guanine nucleotide exchange factor DBS isoform X4 [Rattus norvegicus]
Protein Classification
guanine nucleotide exchange factor DBS( domain architecture ID 11271215)
guanine nucleotide exchange factor DBS, similar to Mus musculus guanine nucleotide exchange factor OSTIII; contains spectrin repeats, a rhoGEF (DH) domain and a PH domain
List of domain hits
| Name | Accession | Description | Interval | E-value | ||||
| PH_Dbs | cd01227 | DBL's big sister protein pleckstrin homology (PH) domain; Dbs (also called MCF2-transforming ... |
886-1017 | 1.98e-77 | ||||
DBL's big sister protein pleckstrin homology (PH) domain; Dbs (also called MCF2-transforming sequence-like protein 2) is a guanine nucleotide exchange factor (GEF), which contains spectrin repeats, a rhoGEF (DH) domain and a PH domain. The Dbs PH domain participates in binding to both the Cdc42 and RhoA GTPases. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes. : Pssm-ID: 269934 [Multi-domain] Cd Length: 126 Bit Score: 250.96 E-value: 1.98e-77
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| RhoGEF | cd00160 | Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ... |
702-879 | 1.31e-55 | ||||
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains. : Pssm-ID: 238091 [Multi-domain] Cd Length: 181 Bit Score: 190.97 E-value: 1.31e-55
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| SEC14 | smart00516 | Domain in homologues of a S. cerevisiae phosphatidylinositol transfer protein (Sec14p); Domain ... |
145-290 | 6.43e-28 | ||||
Domain in homologues of a S. cerevisiae phosphatidylinositol transfer protein (Sec14p); Domain in homologues of a S. cerevisiae phosphatidylinositol transfer protein (Sec14p) and in RhoGAPs, RhoGEFs and the RasGAP, neurofibromin (NF1). Lipid-binding domain. The SEC14 domain of Dbl is known to associate with G protein beta/gamma subunits. : Pssm-ID: 214706 [Multi-domain] Cd Length: 158 Bit Score: 110.85 E-value: 6.43e-28
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| SH3_DBS | cd11857 | Src homology 3 domain of DBL's Big Sister (DBS), a guanine nucleotide exchange factor; DBS, ... |
1153-1205 | 6.91e-22 | ||||
Src homology 3 domain of DBL's Big Sister (DBS), a guanine nucleotide exchange factor; DBS, also called MCF2L (MCF2-transforming sequence-like protein) or OST, is a Rho GTPase guanine nucleotide exchange factor (RhoGEF), facilitating the exchange of GDP and GTP. It was originally isolated from a cDNA screen for sequences that cause malignant growth. It plays roles in regulating clathrin-mediated endocytosis and cell migration through its activation of Rac1 and Cdc42. Depending on cell type, DBS can also activate RhoA and RhoG. DBS contains a Sec14-like domain, spectrin-like repeats, a RhoGEF [or Dbl homology (DH)] domain, a Pleckstrin homology (PH) domain, and an SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies. : Pssm-ID: 212791 Cd Length: 55 Bit Score: 90.04 E-value: 6.91e-22
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| SPEC | cd00176 | Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members ... |
421-623 | 2.09e-16 | ||||
Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; the repeats are independent folding units; tandem repeats are found in differing numbers and arrange in an antiparallel manner to form dimers; the repeats are defined by a characteristic tryptophan (W) residue in helix A and a leucine (L) at the carboxyl end of helix C and separated by a linker of 5 residues; two copies of the repeat are present here : Pssm-ID: 238103 [Multi-domain] Cd Length: 213 Bit Score: 79.41 E-value: 2.09e-16
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| Name | Accession | Description | Interval | E-value | |||||
| PH_Dbs | cd01227 | DBL's big sister protein pleckstrin homology (PH) domain; Dbs (also called MCF2-transforming ... |
886-1017 | 1.98e-77 | |||||
DBL's big sister protein pleckstrin homology (PH) domain; Dbs (also called MCF2-transforming sequence-like protein 2) is a guanine nucleotide exchange factor (GEF), which contains spectrin repeats, a rhoGEF (DH) domain and a PH domain. The Dbs PH domain participates in binding to both the Cdc42 and RhoA GTPases. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes. Pssm-ID: 269934 [Multi-domain] Cd Length: 126 Bit Score: 250.96 E-value: 1.98e-77
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| RhoGEF | cd00160 | Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ... |
702-879 | 1.31e-55 | |||||
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains. Pssm-ID: 238091 [Multi-domain] Cd Length: 181 Bit Score: 190.97 E-value: 1.31e-55
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| RhoGEF | smart00325 | Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange ... |
705-880 | 7.53e-53 | |||||
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains. Improved coverage. Pssm-ID: 214619 [Multi-domain] Cd Length: 180 Bit Score: 182.89 E-value: 7.53e-53
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| RhoGEF | pfam00621 | RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called ... |
705-879 | 1.43e-47 | |||||
RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that pfam00169 domains invariably occur C-terminal to RhoGEF/DH domains. Pssm-ID: 459876 [Multi-domain] Cd Length: 176 Bit Score: 167.86 E-value: 1.43e-47
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| SEC14 | smart00516 | Domain in homologues of a S. cerevisiae phosphatidylinositol transfer protein (Sec14p); Domain ... |
145-290 | 6.43e-28 | |||||
Domain in homologues of a S. cerevisiae phosphatidylinositol transfer protein (Sec14p); Domain in homologues of a S. cerevisiae phosphatidylinositol transfer protein (Sec14p) and in RhoGAPs, RhoGEFs and the RasGAP, neurofibromin (NF1). Lipid-binding domain. The SEC14 domain of Dbl is known to associate with G protein beta/gamma subunits. Pssm-ID: 214706 [Multi-domain] Cd Length: 158 Bit Score: 110.85 E-value: 6.43e-28
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| SH3_DBS | cd11857 | Src homology 3 domain of DBL's Big Sister (DBS), a guanine nucleotide exchange factor; DBS, ... |
1153-1205 | 6.91e-22 | |||||
