Keyword search results for "gtpase"

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Hits in SCOP family and superfamily descriptions:
(5 found)

SCOP family or superfamily Description
   
a.116.1 GTPase activation domain, GAP
a.116.1.1 BCR-homology GTPase activation domain (BH-domain)
a.118.12.1 Ran-GTPase activating protein 1 (RanGAP1), C-terminal domain
c.32.1.1 Tubulin, GTPase domain
d.52.5.1 Probable GTPase Der, C-terminal domain
   


Hits in PDB header description:
(9 found)

PDB Header
   
1am4 COMPLEX (GTPASE-ACTIVATING/GTP-BINDING) 22-JUN-97
1dar TRANSLATIONAL GTPASE
1gnd GTPASE ACTIVATION
1gwn GTPASE
1h65 GTPASE
1qg4 GTPASE
1rrp COMPLEX (SMALL GTPASE/NUCLEAR PROTEIN)
1tx4 COMPLEX(GTPASE ACTIVATN/PROTO-ONCOGENE) 29-JUL-97
1wq1 COMPLEX (GTP-BINDING/GTPASE ACTIVATION) 03-JUL-97
   


Hits in InterPro abstracts:
(283 found, displaying first 50)

SCOP Family InterPro Name InterPro abstract
   
j.65.1.1 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. In fission yeast pak1+ encodes a protein kinase that interacts with Cdc42p and is involved in the control of cell polarity and mating .
   
j.66.1.1 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. In fission yeast pak1+ encodes a protein kinase that interacts with Cdc42p and is involved in the control of cell polarity and mating .
   
b.55.1.3 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 nucleotide 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). 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 utilised in the EVH1-peptide interaction. Nup358 contains four Ran binding domains. The structure of the first of these is known.
   
b.55.1.4 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 nucleotide 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). 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 utilised in the EVH1-peptide interaction. Nup358 contains four Ran binding domains. The structure of the first of these is known.
   
c.32.1.1 IPR000158 In bacteria, FtsZ 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 (UniProtKB Taxonomy ID 562), MinCD Cross-reference to INTERPRO: 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 Cross-reference to PROSITEDOC: PDOC00199 with a GTPase activity. It undergoes GTP-dependent polymerisation 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 (UniProtKB Taxonomy ID 1423), some of which are required for biogenesis of the new hemispherical poles of the two daughter cells. FtsZ can polymerise 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 as well as in archaebacteria. FtsZ shows structural similarity with eukaryotic tubulins. This similarity is probably both evolutionary and functionally significant.
   
d.79.2.1 IPR000158 In bacteria, FtsZ 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 (UniProtKB Taxonomy ID 562), MinCD Cross-reference to INTERPRO: 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 Cross-reference to PROSITEDOC: PDOC00199 with a GTPase activity. It undergoes GTP-dependent polymerisation 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 (UniProtKB Taxonomy ID 1423), some of which are required for biogenesis of the new hemispherical poles of the two daughter cells. FtsZ can polymerise 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 as well as in archaebacteria. FtsZ shows structural similarity with eukaryotic tubulins. This similarity is probably both evolutionary and functionally significant.
   
d.15.1.5 IPR000159 Proteins with this domain are mostly RasGTP effectors and include guanine-nucleotide releasing factor in mammals. 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 an effector molecule for R-ras, K-Ras and Rap. 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.
   
a.69.2.1 IPR000195 Identification of a TBC domain in GYP6_YEAST and GYP7_YEAST, which are GTPase activator proteins of yeast Ypt6 and Ypt7, imply that these domains are GTPase activator proteins of Rab-like small GTPases .
   
a.116.1.1 IPR000198 Members of the Rho family of small G proteins transduce signals from plasma-membrane receptors 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. A number of structure are known for this family. The domain is composed of seven alpha helices. This domain is also known as the breakpoint cluster region-homology (BH) domain.
   
a.108.1.1 IPR000206 Ribosomes are the particles that catalyse 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 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. 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 stabilise 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 organise and stabilise 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. This family of large subunit ribosomal proteins is called the L7/L12 family. L7/L12 is present in each 50S subunit in four copies organised as two dimers. The L8 protein complex consisting of two dimers of L7/L12 and L10 in Escherichia coli (UniProtKB Taxonomy ID 562) ribosomes is assembled on the conserved region of 23 S rRNA termed the GTPase-associated domain. 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.
   
d.45.1.1 IPR000206 Ribosomes are the particles that catalyse 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 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. 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 stabilise 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 organise and stabilise 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. This family of large subunit ribosomal proteins is called the L7/L12 family. L7/L12 is present in each 50S subunit in four copies organised as two dimers. The L8 protein complex consisting of two dimers of L7/L12 and L10 in Escherichia coli (UniProtKB Taxonomy ID 562) ribosomes is assembled on the conserved region of 23 S rRNA termed the GTPase-associated domain. 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.
   
i.1.1.1 IPR000206 Ribosomes are the particles that catalyse 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 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. 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 stabilise 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 organise and stabilise 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. This family of large subunit ribosomal proteins is called the L7/L12 family. L7/L12 is present in each 50S subunit in four copies organised as two dimers. The L8 protein complex consisting of two dimers of L7/L12 and L10 in Escherichia coli (UniProtKB Taxonomy ID 562) ribosomes is assembled on the conserved region of 23 S rRNA termed the GTPase-associated domain. 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.
   
