neurofibromin contains a N-terminal RasGAP domain which is similar to catalytic domain of the mammalian p120RasGAP protein, followed by a Sec14-like domain, and a PH domain, and may stimulate Ras GTPase activity
Ras-GTPase Activating Domain of neurofibromin; Neurofibromin is the product of the ...
1210-1563
0e+00
Ras-GTPase Activating Domain of neurofibromin; Neurofibromin is the product of the neurofibromatosis type 1 gene (NF1) and shares a region of similarity with catalytic domain of the mammalian p120RasGAP protein and an extended similarity with the Saccharomyces cerevisiae RasGAP proteins Ira1 and Ira2. Neurofibromin has been shown to function as a GAP (GTPase-activating protein) which inhibits low molecular weight G proteins such as Ras by stimulating their intrinsic GTPase activity. NF1 is a common genetic disorder characterized by various symptoms ranging from predisposition for the development of tumors to learning disability or mental retardation. Loss of neurofibromin activity can be correlated to the increase in Ras-GTP concentration in neurofibromas of NF1 of patients, supporting the notion that unregulated Ras signaling may contribute to their development.
:
Pssm-ID: 213332 [Multi-domain] Cd Length: 332 Bit Score: 656.70 E-value: 0e+00
Neurofibromin-1 Pleckstrin homology-like domain; Neurofibromin (NF1) contains a N-terminal ...
1740-1849
3.23e-68
Neurofibromin-1 Pleckstrin homology-like domain; Neurofibromin (NF1) contains a N-terminal RasGAP domain, followed by a Sec14-like domain, and a PH domain. Surprisingly, in neurofibromin the PH domain alone is not sufficient for phospholipid binding and instead requires the presence of the Sec-14 domain. The Sec-14 domain has been shown to bind 1-(3-sn-phosphatidyl)-sn-glycerol (PtdGro), (3-sn-phosphatidyl)-ethanolamine (PtdEtn) and -choline (PtdCho) and to a minor extent to (3-sn-phosphatidyl)-l-serine (PtdSer) and 1-(3-sn-phosphatidyl)-d-myo-inositol (PtdIns). Neurofibromatosis type 1 (also known as von Recklinghausen neurofibromatosis or NF1) is a genetic disorder caused by alterations in the tumor suppressor gene NF1. Hallmark symptoms include neural crest derived tumors, pigmentation anomalies, bone deformations, and learning disabilities. Mutations of the tumour suppressor gene NF1 are responsible for disease pathogenesis, with 90% of the alterations being nonsense codons. 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: 270123 Cd Length: 110 Bit Score: 225.46 E-value: 3.23e-68
Divergent CRAL/TRIO domain; This family includes divergent members of the CRAL-TRIO domain ...
1614-1748
1.39e-27
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: 110.11 E-value: 1.39e-27
Ras-GTPase Activating Domain of neurofibromin; Neurofibromin is the product of the ...
1210-1563
0e+00
Ras-GTPase Activating Domain of neurofibromin; Neurofibromin is the product of the neurofibromatosis type 1 gene (NF1) and shares a region of similarity with catalytic domain of the mammalian p120RasGAP protein and an extended similarity with the Saccharomyces cerevisiae RasGAP proteins Ira1 and Ira2. Neurofibromin has been shown to function as a GAP (GTPase-activating protein) which inhibits low molecular weight G proteins such as Ras by stimulating their intrinsic GTPase activity. NF1 is a common genetic disorder characterized by various symptoms ranging from predisposition for the development of tumors to learning disability or mental retardation. Loss of neurofibromin activity can be correlated to the increase in Ras-GTP concentration in neurofibromas of NF1 of patients, supporting the notion that unregulated Ras signaling may contribute to their development.
Pssm-ID: 213332 [Multi-domain] Cd Length: 332 Bit Score: 656.70 E-value: 0e+00
GTPase-activator protein for Ras-like GTPases; All alpha-helical domain that accelerates the ...
1199-1569
2.35e-109
GTPase-activator protein for Ras-like GTPases; All alpha-helical domain that accelerates the GTPase activity of Ras, thereby "switching" it into an "off" position. Improved domain limits from structure.
Pssm-ID: 214617 Cd Length: 344 Bit Score: 353.15 E-value: 2.35e-109
Neurofibromin-1 Pleckstrin homology-like domain; Neurofibromin (NF1) contains a N-terminal ...
