RhoGAP_Graf: GTPase-activator protein (GAP) domain for Rho-like GTPases found in GRAF (GTPase regulator associated with focal adhesion kinase); Graf is a multi-domain protein, containing SH3 and PH domains, that binds focal adhesion kinase and influences cytoskeletal changes mediated by Rho proteins. Graf exhibits GAP activity toward RhoA and Cdc42, but only weakly activates Rac1. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755565821 118 MDGKEPIYHTPITKQ----EEMELNEVGFKFVRKCINFIETKGIKTEGLYRTVGSNIQVQKLLYAFFDPK--CPGDVDFH 191
Cdd:cd04374    1 MDGKEPVYHSPGRLQseveGEAQLDDIGFKFVRKCIEAVETRGINEQGLYRVVGVNSKVQKLLSLGLDPKtsTPGDVDLD 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755565821 192 NSDWDIKTITSSLKFYLRNLSEPVMTYKLHKELVSAAKSDNLDYRLGAIHSLVYKLPEKNREMLELLIKHLVNVCEHSKE 271
Cdd:cd04374   81 NSEWEIKTITSALKTYLRNLPEPLMTYELHNDFINAAKSENLESRVNAIHSLVHKLPEKNREMLELLIKHLTNVSDHSKK 160

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|...
gi 755565821 272 NLMTPSNMGVIFGPTLMRAQEDTVAAMMNIKFQNIVVEILIEH 314
Cdd:cd04374  161 NLMTVSNLGVVFGPTLLRPQEETVAAIMDIKFQNIVVEILIEN 203

RhoGAP_Graf: GTPase-activator protein (GAP) domain for Rho-like GTPases found in GRAF (GTPase regulator associated with focal adhesion kinase); Graf is a multi-domain protein, containing SH3 and PH domains, that binds focal adhesion kinase and influences cytoskeletal changes mediated by Rho proteins. Graf exhibits GAP activity toward RhoA and Cdc42, but only weakly activates Rac1. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755565821 118 MDGKEPIYHTPITKQ----EEMELNEVGFKFVRKCINFIETKGIKTEGLYRTVGSNIQVQKLLYAFFDPK--CPGDVDFH 191
Cdd:cd04374    1 MDGKEPVYHSPGRLQseveGEAQLDDIGFKFVRKCIEAVETRGINEQGLYRVVGVNSKVQKLLSLGLDPKtsTPGDVDLD 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755565821 192 NSDWDIKTITSSLKFYLRNLSEPVMTYKLHKELVSAAKSDNLDYRLGAIHSLVYKLPEKNREMLELLIKHLVNVCEHSKE 271
Cdd:cd04374   81 NSEWEIKTITSALKTYLRNLPEPLMTYELHNDFINAAKSENLESRVNAIHSLVHKLPEKNREMLELLIKHLTNVSDHSKK 160

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|...
gi 755565821 272 NLMTPSNMGVIFGPTLMRAQEDTVAAMMNIKFQNIVVEILIEH 314
Cdd:cd04374  161 NLMTVSNLGVVFGPTLLRPQEETVAAIMDIKFQNIVVEILIEN 203