a.87.1.1 IPR000219 The Rho family GTPases Rho, Rac and CDC42 regulate a diverse array of cellular processes. 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 catalysed 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 (Cross-reference to INTERPRO: IPR001849). Trio and its homologue 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 oligomerisation 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 alpha helices that are folded into a flattened, elongated alpha-helix bundle in which two of the three conserved regions, conserved region 1 (CR1) and conserved region 3 (CR3), are exposed near the centre of one surface. CR1 and CR3, together with a part of alpha-6 and the DH/PH junction site, constitute the Rho GTPase interacting pocket.
   
b.1.1.4 IPR000219 The Rho family GTPases Rho, Rac and CDC42 regulate a diverse array of cellular processes. 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 catalysed 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 (Cross-reference to INTERPRO: IPR001849). Trio and its homologue 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 oligomerisation 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 alpha helices that are folded into a flattened, elongated alpha-helix bundle in which two of the three conserved regions, conserved region 1 (CR1) and conserved region 3 (CR3), are exposed near the centre of one surface. CR1 and CR3, together with a part of alpha-6 and the DH/PH junction site, constitute the Rho GTPase interacting pocket.
   
b.1.2.1 IPR000219 The Rho family GTPases Rho, Rac and CDC42 regulate a diverse array of cellular processes. 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 catalysed 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 (Cross-reference to INTERPRO: IPR001849). Trio and its homologue 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 oligomerisation 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 alpha helices that are folded into a flattened, elongated alpha-helix bundle in which two of the three conserved regions, conserved region 1 (CR1) and conserved region 3 (CR3), are exposed near the centre of one surface. CR1 and CR3, together with a part of alpha-6 and the DH/PH junction site, constitute the Rho GTPase interacting pocket.
   
b.55.1.1 IPR000219 The Rho family GTPases Rho, Rac and CDC42 regulate a diverse array of cellular processes. 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 catalysed 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 (Cross-reference to INTERPRO: IPR001849). Trio and its homologue 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 oligomerisation 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 alpha helices that are folded into a flattened, elongated alpha-helix bundle in which two of the three conserved regions, conserved region 1 (CR1) and conserved region 3 (CR3), are exposed near the centre of one surface. CR1 and CR3, together with a part of alpha-6 and the DH/PH junction site, constitute the Rho GTPase interacting pocket.
   
d.144.1.7 IPR000219 The Rho family GTPases Rho, Rac and CDC42 regulate a diverse array of cellular processes. 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 catalysed 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 (Cross-reference to INTERPRO: IPR001849). Trio and its homologue 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 oligomerisation 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 alpha helices that are folded into a flattened, elongated alpha-helix bundle in which two of the three conserved regions, conserved region 1 (CR1) and conserved region 3 (CR3), are exposed near the centre of one surface. CR1 and CR3, together with a part of alpha-6 and the DH/PH junction site, constitute the Rho GTPase interacting pocket.
   
a.11.2.1 IPR000299 The FERM domain (F for 4.1 protein, E for ezrin, R for radixin and M for moesin) is a widespread protein module involved in localising proteins to the plasma membrane. FERM domains are found in a number of cytoskeletal-associated proteins that associate with various proteins at the interface between the plasma membrane and the cytoskeleton. The FERM domain is located at the N terminus of the majority of FERM-containing proteins, which includes:
   
b.55.1.5 IPR000299 The FERM domain (F for 4.1 protein, E for ezrin, R for radixin and M for moesin) is a widespread protein module involved in localising proteins to the plasma membrane. FERM domains are found in a number of cytoskeletal-associated proteins that associate with various proteins at the interface between the plasma membrane and the cytoskeleton. The FERM domain is located at the N terminus of the majority of FERM-containing proteins, which includes:
   
d.15.1.4 IPR000299 The FERM domain (F for 4.1 protein, E for ezrin, R for radixin and M for moesin) is a widespread protein module involved in localising proteins to the plasma membrane. FERM domains are found in a number of cytoskeletal-associated proteins that associate with various proteins at the interface between the plasma membrane and the cytoskeleton. The FERM domain is located at the N terminus of the majority of FERM-containing proteins, which includes:
   
e.55.1.1 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. 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 beta-strand and a longer alpha-helix that results in a beta-alpha hairpin motif. The domain is also present in tuberin (a tuberous sclerosis homologue 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.
   
d.15.1.5 IPR000341 Phosphatidylinositol 3-kinase (PI3K) (Cross-reference to 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 recognised as one of the principal effectors of Ras signalling to the cell-cycle control machinery. In the structure of the Ras-PI3K 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 beta-sheet, flanked by two alpha-helices. Interaction between Ras and the PI3K RBD is primarily polar in character and, as characterised by kinetic measurements, is reversible and transient.
   