1740-1849
3.23e-68
Neurofibromin-1 Pleckstrin homology-like domain; Neurofibromin (NF1) contains a N-terminal RasGAP domain, followed by a Sec14-like domain, and a PH domain. Surprisingly, in neurofibromin the PH domain alone is not sufficient for phospholipid binding and instead requires the presence of the Sec-14 domain. The Sec-14 domain has been shown to bind 1-(3-sn-phosphatidyl)-sn-glycerol (PtdGro), (3-sn-phosphatidyl)-ethanolamine (PtdEtn) and -choline (PtdCho) and to a minor extent to (3-sn-phosphatidyl)-l-serine (PtdSer) and 1-(3-sn-phosphatidyl)-d-myo-inositol (PtdIns). Neurofibromatosis type 1 (also known as von Recklinghausen neurofibromatosis or NF1) is a genetic disorder caused by alterations in the tumor suppressor gene NF1. Hallmark symptoms include neural crest derived tumors, pigmentation anomalies, bone deformations, and learning disabilities. Mutations of the tumour suppressor gene NF1 are responsible for disease pathogenesis, with 90% of the alterations being nonsense codons. 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: 270123 Cd Length: 110 Bit Score: 225.46 E-value: 3.23e-68
GTPase-activator protein for Ras-like GTPase; All alpha-helical domain that accelerates the ...
1275-1463
7.83e-32
GTPase-activator protein for Ras-like GTPase; All alpha-helical domain that accelerates the GTPase activity of Ras, thereby "switching" it into an "off" position.
Pssm-ID: 459871 Cd Length: 207 Bit Score: 125.09 E-value: 7.83e-32
Divergent CRAL/TRIO domain; This family includes divergent members of the CRAL-TRIO domain ...
1614-1748
1.39e-27
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: 110.11 E-value: 1.39e-27
Domain in homologues of a S. cerevisiae phosphatidylinositol transfer protein (Sec14p); Domain ...
1595-1739
3.15e-20
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: 89.67 E-value: 3.15e-20
Sec14p-like lipid-binding domain; Sec14p-like lipid-binding domains are found in secretory ...
1594-1740
5.49e-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: 71.98 E-value: 5.49e-14
Ras-GTPase Activating Domain of neurofibromin; Neurofibromin is the product of the ...
1210-1563
0e+00
Ras-GTPase Activating Domain of neurofibromin; Neurofibromin is the product of the neurofibromatosis type 1 gene (NF1) and shares a region of similarity with catalytic domain of the mammalian p120RasGAP protein and an extended similarity with the Saccharomyces cerevisiae RasGAP proteins Ira1 and Ira2. Neurofibromin has been shown to function as a GAP (GTPase-activating protein) which inhibits low molecular weight G proteins such as Ras by stimulating their intrinsic GTPase activity. NF1 is a common genetic disorder characterized by various symptoms ranging from predisposition for the development of tumors to learning disability or mental retardation. Loss of neurofibromin activity can be correlated to the increase in Ras-GTP concentration in neurofibromas of NF1 of patients, supporting the notion that unregulated Ras signaling may contribute to their development.
Pssm-ID: 213332 [Multi-domain] Cd Length: 332 Bit Score: 656.70 E-value: 0e+00
GTPase-activator protein for Ras-like GTPases; All alpha-helical domain that accelerates the ...
1199-1569
2.35e-109
GTPase-activator protein for Ras-like GTPases; All alpha-helical domain that accelerates the GTPase activity of Ras, thereby "switching" it into an "off" position. Improved domain limits from structure.
Pssm-ID: 214617 Cd Length: 344 Bit Score: 353.15 E-value: 2.35e-109
Neurofibromin-1 Pleckstrin homology-like domain; Neurofibromin (NF1) contains a N-terminal ...
