11.1), Leishmania chagasi and Paramecium tetraurelia.\ In A. thaliana, the kinase associated protein phosphatase (KAPP) [MEDLINE:95063913]\ is an enzyme that dephosphorylates the Ser/Thr receptor-like kinase RLK5 and\ which contains a C-terminal PP2C domain.\

\ \ protein serine/threonine phosphatase activity ; GO:0004722 protein serine/threonine phosphatase complex ; GO:0008287 protein amino acid dephosphorylation ; GO:0006470 18979 IPR000223

At least 3 eubacterial leader peptidases are known: murein prelipoprotein\ peptidase, which cleaves the leader peptide from a component of the\ bacterial outer membrane; type IV prepilin leader peptidase; and the serine-dependent\ leader peptidase 1, which has the more general role of cleaving\ the leader peptide from a variety of secreted proteins and proteins directed\ to the periplasm and periplasmic membrane [MEDLINE:95147689]. Leader peptidase 1 is\ similar to the eukaryotic signal peptidase, although the bacterial protein\ is monomeric, while the eukaryotic protein is multimeric [MEDLINE:95147689].

Mitochondria contain a similar two-subunit serine protease that removes\ leader peptides from nuclear- and mitochondrially-encoded proteins, which\ localise in the inner mitochondrial space [MEDLINE:95147689]. The catalytic residues of a\ number of these peptides have been identified as a serine/lysine dyad [MEDLINE:95147689].

\ \ serine-type peptidase activity ; GO:0008236 membrane ; GO:0016020 proteolysis and peptidolysis ; GO:0006508 18974 IPR000218

\ \ \

Ribosomal protein L14 is one of the proteins from the large ribosomal subunit.\ In eubacteria, L14 is known to bind directly to the 23S rRNA. It belongs to a\ family of ribosomal proteins which have been grouped on the basis of sequence\ similarities PUB00005071.\ L14 is a protein of 119 to 137 amino-acid residues.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 18975 IPR000219

The Rho family GTPases Rho, Rac and CDC42 regulate a diverse array of cellularprocesses. Like all members of the Ras superfamily, the Rho proteins cycle between active GTP-bound and inactive GDP-bound conformational states.\ Activation of Rho proteins through release of bound GDP and subsequent\ binding of GTP, is catalyzed by guanine nucleotide exchange factors (GEFs) in\ the Dbl family. The proteins encoded by members of the Dbl family share a\ common domain, presented in this entry, of about 200 residues (designated the Dbl homology or DH domain)\ that has been shown to encode a GEF activity specific for a number of Rho\ family members. In addition, all family members possess a second, shared\ domain designated the pleckstrin homology (PH) domain (IPR001849). Trio\ and its homolog UNC-73 are unique within the Dbl family insomuch as they\ encode two distinct DH/PH domain modules. The PH domain is invariably located\ immediately C-terminal to the DH domain and this invariant topography suggests\ a functional interdependence between these two structural modules. Biochemical\ data have established the role of the conserved DH domain in Rho GTPase\ interaction and activation, and the role of the tandem PH domain in\ intracellular targeting and/or regulation of DH domain function. The DH domain\ of Dbl has been shown to mediate oligomerization that is mostly homophilic in\ nature. In addition to the tandem DH/PH domains Dbl family GEFs contain\ diverse structural motifs like serine/threonine kinase, RBD,\ PDZ, RGS, IQ, REM, Cdc25\ RasGEF, CH, SH2, SH3, EF, spectrin or Ig.

\ \

The DH domain is composed of three structurally conserved regions separated by\ more variable regions. It does not share significant sequence homology with\ other subtypes of small G-protein GEF motifs such as the Cdc25 domain and the\ Sec7 domain, which specifically interact with Ras and ARF\ family small GTPases, respectively, nor with other Rho protein interactive\ motifs, indicating that the Dbl family proteins are evolutionarily unique. The\ DH domain is composed of 11 helices that are folded into a flattened,\ elongated -helix bundle in which two of the three conserved regions,\ conserved region 1 (CR1) and conserved region 3 (CR3), are exposed near the\ center of one surface. CR1 and CR3, together with a part of -6 and the\ DH/PH junction site, constitute the Rho GTPase interacting pocket.

\ \ \ \N \N \N 18969 IPR000212

Members of this family are helicases that catalyse ATP dependentunwinding of double stranded DNA to single stranded DNA. THe family\ includes both Rep and UvrD helcases.\ The Rep family helicases are composed of four structural domains [MEDLINE:97433075].\ The Rep proteins function as dimers.

\ \ ATP binding activity ; GO:0005524 \N DNA repair ; GO:0006281 18970 IPR000213 A number of serum transport proteins are known to be evolutionarily related,including albumin,

-fetoprotein, vitamin D-binding protein and afamin\ [MEDLINE:90112461], [MEDLINE:86216223], [MEDLINE:94299534]. Albumin is the main protein of plasma; it binds water, cations (such\ as Ca²⁺, Na⁺ and K⁺), fatty acids, hormones, bilirubin and drugs - its main\ function is to regulate the colloidal osmotic pressure of blood. Alphafeto-\ protein (

-fetoglobulin) is a foetal plasma protein that binds various\ cations, fatty acids and bilirubin. The biological role of afamin \ (

-albumin) has not yet been characterised.\ Vitamin D-binding protein (DBP) is an abundant serum glycoprotein secreted\ by the liver; the protein transports vitamin D sterols, binds to actin, and \ is found on the surface of B-lymphocytes and subpopulations of T-lymphocytes\ [MEDLINE:86140127]. The full length DBP contains 476-amino acids, including a 16-amino\ acid signal sequence. Sequence analysis reveals 23% similarity to albumin\ and to

-fetoprotein [MEDLINE:86140127]. DBP contains a characteristic placement of\ cysteine residues, identical to that in albumin, suggesting a similar\ folding structure. Albumin and

-fetoprotein contain three internally\ repeated domains [MEDLINE:86140127]. DBP shows similarity to the first two domains and\ has a truncated third domain, supporting the view that DBP is a member of\ the albumin/

-fetoprotein multigene family [MEDLINE:86140127]. \ Within the sequence, regularly-spaced disulphide bridges generate a 3-domain\ folding structure, each domain containing ~170 amino acids, with 5 or 6\ internal disulphide bonds, as shown schematically below: \ \

\
                    +---+          +----+                        +-----+\
                    |   |          |    |                        |     |\
 xxCxxxxxxxxxxxxxxxxCCxxCxxxxCxxxxxCCxxxCxxxxxxxxxCxxxxxxxxxxxxxxCCxxxxCxxxx\
   |                 |       |     |              |               |\
   +-----------------+       +-----+              +---------------+\

\ \ carrier activity ; GO:0005386 extracellular space ; GO:0005615 transport ; GO:0006810 18971 IPR000214 This family is the zinc binding site in the C-terminal part of the Formamidopyrimidine-DNA glycosylaseenzyme where fours conserved and essential [MEDLINE:93232071] cysteines are located.\ Formamidopyrimidine-DNA glycosylase (EC: 3.2.2.23) [MEDLINE:95219097] (Fapy-DNA glycosylase)\ (gene fpg) is a bacterial enzyme involved in DNA repair and which excise\ oxidized purine bases to release 2,6-diamino-4-hydroxy-5N-methylformamido-\ pyrimidine (Fapy) and 7,8-dihydro-8-oxoguanine (8-OxoG) residues. In addition\ to its glycosylase activity, FPG can also nick DNA at apurinic/apyrimidinic\ sites (AP sites). FPG is a monomeric protein of about 32 Kd which binds and\ require zinc for its activity.\ \ zinc ion binding activity ; GO:0008270 \N DNA repair ; GO:0006281 18972 IPR000215 Serpins (SERine Proteinase INhibitors) PUB00005319, PUB00005319, [MEDLINE:93114442] are a group of structurallyrelated proteins. They are high molecular weight (400 to 500 amino acids),\ extracellular, irreversible serine protease inhibitors with a well defined\ structural-functional characteristic: a reactive region that acts as a 'bait'\ for an appropriate serine protease. This region is found in the C-terminal\ part of these proteins. Structure is a multi-domain fold containing a bundle of\ helices and a

sandwich.\ On the basis of strong sequence similarities, a number of proteins with no\ known inhibitory activity are said to belong to this family.\ \ serine protease inhibitor activity ; GO:0004867 \N \N 18973 IPR000217

\ \ structural molecule activity ; GO:0005198 microtubule ; GO:0005874 microtubule-based movement ; GO:0007018 18967 IPR000210 The BTB (for BR-C, ttk and bab) [MEDLINE:95024186] or POZ (for Pox virus and Zinc finger)[MEDLINE:95047323] domain is present near the N terminus of a fraction of zinc finger\ (IPR007087 motif such as Kelch and a family of pox virus proteins.\ The BTB/POZ domain mediates homomeric dimerisation and in some instances\ heteromeric dimerisation [MEDLINE:95047323].\ The structure of the dimerised PLZF BTB/POZ domain has been solved and\ consists of a tightly intertwined homodimer. The central scaffolding of\ the protein is made up of a cluster of

-helices flanked by short

-sheets at both the top and bottom of the molecule [MEDLINE:98445335].\ POZ domains from several zinc finger proteins have been shown to mediate\ transcriptional repression and to interact with components of histone\ deacetylase co-repressor complexes including N-CoR and SMRT [MEDLINE:96192327], [MEDLINE:99039764], [MEDLINE:98438551].\ The POZ or BTB domain is also known as BR-C/Ttk or ZiN.\ \ protein binding activity ; GO:0005515 \N \N 18968 IPR000211

The movement of bipartite Geminiviruses such as squash leaf curl virus (SqLCV) requires the cooperativeinteraction of two essential virus-encoded movement proteins, BR1 and BL1. Recent studies of SqLCV and bean dwarf mosaic virus have shown that BR1 and BL1 act in a cooperative manner to move the viral genome intracellularly from the nucleus to the cytoplasm and across the wall cell to cell. BR1 is a nuclear shuttle protein, and it has been proposed to bind newly replicated viral ssDNA genomes and move these between the nucleus and cytoplasm. These BR1-genome complexes are then directed to the cell periphery through interactions between BR1 and\ BL1, where, as the result of BL1 action, the complexes are moved to adjacent uninfected cells. The precise\ mechanism by which BL1 acts to transport these genome complexes across the cell wall, and whether this may differ in different cell\ types, remains at issue [MEDLINE:98440591].

\ \ \N \N \N 18965 IPR000208 Flaviviruses produce a polyprotein from the ssRNA genome. The polyprotein is cleaved to a number of products one of which is NS5. Recombinant dengue type 1 virus NS5 protein expressed in Escherichia coli exhibits RNA-dependent RNA polymerase activity.This RNA-directed RNA polymerase possesses a number of short\ regions and motifs homologous to other RNA-directed RNA \ polymerases [MEDLINE:96182933].\ \ ATP binding activity ; GO:0005524 \N \N 18966 IPR000209

The subtilisin family (S8) is the second largest serine protease family\ characterised to date. Over 200 subtilases are presently known, more than 170 of which with their complete amino acid sequence [MEDLINE:97223819]. It is widespread, being found in eubacteria,\ archaebacteria, eukaryotes and viruses [MEDLINE:95147689]. The vast majority of the\ family are endopeptidases, although there is an exopeptidase, tripeptidyl\ peptidase [MEDLINE:95147689], [MEDLINE:93176119]. Structures have been determined for several\ members of the subtilisin family: they exploit the same catalytic triad as\ the chymotrypsins, although the residues occur in a different order (HDS in\ chymotrypsin and DHS in subtilisin), but the structures show no other\ similarity [MEDLINE:95147689], [MEDLINE:93176119]. Some subtilisins are mosaic proteins, and others\ contain N- and C-terminal extensions that show no sequence similarity to\ any other known protein [MEDLINE:95147689]. Based on sequence homology, a subdivision into six families has been proposed [MEDLINE:97223819].

\ \

The proprotein-processing endopeptidases kexin, furin and related enzymes\ form a distinct subfamily known as the kexin subfamily. These preferentially\ cleave C-terminally to paired basic amino acids. Members of this subfamily\ can be identified by subtly different motifs around the active site [MEDLINE:95147689], [MEDLINE:93176119].\ Members of the kexin family, along with endopeptidases R, T and K from the\ yeast Tritirachium and cuticle-degrading peptidase from Metarhizium, require\ thiol activation. This can be attributed to the presence of Cys-173 near to\ the active histidine [MEDLINE:93176119].Only 1 viral member of the subtilisin family is known, a 56-kDa protease from herpes virus 1, which infects the channel catfish [MEDLINE:95147689].

\ \ subtilase activity ; GO:0004289 \N proteolysis and peptidolysis ; GO:0006508 18964 IPR000207

A limited distribution of -2B receptor mRNA has been demonstrated by\ Northern analysis, it being found for example in only 2 peripheral tissues\ (liver and kidney), and not in the brain . The receptor inhibits adenylyl\ cyclase and L-type calcium channels through a pertussis-toxin-insensitive\ G-protein belonging to the Gi/G0 class PUB00005869.

\ \ alpha2-adrenergic receptor activity ; GO:0004938 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 18962 IPR000205 This is a potential NAD binding domain, and has been found in a wide range of proteins including alcohol dehydrogenases; amine oxidase; phytoene dehydrogenase; glutamate and other dehydrogenases; uptake proteins and several hypothetical proteins.\ \N \N \N 18963 IPR000206

\ \ \

This family of large subunit ribosomal proteins is called the L7/L12\ family. L7/L12 is present in each 50S subunit in four copies organized as two dimers.\ The L8 protein complex consisting of two dimers of L7/L12 and L10 in Escherichia coli\ ribosomes is assembled on the conserved region\ of 23 S rRNA termed the GTPase-associated domain [MEDLINE:99419037].\ The L7/L12 dimer probably interacts with EF-Tu.\ L7 and L12 only differ in a single post translational modification\ of the addition an acetyl group to the N terminus of L7.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 18960 IPR000203

This domain has been termed the GPS domain (for GPCR proteolytic site), because it contains a cleavage site in O97830

GPS domains are about 50 residues long and contain either 2 or 4 cysteine residues that are likely to form disulphide bridges. Based on conservation of these cysteines the following pairing can be predicted.

\ \

\ +-----------------+\ | |\ +-----------------+---------------+ |\ | | | |\ XXXCXXXXXXXXXXXXXXXXXCXXXXXXXXXXXXXXXCXCXXLTXXXXXXX\ ^\ cleavage site\

\ \ \N membrane ; GO:0016020 neuropeptide signaling pathway ; GO:0007218 18961 IPR000204

The hypothalamus plays a central role in the integrated control of feeding\ and energy homeostasis [MEDLINE:98150861]. A new family of neuropeptides, orexins, have\ been identified that bind and activate two closely related (previously)\ orphan GPCRs [MEDLINE:98150861]. Orexins stimulate appetite and food consumption [MEDLINE:98320882].\ Their genes are expressed bilaterally and symmetrically in the lateral\ hypothalamus, which has been shown to be the 'feeding centre'. By contrast,\ the 'satiety centre' is expressed in the ventromedial hypothalamus and is\ dominated by the leptin-regulated neuropeptide network.

\ \ \ orexin receptor activity ; GO:0016499 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 18958 IPR000201 This domain is at the N-terminus of hepadnavirus P proteins and covers the so-called terminal protein and the spacer region of the protein. This domain is always associated with IPR000477.\ DNA-directed DNA polymerase activity ; GO:0003887 \N DNA replication ; GO:0006260 18959 IPR000202

At least eight sub-types of metabotropic receptor (MGR1-8) have been\ identified in cloning studies. The sub-types differ in their agonist\ pharmacology and signal transduction pathways PUB00005885.

mRNA for MGR5 is widespread in the brain, with a unique distribution; it is found in high\ levels in the striatum, cerebral cortex, hippocampus and olfactory bulb .\ MGR5 activates the phosphoinositide pathway, probably via a G-protein of\ the Gq/G11 class; pertussis toxin partially inhibits the response to MGR1,\ but not to MGR5 PUB00005885.

\ \ \ metabotropic glutamate, GABA-B-like receptor activity ; GO:0008067 membrane ; GO:0016020 \N 18956 IPR000199 Picornaviral proteins are expressed as a single polyproteinwhich is cleaved by the viral 3C cysteine protease. The poliovirus polyprotein is selectively cleaved between the Gln-|-Gly bond. In other picornavirus reactions Glu may be substituted for Gln, and Ser or Thr for Gly.\ The 3C cysteine protease has a fold similar to\ chymotrypsin-like serine proteinases [MEDLINE:94217813].\ \ cysteine-type endopeptidase activity ; GO:0004197 \N proteolysis and peptidolysis ; GO:0006508 18957 IPR000200

Cysteine protease activity is dependent on an active dyad of cysteine andhistidine, the order and spacing of these residues varying in the 20 or so\ known families. Families C1, C2 and C10 are loosely termed papain-like.\ Nearly half of all cysteine proteases are found exclusively in viruses [MEDLINE:95147707].

\ \

Streptopain is a cysteine protease found in Streptococcus pyogenes that\ shows some structural and functional similarity to papain (family C1) [MEDLINE:95147707], [MEDLINE:76190087]. The order of the catalytic cysteine/histidine dyad is the same and the\ surrounding sequences are similar. The two proteins also show similar\ specificities, both preferring a hydrophobic residue at the P2 site [MEDLINE:95147707], [MEDLINE:73071842].

\ \

Streptopain shows a high degree of sequence similarity to the S. pyogenes exotoxin B, and strong similarity to the prtT gene product of\ Porphyromonas gingivalis, both of which have been included in the family [MEDLINE:95147707].

\ \ cysteine-type peptidase activity ; GO:0008234 \N proteolysis and peptidolysis ; GO:0006508 18954 IPR000197 CBP and the related protein p300 are large nuclear molecules that interactwith transcriptional activators and repressors. They belong to a class of\ protein containing a histone acetyltransferase activity, which suggest a role\ in chromatin remodeling. They are involved in biological function as diverse \ as cell growth, differentiation, or apoptosis [MEDLINE:96402609].\ CBP/P300 proteins contain in their N and C terminal parts the so called\ transcriptional adaptor putative zinc finger (TAZ finger).\ Each TAZ domain is an around 100 amino acids domain which shows an internal\ triplication of a Cys-x4-Cys-x8-His-x3-Cys motif, although some of the repeats\ are imperfect. The binding sites for YY1, E1A and TFIIB in CBP and P300\ proteins have been mapped in the region that contain the TAZ finger,\ suggesting a possible protein-binding function for this motif.\ Proteins containing this domain have been found to bind phosphorylated CREB.\ \ transcription cofactor activity ; GO:0003712 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 18955 IPR000198 Members of the Rho family of small G proteins transduce signals from plasma-membranereceptors and control cell adhesion, motility and shape by actin cytoskeleton formation.\ Like all other GTPases, Rho proteins act as molecular switches, with an active\ GTP-bound form and an inactive GDP-bound form. The active conformation is promoted by\ guanine-nucleotide exchange factors, and the inactive state by GTPase-activating proteins\ (GAPs) which stimulate the intrinsic GTPase activity of small G proteins.\ This entry is a Rho/Rac/Cdc42-like GAP domain, that is found in a wide variety of large,\ multi-functional proteins [MEDLINE:97162209].\ A number of structure are known for this family\ [MEDLINE:97162209], [MEDLINE:97121392], [MEDLINE:97404320].\ The domain is composed of seven

helices.\ This domain is also known as the breakpoint cluster region-homology (BH) domain.\ \ \N \N \N 18950 IPR000193 Urocanase [MEDLINE:95031059] (EC: 4.2.1.49) (also known as imidazolonepropionate hydrolase orurocanate hydratase) is the enzyme that catalyzes the second step in the\ degradation of histidine, the hydration of urocanate into\ imidazolonepropionate.\

\
urocanate + H₂O = 4,5-dihydro-4-oxo-5-imidazolepropanoate \

\ Urocanase is found in some bacteria (gene hutU), in the\ liver of many vertebrates and has also been found in the plant Trifolium\ repens (white clover).\ Urocanase is a protein of about 60 Kd, it binds tightly to NAD⁺ and uses it\ as an electrophil cofactor. A conserved cysteine has been found to be\ important for the catalytic mechanism and could be involved in the binding of\ the NAD⁺.\ \ urocanate hydratase activity ; GO:0016153 \N histidine catabolism ; GO:0006548 18951 IPR000194

\ \

\ \ \ \ \ \ \

This family includes the ATP synthase and subunits the ATP synthase associated with flagella. The sequences of the and subunits are related and both contain a\ nucleotide-binding site for ATP and ADP. The central region is almost always associated with the N-terminal domain (see IPR004100).

Vacuolar ATPases [MEDLINE:90078145] (V-ATPases) are responsible for acidifying a variety of\ intracellular compartments in eukaryotic cells. Like F-ATPases, they are\ oligomeric complexes of a transmembrane and a catalytic sector. The sequence\ of the largest subunit of the catalytic sector (70 Kd) is related to that of\ F-ATPase subunit, while a 60 Kd subunit, from the same sector, is related\ to the F-ATPases subunit [MEDLINE:89367309].\ Archaebacterial membrane-associated ATPases are composed of three subunits.\ The chain is related to F-ATPases chain and the chain is\ related to F-ATPases chain [MEDLINE:89367309].\ A protein highly similar to F-ATPase subunits is found [MEDLINE:93259961] in some\ bacterial apparatus involved in a specialized protein export pathway that\ proceeds without signal peptide cleavage. This protein is known as fliI in\ Bacillus subtilis and Salmonella typhimurium, Spa47 (mxiB) in Shigella flexneri, HrpB6 in\ Xanthomonas campestris and yscN in Yersinia pestis virulence plasmids.