a.91.1.1 IPR000342 RGS (Regulator of G Protein Signalling) proteins are multi-functional, GTPase-accelerating proteins that promote GTP hydrolysis by the alpha subunit of heterotrimeric G proteins, thereby inactivating the G protein and rapidly switching off G protein-coupled receptor signalling pathways. Upon activation by GPCRs, heterotrimeric G proteins exchange GDP for GTP, are released from the receptor, and dissociate into free, active GTP-bound alpha subunit and beta-gamma dimer, both of which activate downstream effectors. The response is terminated upon GTP hydrolysis by the alpha subunit (Cross-reference to INTERPRO: IPR001019), which can then bind the beta-gamma dimer (Cross-reference to INTERPRO: IPR001632, Cross-reference to INTERPRO: IPR001770) and the receptor. RGS proteins markedly reduce the lifespan of GTP-bound alpha subunits by stabilising the G protein transition state. All RGS proteins contain an 'RGS-box' (or RGS domain), which is required for activity. Some small RGS proteins such as RGS1 and RGS4 are comprised of little more than an RGS domain, while others also contain additional domains that confer further functionality. RGS domains can be found in conjunction with a variety of domains, including: DEP for membrane targeting (Cross-reference to INTERPRO: IPR000591), PDZ for binding to GPCRs (Cross-reference to INTERPRO: IPR001478), PTB for phosphotyrosine-binding (Cross-reference to INTERPRO: IPR006020), RBD for Ras-binding (Cross-reference to INTERPRO: IPR003116), GoLoco for guanine nucleotide inhibitor activity (Cross-reference to INTERPRO: IPR003109), PX for phosphatidylinositol-binding (Cross-reference to INTERPRO: IPR001683), PXA that is associated with PX (Cross-reference to INTERPRO: IPR003114), PH for stimulating guanine nucleotide exchange (Cross-reference to INTERPRO: IPR001849), and GGL (G protein gamma subunit-like) for binding G protein beta subunits (Cross-reference to INTERPRO: IPR001770). Those RGS proteins that contain GGL domains can interact with G protein beta subunits to form novel dimers that prevent G protein gamma subunit binding and G protein alpha subunit association, thereby preventing heterotrimer formation.
   
c.37.1.8 IPR000375 Dynamin is a microtubule-associated force-producing protein of 100 Kd which is involved in the production of microtubule bundles. At the N terminus of dynamin is a GTPase domain (see Cross-reference to INTERPRO: IPR001401), and at the C terminus is a PH domain (see Cross-reference to INTERPRO: IPR001849). Between these two domains lies a central region of unknown function.
   
b.69.5.1 IPR000408 The regulator of chromosome condensation (RCC1) is a eukaryotic protein which binds to chromatin and interacts with ran, a nuclear GTP-binding protein Cross-reference to INTERPRO: 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. (Not available from BioMart). The RCC1-type of repeat is also found in the X-linked retinitis pigmentosa GTPase regulator. The RCC repeats form a beta-propeller structure.
   
b.69.5.2 IPR000408 The regulator of chromosome condensation (RCC1) is a eukaryotic protein which binds to chromatin and interacts with ran, a nuclear GTP-binding protein Cross-reference to INTERPRO: 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. (Not available from BioMart). The RCC1-type of repeat is also found in the X-linked retinitis pigmentosa GTPase regulator. The RCC repeats form a beta-propeller structure.
   
a.66.1.1 IPR000469 Guanine nucleotide binding proteins (G proteins) are membrane-associated, heterotrimeric proteins composed of three subunits: alpha (Cross-reference to INTERPRO: IPR001019), beta (Cross-reference to INTERPRO: IPR001632) and gamma (Cross-reference to INTERPRO: IPR001770). G proteins and their receptors (GPCRs) form one of the most prevalent signalling systems in mammalian cells, regulating systems as diverse as sensory perception, cell growth and hormonal regulation. At the cell surface, the binding of ligands such as hormones and neurotransmitters to a GPCR activates the receptor by causing a conformational change, which in turn activates the bound G protein on the intracellular-side of the membrane. The activated receptor promotes the exchange of bound GDP for GTP on the G protein alpha subunit. GTP binding changes the conformation of switch regions within the alpha subunit, which allows the bound trimeric G protein (inactive) to be released from the receptor, and to dissociate into active alpha subunit (GTP-bound) and beta/gamma dimer. The alpha subunit and the beta/gamma dimer go on to activate distinct downstream effectors, such as adenylyl cyclase, phosphodiesterases, phospholipase C, and ion channels. These effectors in turn regulate the intracellular concentrations of secondary messengers, such as cAMP, diacylglycerol, sodium or calcium cations, which ultimately lead to a physiological response, usually via the downstream regulation of gene transcription. The cycle is completed by the hydrolysis of alpha subunit-bound GTP to GDP, resulting in the re-association of the alpha and beta/gamma subunits and their binding to the receptor, which terminates the signal. The length of the G protein signal is controlled by the duration of the GTP-bound alpha subunit, which can be regulated by RGS (regulator of G protein signalling) proteins (Cross-reference to INTERPRO: IPR000342) or by covalent modifications. There are several isoforms of each subunit, many of which have splice variants, which together can make up hundreds of combinations of G proteins. The specific combination of subunits in heterotrimeric G proteins affects not only which receptor it can bind to, but also which downstream target is affected, providing the means to target specific physiological processes in response to specific external stimuli. G proteins carry lipid modifications on one or more of their subunits to target them to the plasma membrane and to contribute to protein interactions. This family consists of the class 12 G-protein alpha subunit, which includes both G(12)alpha and G(13)alpha. G(12)alpha and G(13)alpha are ubiquitously expressed and can induce many cellular responses, including phospholipase C-epsilon activation, phospholipase D activation, cytoskeletal change, oncogenic response, apoptosis, MAP kinase activation and Na/H-exchange activation. G(12)alpha and G(13)alpha can activate several effectors, including small GTPases such as Rho.
   