1740-1849
3.23e-68
Neurofibromin-1 Pleckstrin homology-like domain; Neurofibromin (NF1) contains a N-terminal RasGAP domain, followed by a Sec14-like domain, and a PH domain. Surprisingly, in neurofibromin the PH domain alone is not sufficient for phospholipid binding and instead requires the presence of the Sec-14 domain. The Sec-14 domain has been shown to bind 1-(3-sn-phosphatidyl)-sn-glycerol (PtdGro), (3-sn-phosphatidyl)-ethanolamine (PtdEtn) and -choline (PtdCho) and to a minor extent to (3-sn-phosphatidyl)-l-serine (PtdSer) and 1-(3-sn-phosphatidyl)-d-myo-inositol (PtdIns). Neurofibromatosis type 1 (also known as von Recklinghausen neurofibromatosis or NF1) is a genetic disorder caused by alterations in the tumor suppressor gene NF1. Hallmark symptoms include neural crest derived tumors, pigmentation anomalies, bone deformations, and learning disabilities. Mutations of the tumour suppressor gene NF1 are responsible for disease pathogenesis, with 90% of the alterations being nonsense codons. 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: 270123 Cd Length: 110 Bit Score: 225.46 E-value: 3.23e-68
Ras GTPase Activating Domain; RasGAP functions as an enhancer of the hydrolysis of GTP that is ...
1222-1496
2.59e-61
Ras GTPase Activating Domain; RasGAP functions as an enhancer of the hydrolysis of GTP that is bound to Ras-GTPases. Proteins having a RasGAP domain include p120GAP, IQGAP, Rab5-activating protein 6, and Neurofibromin, among others. Although the Rho (Ras homolog) GTPases are most closely related to members of the Ras family, RhoGAP and RasGAP exhibit no similarity at their amino acid sequence level. RasGTPases function as molecular switches in a large number of signaling pathways. They are in the on state when bound to GTP, and in the off state when bound to GDP. The RasGAP domain speeds up the hydrolysis of GTP in Ras-like proteins acting as a negative regulator.
Pssm-ID: 213328 Cd Length: 256 Bit Score: 211.58 E-value: 2.59e-61
Ras-GTPase Activating Domain of proteins similar to neurofibromin; Neurofibromin-like proteins ...
1215-1536
6.36e-60
Ras-GTPase Activating Domain of proteins similar to neurofibromin; Neurofibromin-like proteins include the Saccharomyces cerevisiae RasGAP proteins Ira1 and Ira2, the closest homolog of neurofibromin, which is responsible for the human autosomal dominant disease neurofibromatosis type I (NF1). The RasGAP Ira1/2 proteins are negative regulators of the Ras-cAMP signaling pathway and conserved from yeast to human. In yeast Ras proteins are activated by GEFs, and inhibited by two GAPs, Ira1 and Ira2. Ras proteins activate the cAMP/protein kinase A (PKA) pathway, which controls metabolism, stress resistance, growth, and meiosis. Recent studies showed that the kelch proteins Gpb1 and Gpb2 inhibit Ras activity via association with Ira1 and Ira2. Gpb1/2 bind to a conserved C-terminal domain of Ira1/2, and loss of Gpb1/2 results in a destabilization of Ira1 and Ira2, leading to elevated levels of Ras2-GTP and uninhibited cAMP-PKA signaling. Since the Gpb1/2 binding domain on Ira1/2 is conserved in the human neurofibromin protein, the studies suggest that an analogous signaling mechanism may contribute to the neoplastic development of NF1.
Pssm-ID: 213341 Cd Length: 317 Bit Score: 209.83 E-value: 6.36e-60
Ras-GTPase Activating Domain of DAB2IP and similar proteins; The DAB2IP family of Ras ...
1249-1525
7.14e-43
Ras-GTPase Activating Domain of DAB2IP and similar proteins; The DAB2IP family of Ras GTPase-activating proteins includes DAB2IP, nGAP, and Syn GAP. Disabled 2 interactive protein, (DAB2IP; also known as ASK-interacting protein 1 (AIP1)), is a member of the GTPase-activating proteins, down-regulates Ras-mediated signal pathways, and mediates TNF-induced activation of ASK1-JNK signaling pathways. The mechanism by which TNF signaling is coupled to DAB2IP is not known.
Pssm-ID: 213338 Cd Length: 324 Bit Score: 160.83 E-value: 7.14e-43
Ras-GTPase Activating Domain of GAP1 and similar proteins; The GAP1 family of Ras ...