GTPase Regulator Associated with Focal adhesion and related proteins Pleckstrin homology (PH) domain; This hierarchy contains GRAF family members: OPHN1/oligophrenin1, GRAF1 (also called ARHGAP26/Rho GTPase activating protein 26), GRAF2 (also called ARHGAP10/ARHGAP42), AK057372, and LOC129897, all of which are members of the APPL family. OPHN1 is a RhoGAP involved in X-linked mental retardation, epilepsy, rostral ventricular enlargement, and cerebellar hypoplasia. Affected individuals have morphological abnormalities of their brain with enlargement of the cerebral ventricles and cerebellar hypoplasia. OPHN1 negatively regulates RhoA, Cdc42, and Rac1 in neuronal and non-neuronal cells. GRAF1 sculpts the endocytic membranes of the CLIC/GEEC (clathrin-independent carriers/GPI-enriched early endosomal compartments) endocytic pathway. It strongly interacts with dynamin and inhibition of dynamin abolishes CLIC/GEEC endocytosis. GRAF2, GRAF3 and oligophrenin are likely to play similar roles during clathrin-independent endocytic events. GRAF1 mutations are linked to leukaemia. All members are composed of a N-terminal BAR-PH domain, followed by a RhoGAP domain, a proline rich region, and a C-terminal SH3 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755565821  22 TIEGYLYTQEKWALGISWAKYYCRYEKETRMLTMIPMEQKPGAK-QGPVDLTLKYCVRRKTESIDKRFCFDIETNERPGT 100
Cdd:cd01249    1 TKEGYLYLQEKKPLGSTWTKHYCTYRKESKMFTMIPYNQQSSGKlGTTEVVTLKSCVRRKTDSIDRRFCFDIEVVDRPTV 80

                         90       100
                 ....*....|....*....|....*
gi 755565821 101 ITLQAPSEANRRLWMEAMDGKEPIY 125
Cdd:cd01249   81 LTLQALSEEDRKLWLEAMDGKEPIY 105

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755565821    21 PTIEGYLYTQEKWALGiSWAKYYCRYeKETRMLTMIPMEQKPGAK-QGPVDLTLKYCVRR-KTESIDKRFCFDIETNERp 98
Cdd:smart00233   1 VIKEGWLYKKSGGGKK-SWKKRYFVL-FNSTLLYYKSKKDKKSYKpKGSIDLSGCTVREApDPDSSKKPHCFEIKTSDR- 77

                           90       100
                   ....*....|....*....|
gi 755565821    99 GTITLQAPSEANRRLWMEAM 118
Cdd:smart00233  78 KTLLLQAESEEEREKWVEAL 97

RhoGAP_Graf: GTPase-activator protein (GAP) domain for Rho-like GTPases found in GRAF (GTPase regulator associated with focal adhesion kinase); Graf is a multi-domain protein, containing SH3 and PH domains, that binds focal adhesion kinase and influences cytoskeletal changes mediated by Rho proteins. Graf exhibits GAP activity toward RhoA and Cdc42, but only weakly activates Rac1. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755565821 118 MDGKEPIYHTPITKQ----EEMELNEVGFKFVRKCINFIETKGIKTEGLYRTVGSNIQVQKLLYAFFDPK--CPGDVDFH 191
Cdd:cd04374    1 MDGKEPVYHSPGRLQseveGEAQLDDIGFKFVRKCIEAVETRGINEQGLYRVVGVNSKVQKLLSLGLDPKtsTPGDVDLD 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755565821 192 NSDWDIKTITSSLKFYLRNLSEPVMTYKLHKELVSAAKSDNLDYRLGAIHSLVYKLPEKNREMLELLIKHLVNVCEHSKE 271
Cdd:cd04374   81 NSEWEIKTITSALKTYLRNLPEPLMTYELHNDFINAAKSENLESRVNAIHSLVHKLPEKNREMLELLIKHLTNVSDHSKK 160

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|...
gi 755565821 272 NLMTPSNMGVIFGPTLMRAQEDTVAAMMNIKFQNIVVEILIEH 314
Cdd:cd04374  161 NLMTVSNLGVVFGPTLLRPQEETVAAIMDIKFQNIVVEILIEN 203