c.37.1.8 IPR000469 Guanine nucleotide binding proteins (G proteins) are membrane-associated, heterotrimeric proteins composed of three subunits: alpha (Cross-reference to INTERPRO: IPR001019), beta (Cross-reference to INTERPRO: IPR001632) and gamma (Cross-reference to INTERPRO: IPR001770). G proteins and their receptors (GPCRs) form one of the most prevalent signalling systems in mammalian cells, regulating systems as diverse as sensory perception, cell growth and hormonal regulation. At the cell surface, the binding of ligands such as hormones and neurotransmitters to a GPCR activates the receptor by causing a conformational change, which in turn activates the bound G protein on the intracellular-side of the membrane. The activated receptor promotes the exchange of bound GDP for GTP on the G protein alpha subunit. GTP binding changes the conformation of switch regions within the alpha subunit, which allows the bound trimeric G protein (inactive) to be released from the receptor, and to dissociate into active alpha subunit (GTP-bound) and beta/gamma dimer. The alpha subunit and the beta/gamma dimer go on to activate distinct downstream effectors, such as adenylyl cyclase, phosphodiesterases, phospholipase C, and ion channels. These effectors in turn regulate the intracellular concentrations of secondary messengers, such as cAMP, diacylglycerol, sodium or calcium cations, which ultimately lead to a physiological response, usually via the downstream regulation of gene transcription. The cycle is completed by the hydrolysis of alpha subunit-bound GTP to GDP, resulting in the re-association of the alpha and beta/gamma subunits and their binding to the receptor, which terminates the signal. The length of the G protein signal is controlled by the duration of the GTP-bound alpha subunit, which can be regulated by RGS (regulator of G protein signalling) proteins (Cross-reference to INTERPRO: IPR000342) or by covalent modifications. There are several isoforms of each subunit, many of which have splice variants, which together can make up hundreds of combinations of G proteins. The specific combination of subunits in heterotrimeric G proteins affects not only which receptor it can bind to, but also which downstream target is affected, providing the means to target specific physiological processes in response to specific external stimuli. G proteins carry lipid modifications on one or more of their subunits to target them to the plasma membrane and to contribute to protein interactions. This family consists of the class 12 G-protein alpha subunit, which includes both G(12)alpha and G(13)alpha. G(12)alpha and G(13)alpha are ubiquitously expressed and can induce many cellular responses, including phospholipase C-epsilon activation, phospholipase D activation, cytoskeletal change, oncogenic response, apoptosis, MAP kinase activation and Na/H-exchange activation. G(12)alpha and G(13)alpha can activate several effectors, including small GTPases such as Rho.
   
a.4.5.31 IPR000591 This entry represents the DEP (Dishevelled, Egl-10 and Pleckstrin) domain, a globular domain of about 80 residues that is found in over 50 proteins involved in G-protein signalling pathways. It was named after the three proteins it was initially found in:
   
a.117.1.1 IPR000651 This domain is found in several guanine nucleotide exchange factors for Ras-like small GTPases, and lies N-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.
   
c.5.1.1 IPR000713 The bacterial cell wall provides strength and rigidity to counteract internal osmotic pressure, and protection against the environment. The peptidoglycan layer gives the cell wall its strength, and helps maintain the overall shape of the cell. The basic peptidoglycan structure of both Gram-positive and Gram-negative bacteria is comprised of a sheet of glycan chains connected by short cross-linking polypeptides. Biosynthesis of peptidoglycan is a multi-step (11-12 steps) process comprising three main stages:
   
c.72.2.1 IPR000713 The bacterial cell wall provides strength and rigidity to counteract internal osmotic pressure, and protection against the environment. The peptidoglycan layer gives the cell wall its strength, and helps maintain the overall shape of the cell. The basic peptidoglycan structure of both Gram-positive and Gram-negative bacteria is comprised of a sheet of glycan chains connected by short cross-linking polypeptides. Biosynthesis of peptidoglycan is a multi-step (11-12 steps) process comprising three main stages:
   
c.98.1.1 IPR000713 The bacterial cell wall provides strength and rigidity to counteract internal osmotic pressure, and protection against the environment. The peptidoglycan layer gives the cell wall its strength, and helps maintain the overall shape of the cell. The basic peptidoglycan structure of both Gram-positive and Gram-negative bacteria is comprised of a sheet of glycan chains connected by short cross-linking polypeptides. Biosynthesis of peptidoglycan is a multi-step (11-12 steps) process comprising three main stages:
   