Src homology 3 domain of DBL's Big Sister (DBS), a guanine nucleotide exchange factor; DBS, also called MCF2L (MCF2-transforming sequence-like protein) or OST, is a Rho GTPase guanine nucleotide exchange factor (RhoGEF), facilitating the exchange of GDP and GTP. It was originally isolated from a cDNA screen for sequences that cause malignant growth. It plays roles in regulating clathrin-mediated endocytosis and cell migration through its activation of Rac1 and Cdc42. Depending on cell type, DBS can also activate RhoA and RhoG. DBS contains a Sec14-like domain, spectrin-like repeats, a RhoGEF [or Dbl homology (DH)] domain, a Pleckstrin homology (PH) domain, and an SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies. Pssm-ID: 212791 Cd Length: 55 Bit Score: 90.04 E-value: 6.91e-22
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| CRAL_TRIO_2 | pfam13716 | Divergent CRAL/TRIO domain; This family includes divergent members of the CRAL-TRIO domain ... |
160-293 | 1.05e-17 | |||||
Divergent CRAL/TRIO domain; This family includes divergent members of the CRAL-TRIO domain family. This family includes ECM25 that contains a divergent CRAL-TRIO domain identified by Gallego and colleagues. Pssm-ID: 463965 [Multi-domain] Cd Length: 140 Bit Score: 80.83 E-value: 1.05e-17
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| SPEC | cd00176 | Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members ... |
421-623 | 2.09e-16 | |||||
Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; the repeats are independent folding units; tandem repeats are found in differing numbers and arrange in an antiparallel manner to form dimers; the repeats are defined by a characteristic tryptophan (W) residue in helix A and a leucine (L) at the carboxyl end of helix C and separated by a linker of 5 residues; two copies of the repeat are present here Pssm-ID: 238103 [Multi-domain] Cd Length: 213 Bit Score: 79.41 E-value: 2.09e-16
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| SEC14 | cd00170 | Sec14p-like lipid-binding domain; Sec14p-like lipid-binding domains are found in secretory ... |
140-288 | 7.24e-14 | |||||
Sec14p-like lipid-binding domain; Sec14p-like lipid-binding domains are found in secretory proteins, such as S. cerevisiae phosphatidylinositol transfer protein (Sec14p), and in lipid regulated proteins such as RhoGAPs, RhoGEFs and neurofibromin (NF1). SEC14 domain of Dbl is known to associate with G protein beta/gamma subunits. Pssm-ID: 469559 [Multi-domain] Cd Length: 156 Bit Score: 70.44 E-value: 7.24e-14
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| PH | smart00233 | Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ... |
900-1014 | 6.54e-12 | |||||
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids. Pssm-ID: 214574 [Multi-domain] Cd Length: 102 Bit Score: 62.95 E-value: 6.54e-12
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| SPEC | smart00150 | Spectrin repeats; |
423-523 | 5.09e-11 | |||||
Spectrin repeats; Pssm-ID: 197544 [Multi-domain] Cd Length: 101 Bit Score: 60.42 E-value: 5.09e-11
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| PH | pfam00169 | PH domain; PH stands for pleckstrin homology. |
900-1014 | 3.68e-07 | |||||
PH domain; PH stands for pleckstrin homology. Pssm-ID: 459697 [Multi-domain] Cd Length: 105 Bit Score: 49.87 E-value: 3.68e-07
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| Spectrin | pfam00435 | Spectrin repeat; Spectrin repeat-domains are found in several proteins involved in ... |
423-523 | 2.88e-06 | |||||
Spectrin repeat; Spectrin repeat-domains are found in several proteins involved in cytoskeletal structure. These include spectrin, alpha-actinin and dystrophin. The sequence repeat used in this family is taken from the structural repeat in reference. The spectrin domain- repeat forms a three helix bundle. The second helix is interrupted by proline in some sequences. The repeats are defined by a characteriztic tryptophan (W) residue at position 17 in helix A and a leucine (L) at 2 residues from the carboxyl end of helix C. Although the domain occurs in multiple repeats along sequences, the domains are actually stable on their own - ie they act, biophysically, like domains rather than repeats that along function when aggregated. Pssm-ID: 395348 [Multi-domain] Cd Length: 105 Bit Score: 47.31 E-value: 2.88e-06
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| SH3 | smart00326 | Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences ... |
1150-1206 | 2.05e-05 | |||||
Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations. Pssm-ID: 214620 [Multi-domain] Cd Length: 56 Bit Score: 43.30 E-value: 2.05e-05
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| ROM1 | COG5422 | RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction ... |
700-948 | 2.76e-05 | |||||
RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction mechanisms]; Pssm-ID: 227709 [Multi-domain] Cd Length: 1175 Bit Score: 48.73 E-value: 2.76e-05
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| SH3_1 | pfam00018 | SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal ... |
1155-1202 | 2.06e-04 | |||||
SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel. Pssm-ID: 394975 [Multi-domain] Cd Length: 47 Bit Score: 39.88 E-value: 2.06e-04
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| Name | Accession | Description | Interval | E-value | |||||
| PH_Dbs | cd01227 | DBL's big sister protein pleckstrin homology (PH) domain; Dbs (also called MCF2-transforming ... |
886-1017 | 1.98e-77 | |||||
DBL's big sister protein pleckstrin homology (PH) domain; Dbs (also called MCF2-transforming sequence-like protein 2) is a guanine nucleotide exchange factor (GEF), which contains spectrin repeats, a rhoGEF (DH) domain and a PH domain. The Dbs PH domain participates in binding to both the Cdc42 and RhoA GTPases. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes. Pssm-ID: 269934 [Multi-domain] Cd Length: 126 Bit Score: 250.96 E-value: 1.98e-77
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| RhoGEF | cd00160 | Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ... |
702-879 | 1.31e-55 | |||||
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains. Pssm-ID: 238091 [Multi-domain] Cd Length: 181 Bit Score: 190.97 E-value: 1.31e-55
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| RhoGEF | smart00325 | Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange ... |
705-880 | 7.53e-53 | |||||