1249-1497
1.85e-34
Ras-GTPase Activating Domain of GAP1 and similar proteins; The GAP1 family of Ras GTPase-activating proteins includes GAP1(m) (or RASA2), GAP1_IP4BP (or RASA3), Ca2+ -promoted Ras inactivator (CAPRI, or RASAL4), and Ras GTPase activating-like proteins (RASAL) or RASAL1. The members are characterized by a conserved domain structure comprising N-terminal tandem C2 domains, a highly conserved central RasGAP domain, and a C-terminal pleckstrin homology domain that is associated with a Bruton's tyrosine kinase motif. While this domain structure is conserved, a small change in the function of each individual domain and the interaction between domains has a marked effect on the regulation of each protein.
Pssm-ID: 213330 Cd Length: 269 Bit Score: 134.69 E-value: 1.85e-34
Ras-GTPase Activating Domain of CLA2/BUD2; CLA2/BUD2 functions as a GTPase-activating protein ...
1285-1483
7.16e-34
Ras-GTPase Activating Domain of CLA2/BUD2; CLA2/BUD2 functions as a GTPase-activating protein (GAP) for BUD1/RSR1 and is necessary for proper bud-site selection in yeast. BUD2 has sequence similarity to the catalytic domain of RasGAPs, and stimulates the hydrolysis of BUD1-GTP to BUD1-GDP. Elimination of Bud2p activity by mutation causes a random budding pattern with no growth defect. Overproduction of Bud2p also alters the budding pattern.
Pssm-ID: 213339 [Multi-domain] Cd Length: 356 Bit Score: 135.38 E-value: 7.16e-34
GTPase-activator protein for Ras-like GTPase; All alpha-helical domain that accelerates the ...
1275-1463
7.83e-32
GTPase-activator protein for Ras-like GTPase; All alpha-helical domain that accelerates the GTPase activity of Ras, thereby "switching" it into an "off" position.
Pssm-ID: 459871 Cd Length: 207 Bit Score: 125.09 E-value: 7.83e-32
Ras-GTPase Activating Domain of p120; p120GAP is a negative regulator of Ras that stimulates ...
1215-1522
2.42e-29
Ras-GTPase Activating Domain of p120; p120GAP is a negative regulator of Ras that stimulates hydrolysis of bound GTP to GDP. Once the Ras regulator p120GAP, a member of the GAP protein family, is recruited to the membrane, it is transiently immobilized to interact with Ras-GTP. The down-regulation of Ras by p120GAP is a critical step in the regulation of many cellular processes, which is disrupted in approximately 30% of human cancers. p120GAP contains SH2, SH3, PH, calcium- and lipid-binding domains, suggesting its involvement in a complex network of cellular interactions in vivo.
Pssm-ID: 213340 Cd Length: 328 Bit Score: 121.44 E-value: 2.42e-29
Ras-GTPase Activating Domain of GAPA; GAPA is an IQGAP-related protein and is predicted to ...
1251-1561
1.22e-28
Ras-GTPase Activating Domain of GAPA; GAPA is an IQGAP-related protein and is predicted to bind to small GTPases, which are yet to be identified. IQGAP proteins are integral components of cytoskeletal regulation. Results from truncated GAPAs indicated that almost the entire region of GAPA homologous to IQGAP is required for cytokinesis in Dictyostelium. More members of the IQGAP family are emerging, and evidence suggests that there are both similarities and differences in their function.
Pssm-ID: 213334 Cd Length: 352 Bit Score: 120.15 E-value: 1.22e-28
Divergent CRAL/TRIO domain; This family includes divergent members of the CRAL-TRIO domain ...
1614-1748
1.39e-27
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: 110.11 E-value: 1.39e-27
Ras-GTPase Activating Domain of RASA3; RASA3 (or GAP1_IP4BP) is a member of the GAP1 family ...
1214-1496
1.66e-26
Ras-GTPase Activating Domain of RASA3; RASA3 (or GAP1_IP4BP) is a member of the GAP1 family and has been shown to specifically bind 1,3,4,5-tetrakisphosphate (IP4). Thus, RASA3 may function as an IP4 receptor. The members of GAP1 family are characterized by a conserved domain structure comprising N-terminal tandem C2 domains, a highly conserved central RasGAP domain, and a C-terminal pleckstrin-homology domain that is associated with a Bruton's tyrosine kinase motif. Purified RASA3 stimulates GAP activity on Ras with about a five-fold lower potency than p120RasGAP, but shows no GAP-stimulating activity at all against Rac or Rab3A.