GTPase Regulator Associated with Focal adhesion and related proteins Pleckstrin homology (PH) domain; This hierarchy contains GRAF family members: OPHN1/oligophrenin1, GRAF1 (also called ARHGAP26/Rho GTPase activating protein 26), GRAF2 (also called ARHGAP10/ARHGAP42), AK057372, and LOC129897, all of which are members of the APPL family. OPHN1 is a RhoGAP involved in X-linked mental retardation, epilepsy, rostral ventricular enlargement, and cerebellar hypoplasia. Affected individuals have morphological abnormalities of their brain with enlargement of the cerebral ventricles and cerebellar hypoplasia. OPHN1 negatively regulates RhoA, Cdc42, and Rac1 in neuronal and non-neuronal cells. GRAF1 sculpts the endocytic membranes of the CLIC/GEEC (clathrin-independent carriers/GPI-enriched early endosomal compartments) endocytic pathway. It strongly interacts with dynamin and inhibition of dynamin abolishes CLIC/GEEC endocytosis. GRAF2, GRAF3 and oligophrenin are likely to play similar roles during clathrin-independent endocytic events. GRAF1 mutations are linked to leukaemia. All members are composed of a N-terminal BAR-PH domain, followed by a RhoGAP domain, a proline rich region, and a C-terminal SH3 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755565821  22 TIEGYLYTQEKWALGISWAKYYCRYEKETRMLTMIPMEQKPGAK-QGPVDLTLKYCVRRKTESIDKRFCFDIETNERPGT 100
Cdd:cd01249    1 TKEGYLYLQEKKPLGSTWTKHYCTYRKESKMFTMIPYNQQSSGKlGTTEVVTLKSCVRRKTDSIDRRFCFDIEVVDRPTV 80

                         90       100
                 ....*....|....*....|....*
gi 755565821 101 ITLQAPSEANRRLWMEAMDGKEPIY 125
Cdd:cd01249   81 LTLQALSEEDRKLWLEAMDGKEPIY 105

RhoGAP domain; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755565821  143 KFVRKCINFIETKGIKTEGLYRTVGSNIQVQKLLYAFfdpKCPGDVDFHNSDWDIKTITSSLKFYLRNLSEPVMTYKLHK 222
Cdd:pfam00620   2 LIVRKCVEYLEKRGLDTEGIFRVSGSASRIKELREAF---DRGPDVDLDLEEEDVHVVASLLKLFLRELPEPLLTFELYE 78

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 755565821  223 ELVSAAKSDNLDYRLGAIHSLVYKLPEKNREMLELLIKHLVNVCEHSKENLMTPSNMGVIFGPTLMR 289
Cdd:pfam00620  79 EFIEAAKLPDEEERLEALRELLRKLPPANRDTLRYLLAHLNRVAQNSDVNKMNAHNLAIVFGPTLLR 145

RhoGAP_chimaerin: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of chimaerins. Chimaerins are a family of phorbolester- and diacylglycerol-responsive GAPs specific for the Rho-like GTPase Rac. Chimaerins exist in two alternative splice forms that each contain a C-terminal GAP domain, and a central C1 domain which binds phorbol esters, inducing a conformational change that activates the protein; one splice form is lacking the N-terminal Src homology-2 (SH2) domain. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755565821 145 VRKCINFIETKGIKTEGLYRTVGSNIQVQKLLYAFfdpkcpgDVDFHNSDW------DIKTITSSLKFYLRNLSEPVMTY 218
Cdd:cd04372   20 VDMCIREIEARGLQSEGLYRVSGFAEEIEDVKMAF-------DRDGEKADIsatvypDINVITGALKLYFRDLPIPVITY 92

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755565821 219 KLHKELVSAAKSDNLDYRLGAIHSLVYKLPEKNREMLELLIKHLVNVCEHSKENLMTPSNMGVIFGPTLMRA-QEDTVAA 297
Cdd:cd04372   93 DTYPKFIDAAKISNPDERLEAVHEALMLLPPAHYETLRYLMEHLKRVTLHEKDNKMNAENLGIVFGPTLMRPpEDSALTT 172

