Rho GTPase activating protein 25 and related proteins Pleckstrin homology (PH) domain; RhoGAP25 (also called ArhGap25) like other RhoGaps are involved in cell polarity, cell morphology and cytoskeletal organization. They act as GTPase activators for the Rac-type GTPases by converting them to an inactive GDP-bound state and control actin remodeling by inactivating Rac downstream of Rho leading to suppress leading edge protrusion and promotes cell retraction to achieve cellular polarity and are able to suppress RAC1 and CDC42 activity in vitro. Overexpression of these proteins induces cell rounding with partial or complete disruption of actin stress fibers and formation of membrane ruffles, lamellipodia, and filopodia. This hierarchy contains RhoGAP22, RhoGAP24, and RhoGAP25. Members here contain an N-terminal PH domain followed by a RhoGAP domain and either a BAR or TATA Binding Protein (TBP) Associated Factor 4 (TAF4) 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 1423310317  19 ERPIKMGWLKKQRSIVKNWQQRYFVLRAQQLYYYKDEEDTKPQGCMYLPGCTIKEIATNPEEAGKFVFEIIPASW-DQNR 97
Cdd:cd13263     1 ERPIKSGWLKKQGSIVKNWQQRWFVLRGDQLYYYKDEDDTKPQGTIPLPGNKVKEVPFNPEEPGKFLFEIIPGGGgDRMT 80

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1423310317  98 MGQDSYVLMASSQAEMEEWVKFLRRVAGTPCGAV 131
Cdd:cd13263    81 SNHDSYLLMANSQAEMEEWVKVIRRVIGSPFGGG 114

Rho GTPase activating protein 25 and related proteins Pleckstrin homology (PH) domain; RhoGAP25 (also called ArhGap25) like other RhoGaps are involved in cell polarity, cell morphology and cytoskeletal organization. They act as GTPase activators for the Rac-type GTPases by converting them to an inactive GDP-bound state and control actin remodeling by inactivating Rac downstream of Rho leading to suppress leading edge protrusion and promotes cell retraction to achieve cellular polarity and are able to suppress RAC1 and CDC42 activity in vitro. Overexpression of these proteins induces cell rounding with partial or complete disruption of actin stress fibers and formation of membrane ruffles, lamellipodia, and filopodia. This hierarchy contains RhoGAP22, RhoGAP24, and RhoGAP25. Members here contain an N-terminal PH domain followed by a RhoGAP domain and either a BAR or TATA Binding Protein (TBP) Associated Factor 4 (TAF4) 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 1423310317  19 ERPIKMGWLKKQRSIVKNWQQRYFVLRAQQLYYYKDEEDTKPQGCMYLPGCTIKEIATNPEEAGKFVFEIIPASW-DQNR 97
Cdd:cd13263     1 ERPIKSGWLKKQGSIVKNWQQRWFVLRGDQLYYYKDEDDTKPQGTIPLPGNKVKEVPFNPEEPGKFLFEIIPGGGgDRMT 80

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1423310317  98 MGQDSYVLMASSQAEMEEWVKFLRRVAGTPCGAV 131
Cdd:cd13263    81 SNHDSYLLMANSQAEMEEWVKVIRRVIGSPFGGG 114

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1423310317 152 PILVEKCAEFILEHGRNEEGIFRLPGQDNLVKQLRDAFDAGERPSFD-RDTDVHTVASLLKLYLRDLPEPVVPWSQYEGF 230
Cdd:pfam00620   1 PLIVRKCVEYLEKRGLDTEGIFRVSGSASRIKELREAFDRGPDVDLDlEEEDVHVVASLLKLFLRELPEPLLTFELYEEF 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1423310317 231 LLCGQLTNADEakaQQELMKQL-SILPRDNYSLLSYICRFLHEIQLNCAVNKMSVDNLATVIGVNLIRSKV 300
Cdd:pfam00620  81 IEAAKLPDEEE---RLEALRELlRKLPPANRDTLRYLLAHLNRVAQNSDVNKMNAHNLAIVFGPTLLRPPD 148

PH domain; PH stands for pleckstrin homology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1423310317  21 PIKMGWLKKQRSIVK-NWQQRYFVLRAQQLYYYKDE---EDTKPQGCMYLPGCTIKEIATNPEEAGKFVFEIIPASWDQN 96
Cdd:pfam00169   1 VVKEGWLLKKGGGKKkSWKKRYFVLFDGSLLYYKDDksgKSKEPKGSISLSGCEVVEVVASDSPKRKFCFELRTGERTGK 80

                          90       100
                  ....*....|....*....|....*..
gi 1423310317  97 RmgqdSYVLMASSQAEMEEWVKFLRRV 123
Cdd:pfam00169  81 R----TYLLQAESEEERKDWIKAIQSA 103

helix-rich Mycoplasma protein; Members of this family occur strictly within a subset of Mycoplasma species. Members average 750 amino acids in length, including signal peptide. Sequences are predicted (Jpred 3) to be almost entirely alpha-helical. These sequences show strong periodicity (consistent with long alpha helical structures) and low complexity rich in D,E,N,Q, and K. Genes encoding these proteins are often found in tandem. The function is unknown.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1423310317 522 EEEIDSLQRMVQELRKEIETQKQMYE---EQIKNLEKENYDVWAKVVRLNEELEKEKKKSAALEISLRNMERSREDVEK- 597
Cdd:TIGR04523 411 DEQIKKLQQEKELLEKEIERLKETIIknnSEIKDLTNQDSVKELIIKNLDNTRESLETQLKVLSRSINKIKQNLEQKQKe 490