c.37.1.1 IPR000897 The signal recognition particle (SRP) is a multimeric protein, which along with its conjugate receptor (SR), is involved in targeting secretory proteins to the rough endoplasmic reticulum (RER) membrane in eukaryotes, or to the plasma membrane in prokaryotes. SRP recognises the signal sequence of the nascent polypeptide on the ribosome, retards its elongation, and docks the SRP-ribosome-polypeptide complex to the RER membrane via the SR receptor. SRP consists of six polypeptides (SRP9, SRP14, SRP19, SRP54, SRP68 and SRP72) and a single 300 nucleotide 7S RNA molecule. The RNA component catalyses the interaction of SRP with its SR receptor. In higher eukaryotes, the SRP complex consists of the Alu domain and the S domain linked by the SRP RNA. The Alu domain consists of a heterodimer of SRP9 and SRP14 bound to the 5' and 3' terminal sequences of SRP RNA. This domain is necessary for retarding the elongation of the nascent polypeptide chain, which gives SRP time to dock the ribosome-polypeptide complex to the RER membrane. This entry represents the GTPase domain of the 54 kDa SRP54 component, a GTP-binding protein that interacts with the signal sequence when it emerges from the ribosome. SRP54 of the signal recognition particle has a three-domain structure: an N-terminal helical bundle domain, a GTPase domain, and the M-domain that binds the 7s RNA and also binds the signal sequence. The extreme C-terminal region is glycine-rich and lower in complexity and poorly conserved between species. The GTPase domain is evolutionary related to P-loop NTPase domains found in a variety of other proteins. These proteins include Escherichia coli (UniProtKB Taxonomy ID 562) and Bacillus subtilis (UniProtKB Taxonomy ID 1423) ffh protein (P48), which seems to be the prokaryotic counterpart of SRP54; signal recognition particle receptor alpha 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 (UniProtKB Taxonomy ID 485), the homologue of ftsY; and bacterial flagellar biosynthesis protein flhF.
   
c.37.1.10 IPR000897 The signal recognition particle (SRP) is a multimeric protein, which along with its conjugate receptor (SR), is involved in targeting secretory proteins to the rough endoplasmic reticulum (RER) membrane in eukaryotes, or to the plasma membrane in prokaryotes. SRP recognises the signal sequence of the nascent polypeptide on the ribosome, retards its elongation, and docks the SRP-ribosome-polypeptide complex to the RER membrane via the SR receptor. SRP consists of six polypeptides (SRP9, SRP14, SRP19, SRP54, SRP68 and SRP72) and a single 300 nucleotide 7S RNA molecule. The RNA component catalyses the interaction of SRP with its SR receptor. In higher eukaryotes, the SRP complex consists of the Alu domain and the S domain linked by the SRP RNA. The Alu domain consists of a heterodimer of SRP9 and SRP14 bound to the 5' and 3' terminal sequences of SRP RNA. This domain is necessary for retarding the elongation of the nascent polypeptide chain, which gives SRP time to dock the ribosome-polypeptide complex to the RER membrane. This entry represents the GTPase domain of the 54 kDa SRP54 component, a GTP-binding protein that interacts with the signal sequence when it emerges from the ribosome. SRP54 of the signal recognition particle has a three-domain structure: an N-terminal helical bundle domain, a GTPase domain, and the M-domain that binds the 7s RNA and also binds the signal sequence. The extreme C-terminal region is glycine-rich and lower in complexity and poorly conserved between species. The GTPase domain is evolutionary related to P-loop NTPase domains found in a variety of other proteins. These proteins include Escherichia coli (UniProtKB Taxonomy ID 562) and Bacillus subtilis (UniProtKB Taxonomy ID 1423) ffh protein (P48), which seems to be the prokaryotic counterpart of SRP54; signal recognition particle receptor alpha 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 (UniProtKB Taxonomy ID 485), the homologue of ftsY; and bacterial flagellar biosynthesis protein flhF.
   