In bacteria the chain is the regulatory subunit and the chain is the catalytic subunit. In V-type ATP synthase the archaeal chain is the catalytic subunit while the chain is the regulatory subunit.

\ \ \ ATP binding activity ; GO:0005524 \N proton transport ; GO:0015992 18952 IPR000195 Identification of a TBC domain in GYP6_YEAST and GYP7_YEAST, which areGTPase activator proteins of yeast Ypt6 and Ypt7, imply that these domains\ are GTPase activator proteins of Rab-like small GTPases.\ \ \N \N \N 18953 IPR000196

\ \ \

Three genes from the spc operon in the archaeon (Crenarchaeota) Sulfolobus acidocaldarius, coding for ribosomal proteins S4E, L32E, and L19E (equivalent to rat ribosomal proteins S4, L32, and L19), were sequenced and the structure of the putative proteins was determined. The order of the ribosomal protein genes in the spc operon of the Crenarchaeota kingdom of archaea is identical to that present in the euryarchaeota kingdom of archaea. The genes for r-proteins S4E, L32E, and L19E are absent in bacteria. The archaeal r-proteins showed substantial identity to their eucaryotic equivalents, but in all cases the archaeal proteins formed a separate group from the eukaryotic proteins [MEDLINE:99310781].

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 18948 IPR000191

Formamidopyrimidine-DNA glycosylase (EC: 3.2.2.23) [MEDLINE:95219097] (Fapy-DNA glycosylase)(gene fpg) is a bacterial enzyme involved in DNA repair and which excise\ oxidized purine bases to release 2,6-diamino-4-hydroxy-5N-methylformamido-\ pyrimidine (Fapy) and 7,8-dihydro-8-oxoguanine (8-OxoG) residues. In addition\ to its glycosylase activity, FPG can also nick DNA at apurinic/apyrimidinic\ sites (AP sites). FPG is a monomeric protein of about 32 Kd which binds and\ require zinc for its activity.

The N-terminal section (PS01242) is the zinc binding site in the C-terminal part of the Formamidopyrimidine-DNA glycosylase\ enzyme where fours conserved and essential [MEDLINE:93232071] cysteines are located.

\ \ \N \N DNA repair ; GO:0006281 18949 IPR000192 Aminotransferases share certain mechanistic features with other pyridoxal-phosphate dependent enzymes, such as the covalent binding of the pyridoxal-\ phosphate group to a lysine residue. On the basis of sequence similarity,\ these various enzymes can be grouped [MEDLINE:93245981] into subfamilies.\ This family is called class-V.\ \ transaminase activity ; GO:0008483 \N metabolism ; GO:0008152 18947 IPR000190

\ \

AT1 receptors are the major subclass of the angiotensin family. The\ receptors are found in blood vessels, other smooth muscles (e.g., the\ uterus and bladder), and endocrine glands. Receptors are also present\ in the kidney, liver and on presynaptic nerve terminals, where they\ potentiate release of noradrenaline. They are distributed widely in\ the CNS and are present in high levels in the hypothalamus and anterior\ pituitary, where they stimulate release of vasopressin and ACTH res.\ AT1 receptors inhibit adenylyl cyclase and activate phosphoinositide\ metabolism via a pertussis-toxin-insensitive G-protein, probably of the\ Gq/G11 class PUB00005870.

\ \ angiotensin type II receptor activity ; GO:0004945 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 18946 IPR000189 Bacterial lytic transglycosylases degrade murein via cleavage of the

-1,4-glycosidic bond between N-acetylmuramic acid and N-acetylglucosamine, with the\ concomitant formation of a 1,6-anhydrobond in the muramic acid residue.\ Escherichia coli has at least three different lytic transglycosylases: two\ soluble isozymes of 65 Kd and 35 Kd and a membrane-bound enzyme of 38 Kd. The\ sequence of the 65 Kd enzyme (gene slt) has been determined [MEDLINE:92041559]. A domain of\ about 90 residues located near the C-terminal section of slt was recently\ shown to be present in a number of other prokaryotic and phage proteins [MEDLINE:94262160].\ This SLT domain shared by these proteins is involved in catalytic\ activity. The most conserved part of this domain is its N-terminal extremity\ that contains two conserved serines and a\ glutamate which has been shown [MEDLINE:94150707] to be involved in the catalytic mechanism.\ This family is distantly related to IPR001916.\ The structure of he SLT domain is known [MEDLINE:96038236].\ \ \N \N \N 18945 IPR000187

\ \ hormone activity ; GO:0005179 extracellular ; GO:0005576 \N 18943 IPR000185

SecA is a cytoplasmic protein of 800 to 960 amino acid residues.\ Homologs of secA are also encoded in the chloroplast genome of some algae [MEDLINE:93173098]\ as well as in the nuclear genome of plants [MEDLINE:95278349]. It could be involved in the\ intraorganellar protein transport into thylakoids.

\ \ ATP binding activity ; GO:0005524 \N intracellular protein transport ; GO:0006886 18944 IPR000186 Interleukin-5 (IL5), also known as eosinophil differentiation factor (EDF),is a lineage-specific cytokine for eosinophilpoiesis [MEDLINE:88016145], [MEDLINE:93247642]. It regulates \ eosinophil growth and activation [MEDLINE:88016145], and thus plays an important role in\ diseases associated with increased levels of eosinophils, including asthma\ [MEDLINE:93247642]. \ IL5 has a similar overall fold to other cytokines (e.g., IL2, IL4 and GCSF)\ [MEDLINE:93247642], but while these exist as monomeric structures, IL5 is a homodimer. The\ fold contains an anti-parallel 4-

-helix bundle with a left handed twist,\ connected by a 2-stranded anti-parallel

-sheet [MEDLINE:93247642], [MEDLINE:91243878]. The monomers are\ held together by 2 interchain disulphide bonds [MEDLINE:91243878].\ \ growth factor activity ; GO:0008083 extracellular ; GO:0005576 immune response ; GO:0006955 18940 IPR000183 These enzymes are collectively known as group IV decarboxylases [MEDLINE:94237165].Pyridoxal-dependent decarboxylases acting on ornithine, lysine, arginine and\ related substrates can be classified into two different families on the basis\ of sequence similarities [MEDLINE:89056708], [MEDLINE:94237165].\ Members of this family while most probably evolutionary related, do not share\ extensive regions of sequence similarities. The proteins contain a conserved lysine\ residue which is known, in mouse ODC [MEDLINE:92112641], to be the site of attachment of the\ pyridoxal-phosphate group. The proteins also contain a stretch of three\ consecutive glycine residues and has been proposed to be part of a substrate-\ binding region [MEDLINE:90330576].\ \ enzyme activity ; GO:0003824 \N \N 18941 IPR000183 These enzymes are collectively known as group IV decarboxylases [MEDLINE:94237165].Pyridoxal-dependent decarboxylases acting on ornithine, lysine, arginine and\ related substrates can be classified into two different families on the basis\ of sequence similarities [MEDLINE:89056708], [MEDLINE:94237165].\ Members of this family while most probably evolutionary related, do not share\ extensive regions of sequence similarities. The proteins contain a conserved lysine\ residue which is known, in mouse ODC [MEDLINE:92112641], to be the site of attachment of the\ pyridoxal-phosphate group. The proteins also contain a stretch of three\ consecutive glycine residues and has been proposed to be part of a substrate-\ binding region [MEDLINE:90330576].\ \ enzyme activity ; GO:0003824 \N \N 18942 IPR000184 The protein sequences of d15 from various strains of Haemophilus influenzae are highly conserved, with only a small variable region identified near the carboxyl terminus of the protein [MEDLINE:95255676]. D15 is a highly conserved antigen that is protective in animal models and it may be a useful component of a universal subunit vaccine against Haemophilus infection and disease [MEDLINE:97427952]. Membrane proteins from other bacteria have been shown to elicit protective immunity. Oma87 is a protective outer membrane antigen of Pasteurella multocida\ \ \ [MEDLINE:96333354].\ \ \N \N \N 18939 IPR000182 The predominant mechanism of antibiotic resistance employed by pathogenic bacteria against the clinically used aminoglycosides is chemical modification of the drug. The detoxification reactions are catalyzed by enzymes that promote either the phosphorylation, adenylation or acetylation of aminoglycosides. Structural studies of these aminoglycoside-modifying enzymes may assist in the development of therapeutic agents that could circumvent antibiotic resistance. In addition, such studies may shed light on the development of antibiotic resistance and the evolution of different enzyme classes. The GCN5-related N-acetyltransferase superfamily includes such enzymes as the histone acetyltransferases GCN5 and Hat1 [MEDLINE:97318594].\

The yeast GCN5 (yGCN5) transcriptional coactivator functions as a histone acetyltransferase (HAT) to promote transcriptional activation. The crystal structure of the yeast histone acetyltransferase Hat1-acetyl coenzyme A (AcCoA) shows that Hat1 has an elongated, curved structure, and the AcCoA molecule is bound in a cleft on the concave surface of the protein, marking the active site of the enzyme. A channel of variable width and depth that runs across the protein is probably the binding site for the histone substrate [MEDLINE:98394469]. The central protein core associated with AcCoA binding that appears to be structurally conserved among a superfamily of N-acetyltransferases, including yeast histone acetyltransferase 1 and Serratia marcescens aminoglycoside 3-N-acetyltransferase [MEDLINE:99362688].

\ \ N-acetyltransferase activity ; GO:0008080 \N \N 18936 IPR000178 Initiation factor 2 (IF-2) (gene infB) [MEDLINE:92215857] is one of the three factorsrequired for the initiation of protein biosynthesis in bacteria. IF-2\ promotes the GTP-dependent binding of the initiator tRNA to the small subunit\ of the ribosome. IF-2 is a protein of about 70 to 95 Kd which contains a\ central GTP-binding domain flanked by a highly variable N-terminal domain and\ a more conserved C-terminal domain.\ Bacterial IF-2 is structurally and functionally related to eukaryotic\ mitochondrial IF-2 (IF-2(mt)) [MEDLINE:95130568] as well as to algal and plants chloroplast\ IF-2 (IF-2(chl)). Both IF-2(mt) and IF-2(chl) are encoded by nuclear genes and\ are produced as precursor proteins with a transit peptide. An exception are\ red algae where IF-2(chl) is encoded by the plastid genome [MEDLINE:94033298].\ \ GTP binding activity ; GO:0005525 \N translational initiation ; GO:0006413 18937 IPR000180 Renal dipeptidase (rDP) (EC: 3.4.13.19), also known as microsomal dipeptidase,is a zinc-dependent metalloenzyme that hydrolyzes a wide range of dipeptides.\ It is involved in renal metabolism of glutathione and its conjugates. It is a\ homodimeric disulfide-linked glycoprotein attached to the renal brush border\ microvilli membrane by a GPI-anchor.\ A glutamate residue has recently been shown [MEDLINE:93237320] to be important for the\ catalytic activity of rDP.\ rDP seems to be evolutionary related to hypothetical proteins in the PQQ\ biosynthesis operons of Acinetobacter calcoaceticus and Klebsiella pneumoniae.\ \ dipeptidyl-peptidase activity ; GO:0008239 \N proteolysis and peptidolysis ; GO:0006508 18938 IPR000181

Peptide deformylase (PDF) is an essential metalloenzyme required for the removal of the formyl group at the N-terminus of nascent polypeptide chains\ in eubacteria [MEDLINE:99061332]\ \ \ \ EC: 3.5.1.31. The enzyme acts as a monomer and binds a single zinc ion, catalysing the reaction::\

\
N-formyl-L-methionine + H₂O = formate + L-methionine\

\ Catalytic efficiency strongly depends on the identity of the bound metal [MEDLINE:98234316].

The structure\ of these enymes is known [MEDLINE:97002011], [MEDLINE:98332750]. PDF, a member of the zinc metalloproteases family, comprises an active core\ domain of 147 residues and a C-terminal tail of 21 residue.\ The 3D fold of the catalytic core has been determined by X-ray crystallography and NMR.\ Overall, the structure contains a series of anti-parallel -\ strands that surround two perpendicular -helices. The C-terminal \ helix contains the characteristic HEXXH motif of metalloenzymes, which is\ crucial for activity. The helical arrangement, and the way the histidine\ residues bind the zinc ion, is reminiscent of other metalloproteases, such\ as thermolysin or metzincins. However, the arrangement of secondary and\ tertiary structures of PDF, and the positioning of its third zinc ligand (a\ cysteine residue), are quite different. These discrepancies, together with \ notable biochemical differences, suggest that PDF constitutes a new class of\ zinc-metalloproteases. \ [MEDLINE:97002011].

\ \ formylmethionine deformylase activity ; GO:0008463 \N protein biosynthesis ; GO:0006412 18934 IPR000176 This family contains viral proteins that are regulatory subunits of Poly(A)polymerase IPR001290. This protein binds to Poly(A)\ but has no catalytic activity. The structure of this protein is known [MEDLINE:96200776].\ \ \N \N transcription ; GO:0006350 18935 IPR000177 Plasma kallikrein (EC: 3.4.21.34) and coagulation factor XI (EC: 3.4.21.27) aretwo related plasma serine proteases activated by factor XIIA and which share\ the same domain topology: an N-terminal region that contains four tandem\ repeats of about 90 amino acids and a C-terminal catalytic domain.\ The 90 amino-acid repeated domain contains 6 conserved cysteines. It has been\ shown [MEDLINE:91152016] that three disulfide bonds link the first and sixth, second and\ fifth, and third and fourth cysteines. The domain can be drawn in the shape of\ an apple (see below) and has been accordingly called the 'apple domain'.\

\ x x x x x x\ x C---C x\ x x x x\ x Cx x x x\ x | x x x Schematic representation of an\ x Cx x x x apple domain.\ x x x x\ x x x x\ x x x x x\ x x\ x x x x\ C---C\ .....x x.....\

\ Apart from the cysteines, there are a number of other conserved positions in\ the apple domain.\ \ serine-type endopeptidase activity ; GO:0004252 extracellular ; GO:0005576 blood coagulation ; GO:0007596 18933 IPR000175

\ \ neurotransmitter:sodium symporter activity ; GO:0005328 membrane ; GO:0016020 neurotransmitter transport ; GO:0006836 18931 IPR000173 Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) plays an important role in glycolysis and gluconeogenesis [MEDLINE:89236409] by reversibly catalysing the oxidation and phosphorylation of D-glyceraldehyde-3-phosphate to 1,3-diphospho- glycerate. The enzyme exists as a tetramer of identical subunits, each containing 2 conserved functional domains: an NAD-binding domain, and a highly conserved catalytic domain [MEDLINE:83204759]. The enzyme has been found to bind to actin and tropomyosin, and may thus have a role in cytoskeleton assembly. Alternatively, the cytoskeleton may provide a framework for precise positioning of the glycolytic enzymes, thus permitting efficient passage of metabolites from enzyme to enzyme [MEDLINE:83204759].\ glyceraldehyde 3-phosphate dehydrogenase (phosphorylating) activity ; GO:0004365 \N glycolysis ; GO:0006096 18932 IPR000174

\ \ \ interleukin-8 receptor activity ; GO:0004918 integral to membrane ; GO:0016021 chemotaxis ; GO:0006935 18929 IPR000172 The glucose-methanol-choline (GMC) oxidoreductase oxidoreductases are FADflavoproteins oxidoreductases [MEDLINE:92177421], [MEDLINE:94032271].\ These enzymes include a variety of proteins; choline dehydrogenase (CHD), methanol oxidase (MOX) and cellobiose dehydrogenase (EC: 1.1.99.18) [MEDLINE:20191614] which share a number of regions of sequence similarities. One of\ these regions, located in the N-terminal section, corresponds to the FAD ADP-\ binding domain. The function of the other conserved domains is not yet known.\ \ oxidoreductase activity ; GO:0016491 \N electron transport ; GO:0006118 18930 IPR000173 Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) plays an important role in glycolysis and gluconeogenesis [MEDLINE:89236409] by reversibly catalysing the oxidation and phosphorylation of D-glyceraldehyde-3-phosphate to 1,3-diphospho- glycerate. The enzyme exists as a tetramer of identical subunits, each containing 2 conserved functional domains: an NAD-binding domain, and a highly conserved catalytic domain [MEDLINE:83204759]. The enzyme has been found to bind to actin and tropomyosin, and may thus have a role in cytoskeleton assembly. Alternatively, the cytoskeleton may provide a framework for precise positioning of the glycolytic enzymes, thus permitting efficient passage of metabolites from enzyme to enzyme [MEDLINE:83204759].\ glyceraldehyde 3-phosphate dehydrogenase (phosphorylating) activity ; GO:0004365 \N glycolysis ; GO:0006096 18925 IPR000167

A number of proteins are produced by plants that experience water-stress.Water-stress takes place when the water available to a plant falls below a\ critical level. The plant hormone abscisic acid (ABA) appears to modulate the\ response of plant to water-stress. Proteins that are expressed during water-\ stress are called dehydrins [MEDLINE:93357436], [MEDLINE:92379257]\ or LEA group 2 proteins PUB00004531.

\ \

Dehydrins share a number of structural features. One of the most notable\ features is the presence, in their central region, of a continuous run of\ five to nine serines followed by a cluster of charged residues. Such a region\ has been found in all known dehydrins so far with the exception of pea\ dehydrins. A second conserved feature is the presence of two copies of a\ lysine-rich octapeptide; the first copy is located just after the cluster\ of charged residues that follows the poly-serine region and the second copy\ is found at the C-terminal extremity.

\ \ \N \N response to water ; GO:0009415 18927 IPR000169

Eukaryotic thiol proteases (EC: 3.4.22.-) [MEDLINE:89166642] are a family of proteolyticenzymes which contain an active site cysteine. Catalysis proceeds through a\ thioester intermediate and is facilitated by a nearby histidine side chain; an\ asparagine completes the essential catalytic triad. The order and spacing of these residues in the active sites vary in the 20 or so\ known families. Families C1, C2 and C10 are loosely termed papain-like, and \ nearly half of all cysteine proteases are found exclusively in viruses [MEDLINE:95147707].\

\ \

The allergens in this family include allergens with the following designations: Der f 1, Der m 1 and Der p 1.

\ \ cysteine-type endopeptidase activity ; GO:0004197 \N proteolysis and peptidolysis ; GO:0006508 18928 IPR000170 High potential iron-sulfur proteins (HiPIP) [MEDLINE:92011624] are a specific class ofhigh-redox potential 4Fe-4S ferredoxins that functions in anaerobic electron\ transport and which occurs in photosynthetic bacteria and in Paracoccus\ denitrificans.\ The HiPIPs are small proteins which show significant variation in their\ sequences, their sizes (from 63 to 85 amino acids), and in their oxidation-\ reduction potentials. As shown in the following schematic representation the\ iron-sulfur cluster is bound by four conserved cysteine residues.\

\
                           [ 4Fe-4S cluster]\
                           | |       |     |\
        xxxxxxxxxxxxxxxxxxxCxCxxxxxxxCxxxxxCxxxx\
\
'C': conserved cysteine involved in the binding of the iron-sulfur cluster.\

\ \ electron transporter activity ; GO:0005489 \N electron transport ; GO:0006118 18926 IPR000168

\ \ G-protein coupled receptor activity ; GO:0004930 membrane ; GO:0016020 \N 18923 IPR000164 Histone H3 is one of the four histones, along with H2A, H2B and H4, whichform the eukaryotic nucleosome octomer core [MEDLINE:94167243];\ the nucleosome octamer winds ~146 DNA base-pairs. It is a highly conserved protein of 135\ amino acid residues [MEDLINE:94167243], [MEDLINE:91252337].\ \ DNA binding activity ; GO:0003677 nucleus ; GO:0005634 chromosome organization and biogenesis (sensu Eukarya) ; GO:0007001 18924 IPR000165

Glycoside hydrolase family 15 CAZY:GH_15).

\ \ \

Glucoamylase (GA) catalyses the release of\ D-glucose from the non-reducing ends of starch and other oligo- or poly-saccharides. Studies of fungal GA have indicated 3 closely-clustered acidic\ residues that play a role in the catalytic mechanism [MEDLINE:90231978]. This region is also conserved in a recently sequenced bacterial GA [MEDLINE:92339427].

The 3D structure of the pseudo-tetrasaccharide acarbose complexed with\ glucoamylase II(471) from Aspergillus awamori var. X100 has been determined\ to 2.4A resolution [MEDLINE:94253149]. The protein belongs to the mainly- class, and contains 19 helices and 9 strands.

\ \ glucan 1,4-alpha-glucosidase activity ; GO:0004339 \N polysaccharide metabolism ; GO:0005976 18921 IPR000162

At least eight sub-types of metabotropic receptor (MGR1-8) have been\ identified in cloning studies. The sub-types differ in their agonist\ pharmacology and signal transduction pathways PUB00005885.