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains. Improved coverage. Pssm-ID: 214619 [Multi-domain] Cd Length: 180 Bit Score: 182.89 E-value: 7.53e-53
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| RhoGEF | pfam00621 | RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called ... |
705-879 | 1.43e-47 | |||||
RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that pfam00169 domains invariably occur C-terminal to RhoGEF/DH domains. Pssm-ID: 459876 [Multi-domain] Cd Length: 176 Bit Score: 167.86 E-value: 1.43e-47
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| SEC14 | smart00516 | Domain in homologues of a S. cerevisiae phosphatidylinositol transfer protein (Sec14p); Domain ... |
145-290 | 6.43e-28 | |||||
Domain in homologues of a S. cerevisiae phosphatidylinositol transfer protein (Sec14p); Domain in homologues of a S. cerevisiae phosphatidylinositol transfer protein (Sec14p) and in RhoGAPs, RhoGEFs and the RasGAP, neurofibromin (NF1). Lipid-binding domain. The SEC14 domain of Dbl is known to associate with G protein beta/gamma subunits. Pssm-ID: 214706 [Multi-domain] Cd Length: 158 Bit Score: 110.85 E-value: 6.43e-28
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| PH_puratrophin-1 | cd13242 | Puratrophin-1 pleckstrin homology (PH) domain; Puratrophin-1 (also called Purkinje cell ... |
879-1022 | 1.19e-27 | |||||
Puratrophin-1 pleckstrin homology (PH) domain; Puratrophin-1 (also called Purkinje cell atrophy-associated protein 1 or PLEKHG4/Pleckstrin homology domain-containing family G member 4) contains a spectrin repeat, a RhoGEF (DH) domain, and a PH domain. It is thought to function in intracellular signaling and cytoskeleton dynamics at the Golgi. Puratrophin-1 is expressed in kidney, Leydig cells in the testis, epithelial cells in the prostate gland and Langerhans islet in the pancreas. A single nucleotide substitution in the puratrophin-1 gene were once thought to result in autosomal dominant cerebellar ataxia (ADCA), but now it has been demonstrated that this ataxia is a result of defects in the BEAN gene. Puratrophin contains a domain architecture similar to that of Dbl family members Dbs and Trio. Dbs is a guanine nucleotide exchange factor (GEF), which contains spectrin repeats, a RhoGEF (DH) domain and a PH domain. The Dbs PH domain participates in binding to both the Cdc42 and RhoA GTPases. Trio plays an essential role in regulating the actin cytoskeleton during axonal guidance and branching. Trio is a multidomain signaling protein that contains two RhoGEF(DH)-PH domains in tandem. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes. Pssm-ID: 270062 Cd Length: 136 Bit Score: 109.30 E-value: 1.19e-27
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| SH3_DBS | cd11857 | Src homology 3 domain of DBL's Big Sister (DBS), a guanine nucleotide exchange factor; DBS, ... |
1153-1205 | 6.91e-22 | |||||
Src homology 3 domain of DBL's Big Sister (DBS), a guanine nucleotide exchange factor; DBS, also called MCF2L (MCF2-transforming sequence-like protein) or OST, is a Rho GTPase guanine nucleotide exchange factor (RhoGEF), facilitating the exchange of GDP and GTP. It was originally isolated from a cDNA screen for sequences that cause malignant growth. It plays roles in regulating clathrin-mediated endocytosis and cell migration through its activation of Rac1 and Cdc42. Depending on cell type, DBS can also activate RhoA and RhoG. DBS contains a Sec14-like domain, spectrin-like repeats, a RhoGEF [or Dbl homology (DH)] domain, a Pleckstrin homology (PH) domain, and an SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies. Pssm-ID: 212791 Cd Length: 55 Bit Score: 90.04 E-value: 6.91e-22
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| PH2_Kalirin_Trio_p63RhoGEF | cd13241 | p63RhoGEF pleckstrin homology (PH) domain, repeat 2; The guanine nucleotide exchange factor ... |
889-1018 | 5.75e-21 | |||||
p63RhoGEF pleckstrin homology (PH) domain, repeat 2; The guanine nucleotide exchange factor p63RhoGEF is an effector of the heterotrimeric G protein, Galphaq and linking Galphaq-coupled receptors (GPCRs) to the activation of RhoA. The Dbl(DH) and PH domains of p63RhoGEF interact with the effector-binding site and the C-terminal region of Galphaq and appear to relieve autoinhibition of the catalytic DH domain by the PH domain. Trio, Duet, and p63RhoGEF are shown to constitute a family of Galphaq effectors that appear to activate RhoA both in vitro and in intact cells. Dbs is a guanine nucleotide exchange factor (GEF), which contains spectrin repeats, a rhoGEF (DH) domain and a PH domain. The Dbs PH domain participates in binding to both the Cdc42 and RhoA GTPases. Trio plays an essential role in regulating the actin cytoskeleton during axonal guidance and branching. Trio is a multidomain signaling protein that contains two RhoGEF(DH)-PH domains in tandem. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes. Pssm-ID: 270061 Cd Length: 140 Bit Score: 90.40 E-value: 5.75e-21
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| PH1_Kalirin_Trio_like | cd13240 | Triple functional domain pleckstrin homology pleckstrin homology (PH) domain, repeat 1; ... |
887-1014 | 2.87e-18 | |||||
Triple functional domain pleckstrin homology pleckstrin homology (PH) domain, repeat 1; RhoGEFs, Kalirin and Trio, the mammalian homologs of Drosophila Trio and Caenorhabditis elegans UNC-73 regulate a novel step in secretory granule maturation. Their signaling modulates the extent to which regulated cargo enter and remain in the regulated secretory pathway. This allows for fine tuning of peptides released by a single secretory cell type with impaired signaling leading to pathological states. Trio plays an essential role in regulating the actin cytoskeleton during axonal guidance and branching. Kalirin and Trio are encoded by separate genes in mammals and by a single one in invertebrates. Kalirin and Trio share the same complex multidomain structure and display several splice variants. The longest Kalirin and Trio proteins have a Sec14 domain, a stretch of spectrin repeats, a RhoGEF(DH)/PH cassette (also called GEF1), an SH3 domain, a second RhoGEF(DH)/PH cassette (also called GEF2), a second SH3 domain, Ig/FNIII domains, and a kinase domain. The first RhoGEF(DH)/PH cassette catalyzes exchange on Rac1 and RhoG while the second RhoGEF(DH)/PH cassette is specific for RhoA. Kalirin and Trio are closely related to p63RhoGEF and have PH domains of similar function. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. Pssm-ID: 270060 Cd Length: 123 Bit Score: 82.05 E-value: 2.87e-18