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1423310317 598 -------------RNKALEEEVKEFVKSMKEPKTE 619
Cdd:TIGR04523 491 lkskekelkklneEKKELEEKVKDLTKKISSLKEK 525

Rho GTPase activating protein 25 and related proteins Pleckstrin homology (PH) domain; RhoGAP25 (also called ArhGap25) like other RhoGaps are involved in cell polarity, cell morphology and cytoskeletal organization. They act as GTPase activators for the Rac-type GTPases by converting them to an inactive GDP-bound state and control actin remodeling by inactivating Rac downstream of Rho leading to suppress leading edge protrusion and promotes cell retraction to achieve cellular polarity and are able to suppress RAC1 and CDC42 activity in vitro. Overexpression of these proteins induces cell rounding with partial or complete disruption of actin stress fibers and formation of membrane ruffles, lamellipodia, and filopodia. This hierarchy contains RhoGAP22, RhoGAP24, and RhoGAP25. Members here contain an N-terminal PH domain followed by a RhoGAP domain and either a BAR or TATA Binding Protein (TBP) Associated Factor 4 (TAF4) 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 1423310317  19 ERPIKMGWLKKQRSIVKNWQQRYFVLRAQQLYYYKDEEDTKPQGCMYLPGCTIKEIATNPEEAGKFVFEIIPASW-DQNR 97
Cdd:cd13263     1 ERPIKSGWLKKQGSIVKNWQQRWFVLRGDQLYYYKDEDDTKPQGTIPLPGNKVKEVPFNPEEPGKFLFEIIPGGGgDRMT 80

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1423310317  98 MGQDSYVLMASSQAEMEEWVKFLRRVAGTPCGAV 131
Cdd:cd13263    81 SNHDSYLLMANSQAEMEEWVKVIRRVIGSPFGGG 114

RhoGAP: GTPase-activator protein (GAP) for Rho-like GTPases; GAPs towards Rho/Rac/Cdc42-like small GTPases. Small GTPases (G proteins) cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when bound to GDP. The Rho family of small G proteins, which includes Cdc42Hs, activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. G proteins 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. The RhoGAPs are one of the major classes of regulators of Rho G proteins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1423310317 152 PILVEKCAEFILEHGRNEEGIFRLPGQDNLVKQLRDAFDAGERPSFDRDTDVHTVASLLKLYLRDLPEPVVPWSQYEGFL 231
Cdd:cd00159     1 PLIIEKCIEYLEKNGLNTEGIFRVSGSASKIEELKKKFDRGEDIDDLEDYDVHDVASLLKLYLRELPEPLIPFELYDEFI 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1423310317 232 LCgqLTNADEAKAQQELMKQLSILPRDNYSLLSYICRFLHEIQLNCAVNKMSVDNLATVIGVNLIRSKVEDPAVIMRgTP 311
Cdd:cd00159    81 EL--AKIEDEEERIEALKELLKSLPPENRDLLKYLLKLLHKISQNSEVNKMTASNLAIVFAPTLLRPPDSDDELLED-IK 157

                         170
                  ....*....|..
gi 1423310317 312 QIQRVMTMMIRD 323
Cdd:cd00159   158 KLNEIVEFLIEN 169

Rho GTPase activating protein 2 Pleckstrin homology (PH) domain; RhoGAP2 (also called RhoGap22 or ArhGap22) are involved in cell polarity, cell morphology and cytoskeletal organization. They activate a GTPase belonging to the RAS superfamily of small GTP-binding proteins. The encoded protein is insulin-responsive, is dependent on the kinase Akt, and requires the Akt-dependent 14-3-3 binding protein which binds sequentially to two serine residues resulting in regulation of cell motility. Members here contain an N-terminal PH domain followed by a RhoGAP domain and either a BAR or TATA Binding Protein (TBP) Associated Factor 4 (TAF4) 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 1423310317  19 ERPIKMGWLKKQRSIVKNWQQRYFVLRAQQLYYYKDEEDTKPQGCMYLPGCTIKEIATNPEEAGKFVFEIIPASW---DQ 95
Cdd:cd13378     1 EGVLKAGWLKKQRSIMKNWQQRWFVLRGDQLFYYKDEEETKPQGCISLQGSQVNELPPNPEEPGKHLFEILPGGAgdrEK 80

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1423310317  96 NRMGQDSYVLMASSQAEMEEWVKFLRRVAGTPCG 129
Cdd:cd13378    81 VPMNHEAFLLMANSQSDMEDWVKAIRRVIWAPFG 114