\ \ metabotropic glutamate, GABA-B-like receptor activity ; GO:0008067 membrane ; GO:0016020 \N 18922 IPR000163 Genes that negatively regulate proliferation inside the cell are ofconsiderable interest because of the implications in processes such as\ development and cancer [MEDLINE:91141485]. Prohibitin, a novel cytoplasmic anti-\ proliferative protein widely expressed in a variety of tissues, inhibits\ DNA synthesis. Studies have suggested that prohibitin may be a suppressor\ gene and is associated with tumor development and/or progression of at\ least some breast cancers [MEDLINE:92174193]. Sequence comparisons suggest that the\ prohibitin gene is an analogue of Cc, a Drosophila melanogaster gene that is vital for\ normal development [MEDLINE:91141485].\ \ \N \N \N 18918 IPR000159 Proteins with this domain are mostly RasGTP effectors and include guanine-nucleotide releasing factor in mammals [MEDLINE:97141023]. This factor stimulates the dissociation of GDP from the Ras-related RALA and RALB GTPases which allows GTP binding and activation of the GTPases. It interacts and acts as as effector molecule for R-ras, K-Ras and Rap [MEDLINE:95062211].\ The domain is also present in a number of other proteins among them the sexual differentiation protein in yeast that is essential for mating and meiosis and yeast adenylate cyclase. These proteins contain repeated leucine-rich (LRR) segments.\ \ \N \N neuropeptide signaling pathway ; GO:0007218 18919 IPR000160 This domain is found linked to a wide range of non-homologous domains in a variety of bacteria. The function of this domain is unknown, however it has been shown to be homologous to the adenylyl cyclase catalytic domain [MEDLINE:20569416]. This prediction correlates with the functional information available on two GGDEF-containing proteins, namely diguanylate cyclase and\ phosphodiesterase A of Acetobacter xylinum, both of which regulate the turnover of cyclic diguanosine monophosphate. \ \ molecular_function unknown ; GO:0005554 \N \N 18920 IPR000161

Vasopressin and oxytocin are members of the neurohypophyseal hormone family\ found in all mammalian species. They are present in high levels in the\ posterior pituitary. Vasopressin has an essential role in the control of\ the water content of the body, acting in the kidney to increase water and\ sodium absorption. In higher concentrations, vasopressin stimulates\ contraction of vascular smooth muscle, stimulates glycogen breakdown in the\ liver, induces platelet activation, and evokes release of corticotrophin\ from the anterior pituitary. Vasopressin and its analogues are used\ clinically to treat diabetes insipidus PUB00005908.

The V2 receptor is found in high levels in the osmoregulatory epithelia of\ the terminal urinary tract, where it stimulates water reabsorption. It\ is also present in lower levels in the endothelium and blood vessels of some\ species, where it induces vasodilation . In the CNS, binding sites are\ found in the subiculum, with lower levels in caudate-putamen and islands\ of Calleja. The receptor is involved in an effector pathway that forms\ cAMP through activation of Gs PUB00005908.

\ \ vasopressin receptor activity ; GO:0005000 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 18915 IPR000156

Ran is an evolutionary conserved member of the Ras superfamily that regulates all receptor-mediated transport between the nucleus and the cytoplasm. Ran Binding Protein 1 (RanBP1) has guanine nucleutide dissociation inhibitory activity, specific for the GTP form of Ran and also functions to stimulate Ran GTPase activating protein(GAP)-mediated GTP hydrolysis by Ran. RanBP1 contributes to maintaining the gradient of RanGTP across the nuclear envelope high (GDI activity) or the cytoplasmic levels of RanGTP low (GAP cofactor) [MEDLINE:22014335].

All RanBP1 proteins contain an approx 150 amino acid residue Ran binding domain. Ran BP1 binds directly to RanGTP with high affinity.\ There are four sites of contact\ between Ran and the Ran binding domain. One of these\ involves binding of the C-terminal segment of Ran to a groove on the Ran binding domain that is\ analogous to the surface utilized in the EVH1peptide\ interaction [MEDLINE:99332057]. Nup358 \ contains four Ran binding domains. The structure of the first of these is known [MEDLINE:99176415].

\ \ \N \N \N 18916 IPR000157

In Drosophila melanogaster the Toll protein is involved in establishment of dorso-ventralpolarity in the embryo. In addition, members of the Toll family play a key\ role in innate antibacterial and antifungal immunity in insects as well as in\ mammals. These proteins are type-I transmembrane receptors that share an\ intracellular 200 residue domain with the interleukin-1 receptor (IL-1R), the\ Toll/IL-1R homologous region (TIR). The similarity between Toll-like receptors\ (LTRs) and IL-1R is not restricted to sequence homology since these proteins\ also share a similar signaling pathway. They both induce the activation of a\ Rel type transcription factor via an adaptor protein and a protein kinase [MEDLINE:96215042].\ Interestingly, MyD88, a cytoplasmic adaptor protein found in mammals, contains\ a TIR domain associated to a DEATH domain (see IPR000488. As MyD88, these proteins are cytoplasmic.

Site directed mutagenesis and deletion analysis have shown that the TIR domain is essential for Toll and IL-1R activities. Sequence analysis have revealed\ the presence of three highly conserved regions among the different members of\ the family: box 1 (FDAFISY), box 2 (GYKLC-RD-PG), and box 3 (a conserved W\ surrounded by basic residues). It has been proposed that boxes 1 and 2 are\ involved in the binding of proteins involved in signaling, whereas box 3 is\ primarily involved in directing localization of receptor, perhaps through\ interactions with cytoskeletal elements [MEDLINE:20138200].

\ \ transmembrane receptor activity ; GO:0004888 membrane ; GO:0016020 \N 18917 IPR000158

In bacteria, FtsZ [MEDLINE:94018635], [MEDLINE:95163089], [MEDLINE:22047837]is an essential cell division protein which appears to be involved in the initiation of this event. It assembles into a cytokinetic ring on the inner surface of the cytoplasmic\ membrane at the place where division will occur. The ring serves as a scaffold\ that is disassembled when septation is completed. FtsZ ring formation is initiated at a single\ site on one side of the bacterium and appears to grow bidirectionally. In Escherichia coli, MinCD IPR005526, encoded by the MinB locus, form a complex which appears to block the formation of FtsZ rings at the cell poles, at the ancient mid cell division\ sites, whilst MinE, encoded at the same locus, specifically prevents the action of MinCD at mid cell.

FtsZ is a GTP binding\ protein IPR005526/> with a GTPase activity.\ It undergoes GTP-dependent polymerization into\ filaments (or tubules) that seem to form a cytoskeleton involved in septum\ synthesis. The structure and the properties of\ FtsZ clearly provide it with the capacity for the cytoskeletal, perhaps motor role, necessary for "contraction" along the division plane. In addition, however, the FtsZ\ ring structure provides the framework for the recruitment or assembly of the ten or so membrane and cytoplasmic proteins, uniquely required for cell division in\ E. coli or Bacillus subtilis, some of which are required for biogenesis of the new hemispherical poles of the two daughter cells. FtsZ can polymerize into various structures, for example a single linear polymer of FtsZ monomers, called a\ protofilament. Protofilaments can associate laterally to form pairs (sometimes called thick filaments, bundles (ill-defined linear associations of multiple\ protofilaments or thick filaments, sheets (parallel or anti-parallel two-dimensional associations of thick filaments and tubes\ (anti-parallel associations of thick filaments in a circular fashion to form a tubular structure). In addition, small\ circles of FtsZ monomers (a short protofilament bent around to join itself, apparently head to tail) have been observed and termed mini-rings.

\ FtsZ is a protein of about 400 residues which is well conserved across\ bacterial species and which is also present in the chloroplast of plants [MEDLINE:95364919]\ as well as in archaebacteria [MEDLINE:96200101]. FtsZ shows structural similarity with\ eukaryotic tubulins. This similarity is probably both evolutionary and\ functionally significant.

\ \ \N \N \N 18914 IPR000155

Adrenocorticotrophin (ACTH), melanocyte-stimulating hormones (MSH) and -endorphin are peptide products of pituitary pro-opiomelanocortin.\ ACTH regulates synthesis and release of glucocorticoids and aldosterone\ in the adrenal cortex; it also has a trophic action on these cells PUB00005891.\ ACTH and -endorphin are synthesised and released in response to\ corticotrophin-releasing factor at times of stress (heat, cold, infections,\ etc.) - their release leads to increased metabolism and analgesia res..\ MSH has a trophic action on melanocytes, and regulates pigment production\ in fish and amphibia . The ACTH receptor is found in high levels in\ the adrenal cortex - binding sites are present in lower levels in the\ CNS. The MSH receptor is expressed in high levels in melanocytes,\ melanomas and their derived cell lines PUB00005891. Receptors are found in low\ levels in the CNS. MSH regulates temperature control in the septal region\ of the brain and releases prolactin from the pituitary.

A further gene, which encodes a melanocortin receptor that is functionally\ distinct from the ACTH and MSH receptors, has also been characterised [MEDLINE:93216807], [MEDLINE:94226597], [MEDLINE:94022273], [MEDLINE:96387362], [MEDLINE:95157557].\ The protein contains ~300 amino acids, with calculated molecular mass of\ ~36 KDa, and potential N-linked glycosylation and phosphorylation sites\ [MEDLINE:94226597]. The melanocortin 4 receptor (MC4-R) is regulated by opiate\ administration [MEDLINE:96387362]. Rat MC4-R is 95% identical to human MC4-R, and the\ potency of melanocortin peptides to stimulate cAMP production is similar in\ these two species homologues [MEDLINE:96387362]. Expression of MC4-R mRNA was found to be\ enriched in the striatum, nucleus accumbens, and periaque-ductal gray, all\ of which are regions implicated in the behavioral effects of opiates\ (and are regions in which MC1-, MC3- and MC5-R are expressed at low or\ undetectable levels) [MEDLINE:96387362]. MC4-R mRNA has been found in multiple sites in\ virtually every brain region, including the cortex, thalamus, hypothalamus,\ brainstem, and spinal cord [MEDLINE:95157557]. Unlike the MC3-R, MC4-R mRNA is found in\ both parvicellular and magnocellular neurons of the paraventricular nucleus\ of the hypothalamus, suggesting a role in the central control of pituitary\ function [MEDLINE:95157557].

\ \ \ melanocortin receptor activity ; GO:0004977 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 18911 IPR000152 Post-translational hydroxylation of aspartic acid or asparagine [MEDLINE:88087092] to formerythro-

-hydroxyaspartic acid or erythro-

-hydroxyasparagine has been\ identified in a number of proteins with domains homologous to epidermal growth\ factor (EGF). Examples of such proteins are the blood coagulation protein\ factors VII, IX and X, proteins C, S, and Z, the LDL receptor, thrombomodulin,\ etc. Based on sequence comparisons of the EGF-homology region that contains\ hydroxylated Asp or Asn, a consensus sequence has been identified that seems\ to be required by the hydroxylase(s).\ \ \N \N \N 18912 IPR000153 Sigma 3 is the major outer capsid protein of reovirus [MEDLINE:96211481].Sigma 3 is encoded by genome segment 4. Sigma 3 binds to \ double stranded RNA and associates with polypeptide u1 and \ its cleavage product u1C to form the outer shell of the virion.\ The Sigma 3 protein possesses a zinc-finger motif and an\ RNA-binding domain in the N and C termini respectively.\ This protein is also thought to play a role in pathogenesis.\ \ structural molecule activity ; GO:0005198 \N viral infectious cycle ; GO:0019058 18913 IPR000154

EP3 receptors mediate contraction in a wide range of smooth muscles,\ including gastrointestinal and uterine . They also inhibit neurotransmitter release in central and autonomic nerves through a presynaptic action,\ and inhibit secretion in glandular tissues (e.g., acid secretion from\ gastric mucosa, and sodium and water reabsorption in the kidney) PUB00005901. mRNA\ is found in high levels in the kidney and uterus, and in lower levels in\ the brain, thymus, lung, heart, stomach and spleen. The receptors activate\ adenylate cyclase via an uncharacterised G-protein, probably of the Gi/Go\ class PUB00005901.

Sequence analysis shows the EP3 receptors to fall into distinct classes,\ based on their N- and C-terminal and loop signatures. For convenience, we\ have designated these classes types 1 to 3.

\ \ prostaglandin E receptor activity ; GO:0004957 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 18908 IPR000149 The haemagglutinin (HA) glycoprotein of influenza is a trimer containing three structurally distinct regions: a globular head of anti-parallel

-helical stalk; and a globular foot of\ anti-parallel

-sheet [MEDLINE:88232903], [MEDLINE:85012744], [MEDLINE:81123029], [MEDLINE:81123030]. \

\ \ \N \N \N 18909 IPR000150 This family of hydrophilic proteins of about 250 to 280 amino acid residues is a COF subfamily of subfamily IIB of HAD-superfamily hydrolase. Its members are restricted almost exclusively to eubacteria and archaebacteria.\ molecular_function unknown ; GO:0005554 \N \N 18910 IPR000151

Ciliary neurotrophic factor (CNTF) is a member of the gp130 family of cytokines. CNTF is a survival factor for variousneuronal cell types and seems to prevent the degeneration of motor\ axons after axotomy suggesting it may be a potential therapeutic for treating\ neurodegeneration and nerve injury. CNTF acts on oligodendrocytes by favoring their final maturation, and this effect is mediated through the 130 kDa glycoprotein receptor common to the CNTF family and transduced through the Janus kinase pathway. The functional receptor complex of CNTF is composed of the CNTF receptor (CNTFR), gp130 and the leukemia inhibitory factor receptor (LIFR).

The structure of CNTF is a four helical bundle\ [MEDLINE:95317288]. CNTF acts as a homodimer. Three regions on CNTF have been identified as binding sites for its receptors. The ligand-receptor interactions are mediated through the cytokine binding domains (CBDs) and/or the immunoglobulin-like domains of the receptors. However, in the case of CNTF, the precise nature of the protein-protein contacts in the signaling complex has not yet been resolved however there is evidence that the membrane distal CBD (CBD1) of LIFR associates in vitro with soluble CNTFR in the absence of CNTF [MEDLINE:21940537].

\ \ \N \N \N 18906 IPR000147

Angiotensin II is the principal mediator of the renin-angiotensin system;\ it circulates in the bloodstream, stimulating vasoconstriction and\ retention of salt and water . It also stimulates increased fluid intake\ and regulates the neuroendocrine system. Many of its actions are mediated\ by release of hormones from endocrine glands, e.g. vasopressin, catecholamines, aldosterone, growth-hormone, etc.. Molecular cloning studies have\ identifed 2 major receptor subtypes, designated AT1 and AT2.

\ \

The AT2 receptor is abundant in the adrenal medulla, uterus and brain .\ Activation of AT2 receptors has been reported to decrease basal cGMP levels\ and to inhibit atrial natriuretic peptide-stimulated formation of cGMP,\ possibly by activation of a protein tyrosine phosphatase PUB00005870.

\ \ angiotensin type II receptor activity ; GO:0004945 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 18907 IPR000148 This family includes the E7 oncoprotein from various papillomaviruses [MEDLINE:21316274]. Along with E5 and E6 their activities seem to be especially important for viral oncogenesis. E5 is located at the cell surface and reduces cell gap-gap junction communication. In cervical cancer E5 is expressed in earlier stages of neoplastic transformation of the cervical epithelium during viral infection. The role of E7 is less well understood but it has been shown to impede growth arrest signals in both NIH 3T3 cells and HFKs and that this correlates with elevated cdc25A gene expression. This deregulation of cdc25A is\ linked to disruption of cell cycle arrest [MEDLINE:21624262].\ \ \ \N \N \N 18904 IPR000145 The orbivirus VP5 protein is one of the two proteins (with VP2) which make up the virus particle outer capsid. Cryoelectron microscopy indicates that VP5 is a trimer suggesting \ that there are 360 copies of VP5 per virion [MEDLINE:97428566].\ \ structural molecule activity ; GO:0005198 viral capsid ; GO:0019028 \N 18905 IPR000146 Inositol polyphosphate 1-phosphatase (1PTASE) and inositol monophosphatase(MPTASE) are enzymes of the inositol signalling pathway that share similar\ enzymatic activity [MEDLINE:95281614]. Both enzymes exhibit an absolute requirement for\ metal ions (Mg²⁺ is preferred), and both are uncompetitively inhibited by\ submillimolar concentrations of Li⁺. Their amino acid sequences contain\ a number of conserved motifs, which are also shared by several other \ proteins related to MPTASE (including products of fungal QaX and qutG,\ bacterial suhB and cysQ, and yeast hal2) [MEDLINE:95281614]. \

Structural analysis of these proteins has revealed a common core of 155\ residues: the core comprises 5 -helices and 11 -strands, and\ includes residues essential for metal binding and catalysis. While the\ core has been conserved presumably to impart catalytic function, the\ loops and regions of structure outside the core have evolved unique\ regulatory domains [MEDLINE:95281614].

An interesting property of the enzymes of this family is their sensitivity\ to Li⁺ at levels achieved in patients undergoing therapy for manic\ depression. The targets and mechanism of action of Li⁺ are unknown, but\ overactive inositol phosphate signalling may account for symptoms of the\ disease [MEDLINE:90030415]. It has been proposed that these Li⁺-sensitive proteins \ could represent targets for Li⁺ in manic depressive disease [MEDLINE:95281614]. \ Recently, the fold of fructose 1,6-bisphosphatase (FBPTASE) was noted to\ be identical to that of MPTASE [MEDLINE:93176151]. FBPTASE is a critical enzyme in the\ gluconeogenic pathway that removes the 1-phosphate from fructose 1,6-bis-\ phosphate to form fructose 6-phosphate [MEDLINE:90247882], [MEDLINE:86186761]. FBTASE also requires metal\ ions for catalysis (Mg²⁺ and Mn²⁺ being preferred) and the enzyme is \ potently inhibited by Li⁺.\ 1PTASE, MPTASE and FBPTASE share a sequence motif (Asp-Pro-Ile/Leu-Asp-\ Gly/Ser-Thr/Ser) which has been shown to bind metal ions and participate\ in catalysis. This motif is also found in the distantly-related fungal,\ bacterial and yeast MPTASE homologues. It has been suggested that these\ proteins define an ancient structurally conserved family involved in\ diverse metabolic pathways, including inositol signalling, gluconeogenesis,\ sulphate assimilation and possibily quinone metabolism [MEDLINE:95281614].

\ \ \N \N \N 18903 IPR000144

At least eight sub-types of metabotropic receptor (MGR1-8) have been\ identified in cloning studies. The sub-types differ in their agonist\ pharmacology and signal transduction pathways PUB00005885.

MGR8 has a strong expression in olfactory bulb, pontine gray, lateral reticular nucleus of\ the thalamus, and piriform cortex; less abundant expression has been\ detected in cerebral cortex, hippocampus, cerebellum, mammillary body and\ retina PUB00005885, [MEDLINE:97168760]. Glutamate evokes pertussis toxin-sensitive potassium currents\ in Xenopus laevis oocytes co-expressing MGR8 and G-protein-coupled inwardly\ rectifying potassium channels [MEDLINE:97168760]. The pharmacology and expression of MGR8\ in mitral/tufted cells suggest it could be a presynaptic receptor modulating\ glutamate release by these cells at their axon terminals in the entorhinal\ cortex [MEDLINE:95239344].

\ \ metabotropic glutamate, GABA-B-like receptor activity ; GO:0008067 membrane ; GO:0016020 \N 18902 IPR000143 Geminiviruses are characterised by a genome of circular single-strandedDNA encapsidated in twinned (geminate) quasi-isometric particles, from\ which the group derives its name PUB00001145. Most geminiviruses can be divided\ into 2 subgroups on the basis of host range and/or insect vector: i.e.\ those that infect dicotyledenous plants and are transmitted by the same\ whitefly species, and those that infect monocotyledenous plants and are\ transmitted by different leafhopper vectors. The genomes of the whitefly-\ transmitted cassava latent (CLV), tomato golden mosaic (TGMV) and bean\ golden mosaic (BGMV) viruses possess a bipartite genome. By contrast, only\ a single DNA component has been identified for the leafhopper-transmitted \ maize streak (MSV) and wheat dwarf (WDV) viruses PUB00001145, [MEDLINE:88124198]. Beet curly top\ (BCTV), bean summer death and tobacco yellow dwarf viruses belong to a \ third possible subgroup. Like MSV and WDV, BCTV is transmitted by a \ specific leafhopper species, yet like the whitefly-transmitted geminiviruses it has a host range confined to dicotyledenous plants.\ Comparison of the MSV DNA sequence with those of CLV and TGMV shows no \ detectable similarity [MEDLINE:85126910]. Amino acid sequence comparison of MSV DNA- \ encoded proteins with those of other geminiviruses infecting monocotyledonous plants, including Panicum streak virus\ \ \ \ [MEDLINE:92268861] and miscanthus\ streak virus\ \ \ \ [MEDLINE:92013947], reveal high levels of similarity.\ \ structural molecule activity ; GO:0005198 viral capsid ; GO:0019028 \N 18901 IPR000142

\ \ purinergic nucleotide receptor activity, G-protein coupled ; GO:0045028 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 18897 IPR000135 High mobility group (HMG, or HMG-T in fish) proteins constitute a family of relatively low molecular weight non-histone components in chromatin. HMG1\ and HMG2 are highly similar, and preferentially bind single-stranded DNA \ and unwind double-stranded DNA [MEDLINE:90344865]. They are generally basic proteins of\ ~200 residues, but contain a highly acidic C-terminal tail of 20-30 aspartic\ and glutamic acid residues.\

The 3D structure of part of the sequence (57-136), termed box 2, has been\ determined using 3D NMR [MEDLINE:93347974]. The protein exhibits an unusual all- fold,\ which forms a V-shaped arrow-head, with helices along two edges and one\ rather flat face [MEDLINE:93347974]. Such an architecture is not shown by any of the \ currently known DNA-binding motifs. The majority of conserved residues \ in the HMG box family are those involved in maintaining the 3D fold.