Pssm-ID: 213336 Cd Length: 269 Bit Score: 111.65 E-value: 1.66e-26
Domain in homologues of a S. cerevisiae phosphatidylinositol transfer protein (Sec14p); Domain ...
1595-1739
3.15e-20
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: 89.67 E-value: 3.15e-20
Ras-GTPase Activating Domain of IQ motif containing GTPase activating proteins; This family ...
1268-1530
2.46e-19
Ras-GTPase Activating Domain of IQ motif containing GTPase activating proteins; This family represents IQ motif containing GTPase activating protein (IQGAP) which associated with the Ras GTP-binding protein. A primary function of IQGAP proteins is to modulate cytoskeletal architecture. There are three known IQGAP family members: IQGAP1, IQGAP2 and IQGAP3. Human IQGAP1 and IQGAP2 share 62% identity. IQGAPs are multi-domain molecules having a calponin-homology (CH) domain which binds F-actin, IQGAP-specific repeats, a single WW domain, four IQ motifs that mediate interactions with calmodulin, and a RasGAP related domain that binds active Rho family GTPases. IQGAP is an essential regulator of cytoskeletal function. IQGAP1 negatively regulates Ras family GTPases by stimulating their intrinsic GTPase activity, the protein actually lacks GAP activity. Both IQGAP1 and IQGAP2 specifically bind to Cdc42 and Rac1, but not to RhoA. Despite of their similarities to part of the sequence of RasGAP, neither IQGAP1 nor IQGAP2 interacts with Ras. IQGAP3, only present in mammals, regulates the organization of the cytoskeleton under the regulation of Rac1 and Cdc42 in neuronal cells. The depletion of IQGAP3 is shown to impair neurite or axon outgrowth in neuronal cells with disorganized cytoskeleton.
Pssm-ID: 213329 [Multi-domain] Cd Length: 331 Bit Score: 91.88 E-value: 2.46e-19
Ras-GTPase Activating Domain of RASA2; RASA2 (or GAP1(m)) is a member of the GAP1 family of ...
1276-1469
4.41e-19
Ras-GTPase Activating Domain of RASA2; RASA2 (or GAP1(m)) is a member of the GAP1 family of Ras GTPase-activating proteins that includes GAP1_IP4BP (or RASA3), CAPRI, and RASAL. In vitro, RASA2 has been shown to bind inositol 1,3,4,5-tetrakisphosphate (IP4), the water soluble inositol head group of the lipid second messenger phosphatidylinositol 3,4,5-trisphosphate (PIP3). In vivo studies also demonstrated that RASA2 binds PIP3, and it is recruited to the plasma membrane following agonist stimulation of PI 3-kinase. Furthermore, the membrane translocation is a consequence of the ability of its pleckstrin homology (PH) domain to bind PIP3.
Pssm-ID: 213342 Cd Length: 272 Bit Score: 89.95 E-value: 4.41e-19
Ras-GTPase Activating Domain of RASAL1 and similar proteins; Ras GTPase activating-like ...
1220-1493
5.13e-19
Ras-GTPase Activating Domain of RASAL1 and similar proteins; Ras GTPase activating-like protein (RASAL) or RASAL1 is a member of the GAP1 family, and a Ca2+ sensor responding in-phase to repetitive Ca2+ signals by associating with the plasma membrane and deactivating Ras. It contains a conserved domain structure comprising N-terminal tandem C2 domains, a highly conserved central RasGAP domain, and a C-terminal pleckstrin-homology domain that is associated with a Bruton's tyrosine kinase motif. RASAL, like Ca2+ -promoted Ras inactivator (CAPRI, or RASAL4), is a cytosolic protein that undergoes a rapid translocation to the plasma membrane in response to receptor-mediated elevation in the concentration of intracellular free Ca2+, a translocation that activates its ability to function as a RasGAP. However, unlike RASAL4, RASAL undergoes an oscillatory translocation to the plasma membrane that occurs in synchrony with repetitive Ca2+ spikes.
Pssm-ID: 213337 Cd Length: 287 Bit Score: 90.26 E-value: 5.13e-19
Ras-GTPase Activating Domain of RASA4; Ras GTPase activating-like 4 protein (RASAL4), also ...