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| CRAL_TRIO_2 | pfam13716 | Divergent CRAL/TRIO domain; This family includes divergent members of the CRAL-TRIO domain ... |
160-293 | 1.05e-17 | |||||
Divergent CRAL/TRIO domain; This family includes divergent members of the CRAL-TRIO domain family. This family includes ECM25 that contains a divergent CRAL-TRIO domain identified by Gallego and colleagues. Pssm-ID: 463965 [Multi-domain] Cd Length: 140 Bit Score: 80.83 E-value: 1.05e-17
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| SPEC | cd00176 | Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members ... |
421-623 | 2.09e-16 | |||||
Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; the repeats are independent folding units; tandem repeats are found in differing numbers and arrange in an antiparallel manner to form dimers; the repeats are defined by a characteristic tryptophan (W) residue in helix A and a leucine (L) at the carboxyl end of helix C and separated by a linker of 5 residues; two copies of the repeat are present here Pssm-ID: 238103 [Multi-domain] Cd Length: 213 Bit Score: 79.41 E-value: 2.09e-16
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| PH_Obscurin | cd13239 | Obscurin pleckstrin homology (PH) domain; Obscurin (also called Obscurin-RhoGEF; ... |
887-1013 | 5.64e-16 | |||||
Obscurin pleckstrin homology (PH) domain; Obscurin (also called Obscurin-RhoGEF; Obscurin-myosin light chain kinase/Obscurin-MLCK) is a giant muscle protein that is concentrated at the peripheries of Z-disks and M-lines. It binds small ankyrin I, a component of the sarcoplasmic reticulum (SR) membrane. It is associated with the contractile apparatus through binding with titin and sarcomeric myosin. It plays important roles in the organization and assembly of the myofibril and the SR. Obscurin has been observed as alternatively-spliced isoforms. The major isoform in sleletal muscle, approximately 800 kDa in size, is composed of many adhesion modules and signaling domains. It harbors 49 Ig and 2 FNIII repeats at the N-terminues, a complex middle region with additional Ig domains, an IQ motif, and a conserved SH3 domain near RhoGEF and PH domains, and a non-modular C-terminus with phosphorylation motifs. The obscurin gene also encodes two kinase domains, which are not part of the 800 kDa form of the protein, but is part of smaller spliced products that present in heart muscle. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes. Pssm-ID: 270059 Cd Length: 125 Bit Score: 75.66 E-value: 5.64e-16
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| SEC14 | cd00170 | Sec14p-like lipid-binding domain; Sec14p-like lipid-binding domains are found in secretory ... |
140-288 | 7.24e-14 | |||||
Sec14p-like lipid-binding domain; Sec14p-like lipid-binding domains are found in secretory proteins, such as S. cerevisiae phosphatidylinositol transfer protein (Sec14p), and in lipid regulated proteins such as RhoGAPs, RhoGEFs and neurofibromin (NF1). SEC14 domain of Dbl is known to associate with G protein beta/gamma subunits. Pssm-ID: 469559 [Multi-domain] Cd Length: 156 Bit Score: 70.44 E-value: 7.24e-14
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| PH | smart00233 | Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ... |
900-1014 | 6.54e-12 | |||||
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids. Pssm-ID: 214574 [Multi-domain] Cd Length: 102 Bit Score: 62.95 E-value: 6.54e-12
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| SPEC | smart00150 | Spectrin repeats; |
423-523 | 5.09e-11 | |||||
Spectrin repeats; Pssm-ID: 197544 [Multi-domain] Cd Length: 101 Bit Score: 60.42 E-value: 5.09e-11
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| SPEC | cd00176 | Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members ... |
324-527 | 3.77e-09 | |||||
Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; the repeats are independent folding units; tandem repeats are found in differing numbers and arrange in an antiparallel manner to form dimers; the repeats are defined by a characteristic tryptophan (W) residue in helix A and a leucine (L) at the carboxyl end of helix C and separated by a linker of 5 residues; two copies of the repeat are present here Pssm-ID: 238103 [Multi-domain] Cd Length: 213 Bit Score: 58.23 E-value: 3.77e-09
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| SH3_p47phox_like | cd11856 | Src homology 3 domains of the p47phox subunit of NADPH oxidase and similar domains; This ... |
1153-1205 | 5.78e-09 | |||||
Src homology 3 domains of the p47phox subunit of NADPH oxidase and similar domains; This family is composed of the tandem SH3 domains of p47phox subunit of NADPH oxidase and Nox Organizing protein 1 (NoxO1), the four SH3 domains of Tks4 (Tyr kinase substrate with four SH3 domains), the five SH3 domains of Tks5, the SH3 domain of obscurin, Myosin-I, and similar domains. Most members of this group also contain Phox homology (PX) domains, except for obscurin and Myosin-I. p47phox and NoxO1 are regulators of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) and nonphagocytic NADPH oxidase Nox1, respectively. They play roles in the activation of their respective NADPH oxidase, which catalyzes the transfer of electrons from NADPH to molecular oxygen to form superoxide. Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Obscurin is a giant muscle protein that plays important roles in the organization and assembly of the myofibril and the sarcoplasmic reticulum. Type I myosins (Myosin-I) are actin-dependent motors in endocytic actin structures and actin patches. They play roles in membrane traffic in endocytic and secretory pathways, cell motility, and mechanosensing. Myosin-I contains an N-terminal actin-activated ATPase, a phospholipid-binding TH1 (tail homology 1) domain, and a C-terminal extension which includes an F-actin-binding TH2 domain, an SH3 domain, and an acidic peptide that participates in activating the Arp2/3complex. The SH3 domain of myosin-I is required for myosin-I-induced actin polymerization. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies. Pssm-ID: 212790 [Multi-domain] Cd Length: 53 Bit Score: 53.02 E-value: 5.78e-09