\ \ DNA binding activity ; GO:0003677 nucleus ; GO:0005634 \N 18898 IPR000136 Oleosins [MEDLINE:91113733] are the proteinaceous components of plants' lipid storage bodiescalled oil bodies. Oil bodies are small droplets (0.2 to 1.5 mu-m in diameter)\ containing mostly triacylglycerol that are surrounded by a phospholipid/\ oleosin annulus. Oleosins may have a structural role in stabilizing the lipid\ body during dessication of the seed, by preventing coalescence of the oil.\ They may also provide recognition signals for specific lipase anchorage in\ lipolysis during seedling growth. Oleosins are found in the monolayer lipid/\ water interface of oil bodies and probably interact with both the lipid and\ phospholipid moieties.\ Oleosins are proteins of 16 Kd to 24 Kd and are composed of three domains: an\ N-terminal hydrophilic region of variable length (from 30 to 60 residues); a\ central hydrophobic domain of about 70 residues and a C-terminal amphipathic\ region of variable length (from 60 to 100 residues). The central hydrophobic\ domain is proposed to be made up of

-strand structure and to interact with\ the lipids [MEDLINE:92348421]. It is the only domain whose sequence\ is conserved.\ \ \N \N \N 18900 IPR000141

FP receptors mediate contraction in a wide range of smooth muscle, including\ intraocular, myomretrial and bronchial tissues, and are potent stimulants of\ luteolysis . The receptors activate the phosphoinositide pathway through\ a pertussis-toxin-insensitive G-protein, probably of the Gq/G11 class PUB00005901.

\ \ prostaglandin F receptor activity ; GO:0004958 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 18899 IPR000138 3-hydroxy-3-methylglutaryl-coenzyme A lyase (HMG-CoA lyase or HL) (EC: 4.1.3.4)catalyzes the transformation of HMG-CoA into acetyl-CoA and acetoacetate. In\ vertebrates it is a mitochondrial enyme which is involved in ketogenesis and\ in leucine catabolism [MEDLINE:93179448]. In some bacteria, such as Pseudomonas mevalonii,\ it is involved in mevalonate catabolism (gene mvaB). A cysteine has been shown\ [MEDLINE:92345242], in mvaB, to be required for the activity of the enzyme.\ \ hydroxymethylglutaryl-CoA lyase activity ; GO:0004419 \N \N 18894 IPR000132 This family includes both nitrilases and cyanide hydratase. Nitrilases (EC: 3.5.5.1) are enzymes that convert nitriles into their\ corresponding acids and ammonia. They are widespread in microbes as well as in\ plants where they convert indole-3-acetonitrile to the hormone indole-3-\ acetic acid. A conserved cysteine has been shown [MEDLINE:93126352], [MEDLINE:93015976] to be essential for\ enzyme activity; it seems to be involved in a nucleophilic attack on the\ nitrile carbon atom. Cyanide hydratase (EC: 4.2.1.66) converts HCN to formamide. In phytopathogenic fungi, it is used to avoid the toxic effect of cyanide released by wounded plants [MEDLINE:92412068].\ \ hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds ; GO:0016810 \N \N 18895 IPR000133

Proteins resident in the lumen of the endoplasmic reticulum (ER) contain a C-terminal tetrapeptide (commonly Lys-Asp-Glu-Leu (KDEL) in mammals and His-Asp-Glu-Leu\ (HDEL) in yeast (S.cerevisiae)) that acts as a signal for their retrieval from subsequent\ compartments of the secretory pathway. The receptor for this signal is a ~26 kDa Golgi\ membrane protein, initially identified as the ERD2 gene product in S.cerevisiae. The\ receptor molecule, known variously as the ER lumen protein retaining receptor or the\ 'KDEL receptor', is believed to cycle between the cis side of the Golgi apparatus and\ the ER. It has also been characterised in a number of other species, including plants,\ Plasmodium, Drosophila and mammals. In mammals, 2 highly related forms of the\ receptor are known.

\ \

The KDEL receptor is a highly hydrophobic protein of 220 residues; its sequence\ exhibits 7 hydrophobic regions, all of which have been suggested to traverse the\ membrane [MEDLINE:93327771]. More recently, however, it has been suggested that only 6 of these\ regions are transmembrane (TM), resulting in both N- and C-termini on the cytoplasmic\ side of the membrane.

\ \ \N \N \N 18896 IPR000134

The precursor of hormones and other active peptides which are C-terminallyamidated is always directly followed [MEDLINE:85035764], [MEDLINE:88281599] by a glycine residue which provides\ the amide group, and most often by at least two consecutive basic residues\ (Arg or Lys) which generally function as an active peptide precursor cleavage\ site. Although all amino acids can be amidated, neutral hydrophobic residues\ such as Val or Phe are good substrates, while charged residues such as Asp or\ Arg are much less reactive. C-terminal amidation has not yet been shown to\ occur in unicellular organisms or in plants.

Note: No protein matches are shown due to the low specificity of this rule.

\ \ \N \N \N 18893 IPR000131

\ \

\ \ \ \ \ \ \

The gamma subunit is believed to be important in regulating ATPase activity and the flow\ of protons through the CF(0) complex. The best conserved region of the gamma\ subunit [MEDLINE:88211863] is its C-terminus which seems to be essential for assembly and catalysis.

\ \ hydrogen-transporting two-sector ATPase activity ; GO:0003936 membrane ; GO:0016020 proton transport ; GO:0015992 18891 IPR000127 Ubiquitin-activating enzyme (E1 enzyme) [MEDLINE:91274342], [MEDLINE:92023523] activates ubiquitin by firstadenylating with ATP its C-terminal glycine residue and thereafter linking\ this residue to the side chain of a cysteine residue in E1, yielding an\ ubiquitin-E1 thiolester and free AMP. Later the ubiquitin moiety is\ transferred to a cysteine residue on one of the many forms of ubiquitin-\ conjugating enzymes (E2).\

The ubiquitin activating enzyme is the first enzyme in the\ ubiquitin protein degradation pathway [MEDLINE:98431658]. This domain is found 2 times\ in each member of the ubiquitin activating enzymes and is located\ downstream of the active site cysteine [MEDLINE:92340519].

\ \ ubiquitin activating enzyme activity ; GO:0004839 \N ubiquitin cycle ; GO:0006512 18892 IPR000128 Steroid or nuclear hormone receptors (NRs) constitute an important super- family of transcription regulators that are involved in widely diverse \ physiological functions, including control of embryonic development, cell\ differentiation and homeostasis. Members of the superfamily include the\ steroid hormone receptors and receptors for thyroid hormone, retinoids, \ 1,25-dihydroxy-vitamin D3 and a variety of other ligands. The proteins \ function as dimeric molecules in nuclei to regulate the transcription of \ target genes in a ligand-responsive manner [MEDLINE:95206940], [MEDLINE:94218237]. In addition to C-terminal\ ligand-binding domains, these nuclear receptors contain a highly-conserved,\ N-terminal zinc-finger that mediates specific binding to target DNA \ sequences, termed ligand-responsive elements. In the absence of ligand,\ steroid hormone receptors are thought to be weakly associated with nuclear\ components; hormone binding greatly increases receptor affinity.\ \

The progesterone receptor consists of 3 functional and structural domains:\ an N-terminal (modulatory) domain; a DNA binding domain that mediates\ specific binding to target DNA sequences (ligand-responsive elements);\ and a hormone binding domain. The N-terminal domain is unique to the \ progesterone receptors and spans approximately the first 500 residues;\ the highly-conserved DNA-binding domain is smaller (around 65 residues)\ and occupies the central portion of the protein; and the hormone binding\ domain lies at the receptor C-terminus.\

\ \ steroid binding activity ; GO:0005496 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 18889 IPR000125

Family 14 (EC: 3.2.1.2, CAZY:GH_14) encompasses the -amylases.\ Beta-amylases, which are found in plants and bacteria, hydrolyse 1,4--glucosidic linkages in starch-type polysaccharide substrates, removing\ successive maltose units from the non-reducing ends of the chains PUB00004513. In\ potato plants, the enzyme has been found to work optimally at 40 degrees C,\ becoming unstable above this temperature PUB00004513. On the basis of sequence\ comparisons, plant and bacterial -amylases can be readily distinguished\ from each other.

\ \ beta-amylase activity ; GO:0016161 \N polysaccharide metabolism ; GO:0005976 18890 IPR000126

In a number of prokaryotic proteases the catalytic activity is provided bya charge relay system analagous to that of the trypsin family of serine\ proteases, but which probably evolved by independent convergent evolution\ [MEDLINE:90346117], [MEDLINE:90351379]. The sequences around the catalytic residues (Asp, Ser and His) are\ completely different from those of the corresponding residues in trypsin\ serine proteases, although these proteins also contain the serine protease trypsin family signatures.

These proteins belong to family S2B of the peptidase classification system\ [MEDLINE:95147689]. Members include Staphylococcus aureus V8 protease, which preferentially cleaves\ peptide bonds C-terminal to Asp and Glu residues; Bacillus licheniformis glutamate-specific\ endopeptidase [MEDLINE:92155199], which also cleaves on the C-terminal side of\ acidic residues, but with strong preference for glutamate; Bacillus subtilis\ extracellular 'metalloprotease' [MEDLINE:90130256]; and S. aureus exfoliative (or\ epidermolytic) toxins A and B, which cause impetigous diseases (also known\ as Staphylococcal scalded skin syndrome).

\ \ serine-type peptidase activity ; GO:0008236 \N proteolysis and peptidolysis ; GO:0006508 18888 IPR000124 A family of mammalian sperm proteins has been characterized [MEDLINE:94094867], [MEDLINE:94000385].As shown in the following schematic representation these proteins, which have\ from 110 to 130 amino acid residues, contain four conserved cysteines involved\ in two disulfide bonds.\ Structurally, the spermadhesins consist of a CUB domain [MEDLINE:93287125] (see IPR000859).\ \ \

\ +---------+ +---------+\ | | | |\ xxxxCxxxxxxxxxCxxxxxxxxxxxCxxxxxxxxxCxxxxxxxxxxxxxxxxxx\ \ 'C': conserved cysteine involved in a disulfide bond.\

\ \ \N \N fertilization (sensu Animalia) ; GO:0007338 18887 IPR000123 The use of an RNA template to produce DNA, for integration into the host genome and exploitation of a host cell, is a strategy employed in the replication of retroid elements, such as the retroviruses and bacterial retrons. The enzyme catalysing polymerisation is an RNA-directed DNA-polymerase, or reverse trancriptase (RT) (EC: 2.7.7.49). Reverse transcriptase occurs in a variety of mobile elements, including retrotransposons, retroviruses, group II introns, bacterial msDNAs, hepadnaviruses, and caulimoviruses. The enzymatic reaction leads to the production of a unique RNA-DNA complex called msDNA (multicopy single-stranded DNA) in which a single-stranded DNA branches out from an RNA molecule via a 2',5'-phosphodiester linkage [MEDLINE:92074802].

\ \ RNA-directed DNA polymerase activity ; GO:0003964 \N RNA dependent DNA replication ; GO:0006278 18884 IPR000120 It has been shown [MEDLINE:91072222], [MEDLINE:91159474], [MEDLINE:91088341]that several enzymes from various prokaryotic and\ eukaryotic organisms which are involved in the hydrolysis of amides (amidases)\ are evolutionary related. All these enzymes contains in their central section\ a highly conserved region rich in glycine, serine, and alanine residues.\ \ amidase activity ; GO:0004040 \N \N 18885 IPR000121 A number of enzymes that catalyze the transfer of a phosphoryl group fromphosphoenolpyruvate (PEP) via a phospho-histidine intermediate have been shown\ to be structurally related [MEDLINE:93299364], [MEDLINE:97128775], [MEDLINE:91104996], [MEDLINE:92212299]. All these enzymes share the same catalytic mechanism: they bind PEP and\ transfer the phosphoryl group from it to a histidine residue. The sequence\ around that residue is highly conserved. This family is often found associated with the pyruvate phosphate dikinase, PEP/pyruvate-binding domain (IPR002192) at its N-terminus.\ \ transferase activity, transferring phosphorus-containing groups ; GO:0016772 \N phosphorylation ; GO:0016310 18886 IPR000121 A number of enzymes that catalyze the transfer of a phosphoryl group fromphosphoenolpyruvate (PEP) via a phospho-histidine intermediate have been shown\ to be structurally related [MEDLINE:93299364], [MEDLINE:97128775], [MEDLINE:91104996], [MEDLINE:92212299]. All these enzymes share the same catalytic mechanism: they bind PEP and\ transfer the phosphoryl group from it to a histidine residue. The sequence\ around that residue is highly conserved. This family is often found associated with the pyruvate phosphate dikinase, PEP/pyruvate-binding domain (IPR002192) at its N-terminus.\ \ transferase activity, transferring phosphorus-containing groups ; GO:0016772 \N phosphorylation ; GO:0016310 18882 IPR000118 Granulins [MEDLINE:92179253] are a family of cysteine-rich peptides of about 6 Kd which mayhave multiple biological activity. A precursor protein (known as acrogranin)\ potentially encodes seven different forms of granulin (grnA to grnG) which are\ probably released by post-translational proteolytic processing. \ Granulins are evolutionary related to a PMP-D1, a peptide extracted from the\ pars intercerebralis of migratory locusts [MEDLINE:92155197].\ A schematic representation of the structure of a granulin is shown below:\ \

\ xxxCxxxxxCxxxxxCCxxxxxxxxCCxxxxxxCCxxxxxCCxxxxxCxxxxxxCx\ \ 'C': conserved cysteine probably involved in a disulfide bond.\

\ \ \N \N \N 18883 IPR000119

Bacteria synthesize a set of small, usually basic proteins of about 90residues that bind DNA and are known as histone-like proteins [MEDLINE:88038574],\ [MEDLINE:88330755]. Examples include the HU protein in Escherichia coli is a dimer of closely related and chains and in other bacteria can be a dimer of identical chains. HU-type proteins have been found in a variety of eubacteria, cyanobacteria and archaebacteria, and are also encoded in the chloroplast genome of some algae [MEDLINE:92073372]. The integration host factor (IHF), a dimer of closely related chains which seem to function in genetic recombination as well as in translational and transcriptional control [MEDLINE:89028666] is found in enterobacteria and viral proteins include the African Swine fever virus protein A104R (or LMW5-AR) [MEDLINE:93219137].

The exact\ function of these proteins is not yet clear but they are capable of wrapping\ DNA and stabilizing it from denaturation under extreme environmental\ conditions. The structure is known for one of these proteins [MEDLINE:84270702]. The protein exists as a dimer and two "-arms" function as the non-specific \ binding site for bacterial DNA.

\ \ DNA binding activity ; GO:0003677 \N \N 18881 IPR000117 Kappa-casein is a mammalian milk protein involved in anumber of important physiological processes [MEDLINE:98072500]. In the gut,\ the ingested protein is split into an insoluble peptide\ (para kappa-casein) and a soluble hydrophilic glycopeptide\ (caseinomacropeptide). Caseinomacropeptide is responsible\ for increased efficiency of digestion, prevention of neonate\ hypersensitivity to ingested proteins, and inhibition of\ gastric pathogens.\ \ \N extracellular ; GO:0005576 \N 18879 IPR000115 Phosphoribosylglycinamide synthetase (EC: 6.3.4.13) (GARS) (phosphoribosylamineglycine ligase) [MEDLINE:90078227] catalyzes the second step in the de novo biosynthesis of\ purine:\ \

\
ATP + 5-phosphoribosylamine + glycine = ADP + P_i + 5'-phosphoribosylglycinamide\

\ \ In bacteria GARS is a monofunctional enzyme (encoded by the purD gene), in\ yeast it is part, with phosphoribosylformylglycinamidine cyclo-ligase (AIRS) IPR000728\ of a bifunctional enzyme (encoded by the ADE5,7 gene), in higher eukaryotes it\ is part, with AIRS IPR000728/> and with\ phosphoribosylglycinamide formyltransferase (GART) IPR001555\ of a trifunctional enzyme (GARS-AIRS-GART).\ \ phosphoribosylamine-glycine ligase activity ; GO:0004637 \N purine base biosynthesis ; GO:0009113 18880 IPR000116 Members of the high mobility group HMG-I(Y) family of mammalian non-histone proteins have been shown to bind specifically to the minor groove of \ A.T-rich sequences and to function as gene transcriptional regulatory \ proteins in vivo [MEDLINE:90256776], [MEDLINE:94021372]. The human HMG-I(Y) gene has several potential \ promoter/enhancer regions, a number of different transcription start sites\ and numerous alternatively-spliced exons, making it one of the most complex\ non-histone chromatin protein-encoding genes reported to date [MEDLINE:94021372]. \

Sequence analysis has shown that alternative splicing of precursor mRNAs\ gives rise to the major HMG-I and HMG-Y isoforms found in human cells. Each\ of the three different DNA-binding domain peptides present in an individual\ HMG-I(Y) protein is coded for by sequences present on separate exons, \ suggesting exon 'shuffling' of these functional domains during evolution \ [MEDLINE:94021372]. The gene has been localised to the short arm of chromosome 6 in a \ region known to be involved in rearrangements, translocations and other \ abnormalities associated with human cancers.

HMG-I and HMG-Y are relatively short alternatively spliced forms containing\ ~100 residues (HMG-Y differs from HMG-I by the internal deletion of 11 amino\ acids). The proteins preferentially bind to double-stranded DNA via an\ 11-residue domain known as an A.T-hook [MEDLINE:90256776]. The hook domain is repeated\ three times in the sequence of HMG-I/Y.

\ \ DNA binding activity ; GO:0003677 nucleus ; GO:0005634 chromosome organization and biogenesis (sensu Eukarya) ; GO:0007001 18876 IPR000115 Phosphoribosylglycinamide synthetase (EC: 6.3.4.13) (GARS) (phosphoribosylamineglycine ligase) [MEDLINE:90078227] catalyzes the second step in the de novo biosynthesis of\ purine:\ \

\
ATP + 5-phosphoribosylamine + glycine = ADP + P_i + 5'-phosphoribosylglycinamide\

\
ATP + 5-phosphoribosylamine + glycine = ADP + P_i + 5'-phosphoribosylglycinamide\

\
ATP + 5-phosphoribosylamine + glycine = ADP + P_i + 5'-phosphoribosylglycinamide\

\ \ In bacteria GARS is a monofunctional enzyme (encoded by the purD gene), in\ yeast it is part, with phosphoribosylformylglycinamidine cyclo-ligase (AIRS) IPR000728\ of a bifunctional enzyme (encoded by the ADE5,7 gene), in higher eukaryotes it\ is part, with AIRS IPR000728/> and with\ phosphoribosylglycinamide formyltransferase (GART) IPR001555\ of a trifunctional enzyme (GARS-AIRS-GART).\ \ phosphoribosylamine-glycine ligase activity ; GO:0004637 \N purine base biosynthesis ; GO:0009113 18874 IPR000113 The B proteins secreted by the tubular accessory sex glands of the malemealworm beetle, Tenebrio molitor, share sequence similarity with Drosophila melanogaster\ CS-5 proteins. On the basis of sequence analysis studies, it has been\ suggested that the D. melanogaster proteins are related to abundant antennal\ proteins previously identified in moths, the pheromone-binding protein\ (PBP) family [MEDLINE:95291284], [MEDLINE:94266829]. Together,\ these sequences are believed to represent\ a class of carrier proteins that, like the lipocalins, may have broad\ significance in a number of different tissues [MEDLINE:94266829].\ Sequence similarity within the superfamily is very low.\ \ pheromone binding activity ; GO:0005550 \N transport ; GO:0006810 18875 IPR000114

\ \ \

Ribosomal protein L16 is one of the proteins from the large ribosomal subunit.\ In Escherichia coli, L16 is known to bind directly the 23S rRNA and to be\ located at the A site of the peptidyltransferase center. L16 is a protein\ of 133 to 185 amino-acid residues.

\ \ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 18873 IPR000112

At least eight sub-types of metabotropic receptor (MGR1-8) have been\ identified in cloning studies. The sub-types differ in their agonist\ pharmacology and signal transduction pathways PUB00005885.

MGR6 is restrictedly expressed in retinal ON bipolar cells and, on the basis of its agonist\ selectivity, may have a key physiological role in certain inherited eye\ diseases PUB00005885, [MEDLINE:93280152].

\ \ metabotropic glutamate, GABA-B-like receptor activity ; GO:0008067 membrane ; GO:0016020 \N 18872 IPR000111

Glycosyl hydrolase family 27 together with the family 36 -galactosidases form the glycosyl hydrolase clan GH-D (CAZY:GH), a superfamily of -galactosidases, -N-acetylgalactosaminidases, and isomaltodextranases which are likely to share a common catalytic mechanism and structural topology.

Alpha-galactosidase (EC: 3.2.1.22) (melibiase) [MEDLINE:73004929] catalyzes the hydrolysis of\ melibiose into galactose and glucose. In man, the deficiency of this enzyme is\ the cause of Fabry's disease (X-linked sphingolipidosis). Alpha-galactosidase\ is present in a variety of organisms. There is a considerable degree of\ similarity in the sequence of -galactosidase from various eukaryotic\ species.\ Escherichia coli -galactosidase (gene melA), which requires NAD and\ magnesium as cofactors, is not structurally related to the eukaryotic enzymes;\ by contrast, an Escherichia coli plasmid encoded -galactosidase (gene\ rafA P16551 contains a region of about 50 amino acids which is similar to a\ domain of the eukaryotic -galactosidases.\ Alpha-N-acetylgalactosaminidase (EC: 3.2.1.49) [MEDLINE:91072392] catalyzes the hydrolysis of\ terminal non-reducing N-acetyl-D-galactosamine residues in N-acetyl--D-\ galactosaminides. In man, the deficiency of this enzyme is the cause of\ Schindler and Kanzaki diseases. The sequence of this enzyme is highly related\ to that of the eukaryotic -galactosidases.

