Ras GTPase-activating protein accelerates the GTPase activity of Ras| RasGAP (Ras GTPase-activating protein) domain-containing protein may function as an enhancer of the hydrolysis of GTP that is bound to Ras-GTPases; similar to mammalian plexins
Ras-GTPase Activating Domain of IQ motif containing GTPase activating protein 2; IQGAP2 is a ...
412-770
0e+00
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.
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Pssm-ID: 213333 [Multi-domain] Cd Length: 359 Bit Score: 711.00 E-value: 0e+00
Ras-GTPase Activating Domain of IQ motif containing GTPase activating protein 2; IQGAP2 is a ...
412-770
0e+00
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: 711.00 E-value: 0e+00
GTPase-activator protein for Ras-like GTPases; All alpha-helical domain that accelerates the ...
401-730
2.91e-92
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: 298.45 E-value: 2.91e-92
GTPase-activator protein for Ras-like GTPase; All alpha-helical domain that accelerates the ...
434-646
3.97e-74
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: 243.73 E-value: 3.97e-74
RasGAP C-terminus; This domain can be found in the C terminus of the IQGAP family members, ...
863-995
2.82e-46
RasGAP C-terminus; This domain can be found in the C terminus of the IQGAP family members, including human IQGAP1/2/3, S. cerevisiae Iqg1 and S. pombe Rng2. Some members function in cytoskeletal remodelling. Human IQGAP1 is a scaffolding protein that can assemble multi-protein complexes involved in cell-cell interaction, cell adherence, and movement via actin/tubulin-based cytoskeletal reorganization. IQGAP1 is also a regulator of the MAPK and Wnt/beta-catenin signaling pathways.Iqg1 and Rng2 are required for actomyosin ring construction during cytokinesis.
Pssm-ID: 461071 Cd Length: 137 Bit Score: 162.33 E-value: 2.82e-46
Ras-GTPase Activating Domain of IQ motif containing GTPase activating protein 2; IQGAP2 is a ...
412-770
0e+00
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: 711.00 E-value: 0e+00
Ras-GTPase Activating Domain of IQ motif containing GTPase activating protein 1; IQGAP1 is a ...
412-793
0e+00
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: 570.06 E-value: 0e+00
Ras-GTPase Activating Domain of IQ motif containing GTPase activating proteins; This family ...
422-752
0e+00
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: 536.01 E-value: 0e+00
Ras-GTPase Activating Domain of IQ motif containing GTPase activating protein 3; This family ...
412-759
4.05e-172
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: 508.21 E-value: 4.05e-172
GTPase-activator protein for Ras-like GTPases; All alpha-helical domain that accelerates the ...
401-730
2.91e-92
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: 298.45 E-value: 2.91e-92
GTPase-activator protein for Ras-like GTPase; All alpha-helical domain that accelerates the ...
434-646
3.97e-74
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: 243.73 E-value: 3.97e-74
Ras-GTPase Activating Domain of GAPA; GAPA is an IQGAP-related protein and is predicted to ...
410-731
3.90e-59
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: 207.21 E-value: 3.90e-59
RasGAP C-terminus; This domain can be found in the C terminus of the IQGAP family members, ...
863-995
2.82e-46
RasGAP C-terminus; This domain can be found in the C terminus of the IQGAP family members, including human IQGAP1/2/3, S. cerevisiae Iqg1 and S. pombe Rng2. Some members function in cytoskeletal remodelling. Human IQGAP1 is a scaffolding protein that can assemble multi-protein complexes involved in cell-cell interaction, cell adherence, and movement via actin/tubulin-based cytoskeletal reorganization. IQGAP1 is also a regulator of the MAPK and Wnt/beta-catenin signaling pathways.Iqg1 and Rng2 are required for actomyosin ring construction during cytokinesis.
Pssm-ID: 461071 Cd Length: 137 Bit Score: 162.33 E-value: 2.82e-46
Ras GTPase Activating Domain; RasGAP functions as an enhancer of the hydrolysis of GTP that is ...
427-680
3.78e-40
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: 149.18 E-value: 3.78e-40
Ras-GTPase Activating Domain of proteins similar to neurofibromin; Neurofibromin-like proteins ...
414-689
7.36e-33
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: 130.10 E-value: 7.36e-33
Ras-GTPase Activating Domain of proteins related to IQGAPs; RasGAP: Ras-GTPase Activating ...
408-728
2.69e-27
Ras-GTPase Activating Domain of proteins related to IQGAPs; RasGAP: 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. Although the Rho (Ras homolog) GTPases are most closely related to members of the Ras family, RhoGAP and RasGAP show no sequence homology at their amino acid level. RasGTPases function as molecular switches in a myriad of signaling pathways. When bound to GTP they are in the on state and when bound to GDP they are in the off state. The RasGap domain speeds up the hydrolysis of GTP in Ras-like proteins acting as a negative regulator.
Pssm-ID: 213345 [Multi-domain] Cd Length: 359 Bit Score: 114.73 E-value: 2.69e-27
Ras-GTPase Activating Domain of neurofibromin; Neurofibromin is the product of the ...
539-726
8.11e-14
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: 73.90 E-value: 8.11e-14
Ras-GTPase Activating Domain of Rab5-activating protein 6; Rab5-activating protein 6 (RAP6) is ...
377-686
7.33e-09
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: 58.89 E-value: 7.33e-09
Ras-GTPase Activating Domain of p120; p120GAP is a negative regulator of Ras that stimulates ...
542-696
5.25e-08
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: 55.96 E-value: 5.25e-08
Ras-GTPase Activating Domain of GAP1 and similar proteins; The GAP1 family of Ras ...
430-643
2.58e-07
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: 53.41 E-value: 2.58e-07
Ras-GTPase Activating Domain of CLA2/BUD2; CLA2/BUD2 functions as a GTPase-activating protein ...
534-682
2.84e-07
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: 53.72 E-value: 2.84e-07
Ras-GTPase Activating Domain of RASAL1 and similar proteins; Ras GTPase activating-like ...
477-642
2.33e-06
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: 50.58 E-value: 2.33e-06
Ras-GTPase Activating Domain of DAB2IP and similar proteins; The DAB2IP family of Ras ...
546-731
8.18e-05
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: 46.04 E-value: 8.18e-05
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.
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