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| SH3_p47phox_1 | cd12021 | First or N-terminal Src homology 3 domain of the p47phox subunit of NADPH oxidase, also called ... |
1154-1205 | 4.43e-08 | |||||
First or N-terminal Src homology 3 domain of the p47phox subunit of NADPH oxidase, also called Neutrophil Cytosolic Factor 1; p47phox, or NCF1, is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox), which plays a key role in the ability of phagocytes to defend against bacterial infections. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p47phox is required for activation of NADH oxidase and plays a role in translocation. It contains an N-terminal Phox homology (PX) domain, tandem SH3 domains (N-SH3 and C-SH3), a polybasic/autoinhibitory region, and a C-terminal proline-rich region (PRR). This model characterizes the first SH3 domain (or N-SH3) of p47phox. In its inactive state, the tandem SH3 domains interact intramolecularly with the autoinhibitory region; upon activation, the tandem SH3 domains are exposed through a conformational change, resulting in their binding to the PRR of p22phox and the activation of NADPH oxidase. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies. Pssm-ID: 212954 [Multi-domain] Cd Length: 53 Bit Score: 50.73 E-value: 4.43e-08
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| SH3_Tks5_1 | cd12074 | First Src homology 3 domain of Tyrosine kinase substrate with five SH3 domains; Tks5, also ... |
1153-1205 | 5.66e-08 | |||||
First Src homology 3 domain of Tyrosine kinase substrate with five SH3 domains; Tks5, also called SH3 and PX domain-containing protein 2A (SH3PXD2A) or Five SH (FISH), is a scaffolding protein and Src substrate that is localized in podosomes, which are electron-dense structures found in Src-transformed fibroblasts, osteoclasts, macrophages, and some invasive cancer cells. It binds and regulates some members of the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. It is required for podosome formation, degradation of the extracellular matrix, and cancer cell invasion. Tks5 contains an N-terminal Phox homology (PX) domain and five SH3 domains. This model characterizes the first SH3 domain of Tks5. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies. Pssm-ID: 213007 [Multi-domain] Cd Length: 53 Bit Score: 50.48 E-value: 5.66e-08
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| SH3_Tks5_2 | cd12077 | Second Src homology 3 domain of Tyrosine kinase substrate with five SH3 domains; Tks5, also ... |
1153-1205 | 9.91e-08 | |||||
Second Src homology 3 domain of Tyrosine kinase substrate with five SH3 domains; Tks5, also called SH3 and PX domain-containing protein 2A (SH3PXD2A) or Five SH (FISH), is a scaffolding protein and Src substrate that is localized in podosomes, which are electron-dense structures found in Src-transformed fibroblasts, osteoclasts, macrophages, and some invasive cancer cells. It binds and regulates some members of the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. It is required for podosome formation, degradation of the extracellular matrix, and cancer cell invasion. Tks5 contains an N-terminal Phox homology (PX) domain and five SH3 domains. This model characterizes the second SH3 domain of Tks5. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies. Pssm-ID: 213010 Cd Length: 54 Bit Score: 49.65 E-value: 9.91e-08
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| PH | cd00821 | Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ... |
913-1010 | 1.17e-07 | |||||
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes. Pssm-ID: 275388 [Multi-domain] Cd Length: 92 Bit Score: 50.62 E-value: 1.17e-07
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| SH3_Tks_1 | cd12015 | First Src homology 3 domain of Tyrosine kinase substrate (Tks) proteins; Tks proteins are Src ... |
1153-1205 | 2.17e-07 | |||||
First Src homology 3 domain of Tyrosine kinase substrate (Tks) proteins; Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Vertebrates contain two Tks proteins, Tks4 (Tyr kinase substrate with four SH3 domains) and Tks5 (Tyr kinase substrate with five SH3 domains), which display partially overlapping but non-redundant functions. Both associate with the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. Tks5 interacts with N-WASP and Nck, while Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. Tks proteins contain an N-terminal Phox homology (PX) domain and four or five SH3 domains. This model characterizes the first SH3 domain of Tks proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies. Pssm-ID: 212948 Cd Length: 53 Bit Score: 48.57 E-value: 2.17e-07
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| SH3_Myosin-I_fungi | cd11858 | Src homology 3 domain of Type I fungal Myosins; Type I myosins (myosin-I) are actin-dependent ... |
1154-1205 | 2.68e-07 | |||||
Src homology 3 domain of Type I fungal Myosins; Type I myosins (myosin-I) are actin-dependent motors in endocytic actin structures and actin patches. They play roles in membrane traffic in endocytic and secretory pathways, cell motility, and mechanosensing. Saccharomyces cerevisiae has two myosins-I, Myo3 and Myo5, which are involved in endocytosis and the polarization of the actin cytoskeleton. Myosin-I contains an N-terminal actin-activated ATPase, a phospholipid-binding TH1 (tail homology 1) domain, and a C-terminal extension which includes an F-actin-binding TH2 domain, an SH3 domain, and an acidic peptide that participates in activating the Arp2/3complex. The SH3 domain of myosin-I is required for myosin-I-induced actin polymerization. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies. Pssm-ID: 212792 [Multi-domain] Cd Length: 55 Bit Score: 48.54 E-value: 2.68e-07
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| PH | pfam00169 | PH domain; PH stands for pleckstrin homology. |
900-1014 | 3.68e-07 | |||||
PH domain; PH stands for pleckstrin homology. Pssm-ID: 459697 [Multi-domain] Cd Length: 105 Bit Score: 49.87 E-value: 3.68e-07