\ \ hydrolase activity, hydrolyzing O-glycosyl compounds ; GO:0004553 \N carbohydrate metabolism ; GO:0005975 18868 IPR000106 Low molecular weight (LMW) phosphotyrosine protein phosphatase (or acidphosphatase) acts on tyrosine phosphorylated proteins, low-MW aryl\ phosphates and natural and synthetic acyl phosphates [MEDLINE:92268143], [MEDLINE:93284125]. It is a\ cytoplasmic enzyme that catalyses the reaction:\

\
protein tyrosine phosphate + H₂O = protein tyrosine + P_i\

\ The structure of the protein has been solved by X-ray crystallography [MEDLINE:94329182]\ and is found to form a single structural domain. It belongs to the

class, with 6

-helices and 4

-strands forming a 3-layer

sandwich architecture.\ \ protein tyrosine phosphatase activity ; GO:0004725 \N protein amino acid dephosphorylation ; GO:0006470 18869 IPR000108 Phagocytes form the first line of defence against invasion by micro-organisms. Engulfing of bacteria by neutrophils is accompanied by the\ consumption of large amounts of oxygen - a so-called respiratory burst.\ Defects in phagocytosis involving the lack of a respiratory burst give\ rise to chronic granulomatous disease (CGD), in which patients are pre-\ disposed to infection, often from otherwise non-pathogenic bacteria [MEDLINE:96389574].\

Regulation of the respiratory burst takes place at the phagocytic vacuole.\ The process is mediated by NADPH oxidase, which transports electrons across\ the plasma membrane to form superoxide (an oxygen molecule with an extra\ electron that is toxic to normal cells) in the vacuole interior. The\ electrons are carried across the membrane by a short electron transport\ chain in the form of an unusual flavocytochrome b [MEDLINE:96389574].\ To conserve NADPH and avoid the toxic effects of superoxide, the oxidase \ remains inactive until it receives an appropriate stimulus. Activation\ involves the participation of a number of cytosolic proteins, some of \ which attach to the flavocytochrome.

P47phox, p67phox and p40phox are\ specialised components of phagocytic cells, all of which contain SH3\ domains IPR001452, by means of which they attach to proline-rich regions of other\ proteins. Upon activation, p47phox and p67phox are phosphorylated and,\ with p40phox, translocate to the region of the plasma membrane forming\ the phagocytic vacuole, where they associates with hydrophilic regions\ of the flavocytochrome [MEDLINE:96389574].

\ \ \N \N \N 18870 IPR000109 The transport of peptides into cells is a well-documented biological phenomenon which is accomplished by specific, energy-dependent transporters found in a number\ of organisms as diverse as bacteria and humans. The PTR family of proteins is distinct\ from the ABC-type peptide transporters and was uncovered by sequence analyses of a\ number of recently discovered peptide transport proteins [MEDLINE:96059630].\ These proteins that seem to be mainly\ involved in the intake of small peptides with the concomitant uptake of a\ proton [MEDLINE:95117128].\ \

These integral membrane proteins are predicted to comprise twelve\ transmembrane regions.

\ \ transporter activity ; GO:0005215 membrane ; GO:0016020 oligopeptide transport ; GO:0006857 18871 IPR000110

\ \ \

Ribosomal protein S1 [MEDLINE:83274675] contains the S1 domain that has been found in a large number of RNA-associated proteins. S1 is a prominent component of the Escherichia coli ribosome and is most probably required for translation of most, if not all, natural mRNAs in E. coli in vivo ([MEDLINE:98344098]). It has been suggested that S1 is a RNA-binding protein helping polynucleotide phosphorylase (PNPase, known to be phylogenetically related to S1) to degrade mRNA, or helper molecule involved in other RNase activities ([MEDLINE:97323001]).

Unique among ribosomal proteins, the primary structure of S1 contains four repeating homologous stretches in the central and terminal region of the molecule. S1 is organised into at least two distinct domains; a ribosome-binding domain at the n-terminal region and a nucleic acid-binding domain at the C-terminal region([MEDLINE:83274675]). There may be a flexible region between the two domains permitting free movement of the domains relative to each other.\

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 18866 IPR000104

Marine teleosts from polar oceans can be protected from freezing in icy sea-water by serum antifreeze proteins (AFPs) or glycoproteins (AFGPs) [MEDLINE:95315870]:\ these function by binding to, and preventing the growth of, ice crystals\ within the fish and depressing the non-equilibrium freezing point to below that of the melting point.

Despite functional similarity, antifreeze proteins are\ structurally diverse and include glycosylated and at least 3 non-glycosylated forms: the AFGP of nototheniids and cods are polymers of a\ tripeptide repeat, Ala-Ala-Thr, with a disaccharide attached to the\ threonine residue; type I AFPs are found\ in flounder and sculpin; type II AFPs of sea-raven, smelt and herring are\ Cys-rich proteins; and type III AFPs, found in eel pouts, are rich in -structure. Non-homologous antifreeze proteins have also been identified in insects and plants [MEDLINE:22162998].

Type I AFPs are Ala-rich, amphiphilic, -helical proteins [MEDLINE:93346383]. The ice-binding sites of all AFPs are relatively flat and hydrophobic and have an uninterupted section of alanines running the length of the approximately 16.5A helix repeat. Based\ on the energy-minimised structure [MEDLINE:92148833], a model has been proposed to\ describe the binding of the protein to ice crystals, whereby the protein\ binds to an ice nucleation structure, in a zipper-like fashion, via\ hydrogen bonding of the methyl-group of threonine side chains (with an 11-residue period) to\ oxygen atoms in the ice lattice. The growth of ice crystals is thus\ stopped, or retarded, and the freezing point depressed. The high lysince content of these peptides may serve to promote the solubility of these proteins.

\ \ \N \N \N 18867 IPR000105

The term opioid refers to a class of substance that produces its effects\ via the major classes of opioid receptor, termed mu, delta and kappa PUB00005896.\ In the CNS, the mu opioid receptor is found in the cerebral cortex,\ thalamus, hypothalamus, periaqueductal grey, interpeduncular nucleus and\ median raphe. In the periphery, it is found in the myenteric plexus, and\ in certain smooth muscles, e.g. mouse vas deferens PUB00005896. Mu opioid\ receptors are believed to mediate analgesia, hypothermia, respiratory\ depression, miosis, bradycardia, nausea, euphoria and physical dependence.\ Beta-endorphin is the most potent endogenous ligand.

\ \ mu-opioid receptor activity ; GO:0004988 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 18862 IPR000100 Ribonuclease P (EC: 3.1.26.5) (RNase P) [MEDLINE:90154025], [MEDLINE:91056032], [MEDLINE:92253334] is a site specific endonucleasethat generates mature tRNAs by cleaving-off the leader sequences at their\ 5'ends. In bacteria RNase P is known to be composed of two components: a large\ (about 400 base pairs) RNA (gene rnpB) and a small protein (119 to 133 amino\ acids) (gene rnpA). The RNA moiety of RNase P carries the catalytic activity;\ the function of the protein component is not yet clear although it may act as\ an electrostatic screen allowing the highly negatively charged RNA enzyme-\ substrate complex to fold into the catalytic conformation.\ The sequence of rnpA is not highly conserved, however there is, in the central\ part of the protein, a conserved basic region.\ \ ribonuclease P activity ; GO:0004526 \N tRNA processing ; GO:0008033 18863 IPR000101

Gamma-glutamyltranspeptidase ( EC: 2.3.2.2) (GGT) [MEDLINE:86117796] catalyzes the transfer ofthe gamma-glutamyl moiety of glutathione to an acceptor that may be an amino\ acid, a peptide or water (forming glutamate). GGT plays a key role in the\ gamma-glutamyl cycle, a pathway for the synthesis and degradation of\ glutathione and drug and xenobiotic detoxification [MEDLINE:92337688]. In\ prokaryotes and eukaryotes, it is an enzyme that consists of\ two polypeptide chains, a heavy and a light subunit, processed from a single\ chain precursor. The active site of GGT is known to be located in the light\ subunit.\ The sequences of mammalian and bacterial GGT show a number of regions of\ high similarity [MEDLINE:89359163]. Pseudomonas cephalosporin acylases (EC: 3.5.1.-) that\ convert 7--(4-carboxybutanamido)-cephalosporanic acid (GL-7ACA) into\ 7-aminocephalosporanic acid (7ACA) and glutaric acid are evolutionary related\ to GGT and also show some GGT activity [MEDLINE:93041922].\ Like GGT, these GL-7ACA acylases, are also composed of two subunits.

\ \ gamma-glutamyl transferase activity ; GO:0003840 \N \N 18864 IPR000102 In MAP1B the basic region containing the KKEE and KKEVI motifs is responsible for the interaction between MAP1B and microtubules in vivo. This region bears no sequence relationship to the microtubule binding domains of kinesin, MAP2, or tau [MEDLINE:90094539].Neuraxin is a putative structural protein of the rat central nervous system that is immunologically related to\ microtubule-associated protein 5 (MAP5). Neuraxin may be implicated in neuronal membrane-microtubule interactions [MEDLINE:90059871]. Both proteins contain a region that consists of 12 tandem\ repeats of a 17 residues motif.\ \ \N \N \N 18865 IPR000103 The pyridine nucleotide-disulphide reductases (PNDR) use the isoalloxazine ring of FAD to shuttle reducing equivalents from NAD(P)H to a Cys residue\ that is usually a part of a redox-active disulphide bridge. In a second\ step, the reduced disulphide reduces the substrate. On the basis of \ sequence and structural similarities [MEDLINE:91296031], PNDR can be categorised into 2 groups.\

Class II includes: prokaryotic and eukaryotic thioredoxin reductases [MEDLINE:88243771], [MEDLINE:94148789];\ bacterial alkyl hydroperoxide reductases [MEDLINE:90285183]; bacterial NADH:dehydrogenases\ [MEDLINE:92011449]; a probable oxidoreductase encoded in the Clostridium pasteurianum\ rubredoxin operon [MEDLINE:92344580]; and yeast hypothetical protein YHR106w.

The 3D structure of Escherichia coli thioredoxin reductase (TR) has been solved\ [MEDLINE:91296031], [MEDLINE:94157914].\ The protein exists as a homodimer, with 3 domains per monomer, which\ correspond to the FAD-binding, NAD(P)H-binding and central domains of\ glutathione reductase (GR) (cf. signature PNDRDTASEI). However, TR lacks\ the domain that provides the dimer interface in GR, and forms a completely \ different dimeric structure. The relative orientation of these domains is\ very different in the 2 enzymes: when the FAD-binding domains of TR and GR\ are superimposed, the NADPH-binding domain of one is rotated by 66 degrees\ with respect to the other. The FAD- and NAD(P)H-binding domains have a \ similar doubly-wound / fold, suggesting they evolved by gene\ duplication [MEDLINE:91138759]. While in GR the redox active disulphide is located in\ the FAD-binding domain, in TR it lies in the NADPH-binding domain. This\ suggests that the enzymes diverged from an ancestral nucleotide-binding\ protein and acquired their disulphide reductase activities independently [MEDLINE:91296031].

\ \ oxidoreductase activity ; GO:0016491 \N electron transport ; GO:0006118 18859 IPR000096 The serum amyloid A (SAA) proteins comprise a family of vertebrate proteinsthat associate predominantly with high density lipoproteins (HDL) [MEDLINE:94072032], [MEDLINE:94245191]. The\ synthesis of certain members of the family is greatly increased (as much as a\ 1000 fold) in inflammation; thus making SAA a major acute phase reactant.\ While the major physiological function of SAA is unclear, prolonged elevation\ of plasma SAA levels, as in chronic inflammation, however, results in a\ pathological condition, called amyloidosis, which affects the liver, kidney\ and spleen and which is characterized by the highly insoluble accumulation of\ SAA in these tissues.\ SAA are proteins of about 110 amino acid residues. The most highly conserved \ region is located in the central part of the sequence.\ \ acute-phase response protein activity ; GO:0003794 extracellular ; GO:0005576 acute-phase response ; GO:0006953 18860 IPR000097 DNA damaging agents such as the antitumor drugs bleomycin and neocarzinostatinor those that generate oxygen radicals produce a variety of lesions in DNA.\ Amongst these is base-loss which forms apurinic/apyrimidinic (AP) sites or\ strand breaks with atypical 3'termini. DNA repair at the AP sites is initiated\ by specific endonuclease cleavage of the phosphodiester backbone. Such\ endonucleases are also generally capable of removing blocking groups from the\ 3'terminus of DNA strand breaks.\

AP endonucleases can be classified into two families on the basis of sequence\ similarity. This family contains members of AP endonuclease family 1.\ Except for Rrp1 and arp, these enzymes are proteins of about 300 amino-acid\ residues. Rrp1 and arp both contain additional and unrelated sequences in\ their N-terminal section (about 400 residues for Rrp1 and 270 for arp).\ The proteins contain\ glutamate which has been shown [MEDLINE:95191690], in the Escherichia coli enzyme to bind a\ divalent metal ion such as magnesium or manganese

\ \ endonuclease activity ; GO:0004519 \N DNA repair ; GO:0006281 18861 IPR000098 Interleukin-10 (IL-10) is a protein that inhibits the synthesis of anumber of cytokines, including IFN-gamma, IL-2, IL-3, TNF and GM-CSF produced\ by activated macrophages and by helper T cells.\ Structurally, IL-10 is a protein of about 160 amino acids that contains four\ conserved cysteines involved in disulfide bonds [MEDLINE:96173008].\ \

\ +-------------------------------------+\ | ***** |\ xxxxxxxxxxxCxxxxxxxxxxxxxxxxxxxCxxxxxxxxxxxxxxxxxCxCxxxxxxxxxxxx\ | |\ +-------------------+\ \ 'C': conserved cysteine involved in a disulfide bond.\ '*': position of the pattern.\

\ IL-10 is highly similar to the Epstein-Barr virus BCRF1 protein which inhibits\ the synthesis of gamma-interferon and to Equine herpesvirus type 2 protein E7.\ It is also similar, but to a lesser degree, with human protein mda-7 [MEDLINE:96132699], a\ protein which has antiproliferative properties in human melanoma cells. Mda-7\ only contains two of the four cysteines of IL-10.\ \ cytokine activity ; GO:0005125 extracellular ; GO:0005576 immune response ; GO:0006955 18856 IPR000092 A variety of isoprenoid compounds are synthesized by various organisms. Forexample in eukaryotes the isoprenoid biosynthetic pathway is responsible for\ the synthesis of a variety of end products including cholesterol, dolichol,\ ubiquinone or coenzyme Q. In bacteria this pathway leads to the synthesis of\ isopentenyl tRNA, isoprenoid quinones, and sugar carrier lipids. Among the\ enzymes that participate in that pathway, are a number of polyprenyl\ synthetase enzymes which catalyze a 1'4-condensation between 5 carbon isoprene\ units.\ It has been shown [MEDLINE:90330660], [MEDLINE:91210228], [MEDLINE:91170267], [MEDLINE:93272043], [MEDLINE:92357711] that all the above enzymes share some regions of\ sequence similarity. Two of these regions are rich in aspartic-acid residues\ and could be involved in the catalytic mechanism and/or the binding of the\ substrates.\ \ \N \N isoprenoid biosynthesis ; GO:0008299 18857 IPR000093 The bacterial protein recR seems to play a role in a recombinational processof DNA repair [MEDLINE:89386036]. It may act with recF and recO. RecR is a protein of about\ 200 amino acid residues. This protein contains a putative\ C4-type zinc finger in the N-terminal section.\ \ \N \N DNA recombination ; GO:0006310 18858 IPR000095 The molecular bases of the versatile functions of Rho-like GTPases are still unknown.Small domains that bind Cdc42p- and/or Rho-like small GTPases.\ Also known as the Cdc42/Rac interactive binding (CRIB). The Cdc42/Rac interactive binding\ (CRIB) region has been shown to inhibit transcriptional activation\ and cell transformation mediated by the Ras-Rac pathway [MEDLINE:97227952]. In fission yeast pak1+ encodes a protein kinase that interacts\ with Cdc42p and is involved in the control of cell polarity\ and mating [MEDLINE:96112805].\ \ \N \N \N 18853 IPR000089 The biotin / lipoyl attachment domain has a conserved lysine residue that binds biotin in onesubfamily IPR001882 and lipoic\ acid in the other IPR001882/>. Biotin plays a catalytic role in some carboxyl transfer reactions and is\ covalently attached, via an amide bond, to a lysine residue in enzymes\ requiring this coenzyme [MEDLINE:92406744]. E2 acyltransferases have an essential cofactor, lipoic acid, which is covalently bound\ via an amide linkage to a lysine group [MEDLINE:91152093]. The lipoic acid cofactor is found in a variety of proteins that include, H-protein of the glycine cleavage system (GCS), mammalian and yeast pyruvate dehydrogenases and fast migrating protein (FMP) (gene acoC) from Alcaligenes eutrophus.\ \ \N \N \N 18854 IPR000090

The flagellar motor switch in Escherichia coli and Salmonella typhimurium regulates the direction of flagellar rotation and hence controls swimming behaviour [MEDLINE:94040782].\ The switch is a complex apparatus that responds to signals transduced by the\ chemotaxis sensory signalling system during chemotactic behaviour [MEDLINE:94040782]. CheY,\ the chemotaxis response regulator, is believed to act directly on the switch\ to induce tumbles in the swimming pattern, but no physical interactions of \ CheY and switch proteins have yet been demonstrated.

The switch complex comprises at least three proteins - FliG, FliM and FliN.\ It has been shown that FliG interacts with FliM, FliM interacts with itself,\ and FliM interacts with FliN [MEDLINE:96200097]. Several residues within the middle third\ of FliG appear to be strongly involved in the FliG-FliM interaction, with\ residues near the N- or C-termini being less important [MEDLINE:96200097]. Such clustering\ suggests that FliG-FliM interaction plays a central role in switching.

Analysis of the FliG, FliM and FliN sequences shows that none are especially\ hydrophobic or appear to be integral membrane proteins [MEDLINE:89255090]. This result is\ consistent with other evidence suggesting that the proteins may be \ peripheral to the membrane, possibly mounted on the basal body M ring [MEDLINE:89255090], [MEDLINE:92335286]. FliG is present in about 25 copies per flagellum. This structure of the\ C-terminal domain is known, this domain functions\ specifically in motor rotation [MEDLINE:99366991].

\ \ motor activity ; GO:0003774 flagellum (sensu Bacteria) ; GO:0009288 chemotaxis ; GO:0006935 18855 IPR000091 Huntington's disease (HD) is a mid-life onset, inherited, neurodegenerativedisorder characterised by motor impairment, involuntary movements (chorea),\ psychiatric disorders and dementia [MEDLINE:95375788]. The disease results from the\ expansion of a polyglutamine-encoding CAG repeat in a gene of unknown\ function. Moderate expansion of glutamine-coding CAG repeats has been\ found in other neurological diseases (e.g. spinobulbar muscular atrophy\ and Machado-Joseph disease), in all of which the pathological mechanism\ linked to the expansion of the polyglutamine tract in the protein remains\ a mystery.\

The HD transcript is highly conserved, significant differences, as already\ noted, occurring in the N-terminal Gln-repeat region. Huntingtin normally\ contains 10-35 repeats, but shows 36-120 repeats in the disease form.\ Migration differences between normal and mutated huntingtin in a denaturing\ polyacrylamide gel suggest that the poly-Gln stretch disrupts the protein\ conformation. This finding is consistent with the observation that\ Gln repeats may form tightly-linked -sheets that could act as polar\ zippers [MEDLINE:94261584].

\ \ molecular_function unknown ; GO:0005554 cytoplasm ; GO:0005737 \N 18852 IPR000086 MutT is a small bacterial protein (~12-15Kd) involved in the GO system [MEDLINE:93015679] responsible for removing an oxidatively damaged form of guanine (8-hydroxy-\ guanine or 7,8-dihydro-8-oxoguanine) from DNA and the nucleotide pool.\ 8-oxo-dGTP is inserted opposite dA and dC residues of template DNA with\ near equal efficiency, leading to A.T to G.C transversions. MutT\ specifically degrades 8-oxo-dGTP to the monophosphate, with the concomitant\ release of pyrophosphate. A short conserved N-terminal region of mutT \ (designated the MutT domain) is also found in a variety of other\ prokaryotic, viral, and eukaryotic proteins [MEDLINE:94051617], [MEDLINE:94224150], [MEDLINE:94043152], [MEDLINE:99303955].\ \

The generic name 'NUDIX hydrolases' (NUcleoside DIphosphate linked\ to some other moeity X) has been coined for this domain family [MEDLINE:96411704]. The\ family can be divided into a number of subgroups, of which MutT anti-\ mutagenic activity represents only one type; most of the rest hydrolyse\ diverse nucleoside diphosphate derivatives (including ADP-ribose, GDP-\ mannose, TDP-glucose, NADH, UDP-sugars, dNTP and NTP).