1245-1475
8.86e-16
Ras-GTPase Activating Domain of RASA4; Ras GTPase activating-like 4 protein (RASAL4), also known as Ca2+ -promoted Ras inactivator (CAPRI), is a member of the GAP1 family. Members of the GAP1 family are characterized by a conserved domain structure comprising N-terminal tandem C2 domains, a highly conserved central RasGAP domain, and a C-terminal pleckstrin-homology domain that is associated with a Bruton's tyrosine kinase motif. RASAL4, like RASAL, is a cytosolic protein that undergoes a rapid translocation to the plasma membrane in response to a receptor-mediated elevation in the concentration of intracellular free Ca2+ ([Ca2+]i). However, unlike RASAL, RASAL4 does not sense oscillations in [Ca2+]i.
Pssm-ID: 213343 [Multi-domain] Cd Length: 287 Bit Score: 80.69 E-value: 8.86e-16
Ras-GTPase Activating Domain of IQ motif containing GTPase activating protein 3; This family ...
1328-1574
1.12e-15
Ras-GTPase Activating Domain of IQ motif containing GTPase activating protein 3; This family represents the IQ motif containing GTPase activating protein 3 (IQGAP3), which associates with Ras GTP-binding proteins. A primary function of IQGAP proteins is to modulate cytoskeletal architecture. There are three known IQGAP family members: IQGAP1, IQGAP2 and IQGAP3. Human IQGAP1 and IQGAP2 share 62% identity. IQGAPs are multi-domain molecules having a calponin-homology (CH) domain which binds F-actin, IQGAP-specific repeats, a single WW domain, four IQ motifs that mediate interactions with calmodulin, and a RasGAP related domain that binds active Rho family GTPases. IQGAP is an essential regulator of cytoskeletal function. IQGAP1 negatively regulates Ras family GTPases by stimulating their intrinsic GTPase activity, the protein actually lacks GAP activity. Both IQGAP1 and IQGAP2 specifically bind to Cdc42 and Rac1, but not to RhoA. Despite of their similarities to part of the sequence of RasGAP, neither IQGAP1 nor IQGAP2 interacts with Ras. IQGAP3, only present in mammals, regulates the organization of the cytoskeleton under the regulation of Rac1 and Cdc42 in neuronal cells. The depletion of IQGAP3 is shown to impair neurite or axon outgrowth in neuronal cells with disorganized cytoskeleton.
Pssm-ID: 213346 [Multi-domain] Cd Length: 350 Bit Score: 81.41 E-value: 1.12e-15
Ras-GTPase Activating Domain of IQ motif containing GTPase activating protein 1; IQGAP1 is a ...
1254-1531
2.85e-15
Ras-GTPase Activating Domain of IQ motif containing GTPase activating protein 1; IQGAP1 is a homodimeric protein that is widely expressed among vertebrate cell types from early embryogenesis. Mammalian IQGAP1 protein is the best characterized member of the IQGAP family, and contains several protein-interacting domains. Human IQGAP1 is most similar to mouse Iqgap1 (94% identity) and has 62% identity to human IQGAP2. IQGAP1 binds and cross-links actin filaments in vitro and has been implicated in Ca2+/calmodulin signaling, E-cadherin-dependent cell adhesion, cell motility, and invasion. Yeast IQGAP homologs have a role in the recruitment of actin filaments, are components of the spindle pole body, and are required for actomyosin ring assembly and cytokinesis. Furthermore, IQGAP1 over-expression has also been detected in gastric and colorectal carcinomas and gastric cancer cell lines.
Pssm-ID: 213335 Cd Length: 380 Bit Score: 80.47 E-value: 2.85e-15
Ras-GTPase Activating Domain of IQ motif containing GTPase activating protein 2; IQGAP2 is a ...
1254-1530
1.52e-14
Ras-GTPase Activating Domain of IQ motif containing GTPase activating protein 2; IQGAP2 is a member of the IQGAP family that contains a calponin-homology (CH) domain which binds F-actin, IQGAP-specific repeat, a single WW domain, four IQ motifs which mediate interactions with calmodulin, and a Ras-GTPase-activating protein (GAP)-related domain that binds Rho family GTPases. IQGAP2 and IQGAP3 play important roles in the regulation of the cytoskeleton for axon outgrowth in hippocampal neurons and are thought to stay in a common regulatory pathway. The results of RNA interference studies indicated that IQGAP3 partially compensates functions of IQGAP2, but has lesser ability than IQGAP2 to promote axon outgrowth in hippocampal neuron. Moreover, IQGAP2 is required for the cadherin-mediated cell-to-cell adhesion in Xenopus laevis embryos.