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| SH3_Tks4_1 | cd12075 | First Src homology 3 domain of Tyrosine kinase substrate with four SH3 domains; Tks4, also ... |
1153-1205 | 1.33e-06 | |||||
First Src homology 3 domain of Tyrosine kinase substrate with four SH3 domains; Tks4, also called SH3 and PX domain-containing protein 2B (SH3PXD2B) or HOFI, is a Src substrate and scaffolding protein that plays an important role in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. It is required in the formation of functional podosomes, EGF-induced membrane ruffling, and lamellipodia generation. It plays an important role in cellular attachment and cell spreading. Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. It contains an N-terminal Phox homology (PX) domain and four SH3 domains. This model characterizes the first SH3 domain of Tks4. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies. Pssm-ID: 213008 Cd Length: 55 Bit Score: 46.61 E-value: 1.33e-06
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| Spectrin | pfam00435 | Spectrin repeat; Spectrin repeat-domains are found in several proteins involved in ... |
423-523 | 2.88e-06 | |||||
Spectrin repeat; Spectrin repeat-domains are found in several proteins involved in cytoskeletal structure. These include spectrin, alpha-actinin and dystrophin. The sequence repeat used in this family is taken from the structural repeat in reference. The spectrin domain- repeat forms a three helix bundle. The second helix is interrupted by proline in some sequences. The repeats are defined by a characteriztic tryptophan (W) residue at position 17 in helix A and a leucine (L) at 2 residues from the carboxyl end of helix C. Although the domain occurs in multiple repeats along sequences, the domains are actually stable on their own - ie they act, biophysically, like domains rather than repeats that along function when aggregated. Pssm-ID: 395348 [Multi-domain] Cd Length: 105 Bit Score: 47.31 E-value: 2.88e-06
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| SH3_Tks_3 | cd12017 | Third Src homology 3 domain of Tyrosine kinase substrate (Tks) proteins; Tks proteins are Src ... |
1154-1205 | 9.36e-06 | |||||
Third Src homology 3 domain of Tyrosine kinase substrate (Tks) proteins; Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Vertebrates contain two Tks proteins, Tks4 (Tyr kinase substrate with four SH3 domains) and Tks5 (Tyr kinase substrate with five SH3 domains), which display partially overlapping but non-redundant functions. Both associate with the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. Tks5 interacts with N-WASP and Nck, while Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. Tks proteins contain an N-terminal Phox homology (PX) domain and four or five SH3 domains. This model characterizes the third SH3 domain of Tks proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies. Pssm-ID: 212950 Cd Length: 53 Bit Score: 43.98 E-value: 9.36e-06
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| SH3_Tks4_2 | cd12076 | Second Src homology 3 domain of Tyrosine kinase substrate with four SH3 domains; Tks4, also ... |
1153-1205 | 1.25e-05 | |||||
Second Src homology 3 domain of Tyrosine kinase substrate with four SH3 domains; Tks4, also called SH3 and PX domain-containing protein 2B (SH3PXD2B) or HOFI, is a Src substrate and scaffolding protein that plays an important role in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. It is required in the formation of functional podosomes, EGF-induced membrane ruffling, and lamellipodia generation. It plays an important role in cellular attachment and cell spreading. Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. It contains an N-terminal Phox homology (PX) domain and four SH3 domains. This model characterizes the second SH3 domain of Tks4. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies. Pssm-ID: 213009 [Multi-domain] Cd Length: 54 Bit Score: 43.87 E-value: 1.25e-05
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| PH_Vav | cd01223 | Vav pleckstrin homology (PH) domain; Vav acts as a guanosine nucleotide exchange factor (GEF) ... |
913-1014 | 1.34e-05 | |||||
Vav pleckstrin homology (PH) domain; Vav acts as a guanosine nucleotide exchange factor (GEF) for Rho/Rac proteins. They control processes including T cell activation, phagocytosis, and migration of cells. The Vav subgroup of Dbl GEFs consists of three family members (Vav1, Vav2, and Vav3) in mammals. Vav1 is preferentially expressed in the hematopoietic system, while Vav2 and Vav3 are described by broader expression patterns. Mammalian Vav proteins consist of a calponin homology (CH) domain, an acidic region, a catalytic Dbl homology (DH) domain, a PH domain, a zinc finger cysteine rich domain (C1/CRD), and an SH2 domain, flanked by two SH3 domains. In invertebrates such as Drosophila and C. elegans, Vav is missing the N-terminal SH3 domain. The DH domain is involved in RhoGTPase recognition and selectivity and stimulates the reorganization of the switch regions for GDP/GTP exchange. The PH domain is implicated in directing membrane localization, allosteric regulation of guanine nucleotide exchange activity, and as a phospholipid- dependent regulator of GEF activity. Vavs bind RhoGTPases including Rac1, RhoA, RhoG, and Cdc42, while other members of the GEF family are specific for a single RhoGTPase. This promiscuity is thought to be a result of its CRD. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.polarized. PH domains also have diverse functions. They are often involved in targeting proteins to the plasma membrane, but only a few (less than 10%) display strong specificity in binding inositol phosphates. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinases, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, cytoskeletal associated molecules, and in lipid associated enzymes. Pssm-ID: 269930 Cd Length: 127 Bit Score: 45.70 E-value: 1.34e-05
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| PH_unc89 | cd13325 | unc89 pleckstrin homology (PH) domain; unc89 is a myofibrillar protein. unc89-B the largest ... |
892-1012 | 1.55e-05 | |||||