\ \ \N \N \N 18850 IPR000084 This family is named after a PE motif near to the aminoterminus . The carboxyl terminus of this family\ are variable and fall into several classes. The\ largest class of PE proteins is the highly repetitive\ PGRS class which have a high glycine content.\ The function of these proteins is uncertain but it\ has been suggested that they may be related to\ antigenic variation of Mycobacterium tuberculosis\ \ \ \ [MEDLINE:98295987].\ \ \N \N \N 18851 IPR000085 RuvA forms a complex with RuvB P08577, this complex is a helicase that mediates theholliday junction migration by localized denaturation and reannealing.\ RuvA stimulates, in the presence of DNA, the weak\ ATPase activity of RuvB. RuvA binds binds both single- and double-\ stranded dna (dsDNA). RUVA binds preferentially to supercoiled rather\ than to relaxed dsDNA.\ \ DNA helicase activity ; GO:0003678 \N DNA recombination ; GO:0006310 18849 IPR000083

Fibronectin type I repeats are one of the three repeats found in the fibronectin protein. Fibronectin is a plasma protein that binds cell surfaces and various compounds\ including collagen, fibrin, heparin, DNA, and actin. Type I domain (FN1) is approximately\ 40 residues in length. Four conserved cysteines are involved in disulfide bonds. The 3D\ structure of the FN1 domain has been determined [MEDLINE:90272011], [MEDLINE:92292163], [MEDLINE:96027104]. It consists of two antiparallel -sheets, first a double-stranded one, that is linked by a disulfide bond to a\ triple-stranded -sheet. The second conserved disulfide bridge links the C-terminal\ adjacent strands of the domain.

In human tissue plasminogen activator chain A the FN1 domain together with the\ following epidermal growth factor (EGF)-like domain are involved in\ fibrin-binding [MEDLINE:91161614]. It has been suggested that these two modules form a single structural\ and functional unit [MEDLINE:96027104]. The two domains keep their specific tertiary structure, but interact\ intimately to bury a hydrophobic core; the inter-module linker makes up the third strand of\ the EGF-module's major -sheet.

\ \ \N extracellular ; GO:0005576 \N 18847 IPR000081 This protein is a protease, involved in cleavage of the polyprotein [MEDLINE:98120815], and is found in Picornaviruses. Picornaviruses are ssRNA positive-strand viruses with no DNA stage.\ peptidase activity ; GO:0008233 \N \N 18848 IPR000082 SEA is an extracellular domain associated with O-glycosylation [MEDLINE:95400207].\ Proteins found to contain SEA-modules include, agrin, enterokinase, 63 kDa sea urchin sperm protein, perlecan (heparan sulfate proteoglycan core, mucin 1 and the cell surface antigen, 114/A10, and two functionally uncharacterized,\ probably extracellular, Caenorhabditis elegans proteins. Despite the functional\ diversity of these adhesive proteins, a common denominator seems to be their\ existence in heavily glycosylated environments. In addition, the better characterized\ proteins all contain O-glycosidic-linked carbohydrates such as\ heparan sulfate that contribute considerably to their molecular masses. The common\ module might regulate or assist binding to neighboring carbohydrate moieties.\

Enterokinase, the initiator of intestinal digestion, is a\ mosaic protease composed of a distinctive assortment of\ domains [MEDLINE:94329561].

\ \ \N \N \N 18846 IPR000079

High mobility group (HMG) proteins constitute a family of relatively low molecular weight non-histone components in chromatin. HMG14 and HMG17 are highly-similar proteins of about 100 amino acid residues; the sequence of chicken HMG14 is almost as similar to chicken HMG17 as it is to mammalian HMG14 polypeptides [MEDLINE:88255874]. The proteins bind to the inner side of the nucleosomal DNA, altering the interaction between the DNA and the histone octamer. It is thought that they may be involved in the process that confers specific chromatin conformations to transcribable regions in the genome [MEDLINE:86224021].

The SMART signature describes a nucleosomal binding domain, which facilitates binding of proteins to nucleosomes in chromatin. The domain is most commonly found in the high mobility group (HMG) proteins, HMG14 and HMG17, however, it is also found in other proteins which bind to nucleosomes, eg. NBP-45. NBP-45 is a nucleosomal binding protein, first identified in mice [MEDLINE:20158948], which is related to HMG14 and HMG17. NBP-45 binds specifically to nucleosome core particles, and can function as a transcriptional activator. These findings led to the suggestion that this domain, common to NBP-45, HMG14 and HMG17 is responsible for binding of the proteins to nucleosomes in chromatin.

\ \ DNA binding activity ; GO:0003677 nucleus ; GO:0005634 \N 18845 IPR000077

\ \ \

A number of eukaryotic and archaebacterial large subunit ribosomal proteins can be grouped on the basis of sequence similarities.\ These proteins are very basic. About 50 residues long, they are the smallest\ proteins of eukaryotic-type ribosomes.

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 18843 IPR000074 Human apolipoprotein E, a blood plasma protein, mediates the transport and uptake of cholesterol and lipid by way of its high affinity interaction with different cellular receptors, including the low-density lipoprotein (LDL) receptor. The three-dimensional structure of the LDL receptor-binding domain of apoE indicates that the protein forms an unusually elongated four-helix bundle that may be\ stabilized by a tightly packed hydrophobic core that includes leucine zipper-type\ interactions and by numerous salt bridges on the mostly charged surface. Basic amino\ acids important for LDL receptor binding are clustered into a surface patch on one\ long helix [MEDLINE:91289138].\ \ lipid binding activity ; GO:0008289 \N lipid transport ; GO:0006869 18844 IPR000076

\ \

\ \ transporter activity ; GO:0005215 membrane ; GO:0016020 ion transport ; GO:0006811 18841 IPR000072 Platelet-derived growth factor (PDGF) [MEDLINE:89323168], [MEDLINE:93049175] is a potent mitogen for cells ofmesenchymal origin, including smooth muscle cells and glial cells. PDGF\ consists of two different but closely related chains (A and B chains) which\ assemble to form disulfide linked homo- or heterodimers (A-A, B-B, an A-B).\ Alternate splicing of the A chain transcript can give rise to two different\ forms that differ only in their C-terminal extremity. The transforming protein\ of simian sarcoma virus (SSV), encoded by the v-sis oncogene, is derived from the B chain of PDGF.\

Other growth factors in this family include vascular endothelial growth factors B and C (VEGF-B, VEGF-C) [MEDLINE:96197355], [MEDLINE:96178224] which are active in angiogenesis and endothelial cell growth, and placenta growth factor (PlGF) which is also active in angiogenesis [MEDLINE:93205407].

PDGF is structurally related to a number of other growth factors which also form disulfide-linked homo- or heterodimers.

\ \ growth factor activity ; GO:0008083 membrane ; GO:0016020 cell growth and/or maintenance ; GO:0008151 18842 IPR000073 The

hydrolase fold [MEDLINE:93028317] is common to a number of hydrolytic enzymesof widely differing phylogenetic origin and catalytic function. The core\ of each enzyme is an

-sheet (rather than a barrel), containing 8\ strands connected by helices [MEDLINE:93028317]. The enzymes are believed to have diverged\ from a common ancestor, preserving the arrangement of the catalytic\ residues. All have a catalytic triad, the elements of which are borne on\ loops, which are the best conserved structural features of the fold.\ \ \N \N \N 18840 IPR000071 The HIV/SIV matrix protein forms an icosahedral shell associated withthe inner membrane of the mature virus [MEDLINE:95055757]. The functions of the protein\ include anchoring the transmembrane envelope protein on the surface\ of the virus; assisting in viral penetration; transporting the pro-viral integration complex across the nuclear envelope; and localising\ the assembling virion to the cell membrane.\ The structure of the protein comprises 5

-helices, a short 3.10\ helix and a 3-stranded mixed

-sheet [MEDLINE:95055757]. The first 3 helices and the\ 3.10 region pack around the fourth helix to form a compact globular\ domain that is capped by the

-sheet. The C-terminal helix projects\ away from the sheet to expose C-terminal residues essential for early\ steps in the HIV-1 infectious cycle. Basic residues, implicated in\ membrane binding and nuclear localisation functions, cluster around\ an extruded cationic loop that connects strands 1 and 2.\ \ structural molecule activity ; GO:0005198 \N \N 18839 IPR000070 Pectinesterase (EC: 3.1.1.11) (pectin methylesterase) catalyzes the hydrolysisof pectin into pectate and methanol:\

\
Pectin + N H₂O = N methanol + pectate\

\ In plants, it plays an important role in\ cell wall metabolism during fruit ripening. In plant bacterial pathogens such\ as Erwinia carotovora and in fungal pathogens such as Aspergillus niger,\ pectinesterase is involved in maceration and soft-rotting of plant tissue.\ Prokaryotic and eukaryotic pectinesterases share a few regions of sequence\ similarity [MEDLINE:88225091], [MEDLINE:88246052], [MEDLINE:93271874].\ A region in the N-terminal section of these enzymes\ contains a conserved tyrosine which may play a role in the catalytic mechanism\ [MEDLINE:93271874].\ \ pectinesterase activity ; GO:0030599 cell wall ; GO:0005618 cell wall modification ; GO:0042545 18838 IPR000069 Flaviviruses are small enveloped viruses with virions comprised of3 proteins called C, M and E [MEDLINE:96256767], [MEDLINE:94305413], [MEDLINE:93172390].\ The envelope glycoprotein M is made as a precursor, called prM.\ The precursor portion of the protein is the signal peptide\ for the proteins entry into the membrane. prM is cleaved to form\ M in a late-stage cleavage event. Associated with this cleavage\ is a change in the infectivity and fusion activity of the virus.\ \ \N viral capsid ; GO:0019028 viral infectious cycle ; GO:0019058 18837 IPR000068

\ \

The calcium-sensing receptor (CaSR) is an integral membrane protein that\ senses changes in the extracellular concentration of calcium ions. The\ activity of the receptor is mediated by a G-protein that activates a\ phosphatidyl-inositol-calcium second messenger system. The sequences of the\ receptors show a high degree of similarity to the TM signature that\ characterises the metabotropic glutamate receptors. In addition, the\ sequences contain a large extracellular domain that includes clusters of\ acidic amino acid residues, which may be involved in calcium binding [MEDLINE:94077182].\ Defects in CaSR that result in reduced activity of the receptor cause\ familial hypocalciuric hypercalcemia (FHH) and neonatal severe hyperparathyroidism (NSHPT), inherited conditions characterised by altered calcium\ homeostasis [MEDLINE:97442275], [MEDLINE:96292293]. FHH-affected individuals exhibit mild or modest hypercalcemia, relative hypocalciuria and inappropriately normal PTH levels. By\ contrast, NSHPT is a rare autosomal recessive life-threatening disorder\ characterised by high serum calcium concentrations, skeletal demineralisation and parathyroid hyperplasia. In addition, defects resulting from\ receptor activation at subnormal Ca²⁺ levels cause autosomal dominant\ hypocalcemia [MEDLINE:95179179].

\ \ \ G-protein coupled receptor activity ; GO:0004930 membrane ; GO:0016020 \N 18834 IPR000065 Leptin, a metabolic monitor of food intake and energy need, is expressedby the ob obesity gene. The protein may function as part of a signalling\ pathway from adipose tissue that acts to regulate the size of the body\ fat depot [MEDLINE:95075453], the hormone effectively turning the brain's appetite\ message off when it senses that the body is satiated. Obese humans have\ high levels of the protein, suggesting a similarity to type II (adult\ onset) diabetes, in which sufferers over-produce insulin, but can't respond\ to it metabolically - they have become insulin resistant. Similarly, it is\ thought that obese individuals may be leptin resistant.\ \ hormone activity ; GO:0005179 extracellular ; GO:0005576 signal transduction ; GO:0007165 18835 IPR000066 In photosynthetic bacteria the antenna complexes function as light-harvestingsystems that absorb light radiation and transfer the excitation energy to the\ reaction centers. The antenna complexes are generally composed of two\ polypeptides (

and

chains); two or three bacteriochlorophyll (BChl)\ molecules and some carotenoids [MEDLINE:92249336], [MEDLINE:93094968].\ Both the

and the

chains of antenna complexes are small proteins of\ 42 to 68 residues which share a three-domain organization. They are composed\ of a N-terminal hydrophilic cytoplasmic domain followed by a transmembrane\ region and a C-terminal hydrophilic periplasmic domain. In the transmembrane\ region of both chains there is a conserved histidine which is most probably\ involved in the binding of the magnesium atom of a bacteriochlorophyll group.\ The

chains contain an additional conserved histidine which is located at\ the C-terminal extremity of the cytoplasmic domain and which is also thought\ to be involved in bacteriochlorophyll-binding.\ \ lipoate-protein ligase B activity ; GO:0016978 membrane ; GO:0016020 energy pathways ; GO:0006091 18836 IPR000067 This family corresponds to the FliF protein. FliF is the major proteinof the M-ring in bacterial flagellar basal body [MEDLINE:89291739].\ The basal body consists of four rings (L,P,S and M) surrounding the\ flagellar rod, which is believed to transmit motor rotation to the filament \ [MEDLINE:90172414]. \ The M ring is integral to the inner membrane of the cell, and may be\ connected to the rod via the S (supramembrane) ring, which lies just distal\ to it. The L and P rings reside in the outer membrane and periplasmic space,\ respectively.\ FliF lacks a signal peptide and is predicted to have considerable

-helical structure, including an N-terminal sequence that is likely\ to be membrane-spanning [MEDLINE:89291739]. Overall, however, FliF has a relatively\ hydrophilic sequence, with a high charge density, especially towards its \ C-terminus [MEDLINE:89291739].\ \ motor activity ; GO:0003774 flagellar basal body, MS ring (sensu Bacteria) ; GO:0009431 ciliary/flagellar motility ; GO:0001539 18833 IPR000064 The function of this domain is unknown. It is found in several lipoproteins and is often associated with a domain IPR002482 that may have a general peptidoglycan binding function. The NLP/P60 domain occurs at the C-terminus of a number of different bacterial proteins.\ \N \N \N 18831 IPR000061 SWAP is derived from the Suppressor-of-White-APricot splicing regulator from Drosophila melanogaster. The domain is found in regulators responsible for pervasive, nonsex-specific alternative pre-mRNA\ splicing characteristics and has been found in splicing regulatory proteins [MEDLINE:94266805]. These ancient, conserved\ SWAP proteins share a colinearly arrayed series of novel\ sequence motifs [MEDLINE:95061415].\ \ RNA binding activity ; GO:0003723 \N RNA processing ; GO:0006396 18832 IPR000062 Thymidylate kinase (EC: 2.7.4.9) (dTMP kinase) catalyzes the phosphorylation ofthymidine 5'-monophosphate (dTMP) to thymidine 5'-diphosphate (dTDP) in the\ presence of ATP and magnesium:\

\
ATP + thymidine 5'-phosphate = ADP + thymidine 5'-diphosphate\

\ This enzyme is important in the pathway of\ synthesis of dTTP from dTMP. Thymidylate kinase is an ubiquitous enzyme of\ about 25 Kd.\ \ ATP binding activity ; GO:0005524 \N dTTP biosynthesis ; GO:0006235 18829 IPR000059 The function of this family is unknown. Proteins are of about21 to 39 kDa with a central region that is well conserved. It is often associated with the MutT-like domain IPR000086.\ \ molecular_function unknown ; GO:0005554 \N \N 18830 IPR000060

These prokaryotic transport proteins belong to a family known as BCCT (for Betaine /Carnitine / Choline Transporters) and are specific for compounds containing\ a quaternary nitrogen atom. The BCCT proteins contains 12 transmembrane regions\ and are energized by proton symport. They contains a conserved region with four\ tryptophans in their central region.

\ \ transporter activity ; GO:0005215 membrane ; GO:0016020 transport ; GO:0006810 18828 IPR000058 This domain was first identified as a zinc finger at the C-terminus of An1 Q91889 a ubiquitin-likeprotein in Xenopus laevis\ \ \ \ [MEDLINE:93292985].\ The following pattern describes the zinc finger.\

\
C-X2-C-X(9-12)-C-X(1-2)-C-X4-C-X2-H-X5-H-X-C\

\ where X can be any amino acid, and numbers in brackets indicate the number of residues. It has now been identified in a number of, as yet uncharacterised proteins from various sources.\ \ molecular_function unknown ; GO:0005554 \N \N 18827 IPR000057

IL8RB receptors are found in high density in neutrophils, monocytes,\ basophils, and melanoma cells, and in lower density in T-cells . IL8\ has been reported to stimulate the phosphoinositide pathway through an\ uncharacterised G-protein; pertussis toxin also inhibits several of its\ actions PUB00005876. The IL8RB receptor shares around 80% similarity with the\ IL8RA receptor.

\ \ interleukin-8 receptor activity ; GO:0004918 integral to membrane ; GO:0016021 chemotaxis ; GO:0006935 18825 IPR000055 This domain is also known as the target recognition domain (TRD).Restriction-modification (R-M) systems protect a bacterial cell\ against invasion of foreign DNA by endonucleolytic cleavage of DNA\ that lacks a site specific modification. The host genome is\ protected from cleavage by methylation of specific nucleotides\ in the target sites.

In type I systems, both restriction and\ modification activities are present in one heteromeric enzyme\ complex composed of one DNA specificity subunit (this family),\ two modification (M) subunits and two restriction (R) subunits [MEDLINE:99057973]. Most of the proteins in this family have two copies of the domain.

\ \ DNA binding activity ; GO:0003677 \N DNA modification ; GO:0006304 18826 IPR000056 Ribulose-phosphate 3-epimerase (EC: 5.1.3.1) (also known as pentose-5-phosphate3-epimerase or PPE) is the enzyme that converts D-ribulose 5-phosphate into\ D-xylulose 5-phosphate in Calvin's reductive pentose phosphate cycle. In\ Alcaligenes eutrophus two copies of the gene coding for PPE are known [MEDLINE:93054349],\ one is chromosomally encoded P40117.\ PPE has been found in a wide range of bacteria, archaebacteria, fungi and\ plants. All the proteins have from 209 to 241 amino acid residues.\ The enzyme has a TIM barrel structure.\ \ ribulose-phosphate 3-epimerase activity ; GO:0004750 \N carbohydrate metabolism ; GO:0005975 18824 IPR000054

\ \ \

A number of eukaryotic and archaebacterial large subunit ribosomal\ proteins can be grouped on the basis of sequence similarities.\ These proteins have 87 to 128 amino-acid residues.This family consists of:\

Yeast L34

Archaeal L31 [MEDLINE:91002676]

Plants L31

Mammalian L31 [MEDLINE:87133543]

\ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 18822 IPR000052 Potexviruses and carlaviruses are plant-infecting viruses whose genome consistof a single-stranded RNA molecule encapsided in a coat protein. The genome of\ many potexviruses is known and their coat protein sequence has been shown to\ be rather well conserved [MEDLINE:89293092]. The same observation applies to the coat protein\ of a variety of carlaviruses whose sequences are related to those of\ potexviruses\ \ \ \ [MEDLINE:89279283], [MEDLINE:92333281]. The coat proteins of potexviruses and of carlaviruses\ contain from 190 to 300 amino acid residues.\ The best conserved region of these coat proteins is located in the central\ part.\ \ structural molecule activity ; GO:0005198 viral capsid ; GO:0019028 \N 18823 IPR000053 Thymidine phosphorylase (EC: 2.4.2.4) catalyzes the reversible phosphorolysisof thymidine, deoxyuridine and their analogues to their respective bases and\ 2-deoxyribose 1-phosphate. This enzyme regulates the availability of thymidine\ and is therefore essential to nucleic acid metabolism.\ In Escherichia coli (gene deoA), the enzyme is a dimer of identical subunits\ of about 48 Kd [MEDLINE:90338026]. In humans it was first identified as platelet-derived\ endothelial cell growth factor (PD-ECGF) [MEDLINE:90338026] before being recognized [MEDLINE:92236753] as thymidine phosphorylase.\ Bacterial pyrimidine-nucleoside phosphorylase (EC: 2.4.2.2, gene pdp) [MEDLINE:96134975] is\ an enzyme evolutionary and structurally related to thymidine phosphorylase.\ \ \N \N pyrimidine base metabolism ; GO:0006206 18820 IPR000049 The electron transfer flavoprotein (ETF) [MEDLINE:90222268], [MEDLINE:96099680]serves as a specific electron\ acceptor for various mitochondrial dehydrogenases. ETF transfers electrons to\ the main respiratory chain via ETF-ubiquinone oxidoreductase. ETF is an\ heterodimer that consist of an

and a

subunit and which bind one\ molecule of FAD per dimer. A similar system also exists in some bacteria.\ The

subunit of ETF is a protein of about 28 Kd which is structurally\ related to the bacterial nitrogen fixation protein fixA which could play a\ role in a redox process and feed electrons to ferredoxin.\ The

subunit protein is distantly related to and forms a\ heterodimer with the

subunit IPR001308.\ \ electron transporter activity ; GO:0005489 \N electron transport ; GO:0006118 18821 IPR000051

Methyl transfer from the ubiquitous S-adenosyl-L-methionine (AdoMet) to either nitrogen, oxygen or carbon atoms is frequently employed in diverse organisms ranging from bacteria to plants and mammals. The\ reaction is catalyzed by methyltransferases (Mtases) and modifies DNA, RNA, proteins and small\ molecules, such as catechol for regulatory purposes. The various aspects of the role of DNA methylation in\ prokaryotic restriction-modification systems and in a number of cellular processes in eukaryotes including\ gene regulation and differentiation is well documented.