a.66.1.1 IPR001019 Guanine nucleotide binding proteins (G proteins) are membrane-associated, heterotrimeric proteins composed of three subunits: alpha (Cross-reference to INTERPRO: IPR001019), beta (Cross-reference to INTERPRO: IPR001632) and gamma (Cross-reference to INTERPRO: IPR001770). G proteins and their receptors (GPCRs) form one of the most prevalent signalling systems in mammalian cells, regulating systems as diverse as sensory perception, cell growth and hormonal regulation. At the cell surface, the binding of ligands such as hormones and neurotransmitters to a GPCR activates the receptor by causing a conformational change, which in turn activates the bound G protein on the intracellular-side of the membrane. The activated receptor promotes the exchange of bound GDP for GTP on the G protein alpha subunit. GTP binding changes the conformation of switch regions within the alpha subunit, which allows the bound trimeric G protein (inactive) to be released from the receptor, and to dissociate into active alpha subunit (GTP-bound) and beta/gamma dimer. The alpha subunit and the beta/gamma dimer go on to activate distinct downstream effectors, such as adenylyl cyclase, phosphodiesterases, phospholipase C, and ion channels. These effectors in turn regulate the intracellular concentrations of secondary messengers, such as cAMP, diacylglycerol, sodium or calcium cations, which ultimately lead to a physiological response, usually via the downstream regulation of gene transcription. The cycle is completed by the hydrolysis of alpha subunit-bound GTP to GDP, resulting in the re-association of the alpha and beta/gamma subunits and their binding to the receptor, which terminates the signal. The length of the G protein signal is controlled by the duration of the GTP-bound alpha subunit, which can be regulated by RGS (regulator of G protein signalling) proteins (Cross-reference to INTERPRO: IPR000342) or by covalent modifications. There are several isoforms of each subunit, many of which have splice variants, which together can make up hundreds of combinations of G proteins. The specific combination of subunits in heterotrimeric G proteins affects not only which receptor it can bind to, but also which downstream target is affected, providing the means to target specific physiological processes in response to specific external stimuli. G proteins carry lipid modifications on one or more of their subunits to target them to the plasma membrane and to contribute to protein interactions. This family consists of the G protein alpha subunit, which acts as a weak GTPase. G protein classes are defined based on the sequence and function of their alpha subunits, which in mammals fall into four main categories: G(S)alpha, G(Q)alpha, G(I)alpha and G(12)alpha; there are also fungal and plant classes of alpha subunits. The alpha subunit consists of two domains: a GTP-binding domain and a helical insertion domain (Cross-reference to INTERPRO: IPR011025). The GTP-binding domain is homologous to Ras-like small GTPases, and includes switch regions I and II, which change conformation during activation. The switch regions are loops of alpha-helices with conformations sensitive to guanine nucleotides. The helical insertion domain is inserted into the GTP-binding domain before switch region I and is unique to heterotrimeric G proteins. This helical insertion domain functions to sequester the guanine nucleotide at the interface with the GTP-binding domain and must be displaced to enable nucleotide dissociation.
   
c.37.1.8 IPR001019 Guanine nucleotide binding proteins (G proteins) are membrane-associated, heterotrimeric proteins composed of three subunits: alpha (Cross-reference to INTERPRO: IPR001019), beta (Cross-reference to INTERPRO: IPR001632) and gamma (Cross-reference to INTERPRO: IPR001770). G proteins and their receptors (GPCRs) form one of the most prevalent signalling systems in mammalian cells, regulating systems as diverse as sensory perception, cell growth and hormonal regulation. At the cell surface, the binding of ligands such as hormones and neurotransmitters to a GPCR activates the receptor by causing a conformational change, which in turn activates the bound G protein on the intracellular-side of the membrane. The activated receptor promotes the exchange of bound GDP for GTP on the G protein alpha subunit. GTP binding changes the conformation of switch regions within the alpha subunit, which allows the bound trimeric G protein (inactive) to be released from the receptor, and to dissociate into active alpha subunit (GTP-bound) and beta/gamma dimer. The alpha subunit and the beta/gamma dimer go on to activate distinct downstream effectors, such as adenylyl cyclase, phosphodiesterases, phospholipase C, and ion channels. These effectors in turn regulate the intracellular concentrations of secondary messengers, such as cAMP, diacylglycerol, sodium or calcium cations, which ultimately lead to a physiological response, usually via the downstream regulation of gene transcription. The cycle is completed by the hydrolysis of alpha subunit-bound GTP to GDP, resulting in the re-association of the alpha and beta/gamma subunits and their binding to the receptor, which terminates the signal. The length of the G protein signal is controlled by the duration of the GTP-bound alpha subunit, which can be regulated by RGS (regulator of G protein signalling) proteins (Cross-reference to INTERPRO: IPR000342) or by covalent modifications. There are several isoforms of each subunit, many of which have splice variants, which together can make up hundreds of combinations of G proteins. The specific combination of subunits in heterotrimeric G proteins affects not only which receptor it can bind to, but also which downstream target is affected, providing the means to target specific physiological processes in response to specific external stimuli. G proteins carry lipid modifications on one or more of their subunits to target them to the plasma membrane and to contribute to protein interactions. This family consists of the G protein alpha subunit, which acts as a weak GTPase. G protein classes are defined based on the sequence and function of their alpha subunits, which in mammals fall into four main categories: G(S)alpha, G(Q)alpha, G(I)alpha and G(12)alpha; there are also fungal and plant classes of alpha subunits. The alpha subunit consists of two domains: a GTP-binding domain and a helical insertion domain (Cross-reference to INTERPRO: IPR011025). The GTP-binding domain is homologous to Ras-like small GTPases, and includes switch regions I and II, which change conformation during activation. The switch regions are loops of alpha-helices with conformations sensitive to guanine nucleotides. The helical insertion domain is inserted into the GTP-binding domain before switch region I and is unique to heterotrimeric G proteins. This helical insertion domain functions to sequester the guanine nucleotide at the interface with the GTP-binding domain and must be displaced to enable nucleotide dissociation.
   