Pssm-ID: 213333 [Multi-domain] Cd Length: 359 Bit Score: 78.11 E-value: 1.52e-14
Sec14p-like lipid-binding domain; Sec14p-like lipid-binding domains are found in secretory ...
1594-1740
5.49e-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: 71.98 E-value: 5.49e-14
Ras-GTPase Activating Domain of Rab5-activating protein 6; Rab5-activating protein 6 (RAP6) is ...
1251-1485
3.87e-07
Ras-GTPase Activating Domain of Rab5-activating protein 6; Rab5-activating protein 6 (RAP6) is an endosomal protein with a role in the regulation of receptor-mediated endocytosis. RAP6 contains a Vps9 domain, which is involved in the activation of Rab5, and a Ras GAP domain (RGD). Rab5 is a small GTPase required for the control of the endocytic route, and its activity is regulated by guanine nucleotide exchange factor, such as Rabex5, and GAPs, such as RN-tre. Human Rap6 protein is localized on the plasma membrane and on the endosome. RAP6 binds to Rab5 and Ras through the Vps9 and RGD domains, respectively.
Pssm-ID: 213331 Cd Length: 365 Bit Score: 55.04 E-value: 3.87e-07
Database: CDSEARCH/cdd Low complexity filter: no Composition Based Adjustment: yes E-value threshold: 0.01
References:
Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
of the residues that compose this conserved feature have been mapped to the query sequence.
Click on the triangle to view details about the feature, including a multiple sequence alignment
of your query sequence and the protein sequences used to curate the domain model,
where hash marks (#) above the aligned sequences show the location of the conserved feature residues.
The thumbnail image, if present, provides an approximate view of the feature's location in 3 dimensions.
Click on the triangle for interactive 3D structure viewing options.
Functional characterization of the conserved domain architecture found on the query.
Click here to see more details.
This image shows a graphical summary of conserved domains identified on the query sequence.
The Show Concise/Full Display button at the top of the page can be used to select the desired level of detail: only top scoring hits
(labeled illustration) or all hits
(labeled illustration).
Domains are color coded according to superfamilies
to which they have been assigned. Hits with scores that pass a domain-specific threshold
(specific hits) are drawn in bright colors.
Others (non-specific hits) and
superfamily placeholders are drawn in pastel colors.
if a domain or superfamily has been annotated with functional sites (conserved features),
they are mapped to the query sequence and indicated through sets of triangles
with the same color and shade of the domain or superfamily that provides the annotation. Mouse over the colored bars or triangles to see descriptions of the domains and features.
click on the bars or triangles to view your query sequence embedded in a multiple sequence alignment of the proteins used to develop the corresponding domain model.
The table lists conserved domains identified on the query sequence. Click on the plus sign (+) on the left to display full descriptions, alignments, and scores.
Click on the domain model's accession number to view the multiple sequence alignment of the proteins used to develop the corresponding domain model.
To view your query sequence embedded in that multiple sequence alignment, click on the colored bars in the Graphical Summary portion of the search results page,
or click on the triangles, if present, that represent functional sites (conserved features)
mapped to the query sequence.
Concise Display shows only the best scoring domain model, in each hit category listed below except non-specific hits, for each region on the query sequence.
(labeled illustration) Standard Display shows only the best scoring domain model from each source, in each hit category listed below for each region on the query sequence.
(labeled illustration) Full Display shows all domain models, in each hit category below, that meet or exceed the RPS-BLAST threshold for statistical significance.
(labeled illustration) Four types of hits can be shown, as available,
for each region on the query sequence:
specific hits meet or exceed a domain-specific e-value threshold
(illustrated example)
and represent a very high confidence that the query sequence belongs to the same protein family as the sequences use to create the domain model
non-specific hits
meet or exceed the RPS-BLAST threshold for statistical significance (default E-value cutoff of 0.01, or an E-value selected by user via the
advanced search options)
the domain superfamily to which the specific and non-specific hits belong
multi-domain models that were computationally detected and are likely to contain multiple single domains
Retrieve proteins that contain one or more of the domains present in the query sequence, using the Conserved Domain Architecture Retrieval Tool
(CDART).
Modify your query to search against a different database and/or use advanced search options