\ \

The catalytic domain of AdoMet-MTases is of the / type with a central\ mixed -sheet around which several -helices are arranged. \ Topologically it can be divided into two halves. The first half, formed by\ beta1-alphaA-beta2-alphaB-beta3-alphaC, is mainly responsible for AdoMet binding.\ The second half, beta4-alphaD-beta5-alphaE-beta6-beta7, is primarily\ responsible for catalysis [MEDLINE:95292061].

\ \

Three classes of DNA Mtases transfer the methyl group from AdoMet to the target base to form either\ N-6-methyladenine, or N-4-methylcytosine, or C-5- methylcytosine. In C-5-cytosine Mtases, ten conserved\ motifs are arranged in the same order [MEDLINE:94173650]. Motif I (a glycine-rich or closely related\ consensus sequence; FAGxGG in M.HhaI [MEDLINE:93345018]), shared by other AdoMet-Mtases\ [MEDLINE:90062128], is part of the cofactor binding site, and motif IV (PCQ) is part of the catalytic site. In\ contrast, sequence comparison among N-6-adenine and N-4-cytosine Mtases indicated two of the\ conserved segments [MEDLINE:90098846], although more conserved segments may be present. One of them\ corresponds to motif I in C-5-cytosine Mtases, and the other is named (D/N/S)PP(Y/F). Crystal structures\ are known for a number of methyl transferases [MEDLINE:95331548], [MEDLINE:93345018], [MEDLINE:94173650], [MEDLINE:95062184]. The\ cofactor binding sites are almost identical and the essential catalytic amino acids coincide. The\ comparable protein folding and the existence of equivalent amino acids in similar secondary and tertiary\ positions indicate that many (if not all) AdoMet-Mtases have a common catalytic\ domain structure. This permits tertiary structure prediction of other DNA, RNA, protein, and small-molecule\ AdoMet-Mtases from their amino acid sequences [MEDLINE:95205408].

\ \ S-adenosylmethionine-dependent methyltransferase activity ; GO:0008757 \N \N 18819 IPR000048

Calmodulin (CaM) is recognized as a major calcium sensor and orchestrator of regulatory events through its interaction with a diverse group of cellular proteins. Three classes of recognition motifs exist for many of the known CaM binding proteins; the IQ motif as a consensus for Ca²⁺-independent binding and two related motifs for Ca²⁺-dependent binding, termed18-14 and 1-5-10 based on the position of conserved hydrophobic residues [MEDLINE:97286332].

The regulatory domain of scallop myosin is a three-chain protein complex that\ switches on this motor in response to Ca²⁺ binding. Side-chain interactions link the two light chains in tandem to adjacent segments of the heavy chain bearing the IQ-sequence motif. The Ca²⁺-binding site is a novel EF-hand motif on the essential light chain and is stabilized by linkages involving the heavy chain and both light chains, accounting for the requirement of all three chains for Ca²⁺ binding and regulation in the intact myosin molecule [MEDLINE:94173332].

\ \ \N \N \N 18818 IPR000047 Helix-turn-helix (HTH) motifs are found in all known DNA binding proteinsthat regulate gene expression. The motif consists of approximately 20 \ residues and is characterised by 2

-helices, which make intimate \ contacts with the DNA and are joined by a short turn. The second helix of \ the HTH motif binds to DNA via a number of hydrogen bonds and hydrophobic \ interactions, which occur between specific side chains and the exposed \ bases and thymine methyl groups within the major groove of the DNA [MEDLINE:89123244]. The\ first helix helps to stabilise the structure [MEDLINE:82220161]. \

The HTH motif is very similar in sequence and structure to the N-terminal \ region of the lamda [MEDLINE:84305754] and other repressor proteins, and has also been \ identified in many other DNA-binding proteins on the basis of sequence and \ structural similarity [MEDLINE:89123244]. One of the principal differences between HTH \ motifs in these different proteins arises from the stereochemical \ requirement for glycine in the turn, which is needed to avoid steric \ interference of the -carbon with the main chain: for cro and other \ repressors the Gly appears to be mandatory, while for many of the homeotic\ and other DNA-binding proteins the requirement is relaxed.

\ \ transcription factor activity ; GO:0003700 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 18817 IPR000046

In the brain, high concentrations of the NK1 receptor are found in striatum,\ olfactory bulb, dendate gyrus, locus coeruleus and spinal chord [MEDLINE:20520994]. In\ peripheral tissues NK1 receptors are found in smooth muscle (e.g., ileum\ and bladder), enteric neurons, secretory glands (e.g. parotid), cells of\ the immune system and vascular endothelium. NK1 receptors activate the\ phosphoinositide pathway through a pertussis-toxin-insensitive G-protein [MEDLINE:98236698].

\ \ tachykinin receptor activity ; GO:0004995 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 18816 IPR000045

\ \

Bacteria produce a number of protein precursors that undergo posttranslational\ methylation and proteolysis prior to secretion as active\ proteins. Type IV prepilin leader peptidases, which belong to the C20 family\ of cysteine proteases, are enzymes that mediate this type of posttranslational\ modification. Type IV pilin is a protein found on the surface\ of Pseudomonas aeruginosa, Neisseria gonorrhoeae and other Gram-negative\ pathogens. Pilin subunits attach the infecting organism to the surface of\ host epithelial cells. They are synthesised as prepilin subunits, which\ differ from mature pilin by virtue of containing a 6-8 residue leader\ peptide consisting of charged amino acids. Mature type IV pilins also\ contain a methylated N-terminal phenylalanine residue.

\ \

Prepilin leader peptidases are found on the cytosolic membrane surface,\ where they have dual activity, involving cleavage of glycine-phenylalanine\ bonds and methylation of the newly-revealed N-terminal phenylalanine. The\ consensus sequence for the site of proteolytic cleavage is -G+F-T-L/I-, in\ which the Gly P1 residue is essential [MEDLINE:95147707]. The peptidases are suseptible to\ thiol blocking reagents.

\ \ cysteine-type peptidase activity ; GO:0008234 membrane ; GO:0016020 proteolysis and peptidolysis ; GO:0006508 18814 IPR000043 S-adenosyl-L-homocysteine hydrolase (EC: 3.3.1.1) (AdoHcyase) is an enzyme ofthe activated methyl cycle, responsible for the reversible hydratation of \ S-adenosyl-L-homocysteine into adenosine and homocysteine. AdoHcyase is an\ ubiquitous enzyme which binds and requires NAD⁺ as a cofactor.\ AdoHcyase is a highly conserved protein [MEDLINE:92335291] of about 430 to 470 amino acids.\ The family contains a glycine-rich region in the central part of AdoHcyase; a region thought to be\ involved in NAD-binding.\ \ adenosylhomocysteinase activity ; GO:0004013 \N one-carbon compound metabolism ; GO:0006730 18815 IPR000044 Mycoplasma genitalium has the smallest known genome of any free-living organism. Its complete genome sequence has been determined by whole-genome random sequencing and assembly [MEDLINE:96026346]. Only 470 putative coding regions were identified, including genes for DNA replication, transcription and\ translation, DNA repair, cellular transport and energy metabolism [MEDLINE:96026346]. \ A hypothetical protein from the MG045 gene [MEDLINE:94075230] has a homologue of similarly\ unknown function in Mycoplasma pneumoniae\ \ \ \ [MEDLINE:97105885].\ \ molecular_function unknown ; GO:0005554 \N \N 18812 IPR000042 It has been known for a long time [MEDLINE:73033452] that potential N-glycosylation sites arespecific to the consensus sequence Asn-Xaa-Ser/Thr. It must be noted that the\ presence of the consensus tripeptide is not sufficient to conclude that an\ asparagine residue is glycosylated, due to the fact that the folding of the\ protein plays an important role in the regulation of N-glycosylation [MEDLINE:77102701]. It\ has been shown [MEDLINE:83204013] that the presence of proline between Asn and Ser/Thr will\ inhibit N-glycosylation; this has been confirmed by a recent [MEDLINE:90272642] statistical\ analysis of glycosylation sites, which also shows that about 50% of the sites\ that have a proline C-terminal to Ser/Thr are not glycosylated.\ It must also be noted that there are a few reported cases of glycosylation\ sites with the pattern Asn-Xaa-Cys; an experimentally demonstrated occurrence\ of such a non-standard site is found in the plasma protein C [MEDLINE:90293094].\

Note: No protein matches are shown due to the low specificity of this rule.

\ \ \N \N \N 18813 IPR000043 S-adenosyl-L-homocysteine hydrolase (EC: 3.3.1.1) (AdoHcyase) is an enzyme ofthe activated methyl cycle, responsible for the reversible hydratation of \ S-adenosyl-L-homocysteine into adenosine and homocysteine. AdoHcyase is an\ ubiquitous enzyme which binds and requires NAD⁺ as a cofactor.\ AdoHcyase is a highly conserved protein [MEDLINE:92335291] of about 430 to 470 amino acids.\ The family contains a glycine-rich region in the central part of AdoHcyase; a region thought to be\ involved in NAD-binding.\ \ adenosylhomocysteinase activity ; GO:0004013 \N one-carbon compound metabolism ; GO:0006730 18810 IPR000039

\ \ \

Members of this family are large subunit ribosomal proteins which are found in the Eukaryota and Archaea. These proteins have 115 to 187 amino-acid residues. The family consists of:

Vertebrate L18 (known as L14 in Xenopus) [MEDLINE:94032474]
Plant L18
Yeast L18 (Rp28)
Halobacterium marismortui HL29
Sulfolobus acidocaldarius HL29e

\ \ \ \ structural constituent of ribosome ; GO:0003735 ribosome ; GO:0005840 protein biosynthesis ; GO:0006412 18811 IPR000040 The AML1 gene is rearranged by the t(8;21) translocation in acute myeloid leukemia [MEDLINE:95380294]. The gene is highly similar to the Drosophila melanogaster segmentation \ gene runt and to the mouse transcription factor PEBP2

subunit gene [MEDLINE:95380294].\ The region of shared similarity, known as the Runt domain, is responsible \ for DNA-binding and protein-protein interaction. \

In addition to the highly-conserved Runt domain, the AML-1 gene product\ carries a putative ATP-binding site (GRSGRGKS), and has a C-terminal region\ rich in proline and serine residues. The protein (known as acute myeloid \ leukemia 1 protein, oncogene AML-1, core-binding factor (CBF), -B \ subunit, etc.) binds to the core site, 5'-pygpyggt-3', of a number of\ enhancers and promoters.

The protein is a heterodimer of - and -subunits. The -subunit\ binds DNA as a monomer, and appears to have a role in the development of\ normal hematopoiesis. CBF is a nuclear protein expressed in numerous tissue\ types, except brain and heart; highest levels have been found to occur in \ thymus, bone marrow and peripheral blood.

\ \ ATP binding activity ; GO:0005524 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 18806 IPR000035 Alkylbase DNA glycosidases [MEDLINE:89024568] are DNA repair enzymes that hydrolyze thedeoxyribose N-glycosidic bond to excise various alkylated bases from a damaged\ DNA polymer.\ In Escherichia coli there are two alkylbase DNA glycosidases: one (gene tag)\ which is constitutively expressed and which is specific for the removal of 3-\ methyladenine (EC: 3.2.2.20), and one (gene alkA) which is induced during\ adaptation to alkylation and which can remove a variety of alkylation products\ (EC: 3.2.2.21). Tag and alkA do not share any region of sequence similarity.\ In yeast there is an alkylbase DNA glycosidase (gene MAG1) [MEDLINE:91092283], [MEDLINE:91092284], which can\ remove 3-methyladenine or 7-methyladenine and which is structurally related to\ alkA.\ MAG and alkA are both proteins of about 300 amino acid residues. While the C-\ and N-terminal ends appear to be unrelated, there is a central region of about\ 130 residues which is well conserved.\ \ alkylbase DNA N-glycosylase activity ; GO:0003905 \N DNA repair ; GO:0006281 18807 IPR000036 The omptin family comprises a number of novel outer membrane-associatedserine proteases that are distinct from trypsin-like proteases in that \ they cleave polypeptides between two basically-charged amino acids [MEDLINE:89053885]. The\ enzyme is sensitive to the serine protease inhibitor diisopropylfluoro-\ phosphate, to divalent cations such as Cu²⁺, Zn²⁺ and Fe²⁺ [MEDLINE:89053885], and is\ temperature regulated, activity decreasing at lower temperatures [MEDLINE:89053885], [MEDLINE:94117370].\ Temperature regulation is most prominantly shown in the Yersinia pestis\ coagulase/fibrinolysin protein, where coagulase activity is prevalent \ below 30 degrees Celsius, and fibrinolysin (protease) activity is prevalent\ above this point, the optimum temperature being 37 degrees [MEDLINE:89313306]. It is possible that this assists in 'flea blockage' and transmission of the bacteria to animals [MEDLINE:89313306].\ \ serine-type peptidase activity ; GO:0008236 external outer membrane (sensu Gram-negative Bacteria) ; GO:0009279 proteolysis and peptidolysis ; GO:0006508 18808 IPR000037 In bacteria, SsrA RNA recognizes ribosomes stalled on defective messages and acts as a tRNA and mRNA to mediatethe addition of a short peptide tag to the C-terminus of the partially synthesized nascent polypeptide chain. The\ SsrA-tagged protein is then degraded by C-terminal-specific proteases.

SmpB, a unique RNA-binding protein that is\ conserved throughout the bacterial kingdom is an essential component of the SsrA quality-control\ system. Deletion of the smpB gene in Escherichia coli results in the same phenotypes observed in ssrA-defective cells,\ including a variety of phage development defects and the failure to tag proteins translated from defective mRNAs. Purified\ SmpB binds specifically and with high affinity to SsrA RNA and is required for stable association of SsrA with ribosomes\ in vivo. Formation of an SmpB-SsrA complex appears to be critical in mediating SsrA activity after aminoacylation with\ alanine but prior to the transpeptidation reaction that couples this alanine to the nascent chain. SsrA RNA is present at\ wild-type levels in the smpB mutant arguing against a model of SsrA action that involves direct competition for\ transcription factors [MEDLINE:99321766].

\ \ RNA binding activity ; GO:0003723 \N protein biosynthesis ; GO:0006412 18809 IPR000038 Members of this family are involved in cell division and bind GTP.Members of this family include the cell division control proteins CDC3, CDC10, CDC11 and CDC12/Septin and some uncharacterised proteins involved in cytokinesis.\ \ \N \N \N 18804 IPR000033 Low-density lipoprotein (ldl) receptor repeat is also known as the YWTD motif after the mostconserved region of the repeat. The YWTD repeat is found in\ multiple tandem repeats and has been predicted to form a

-propeller structure [MEDLINE:99009139]. It is found in a variety of proteins that include, vitellogenin receptor from Drosophila melanogaster, low-density lipoprotein (LDL) receptor [MEDLINE:85024898], preproepidermal growth factor, nidogen (entactin) and others.\ \ \N membrane ; GO:0016020 \N 18805 IPR000034 The laminin B domain (also known as domain IV) is an extracellular module of unknown function. It is found in a number of different proteins that include, heparan sulfate proteoglycan from basement membrane, a laminin-like protein from Caenorhabditis elegans and laminin.\ \N \N \N 18801 IPR000030 This mycobacterial family is named after a conserved amino-terminal region of about 180amino acids, the PPE motif. The carboxy termini of proteins belonging to the PPE family are variable, and on the basis of this region at least three groups can be distinguished. The MPTR subgroup is characterized by tandem copies of a motif NXGXGNXG. The second subgroup contains a conserved motif at about position 350.\ The third group shares only similarity in the amino terminal region.\ The function of these proteins is uncertain but it has been suggested that they may be related to antigenic variation of Mycobacterium tuberculosis\ \ \ \ [MEDLINE:98295987].\ \ \N \N \N 18802 IPR000031

PurK, N5-carboxyaminoimidazole ribonucleotide (N5_CAIR) synthetase, catalyzes the conversion of 5-aminoimidazole ribonucleotide (AIR), ATP, and bicarbonate to\ N5-CAIR, ADP, and Pi. PurE converts N5-CAIR to CAIR, the sixth step of de novo purine biosynthesis. In the presence of high concentrations of bicarbonate, PurE is\ reported able to convert AIR to CAIR directly and without ATP. Some members of this family contain two copies of this\ domain.

\ \ phosphoribosylaminoimidazole carboxylase activity ; GO:0004638 phosphoribosylaminoimidazole carboxylase complex ; GO:0009320 'de novo' IMP biosynthesis ; GO:0006189 18803 IPR000032

The phosphoenolpyruvate-dependent sugar phosphotransferase system (PTS)\ is a major carbohydrate transport system in bacteria. The PTS catalyses\ the phosphorylation of sugar substrates during their translocation across\ the cell membrane. The mechanism involves the transfer of a phosphoryl\ group from phosphoenolpyruvate (PEP) via enzyme I (EI) to enzyme II (EII)\ of the PTS system, which in turn transfers it to a phosphocarrier protein\ (HPr) [MEDLINE:95156481], [MEDLINE:95219382].

There is a conserved histidine in the N-terminus of HPr IPR001020, which serves as an acceptor for\ the phosphoryl group of EI. In the central part of HPr there is a conserved serine IPR001020/>\ which, in Gram-positive bacteria only, is phosphorylated by an\ ATP-dependent protein kinase, a process which probably plays a regulatory role in sugar\ transport.

\ \ sugar porter activity ; GO:0005351 \N phosphoenolpyruvate-dependent sugar phosphotransferase system ; GO:0009401 18799 IPR000026 Ribonuclease N1 (RNase N1) is a guanine-specific ribonuclease from fungi. RNase T1 and other bacteria RNases are related.\ \

The enzyme hydrolyses the phosphodiester bonds in RNA and oligoribonucleotides [MEDLINE:94153920], resulting in 3'-nucleoside monophosphates via 2',3'-cyclophosphate intermediates.

\ \ endoribonuclease activity ; GO:0004521 \N \N 18800 IPR000028 Chloroperoxidase (CPO) is a versatile heme-containing enzyme that exhibits peroxidase, catalase and cytochrome P450-likeactivities in addition to catalyzing halogenation reactions [MEDLINE:96363674].\ Despite functional similarities with other heme enzymes, CPO folds into a novel\ tertiary structure dominated by eight helical segments. The catalytic base,\ required to cleave the peroxide O-O bond, is glutamic acid\ rather than histidine as in other peroxidases.\ \ peroxidase activity ; GO:0004601 \N peroxidase reaction ; GO:0006804 18798 IPR000025

Melatonin is secreted by the pineal gland during darkness PUB00005892. It regulates\ a variety of neuroendocrine functions and is thought to play an essential\ role in circadian rhythms. Drugs that modify the action of melatonin,\ and hence influence circadian cycles, are of clinical interest (for example,\ in the treatment of jet-lag). Melatonin receptors are found in the\ retina, in the pars tuberalis of the pituitary, and in discrete areas of\ the brain. The receptor inhibits adenylyl cyclase via a pertussis-toxin-sensitive G-protein, probably of the Gi/Go class PUB00005892.

\ \ melatonin receptor activity ; GO:0008502 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 18797 IPR000024 The Frizzled CRD (cysteine rich domain) is conserved in diverse proteins including several receptor tyrosine kinases[MEDLINE:98301755], [MEDLINE:98348039], [MEDLINE:99069860].\ In Drosophila melanogaster, members of the Frizzled family of tissue-polarity genes encode proteins that appear to function as cell-surface receptors for Wnts. The Frizzled genes belong to the seven transmembrane class of receptors (7TMR) and have in their extracellular region a cysteine-rich domain that has been implicated as the Wnt binding domain. Sequence similarity between the cysteine-rich domain of Frizzled and several receptor tyrosine kinases, which have roles in development include the muscle-specific receptor tyrosine kinase (MuSK), the neuronal specific kinase (NSK2), and ROR1 and ROR2.\ \ The structure of this domain is known and is composed mainly of

helices.\ This domain contains ten conserved cysteines that form five disulphide bridges.\ These are shown in schematic form below\

\
        +--------------+\
        |              |\
--C--C--C--C--C--C--C--C--C--C--\
  |  |     |  |  |  |     |  |\
  |  +-----+  |  |  +-----+  |\
  +-----------+  +-----------+\

\ \ transmembrane receptor activity ; GO:0004888 membrane ; GO:0016020 development ; GO:0007275 18796 IPR000023 The enzyme-catalysed transfer of a phosphoryl group from ATP is animportant reaction in a wide variety of biological processes [MEDLINE:87229041]. One\ enzyme that utilises this reaction is phosphofructokinase (PFK), which\ catalyses the phosphorylation of fructose-6-phosphate to fructose-1,6-\ bisphosphate, a key regulatory step in the glycolytic pathway [MEDLINE:87229041], [MEDLINE:95126102]. \ PFK exists as a homotetramer in bacteria and mammals (where each monomer\ possesses 2 similar domains), and as an octomer in yeast (where there are\ 4

- (PFK1) and 4

-chains (PFK2), the latter, like the mammalian\ monomers, possessing 2 similar domains [MEDLINE:87229041], [MEDLINE:95126102]).

PFK is ~300 amino acids in length, and structural studies of the\ bacterial enzyme have shown it comprises two similar (/) lobes: one involved in\ ATP binding and the other housing both the substrate-binding site and the allosteric site (a regulatory binding site distinct from the active site, but that affects enzyme\ activity). The identical tetramer subunits adopt 2 \ different conformations: in a 'closed' state, the bound magnesium ion\ bridges the phosphoryl groups of the enzyme products (ADP and fructose-1,6-\ bisphosphate); and in an 'open' state, the magnesium ion binds only the ADP\ [MEDLINE:89125622], as the 2 products are now further apart. These conformations are\ thought to be successive stages of a reaction pathway that requires subunit\ closure to bring the 2 molecules sufficiently close to react [MEDLINE:89125622].