                        170
                 ....*....|....*..
gi 755565821 298 MMNIKFQNIVVEILIEH 314
Cdd:cd04372  173 LNDMRYQILIVQLLITN 189

RhoGAP_ARAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in ARAPs. ARAPs (also known as centaurin deltas) contain, besides the RhoGAP domain, an Arf GAP, ankyrin repeat ras-associating, and PH domains. Since their ArfGAP activity is PIP3-dependent, ARAPs are considered integration points for phosphoinositide, Arf and Rho signaling. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755565821 145 VRKCINFIETKGIKTEGLYRTVGSNIQVQKLLYAFfdPKCPGDVDFHNSDWDIKTITSSLKFYLRNLSEPVMTYKLHKEL 224
Cdd:cd04385   19 VDKCIDFITQHGLMSEGIYRKNGKNSSVKKLLEAF--RKDARSVQLREGEYTVHDVADVLKRFLRDLPDPLLTSELHAEW 96

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755565821 225 VSAAKSDNLDYRLGAIHSLVYKLPEKNREMLELLIKHLVNVCEHSKENLMTPSNMGVIFGPTLMRAQEDTVA-AMMNIKf 303
Cdd:cd04385   97 IEAAELENKDERIARYKELIRRLPPINRATLKVLIGHLYRVQKHSDENQMSVHNLALVFGPTLFQTDEHSVGqTSHEVK- 175

                        170
                 ....*....|..
gi 755565821 304 qniVVEILIEHF 315
Cdd:cd04385  176 ---VIEDLIDNY 184

RhoGAP_ARHGAP21: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP21-like proteins. ArhGAP21 is a multi-domain protein, containing RhoGAP, PH and PDZ domains, and is believed to play a role in the organization of the cell-cell junction complex. It has been shown to function as a GAP of Cdc42 and RhoA, and to interact with alpha-catenin and Arf6. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755565821 144 FVRKCINFIETKGIKTEGLYRTVGSNIQVQKLLYAFfdPKCPGDVDFHNSDW-DIKTITSSLKFYLRNLSEPVMTYKLHK 222
Cdd:cd04395   21 IVEVCCNIVEARGLETVGIYRVPGNNAAISALQEEL--NRGGFDIDLQDPRWrDVNVVSSLLKSFFRKLPEPLFTNELYP 98

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755565821 223 ELVSAAKSDNLDYRLGAIHSLVYKLPEKNREMLELLIKHLVNVCEHSKENLMTPSNMGVIFGPTLMRAQEDTVAAMM-NI 301
Cdd:cd04395   99 DFIEANRIEDPVERLKELRRLIHSLPDHHYETLKHLIRHLKTVADNSEVNKMEPRNLAIVFGPTLVRTSDDNMETMVtHM 178

                        170
                 ....*....|...
gi 755565821 302 KFQNIVVEILIEH 314
Cdd:cd04395  179 PDQCKIVETLIQH 191

RhoGAP_MgcRacGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in MgcRacGAP proteins. MgcRacGAP plays an important dual role in cytokinesis: i) it is part of centralspindlin-complex, together with the mitotic kinesin MKLP1, which is critical for the structure of the central spindle by promoting microtuble bundling. ii) after phosphorylation by aurora B MgcRacGAP becomes an effective regulator of RhoA and plays an important role in the assembly of the contractile ring and the initiation of cytokinesis. MgcRacGAP-like proteins contain a N-terminal C1-like domain, and a C-terminal RhoGAP domain. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755565821 144 FVRKCINFIETKGIKTEGLYRTVGSNIQVQKLLYAFFDPKCPGDVdfhnSDWDIKTITSSLKFYLRNLSEPVMTYKLHKE 223
Cdd:cd04382   20 LIVHCVNEIEARGLTEEGLYRVSGSEREVKALKEKFLRGKTVPNL----SKVDIHVICGCLKDFLRSLKEPLITFALWKE 95

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755565821 224 LVSAAK-SDNLDYRLgAIHSLVYKLPEKNREMLELLIKHLVNVCEhSKENLMTPSNMGVIFGPTLM---RAQEDTVAAMM 299
Cdd:cd04382   96 FMEAAEiLDEDNSRA-ALYQAISELPQPNRDTLAFLILHLQRVAQ-SPECKMDINNLARVFGPTIVgysVPNPDPMTILQ 173