g.45.1.1 IPR001164 This entry describes a family of small GTPase activating proteins, for example ARF1-directed GTPase-activating protein, the cycle control GTPase activating protein (GAP) GCS1 which is important for the regulation of the ADP ribosylation factor ARF, a member of the Ras superfamily of GTP-binding proteins. The GTP-bound form of ARF is essential for the maintenance of normal Golgi morphology, it participates in recruitment of coat proteins which are required for budding and fission of membranes. Before the fusion with an acceptor compartment the membrane must be uncoated. This step required the hydrolysis of GTP associated to ARF. These proteins contain a characteristic zinc finger motif (Cys-x2-Cys-x(16,17)-x2-Cys) which displays some similarity to the C4-type GATA zinc finger. The ARFGAP domain display no obvious similarity to other GAP proteins. The 3D structure of the ARFGAP domain of the PYK2-associated protein beta has been solved. It consists of a three-stranded beta-sheet surrounded by 5 alpha helices. The domain is organised around a central zinc atom which is coordinated by 4 cysteines. The ARFGAP domain is clearly unrelated to the other GAP proteins structures which are exclusively helical. Classical GAP proteins accelerate GTPase activity by supplying an arginine finger to the active site. The crystal structure of ARFGAP bound to ARF revealed that the ARFGAP domain does not supply an arginine to the active site which suggests a more indirect role of the ARFGAP domain in the GTPase hydrolysis. The Rev protein of human immunodeficiency virus type 1 (HIV-1) facilitates nuclear export of unspliced and partly-spliced viral RNAs. 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.
   
a.87.1.1 IPR001331 Ras proteins are membrane-associated molecular switches that bind GTP and GDP and slowly hydrolyze GTP to GDP. 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. 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.
   
c.37.1.8 IPR001401 Membrane transport between compartments in eukaryotic cells requires proteins that allow the budding and scission of nascent cargo vesicles from one compartment and their targeting and fusion with another. Dynamins are large GTPases that belong to a protein superfamily that, in eukaryotic cells, includes classical dynamins, dynamin-like proteins, OPA1, Mx proteins, mitofusins and guanylate-binding proteins/atlastins, and are involved in the scission of a wide range of vesicles and organelles. They play a role in many processes including budding of transport vesicles, division of organelles, cytokinesis and pathogen resistance. The minimal distinguishing architectural features that are common to all dynamins and are distinct from other GTPases are the structure of the large GTPase domain (300 amino acids) and the presence of two additional domains; the middle domain and the GTPase effector domain (GED), which are involved in oligomerization and regulation of the GTPase activity. This entry represents the GTPase domain, containing the GTP-binding motifs that are needed for guanine-nucleotide binding and hydrolysis. The conservation of these motifs is absolute except for the the final motif in guanylate-binding proteins. The GTPase catalytic activity can be stimulated by oligomerisation of the protein, which is mediated by interactions between the GTPase domain, the middle domain and the GED.
   
a.118.1.1 IPR001494 The exchange of macromolecules between the nucleus and cytoplasm takes place through nuclear pore complexes within the nuclear membrane. Active transport of large molecules through these pore complexes require carrier proteins, called karyopherins (importins and exportins), which shuttle between the two compartments. Members of the importin-beta (karyopherin-beta) family can bind and transport cargo by themselves, or can form heterodimers with importin-alpha. As part of a heterodimer, importin-beta mediates interactions with the pore complex, while importin-alpha acts as an adaptor protein to bind the nuclear localisation signal (NLS) on the cargo through the classical NLS import of proteins. Importin-beta is a helicoidal molecule constructed from 19 HEAT repeats. Many nuclear pore proteins contain FG sequence repeats that can bind to HEAT repeats within importins, which is important for importin-beta mediated transport. Ran GTPase helps to control the unidirectional transfer of cargo. The cytoplasm contains primarily RanGDP and the nucleus RanGTP through the actions of RanGAP and RanGEF, respectively. In the nucleus, RanGTP binds to importin-beta within the importin/cargo complex, causing a conformational change in importin-beta that releases it from importin-alpha-bound cargo. As a result, the N-terminal auto-inhibitory region on importin-alpha is free to loop back and bind to the major NLS-binding site, causing the cargo to be released. There are additional release factors as well. More information about these proteins can be found at Protein of the Month: Importins.
   
a.271.1.1 IPR001496 The SOCS box was first identified in SH2-domain-containing proteins of the suppressor of cytokines signalling (SOCS) family but was later also found in:
   
b.29.1.22 IPR001496 The SOCS box was first identified in SH2-domain-containing proteins of the suppressor of cytokines signalling (SOCS) family but was later also found in:
   
d.93.1.1 IPR001496 The SOCS box was first identified in SH2-domain-containing proteins of the suppressor of cytokines signalling (SOCS) family but was later also found in:
   