Deficiency in PFK leads to glycogenosis type VII (Tauri's disease), an\ autosomal recessive disorder characterised by severe nausea, vomiting,\ muscle cramps and myoglobinuria in response to bursts of intense or\ vigorous exercise [MEDLINE:95126102]. Sufferers are usually able to lead a reasonably\ ordinary life by learning to adjust activity levels [MEDLINE:95126102].

\ \ \ 6-phosphofructokinase activity ; GO:0003872\ \ 6-phosphofructokinase complex ; GO:0005945\ \N \N glycolysis ; GO:0006096 18795 IPR000022 All of the members in this family are biotin dependent carboxylases[MEDLINE:93358891], [MEDLINE:93374821].\ The carboxyl transferase domain carries out the following reaction;\ transcarboxylation from biotin to an acceptor molecule. There are\ two recognised types of carboxyl transferase. One of them uses acyl-CoA\ and the other uses 2-oxo acid as the acceptor molecule of carbon dioxide. \ All of the members in this family utilise acyl-CoA as the acceptor\ molecule.\ \ biotin carboxylase activity ; GO:0004075 biotin carboxylase complex ; GO:0009343 \N 18794 IPR000021 The hok/gef family of Gram-negative bacterial proteins are toxic to cellswhen over-expressed, killing the cells from within by interfering with a\ vital function in the cell membrane [MEDLINE:89181537]. Some family members (flm) increase\ the stability of unstable RNA [MEDLINE:89181537], some (pnd) induce the degradation of\ stable RNA at higher than optimium growth temperatures [MEDLINE:89150247], and others\ affect the release of cellular magnesium by membrane alterations [MEDLINE:89150247]. The\ proteins are short (50-70 residues), consisting of an N-terminal hydrophobic (possibly membrane spanning) domain, and a C-terminal periplasmic\ region, which contains the toxic domain. The C-terminal region contains a\ conserved cysteine residue that mediates homo-dimerisation in the gef\ protein, although dimerisation is not necessary for the toxic effect [MEDLINE:92048480].\ \ \N \N \N 18793 IPR000020

Fibulin is a secreted\ glycoprotein that becomes incorporated into a fibrillar extracellular matrix when\ expressed by cultured cells or added exogenously to cell monolayers [MEDLINE:91100426]. The amino-terminal portion of fibulin contains a\ repeated element with potential disulfide loop structure resembling that of the\ complement component anaphylatoxins C3a, C4a, and C5a as well as proteins of the\ albumin gene family. The bulk of the remaining portion of the molecule is a series of\ nine EGF-like repeats [MEDLINE:94064787]. The ProDom signature in this entry does not hit the fibulins.

\ \ \N extracellular ; GO:0005576 \N 18792 IPR000018

In addition to their role in energy metabolism, purines (especially\ adenosine and adenine nucleotides) produce a wide range of pharmacological\ effects mediated by activation of cell surface receptors PUB00005868. ATP is a\ co-transmitter in sympathetic nerves in the autonomic nervous system,\ where it exerts an important physiological role in the regulation of\ smooth muscle activity, stimulating relaxation of intestinal smooth muscle\ and contraction of the bladder. Receptors for adenine nucleotides are\ involved in a number of other physiological pathways, including stimulation\ of platelet activation by ADP, which is released from the vascular\ endothelium following injury. ATP has excitatory effects in the CNS PUB00005868.\ Distinct receptors exist for adenosine. The main effects of adenosine in\ the periphery include vasodilation, bronchoconstriction, immunosuppression,\ inhibition of platelet aggregation, cardiac depression, stimulation of\ nociceptive afferents, inhibition of neurotransmitter release, and\ inhibition of the release of hormones. In the CNS, adenosine exerts a\ pre- and post-synaptic depressant action, reducing motor activity,\ depressing respiration, inducing sleep and relieving anxiety. The\ physiological role of adenosine is believed to be to adjust energy demands\ in line with oxygen supply PUB00005868.

Purinoceptors have been classified as P1 or P2, depending on their\ preference for adenosine or adenine nucleotides respectively. Adenosine\ receptors (P1 purinoceptors) are characterised by their affinity for\ adenosine and by the ability of methylxanthines to act as antagonists PUB00005868.\ Adenosine has very low affinity for P2 purinoceptors.

A new subtype of P2 purinoceptors has been isolated PUB00005868. Its deduced amino\ acid sequence is consistent with a GPCR that is 51% identical to the human\ P2Y2 receptor and 35% identical to the chicken P2Y1 receptor [MEDLINE:96125055]. In cells\ stably expressing the receptor, UTP and UDP have been shown to stimulate\ the formation of inositol phosphates with equivalent potency and maximal\ effect, while ATP behaves as a partial agonist, and ADP is almost inactive\ [MEDLINE:96125055]. The receptor is thus a new member of the P2 purinergic receptor family\ that functionally behaves as a pyrimidinergic receptor [MEDLINE:96125055].

\ \ \ purinergic nucleotide receptor activity, G-protein coupled ; GO:0045028 integral to membrane ; GO:0016021 G-protein coupled receptor protein signaling pathway ; GO:0007186 18791 IPR000015 In Gram-negative bacteria the biogenesis of fimbriae (or pili) requires a two-component assembly and transport system which is composed of a periplasmic\ chaperone (see PDOC00552) and an outer membrane protein which has been\ termed a molecular 'usher' [MEDLINE:94230306], [MEDLINE:94148769], [MEDLINE:94143600].

The usher protein is rather large (from 86 to\ 100 Kd) and seems to be mainly composed of membrane-spanning -sheets, a\ structure reminiscent of porins. \ Although the degree of sequence similarity of these proteins is not very high\ they share a number of characteristics. One of these is the presence of two pairs\ of cysteines, the first one located in the N-terminal part and the second\ at the C-terminal extremity that are probably involved in disulfide bonds.\ The best conserved region is located in the central part of these proteins.

\ \ transporter activity ; GO:0005215 membrane ; GO:0016020 transport ; GO:0006810 18790 IPR000014 PAS domains are involved in many signalling proteins where theyare used as a signal sensor domain. PAS domains appear in archaebacteria,\ bacteria and eukaryotes. Several PAS-domain proteins are known to\ detect their signal by way of an associated cofactor. Heme,\ flavin, and a 4-hydroxycinnamyl chromophore are used in different\ proteins. The PAS domain was named after three proteins that it\ occurs in: \

Per- period circadian protein

Arnt- Ah receptor nuclear translocator protein

Sim- single-minded protein.

PAS domains are often associated with\ PAC domains IPR001610.\ Probably the most surprising identification of a PAS domain was that in\ EAG-like K⁺-channels [MEDLINE:97446881].

\ \ signal transducer activity ; GO:0004871 \N signal transduction ; GO:0007165 18789 IPR000013 Metalloproteases are the most diverse of the four main types of protease, with more than 30 families identified to date [MEDLINE:95405261]. Of these, around half contain the HEXXH motif, which has been shown in crystallographic studies to form part of the metal-binding site [MEDLINE:95405261]. The HEXXH motif is relatively common, but can be more stringently defined for metalloproteases as abXHEbbHbc, where a is most often valine or threonine and forms part of the S1' subsite in thermolysin and neprilysin, b is an uncharged residue, and c a hydrophobic residue. Proline is never found in this site, possibly because it would break the helical structure adopted by this motif in metalloproteases [MEDLINE:95405261]. Metalloproteases can be split into five groups on the basis of their metal-binding residues: the first three contain the HEXXH motif, the other two do not [MEDLINE:95405261]. In the first group, a glutamic acid completes the active site. These are termed HEXXH⁺E: all families in this group show some sequence relationship and have been assigned to clan MA [MEDLINE:95405261]. The second group, which have a third histidine as the extra metal-binding residue, are termed HEXXH⁺H and are grouped into clan MB on the basis of their inter-relationship [MEDLINE:95405261].

With a molecular weight of around 16kDa, Streptomyces extracellular neutral protease is one of the smallest known proteases [MEDLINE:95405261]; it is capable of hydrolysing milk proteins [MEDLINE:95405261]. The enzyme is synthesised as a proenzyme with a signal peptide, a propeptide and an active domain that contains the conserved HEXXH motif characteristic of metalloprotease clans MA and MB. Although family M7 shows active site sequence similarity to other members of clan MB, it differs in one major respect: the third zinc ligand appears to be an aspartate residue rather than the usual histidine.

\ \ metallopeptidase activity ; GO:0008237 extracellular ; GO:0005576 proteolysis and peptidolysis ; GO:0006508 18788 IPR000012 HIV is the human retrovirus associated with AIDS (acquired immune deficiency syndrome), and SIV its simian counterpart. Three main groups\ of primate lentivirus are known, designated HIV-1, HIV-2/SIVMAC/SIVSM and\ SIVAGM. SIVMND has been suggested to represent a fourth \ distinct group [MEDLINE:90015168]. These groups are believed to have diverged from a\ common ancestor long before the spread of AIDS in humans.\ Genetic variation in HIV-1 and HIV-2 has been studied extensively, and\ the nucleotide sequences reported for several strains [MEDLINE:90122350].

ORF analysis\ has revealed two open reading frames, yielding the so-called R- and X-ORF\ proteins, whose functions are unknown, but which show a high degree of\ sequence similarity.

\ \ molecular_function unknown ; GO:0005554 \N \N 18787 IPR000011 Ubiquitin-activating enzyme (E1 enzyme) [MEDLINE:91274342], [MEDLINE:92023523] activates ubiquitin by firstadenylating with ATP its C-terminal glycine residue and thereafter linking\ this residue to the side chain of a cysteine residue in E1, yielding an\ ubiquitin-E1 thiolester and free AMP. Later the ubiquitin moiety is\ transferred to a cysteine residue on one of the many forms of ubiquitin-\ conjugating enzymes (E2).\

E1 is a large monomeric protein of about 110 to 115 Kd (about 1000 residues).\ In yeast there are two forms (UBA1 and UBA2) [MEDLINE:95355414], while in plants and mammals\ multiple forms exist including a form which is Y-linked in mouse and some\ other mammals and which may be involved in spermatogenesis.

\ \ ubiquitin activating enzyme activity ; GO:0004839 \N ubiquitin cycle ; GO:0006512 18786 IPR000010

The kininogens, are multifunctional plasma glycoproteins which are inhibitors of cysteine proteases.They are the precursors of the active peptide bradykinin and play a role in blood coagulation by helping to position optimally prekallikrein and factor XI\ next to factor XII. Structurally, kininogens are made of three contiguous type-2 cystatin domains, followed by an additional domain (of variable length) which\ contains the sequence of bradykinin. The first of the three cystatin\ domains seems to have lost its inhibitory activity.

\ \

Polypeptides which lack the cystatin domains but which retain the kininogen signature, IPR002395/>, are associated with the InterPro family IPR002395.\

\ \ cysteine protease inhibitor activity ; GO:0004869 \N \N 18785 IPR000009 Protein phosphatase 2A (PP2A) is a serine/threonine phosphatase implicated in many cellular processes, including the regulation of metabolic enzymes \ and proteins involved in signal transduction [MEDLINE:91198016], [MEDLINE:92114192]. PP2A is a trimer\ composed of a 36 kDa catalytic subunit, a 65 kDa regulatory subunit \ (subunit A) and a variable third subunit (subunit B) [MEDLINE:91198016], [MEDLINE:92114192]. \

One form of the third subunit is a 55 kDa protein (PR55), which exists in\ Drosophila melanogaster and yeast, and has up to three forms in mammals [MEDLINE:91198016], [MEDLINE:92114192]. PR55 may act\ as a substrate recognition unit, or may help to target the enzyme to the\ correct subcellular location [MEDLINE:91198016].

\ \ protein phosphatase type 2A, regulator activity ; GO:0008601 protein phosphatase type 2A complex ; GO:0000159 signal transduction ; GO:0007165 18784 IPR000008 The C2 domain is a Ca2+-dependent membrane-targeting module found in many cellular proteins involved in signal transduction or membrane trafficking. C2 domains are unique among membrane targeting domains in that they show wide range of lipid selectivity for the major components of cell membranes, including phosphatidylserine and phosphatidylcholine. Ths C2 domain is about 116 amino-acid residues and is located between the two copies ofthe C1 domain in Protein Kinase C (that bind phorbol esters and diacylglycerol) (see PDOC00379)\ and the protein kinase catalytic domain (see PDOC00379/>). Regions with\ significant homology [MEDLINE:96027639] to the C2-domain have been found in many proteins.\ The C2 domain is thought to be involved in calcium-dependent phospholipid\ binding [MEDLINE:94075324] and in membrane targetting processes such as subcellular localisation.

The 3D structure of the\ C2 domain of synaptotagmin has been reported\ [MEDLINE:95211844], the domain forms an eight-stranded sandwich constructed around a \ conserved 4-stranded motif, designated a C2 key [MEDLINE:95211844]. Calcium binds in\ a cup-shaped depression formed by the N- and C-terminal loops of the\ C2-key motif. Structural analyses of several C2 domains have shown them to consist of similar ternary structures in which three Ca²⁺-binding loops are located at the end of an 8 stranded antiparallel sandwich.

\ \ \N \N \N 18783 IPR000007

Tubby, an autosomal recessive mutation, mapping to mouse chromosome 7, was recently found to be the result of a splicing defect in a novel gene with unknown\ function. This mutation maps to the tub gene [MEDLINE:96200779], [MEDLINE:96195061].\ The mouse tubby mutation is the cause of maturity-onset obesity, insulin\ resistance and sensory deficits. By contrast with the rapid juvenile-onset weight gain seen in diabetes (db) and obese (ob) mice, obesity in\ tubby mice develops gradually, and strongly resembles the late-onset obesity\ observed in the human population. Excessive deposition of adipose tissue culminates in a two-fold increase of body weight. Tubby mice also suffer\ retinal degeneration and neurosensory hearing loss. The tripartite\ character of the tubby phenotype is highly similar to human obesity\ syndromes, such as Alstrom and Bardet-Biedl. Although these phenotypes\ indicate a vital role for tubby proteins, no biochemical function has yet\ been ascribed to any family member [MEDLINE:20059926], although it has been suggested that the phenotypic features of tubby mice may be the result of cellular \ apoptosis triggered by expression of the mutuated tub gene.

\ \

Mammalian tub is a hydrophilic protein of ~500 residues. The N-terminal\ portion of the protein is conserved neither in length nor sequence, but the \ C-terminal 250 residues are highly conserved. The C-terminal extremity\ contains a cysteine residue that might play an important role in the normal\ functioning of these proteins.\ \ Tubby-like proteins (TULPs), which share the tub C-terminal domain, are \ found in a wide range of multicellular organisms. The crystal structure\ of the C-terminal core domain from mouse tubby has been determined to 1.9A\ resolution, revealing an - protein with a barrel architecture.\ Structural analyses suggest that TULPs constitute a unique family of \ bipartite transcription factors [MEDLINE:20059926].\

\ \ \N \N \N 18782 IPR000006

\ \

The members of family 1 are recognised by the sequence pattern K-x(1,2)-C-C-x-C-C-P-x(2)-C located at the beginning of the third exon. \ The taxonomic range of the members extends to vertebrates. \ Known characteristics: 60 to 68 AAs; 20 Cys (21 in one case), 19 of them are totally conserved; the protein sequence is divided into two structural domains, containing 9 and 11 Cys all binding 3 and 4 bivalent metal ions, respectively. The gene is composed of 3 exons, 2 introns and the splicing sites are conserved. Family 1 includes subfamilies: m1, m2, m3, m4, m, a, a1, a2, b, ba, t, all of them hit the same InterPro entry. \

\ \ heavy metal binding activity ; GO:0005505 \N \N 18781 IPR000005

Many bacterial transcription regulation proteins bind DNA through a'helix-turn-helix' (HTH) motif. One major subfamily of these proteins [MEDLINE:93197143], [MEDLINE:90190362] is related to the arabinose \ operon regulatory protein AraC [MEDLINE:93197143], [MEDLINE:90190362].\ Except for celD [MEDLINE:90185127], all of these proteins seem to be positive transcriptional factors.

\ \

Although the sequences belonging to this family differ somewhat in length, in nearly every case the HTH motif is situated towards the C-terminus in the third quarter of most of the sequences. The minimal DNA binding domain spans roughly 100 residues and comprises two HTH subdomains; the classical HTH domain and another HTH subdomain with similarity to the classical HTH domain but with an insertion of one residue in the turn-region. The N-terminal and central regions of these proteins are presumed\ to interact with effector molecules and may be involved in dimerization [MEDLINE:93296193].

\ \

The known structure of MarA (P27246) shows that the AraC domain is helical and shows the two HTH subdomains both bind the major groove of the DNA. The two HTH subdomains are separated by only 27\ angstroms, which causes the cognate DNA to bend.

\ \ transcription factor activity ; GO:0003700 intracellular ; GO:0005622 regulation of transcription, DNA-dependent ; GO:0006355 18780 IPR000003

\ \ \

The retinoic acid (retinoid X) receptor consists of 3 functional and \ structural domains: an N-terminal (modulatory) domain; a DNA binding domain\ that mediates specific binding to target DNA sequences (ligand-responsive\ elements); and a hormone binding domain. The N-terminal domain differs \ between retinoic acid isoforms; the small highly-conserved DNA-binding\ domain (~65 residues) occupies the central portion of the protein; and \ the ligand binding domain lies at the receptor C-terminus.

Synonym(s): 2B nuclear receptor

\ \ steroid binding activity ; GO:0005496 nucleus ; GO:0005634 regulation of transcription, DNA-dependent ; GO:0006355 18778 IPR000001 Kringles are autonomous structural domains, found throughout the blood clotting and fibrinolytic proteins.Kringle domains are believed to play a role in binding mediators (e.g., membranes,\ other proteins or phospholipids), and in the regulation of proteolytic activity\ [MEDLINE:85182674], [MEDLINE:84208845], [MEDLINE:90219023]. \ Kringle domains [MEDLINE:88230478], [MEDLINE:85228216], [MEDLINE:91348198] are characterised by a triple loop, 3-disulphide bridge structure, whose conformation is defined by a number of hydrogen bonds and small pieces of anti-parallel

-sheet. They are found in a varying number of copies in some serine proteases and\ plasma proteins.\ \ \N \N \N 18779 IPR000002

The Cdc20/Fizzy region is almost always associated with the G-protein WD-40 repeat (IPR001680). Ubiquitin-mediated proteolysis due to the anaphase-promoting complex/cyclosome (APC/C) is essential for separation of sister chromatids, requiring degradation of the anaphase inhibitor Pds1, and for exit from mitosis, requiring inactivation of cyclin B Cdk1 kinases [MEDLINE:20110935]. In yeast Cdc20 is required for two microtubule-dependent processes, nuclear movements prior to anaphase and chromosome separation. APC(Cdc20) allows activation of Cdc14 and promotes exit from mitosis by mediating proteolysis of Pds1 and the S phase cyclin Clb5 in the yeast Saccharomyces cerevisiae.

This domain is also found in a number of, as yet, uncharacterised proteins. These include a mammalian protein, p55CDC, that is present in dividing cells and is\ associated with protein kinase activity.

\ \ \N \N \N 26672 IPR008249 There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function.\ \N \N \N 26673 IPR008250

\ \ \ \N \N \N 26674 IPR008251

Chromo shadow domain is distantly related to chromo domain. It is always found in association with a chromo domain.

The CHROMO (CHRromatin Organization MOdifier) domain PUB00005519, PUB00005519, PUB00004460, PUB00004460 \ is a conserved region of around 60 amino acids, originally identified in Drosophila modifiers of variegation.\ These are proteins that alter the structure of chromatin to the condensed morphology of heterochromatin, \ a cytologically visible condition where gene expression is repressed. In one of these proteins, Polycomb, \ the chromo domain has been shown to be important for chromatin targeting. Proteins that contain a chromo \ domain appear to fall into 3 classes. The first class includes proteins having an N-terminal chromo domain \ followed by a region termed the chromo shadow domain PUB00004460, eg. Drosophila and human heterochromatin \ protein Su(var)205 (HP1); and mammalian modifier 1 and modifier 2. The second class includes proteins with \ a single chromo domain, eg. Drosophila protein Polycomb (Pc); mammalian modifier 3; human Mi-2 autoantigenand \ and several yeast and Caenorhabditis elegans hypothetical proteins. In the third class paired tandem chromo domains are \ found, eg. in mammalian DNA-binding/helicase proteins CHD-1 to CHD-4 and yeast protein CHD1.

\ \ \N \N \N 26675 IPR008252

Lactococcus X-Pro dipeptidyl-peptidase proteins belong to the S15 family ofthe carboxypeptidase (SC) clan PUB00003576, See Protease Database http://merops.sanger.ac.uk/merops.htm, Merops id=S15.001]. These proteins, which have similar\ specificity to mammalian dipeptidyl-peptidase IV, cleave Xaa-Pro-releasing\ N-terminal dipeptides. The penultimate residue must be proline.\ In Lactococcus, the proteins exist as cytoplasmic homodimers PUB00003576.

\ \ \N \N \N 26676 IPR008253

MARVEL domain is often found in lipid-associating proteins - such as Occludin and MAL family proteins [MEDLINE:22357243]. It may be part of the machinery of membrane apposition events, such as transport vesicle biogenesis.

\ \N \N \N