unc89 pleckstrin homology (PH) domain; unc89 is a myofibrillar protein. unc89-B the largest isoform is composed of 53 immunoglobulin (Ig) domains, 2 Fn3 domains, a triplet of SH3, DH and PH domains at its N-terminus, and 2 protein kinase domains (PK1 and PK2) at its C-terminus. unc-89 mutants display disorganization of muscle A-bands, and usually lack M-lines. The COOH-terminal region of obscurin, the human homolog of unc89, interacts via two specific Ig-like domains with the NH(2)-terminal Z-disk region of titin, a protein that connects the Z line to the M line in the sarcomere and contributes to the contraction of striated muscle. obscurin is also thought to be involved in Ca2+/calmodulin via its IQ domains, as well as G protein-coupled signal transduction in the sarcomere via its RhoGEF/DH domain. The DH-PH region of OBSCN and unc89, the C. elegans homolog, has exchange activity for RhoA and Rho-1 respectively, but not for the small GTPases homologous to Cdc42 or Rac. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes. Pssm-ID: 270134 Cd Length: 114 Bit Score: 45.42 E-value: 1.55e-05
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| SH3 | smart00326 | Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences ... |
1150-1206 | 2.05e-05 | |||||
Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations. Pssm-ID: 214620 [Multi-domain] Cd Length: 56 Bit Score: 43.30 E-value: 2.05e-05
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| ROM1 | COG5422 | RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction ... |
700-948 | 2.76e-05 | |||||
RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction mechanisms]; Pssm-ID: 227709 [Multi-domain] Cd Length: 1175 Bit Score: 48.73 E-value: 2.76e-05
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| SH3 | cd00174 | Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction ... |
1153-1203 | 2.94e-05 | |||||
Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction domains that bind proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. Thus, they are referred to as proline-recognition domains (PRDs). SH3 domains are less selective and show more diverse specificity compared to other PRDs. They have been shown to bind peptide sequences that lack the PxxP motif; examples include the PxxDY motif of Eps8 and the RKxxYxxY sequence in SKAP55. SH3 domain containing proteins play versatile and diverse roles in the cell, including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies, among others. Many members of this superfamily are adaptor proteins that associate with a number of protein partners, facilitating complex formation and signal transduction. Pssm-ID: 212690 [Multi-domain] Cd Length: 51 Bit Score: 42.45 E-value: 2.94e-05
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| PH_PLEKHG1_G2_G3 | cd13243 | Pleckstrin homology domain-containing family G members 1, 2, and 3 pleckstrin homology (PH) ... |
862-1014 | 7.36e-05 | |||||
Pleckstrin homology domain-containing family G members 1, 2, and 3 pleckstrin homology (PH) domain; PLEKHG1 (also called ARHGEF41), PLEKHG2 (also called ARHGEF42 or CLG/common-site lymphoma/leukemia guanine nucleotide exchange factor2), and PLEKHG3 (also called ARHGEF43) have RhoGEF DH/double-homology domains in tandem with a PH domain which is involved in phospholipid binding. They function as a guanine nucleotide exchange factor (GEF) and are involved in the regulation of Rho protein signal transduction. Mutations in PLEKHG1 have been associated panic disorder (PD), an anxiety disorder characterized by panic attacks and anticipatory anxiety. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes. Pssm-ID: 270063 [Multi-domain] Cd Length: 147 Bit Score: 44.26 E-value: 7.36e-05
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| SH3_Tks5_3 | cd12079 | Third Src homology 3 domain of Tyrosine kinase substrate with five SH3 domains; Tks5, also ... |
1153-1203 | 1.25e-04 | |||||
Third Src homology 3 domain of Tyrosine kinase substrate with five SH3 domains; Tks5, also called SH3 and PX domain-containing protein 2A (SH3PXD2A) or Five SH (FISH), is a scaffolding protein and Src substrate that is localized in podosomes, which are electron-dense structures found in Src-transformed fibroblasts, osteoclasts, macrophages, and some invasive cancer cells. It binds and regulates some members of the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. It is required for podosome formation, degradation of the extracellular matrix, and cancer cell invasion. Tks5 contains an N-terminal Phox homology (PX) domain and five SH3 domains. This model characterizes the third SH3 domain of Tks5. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies. Pssm-ID: 213012 Cd Length: 54 Bit Score: 40.80 E-value: 1.25e-04
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| SH3_1 | pfam00018 | SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal ... |
1155-1202 | 2.06e-04 | |||||
SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel. Pssm-ID: 394975 [Multi-domain] Cd Length: 47 Bit Score: 39.88 E-value: 2.06e-04
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| SH3_Tks_2 | cd12016 | Second Src homology 3 domain of Tyrosine kinase substrate (Tks) proteins; Tks proteins are Src ... |
1152-1205 | 3.90e-04 | |||||
Second Src homology 3 domain of Tyrosine kinase substrate (Tks) proteins; Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Vertebrates contain two Tks proteins, Tks4 (Tyr kinase substrate with four SH3 domains) and Tks5 (Tyr kinase substrate with five SH3 domains), which display partially overlapping but non-redundant functions. Both associate with the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. Tks5 interacts with N-WASP and Nck, while Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. Tks proteins contain an N-terminal Phox homology (PX) domain and four or five SH3 domains. This model characterizes the second SH3 domain of Tks proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies. Pssm-ID: 212949 Cd Length: 54 Bit Score: 39.36 E-value: 3.90e-04
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| SH3_Tks4_3 | cd12078 | Third Src homology 3 domain of Tyrosine kinase substrate with four SH3 domains; Tks4, also ... |
1153-1203 | 1.13e-03 | |||||