b.55.1.1 IPR001562 The Btk-type zinc finger or Btk motif (BM) is a conserved zinc-binding motif containing conserved cysteines and a histidine that is present in certain eukaryotic signalling proteins. The motif is named after Bruton's tyrosine kinase (Btk), an enzyme which is essential for B cell maturation in humans and mice. Btk is a member of the Tec family of protein tyrosine kinases (PTK). These kinases contain a conserved Tec homology (TH) domain between the N-terminal pleckstrin homology (PH) domain (Cross-reference to INTERPRO: IPR001849) and the Src homology 3 (SH3) domain (Cross-reference to INTERPRO: IPR001452). The N-terminal of the TH domain is highly conserved and known as the Btf motif, while the C-terminal region of the TH domain contains a proline-rich region (PRR). The Btk motif contains a conserved His and three Cys residues that form a zinc finger (although these differ from known zinc finger topologies), while PRRs are commonly involved in protein-protein interactions, including interactions with G proteins. The TH domain may be of functional importance in various signalling pathways in different species. A complete TH domain, containing both the Btk and PRR regions, has not been found outside the Tec family; however, the Btk motif on its own does occur in other proteins, usually C-terminal to a PH domain (note that although a Btk motif always occurs C-terminal to a PH domain, not all PH domains are followed by a Btk motif). The crystal structures of Btk show that the Btk-type zinc finger has a globular core, formed by a long loop which is held together by a zinc ion, and that the Btk motif is packed against the PH domain. The zinc-binding residues are a histidine and three cysteines, which are fully conserved in the Btk motif. Proteins known to contain a Btk-type zinc finger include:
   
c.3.1.3 IPR001738 Rab proteins constitute a family of small GTPases that serve a regulatory role in vesicular membrane traffic; 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. 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. 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.
   
d.16.1.6 IPR001738 Rab proteins constitute a family of small GTPases that serve a regulatory role in vesicular membrane traffic; 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. 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. 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.
   
g.39.1.3 IPR001781 Zinc finger (Znf) domains are relatively small protein motifs which contain multiple finger-like protrusions that make tandem contacts with their target molecule. Some of these domains bind zinc, but many do not; instead binding other metals such as iron, or no metal at all. For example, some family members form salt bridges to stabilise the finger-like folds. They were first identified as a DNA-binding motif in transcription factor TFIIIA from Xenopus laevis (UniProtKB Taxonomy ID 8355) (African clawed frog), however they are now recognised to bind DNA, RNA, protein and/or lipid substrates. Their binding properties depend on the amino acid sequence of the finger domains and of the linker between fingers, as well as on the higher-order structures and the number of fingers. Znf domains are often found in clusters, where fingers can have different binding specificities. There are many superfamilies of Znf motifs, varying in both sequence and structure. They display considerable versatility in binding modes, even between members of the same class (e.g. some bind DNA, others protein), suggesting that Znf motifs are stable scaffolds that have evolved specialised functions. For example, Znf-containing proteins function in gene transcription, translation, mRNA trafficking, cytoskeleton organisation, epithelial development, cell adhesion, protein folding, chromatin remodelling and zinc sensing, to name but a few. Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target. This entry represents LIM-type zinc finger (Znf) domains. LIM domains coordinate one or more zinc atoms, and are named after the three proteins (LIN-11, Isl1 and MEC-3) in which they were first found. They consist of two zinc-binding motifs that resemble GATA-like Znf's, however the residues holding the zinc atom(s) are variable, involving Cys, His, Asp or Glu residues. LIM domains are involved in proteins with differing functions, including gene expression, and cytoskeleton organisation and development. Protein containing LIM Znf domains include:
   
c.37.1.8 IPR001806 Many members of the Ras superfamily of GTPases have been implicated in the regulation of hematopoietic cells, with roles in growth, survival, differentiation, cytokine production, chemotaxis, vesicle-trafficking, and phagocytosis. The Ras superfamily of proteins now includes over 150 small GTPases (distinguished from the large, heterotrimeric GTPases, the G-proteins). It comprises six subfamilies, the Ras, Rho, Ran, Rab, Arf, and Kir/Rem/Rad subfamilies. They exhibit remarkable overall amino acid identities, especially in the regions interacting with the guanine nucleotide exchange factors that catalyse their activation.
   
a.116.1.1 IPR001849 The 'pleckstrin homology' (PH) domain is a domain of about 100 residues that occurs in a wide range of proteins involved in intracellular signalling or as constituents of the cytoskeleton. The function of this domain is not clear, several putative functions have been suggested: binding to the beta/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. All known cases have a common structure consisting of two perpendicular anti-parallel beta sheets, followed by a C-terminal amphipathic helix. The loops connecting the beta-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 beta-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 Saccharomyces cerevisiae (UniProtKB Taxonomy ID 4932) CDC24, GTPase activating proteins like rasGAP and BEM2/IPL2, and the human break point cluster protein bcr; Cytoskeletal proteins such as dynamin (see Cross-reference to INTERPRO: IPR001401), Caenorhabditis elegans (UniProtKB Taxonomy ID 6239) kinesin-like protein unc-104 (see Cross-reference to INTERPRO: IPR001752), spectrin beta-chain, syntrophin (2 PH domains) and S. cerevisiae nuclear migration protein NUM1; Mammalian phosphatidylinositol-specific phospholipase C (PI-PLC) (see Cross-reference to INTERPRO: IPR000909) 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, S. cerevisiae OSH1 and YHR073w; Mouse protein citron, a putative rho/rac effector that binds to the GTP-bound forms of rho and rac;
  • Several S. cerevisiae proteins involved in cell cycle regulation and bud formation like BEM2, BEM3, BUD4 and the BEM1-binding proteins BOI2 (BEB1) and BOI1 (BOB1).C. elegans protein MIG-10; C. elegans hypothetical proteins C04D8.1, K06H7.4 and ZK632.12; S. cerevisiae hypothetical proteins YBR129c and YHR155w.