                        170
                 ....*....|....
gi 755565821 300 NIKFQNIVVEILIE 313
Cdd:cd04382  174 DTVRQPRVVERLLE 187

RhoGAP_p190: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of p190-like proteins. p190, also named RhoGAP5, plays a role in neuritogenesis and axon branch stability. p190 shows a preference for Rho, over Rac and Cdc42, and consists of an N-terminal GTPase domain and a C-terminal GAP domain. The central portion of p190 contains important regulatory phosphorylation sites. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755565821 144 FVRKCINFIETKGIKTEGLYRTVGSNIQVQKLLYAFFDPkcpGDVDFHNSDWDIKTITSSLKFYLRNLSEPVMTYKLHKE 223
Cdd:cd04373   18 FLEKCVEFIEATGLETEGIYRVSGNKTHLDSLQKQFDQD---HNLDLVSKDFTVNAVAGALKSFFSELPDPLIPYSMHLE 94

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755565821 224 LVSAAKSDNLDYRLGAIHSLVYKLPEKNREMLELLIKHLVNVCEHSKENLMTPSNMGVIFGPTLMRAQEDTVAAMMNIKF 303
Cdd:cd04373   95 LVEAAKINDREQRLHALKELLKKFPPENFDVFKYVITHLNKVSQNSKVNLMTSENLSICFWPTLMRPDFTSMEALSATRI 174

                 ....*....
gi 755565821 304 QNIVVEILI 312
Cdd:cd04373  175 YQTIIETFI 183

RhoGAP_myosin_IX: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in class IX myosins. Class IX myosins contain a characteristic head domain, a neck domain, a tail domain which contains a C6H2-zinc binding motif and a RhoGAP domain. Class IX myosins are single-headed, processive myosins that are partly cytoplasmic, and partly associated with membranes and the actin cytoskeleton. Class IX myosins are implicated in the regulation of neuronal morphogenesis and function of sensory systems, like the inner ear. There are two major isoforms, myosin IXA and IXB with several splice variants, which are both expressed in developing neurons. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755565821 145 VRKCINFIETKGIKTEGLYRTVGSNIQVQKLLYAFfdPKCPGDVDFhnSDWDIKTITSSLKFYLRNLSEPVMTYKLHKEL 224
Cdd:cd04377   19 LEKLLEHIEMHGLYTEGIYRKSGSANKIKELRQGL--DTDPDSVNL--EDYPIHVITSVLKQWLRELPEPLMTFELYENF 94

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755565821 225 VSAAKSDNLDYRLGAIHSLVYKLPEKNREMLELLIKHLVNVCEHSKENLMTPSNMGVIFGPTLMRAQE--DTVAAMMNIK 302
Cdd:cd04377   95 LRAMELEEKQERVRALYSVLEQLPRANLNTLERLIFHLVRVALQEEVNRMSANALAIVFAPCILRCPDtaDPLQSLQDVS 174

                        170
                 ....*....|.
gi 755565821 303 FQNIVVEILIE 313
Cdd:cd04377  175 KTTTCVETLIK 185

RhoGAP_GMIP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of GMIP (Gem interacting protein). GMIP plays important roles in neurite growth and axonal guidance, and interacts with Gem, a member of the RGK subfamily of the Ras small GTPase superfamily, through the N-terminal half of the protein. GMIP contains a C-terminal RhoGAP domain. GMIP inhibits RhoA function, but is inactive towards Rac1 and Cdc41. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755565821 139 EVGFkFVRKCINFIETKGIKTEGLYRTVGSNIQVQKLLYAFFDPKCPGDVdfhnSDWDIKTITSSLKFYLRNLSEPVMTY 218
Cdd:cd04408   15 EVPF-VVVRCTAEIENRALGVQGIYRISGSKARVEKLCQAFENGRDLVDL----SGHSPHDITSVLKHFLKELPEPVLPF 89