Third Src homology 3 domain of Tyrosine kinase substrate with four SH3 domains; Tks4, also called SH3 and PX domain-containing protein 2B (SH3PXD2B) or HOFI, is a Src substrate and scaffolding protein that plays an important role in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. It is required in the formation of functional podosomes, EGF-induced membrane ruffling, and lamellipodia generation. It plays an important role in cellular attachment and cell spreading. Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. It contains an N-terminal Phox homology (PX) domain and four SH3 domains. This model characterizes the third SH3 domain of Tks4. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies. Pssm-ID: 213011 Cd Length: 53 Bit Score: 38.13 E-value: 1.13e-03
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| SH3_Bzz1_1 | cd11912 | First Src Homology 3 domain of Bzz1 and similar domains; Bzz1 (or Bzz1p) is a WASP ... |
1156-1203 | 2.96e-03 | |||||
First Src Homology 3 domain of Bzz1 and similar domains; Bzz1 (or Bzz1p) is a WASP/Las17-interacting protein involved in endocytosis and trafficking to the vacuole. It physically interacts with type I myosins and functions in the early steps of endocytosis. Together with other proteins, it induces membrane scission in yeast. Bzz1 contains an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), a central coiled-coil, and two C-terminal SH3 domains. This model represents the first C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies. Pssm-ID: 212845 [Multi-domain] Cd Length: 55 Bit Score: 37.20 E-value: 2.96e-03
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| SH3_ARHGEF9_like | cd11828 | Src homology 3 domain of ARHGEF9-like Rho guanine nucleotide exchange factors; Members of this ... |
1156-1203 | 3.56e-03 | |||||
Src homology 3 domain of ARHGEF9-like Rho guanine nucleotide exchange factors; Members of this family contain a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. They include the Rho guanine nucleotide exchange factors ARHGEF9, ASEF (also called ARHGEF4), ASEF2, and similar proteins. GEFs activate small GTPases by exchanging bound GDP for free GTP. ARHGEF9 specifically activates Cdc42, while both ASEF and ASEF2 can activate Rac1 and Cdc42. ARHGEF9 is highly expressed in the brain and it interacts with gephyrin, a postsynaptic protein associated with GABA and glycine receptors. ASEF plays a role in angiogenesis and cell migration. ASEF2 is important in cell migration and adhesion dynamics. ASEF exists in an autoinhibited form and is activated upon binding of the tumor suppressor APC (adenomatous polyposis coli), leading to the activation of Rac1 or Cdc42. In its autoinhibited form, the SH3 domain of ASEF forms an extensive interface with the DH and PH domains, blocking the Rac binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies. Pssm-ID: 212762 [Multi-domain] Cd Length: 53 Bit Score: 36.59 E-value: 3.56e-03
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| SH3_PSTPIP1 | cd11824 | Src homology 3 domain of Proline-Serine-Threonine Phosphatase-Interacting Protein 1; PSTPIP1, ... |
1153-1205 | 3.59e-03 | |||||
Src homology 3 domain of Proline-Serine-Threonine Phosphatase-Interacting Protein 1; PSTPIP1, also called CD2 Binding Protein 1 (CD2BP1), is mainly expressed in hematopoietic cells. It is a binding partner of the cell surface receptor CD2 and PTP-PEST, a tyrosine phosphatase which functions in cell motility and Rac1 regulation. It also plays a role in the activation of the Wiskott-Aldrich syndrome protein (WASP), which couples actin rearrangement and T cell activation. Mutations in the gene encoding PSTPIP1 cause the autoinflammatory disorder known as PAPA (pyogenic sterile arthritis, pyoderma gangrenosum, and acne) syndrome. PSTPIP1 contains an N-terminal F-BAR domain, PEST motifs, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies. Pssm-ID: 212758 [Multi-domain] Cd Length: 53 Bit Score: 36.58 E-value: 3.59e-03
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| SH3_BOI | cd11886 | Src Homology 3 domain of fungal BOI-like proteins; This subfamily includes the Saccharomyces ... |
1154-1202 | 5.37e-03 | |||||
Src Homology 3 domain of fungal BOI-like proteins; This subfamily includes the Saccharomyces cerevisiae proteins BOI1 and BOI2, and similar proteins. They contain an N-terminal SH3 domain, a Sterile alpha motif (SAM), and a Pleckstrin homology (PH) domain at the C-terminus. BOI1 and BOI2 interact with the SH3 domain of Bem1p, a protein involved in bud formation. They promote polarized cell growth and participates in the NoCut signaling pathway, which is involved in the control of cytokinesis. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies. Pssm-ID: 212819 Cd Length: 55 Bit Score: 36.16 E-value: 5.37e-03
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| SH3_Src_like | cd11845 | Src homology 3 domain of Src kinase-like Protein Tyrosine Kinases; Src subfamily members ... |
1154-1203 | 7.64e-03 | |||||
Src homology 3 domain of Src kinase-like Protein Tyrosine Kinases; Src subfamily members include Src, Lck, Hck, Blk, Lyn, Fgr, Fyn, Yrk, Yes, and Brk. Src (or c-Src) proteins are cytoplasmic (or non-receptor) PTKs which are anchored to the plasma membrane. They contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). However, Brk lacks the N-terminal myristoylation sites. Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. They were identified as the first proto-oncogene products, and they regulate cell adhesion, invasion, and motility in cancer cells, and tumor vasculature, contributing to cancer progression and metastasis. Src kinases are overexpressed in a variety of human cancers, making them attractive targets for therapy. They are also implicated in acute inflammatory responses and osteoclast function. Src, Fyn, Yes, and Yrk are widely expressed, while Blk, Lck, Hck, Fgr, Lyn, and Brk show a limited expression pattern. This subfamily also includes Drosophila Src42A, Src oncogene at 42A (also known as Dsrc41) which accumulates at sites of cell-cell or cell-matrix adhesion, and participates in Drosphila development and wound healing. It has been shown to promote tube elongation in the tracheal system, is essential for proper cell-cell matching during dorsal closure, and regulates cell-cell contacts in developing Drosophila eyes. The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies. Pssm-ID: 212779 [Multi-domain] Cd Length: 52 Bit Score: 35.64 E-value: 7.64e-03
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