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755565821 219 KLHKELVSAAKS---------DNLDYRLGAIHS---LVYKLPEKNREMLELLIKHLVNVCEHSKENLMTPSNMGVIFGPT 286
Cdd:cd04408   90 QLYDDFIALAKElqrdsekaaESPSIVENIIRSlkeLLGRLPVSNYNTLRHLMAHLYRVAERFEDNKMSPNNLGIVFGPT 169

                        170       180       190
                 ....*....|....*....|....*....|.
gi 755565821 287 LMR---AQEDTVAAMMNIKFQNIVVEILIEH 314
Cdd:cd04408  170 LLRplvGGDVSMICLLDTGYQAQLVEFLISN 200

RhoGAP_myosin_IXB: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in myosins IXB. Class IX myosins contain a characteristic head domain, a neck domain and a tail domain which contains a C6H2-zinc binding motif and a Rho-GAP domain. Class IX myosins are single-headed, processive myosins that are partly cytoplasmic, and partly associated with membranes and the actin cytoskeleton. Class IX myosins are implicated in the regulation of neuronal morphogenesis and function of sensory systems, like the inner ear. There are two major isoforms, myosin IXA and IXB with several splice variants, which are both expressed in developing neurons Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755565821 145 VRKCINFIETKGIKTEGLYRTVGSNIQVQKLLYAFfdPKCPGDVDFHNsdWDIKTITSSLKFYLRNLSEPVMTYKLHKEL 224
Cdd:cd04407   19 LEKLLEHVEMHGLYTEGIYRKSGSANRMKELHQLL--QADPENVKLEN--YPIHAITGLLKQWLRELPEPLMTFAQYNDF 94

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755565821 225 VSAAKSDNLDYRLGAIHSLVYKLPEKNREMLELLIKHLVNVCEHSKENLMTPSNMGVIFGPTLMRAQE--DTVAAMMNIK 302
Cdd:cd04407   95 LRAVELPEKQEQLQAIYRVLEQLPTANHNTLERLIFHLVKVALEEDVNRMSPNALAIVFAPCLLRCPDssDPLTSMKDVA 174

                        170
                 ....*....|
gi 755565821 303 FQNIVVEILI 312
Cdd:cd04407  175 KTTTCVEMLI 184

RhoGAP_ARHGAP22_24_25: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ARHGAP22, 24 and 25-like proteins; longer isoforms of these proteins contain an additional N-terminal pleckstrin homology (PH) domain. ARHGAP25 (KIA0053) has been identified as a GAP for Rac1 and Cdc42. Short isoforms (without the PH domain) of ARHGAP24, called RC-GAP72 and p73RhoGAP, and of ARHGAP22, called p68RacGAP, has been shown to be involved in angiogenesis and endothelial cell capillary formation. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755565821 145 VRKCINFIETKGIKTEGLYRTVGSNIQVQKLLYAFfdpKCpGDVDFHNSDWDIKTITSSLKFYLRNLSEPVMTYKLHKEL 224
Cdd:cd04390   26 VEQCVDFIREHGLKEEGLFRLPGQANLVKQLQDAF---DA-GERPSFDSDTDVHTVASLLKLYLRELPEPVIPWAQYEDF 101

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755565821 225 VSAAKSDNLDYR--LGAIHSLVYKLPEKNREMLELLIKHLVNVCEHSKENLMTPSNMGVIFGPTLMRAQ-EDTVAAMMNI 301
Cdd:cd04390  102 LSCAQLLSKDEEkgLGELMKQVSILPKVNYNLLSYICRFLDEVQSNSSVNKMSVQNLATVFGPNILRPKvEDPATIMEGT 181

                        170
                 ....*....|....*...
gi 755565821 302 KFQNIVVEILIEHFGKIY 319
Cdd:cd04390  182 PQIQQLMTVMISKHEPLF 199

RhoGAP_ARHGAP6: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP6-like proteins. ArhGAP6 shows GAP activity towards RhoA, but not towards Cdc42 and Rac1. ArhGAP6 is often deleted in microphthalmia with linear skin defects syndrome (MLS); MLS is a severe X-linked developmental disorder. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755565821 143 KFVRKCINFIETKGIKTEGLYRTVGSNIQVQKLLYAFfdpKCPGDV--DFHNSDWDIKTItssLKFYLRNLSEPVMTYKL 220
Cdd:cd04376   11 RLVESCCQHLEKHGLQTVGIFRVGSSKKRVRQLREEF---DRGIDVvlDENHSVHDVAAL---LKEFFRDMPDPLLPREL 84

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755565821 221 HKELVSAAKSdNLDYRLGAIHSLVYKLPEKNREMLELLIKHLVNVCEHSKE-----------NLMTPSNMGVIFGPTLMR 289
Cdd:cd04376   85 YTAFIGTALL-EPDEQLEALQLLIYLLPPCNCDTLHRLLKFLHTVAEHAADsidedgqevsgNKMTSLNLATIFGPNLLH 163

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 755565821 290 AQ-------EDTVAAMMNIKFQNIVVEILIEHFGKIYLGPPE 324
Cdd:cd04376  164 KQksgerefVQASLRIEESTAIINVVQTMIDNYEELFMVSPE 205

RhoGap_RalBP1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in RalBP1 proteins, also known as RLIP, RLIP76 or cytocentrin. RalBP1 plays an important role in endocytosis during interphase. During mitosis, RalBP1 transiently associates with the centromere and has been shown to play an essential role in the proper assembly of the mitotic apparatus. RalBP1 is an effector of the Ral GTPase which itself is an effector of Ras. RalBP1 contains a RhoGAP domain, which shows weak activity towards Rac1 and Cdc42, but not towards Ral, and a Ral effector domain binding motif. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755565821 145 VRKCINFIETKGIKTEGLYRTVGSNIQVQKLLYAFFDPKCPgdvdfHNSDWDIKTITSSLKFYLRNLSEPVMTYKLHKEL 224
Cdd:cd04381   24 FRECIDYVEKHGMKCEGIYKVSGIKSKVDELKAAYNRRESP-----NLEEYEPPTVASLLKQYLRELPEPLLTKELMPRF 98

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 755565821 225 VSAAKSDNLDYRLGAIHSLVYKLPEKNREMLELLIKHLVNVCEHSKENLMTPSNMGVIFGPTL 287
Cdd:cd04381   99 EEACGRPTEAEREQELQRLLKELPECNRLLLAWLIVHMDHVIAQELETKMNIQNISIVLSPTV 161

RhoGAP-ARHGAP11A: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP11A-like proteins. The mouse homolog of human ArhGAP11A has been detected as a gene exclusively expressed in immature ganglion cells, potentially playing a role in retinal development. The exact function of ArhGAP11A is unknown. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755565821 143 KFVRKCINFIETKgIKTEGLYRTVGSNIQvQKLLYAFFDPKCPGDVDFHNSDwdiktITSSLKFYLRNLSEPVMTYKLHK 222
Cdd:cd04394   22 KFLVDACTFLLDH-LSTEGLFRKSGSVVR-QKELKAKLEGGEACLSSALPCD-----VAGLLKQFFRELPEPLLPYDLHE 94

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755565821 223 ELVSAAKSDNLDYRLGAIHSLVYKLPEKNREMLELLIKHLVNVCEHSKENLMTPSNMGVIFGPTLMRAQED----TVAAM 298
Cdd:cd04394   95 ALLKAQELPTDEERKSATLLLTCLLPDEHVNTLRYFFSFLYDVAQRCSENKMDSSNLAVIFAPNLFQSEEGgekmSSSTE 174

                        170       180
                 ....*....|....*....|
gi 755565821 299 MNIKFQNIVVEILIEHFGKI 318
Cdd:cd04394  175 KRLRLQAAVVQTLIDNASNI 194