RhoGAP_FAM13A1a: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of FAM13A1, isoform a-like proteins. The function of FAM13A1a 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 up several orders of magnitude.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1423310317 131 VFGQRLDETvayeQKFG--PHLVPILVEKCAEFILEHGRNEEGIFRLPGQDNLVKQLRDAFDAGERPSFDRDTDVHTVAS 208
Cdd:cd04393     2 VFGVPLQEL----QQAGqpENGVPAVVRHIVEYLEQHGLEQEGLFRVNGNAETVEWLRQRLDSGEEVDLSKEADVCSAAS 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1423310317 209 LLKLYLRDLPEPVVPWSQYEGFLLCGQLTNADEAKAqQELMKQLSILPRDNYSLLSYICRFLHEIQLNCAVNKMSVDNLA 288
Cdd:cd04393    78 LLRLFLQELPEGLIPASLQIRLMQLYQDYNGEDEFG-RKLRDLLQQLPPVNYSLLKFLCHFLSNVASQHHENRMTAENLA 156

                         170
                  ....*....|....*.
gi 1423310317 289 TVIGVNL--IRSKVED 302
Cdd:cd04393   157 AVFGPDVfhVYTDVED 172

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 1423310317 151 VPILVEKCAEFILEHGRNEEGIFRLPGQDNLVKQLRDAFDAGERPSFDRDTDVHTVASLLKLYLRDLPEPVVPWSQYEGF 230
Cdd:cd04376     9 VPRLVESCCQHLEKHGLQTVGIFRVGSSKKRVRQLREEFDRGIDVVLDENHSVHDVAALLKEFFRDMPDPLLPRELYTAF 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1423310317 231 LLCGQLTNADEAKAQQELmkqLSILPRDNYSLLSYICRFLHEIQLNCAV-----------NKMSVDNLATVIGVNLIR-- 297
Cdd:cd04376    89 IGTALLEPDEQLEALQLL---IYLLPPCNCDTLHRLLKFLHTVAEHAADsidedgqevsgNKMTSLNLATIFGPNLLHkq 165

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|.
gi 1423310317 298 ----SKVEDPAVIMRGTPQIQRVMTMMIRDHEVLFPKSKDI 334
Cdd:cd04376   166 ksgeREFVQASLRIEESTAIINVVQTMIDNYEELFMVSPEL 206

RhoGAP-p50rhoGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of p50RhoGAP-like proteins; p50RhoGAP, also known as RhoGAP-1, contains a C-terminal RhoGAP domain and an N-terminal Sec14 domain which binds phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3). It is ubiquitously expressed and preferentially active on Cdc42. This subgroup also contains closely related ARHGAP8. 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 1423310317 147 GPHLVPILVEKCAEFILEHGRNEEGIFRLPGQDNLVKQLRDAFDAGERPSFDRDTDVHTVASLLKLYLRDLPEPVVPWSQ 226
Cdd:cd04404    19 EQEPIPPVVRETVEYLQAHALTTEGIFRRSANTQVVKEVQQKYNMGEPVDFDQYEDVHLPAVILKTFLRELPEPLLTFDL 98

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1423310317 227 YEGFLLCGQLTNADEAKAQQELMKQlsiLPRDNYSLLSYICRFLHEIQLNCAVNKMSVDNLATVIGVNLIRSKveDPAVI 306
Cdd:cd04404    99 YDDIVGFLNVDKEERVERVKQLLQT---LPEENYQVLKYLIKFLVQVSAHSDQNKMTNSNLAVVFGPNLLWAK--DASMS 173

                         170       180
                  ....*....|....*....|..
gi 1423310317 307 MRGTPQIQRVMTMMIRDHEVLF 328
Cdd:cd04404   174 LSAINPINTFTKFLLDHQDEIF 195

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 1423310317 131 VFGQRLDET-VAYEQKFgphlVPILVEKCAEFILEHGRNEEGIFRLPGQDNLVKQLRDAFDAG--ERPSFD-RDTDVHTV 206
Cdd:cd04395     1 TFGVPLDDCpPSSENPY----VPLIVEVCCNIVEARGLETVGIYRVPGNNAAISALQEELNRGgfDIDLQDpRWRDVNVV 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1423310317 207 ASLLKLYLRDLPEPVVPWSQYEGFLLCGQLTNADEAkaQQELMKQLSILPRDNYSLLSYICRFLHEIQLNCAVNKMSVDN 286
Cdd:cd04395    77 SSLLKSFFRKLPEPLFTNELYPDFIEANRIEDPVER--LKELRRLIHSLPDHHYETLKHLIRHLKTVADNSEVNKMEPRN 154

                         170
                  ....*....|..
gi 1423310317 287 LATVIGVNLIRS 298
Cdd:cd04395   155 LAIVFGPTLVRT 166

RhoGAP_KIAA1688: GTPase-activator protein (GAP) domain for Rho-like GTPases found in KIAA1688-like proteins; KIAA1688 is a protein of unknown function that contains a RhoGAP domain and a myosin tail homology 4 (MyTH4) 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 1423310317 132 FGQRLDETVAYEQKFGPHL-VPILVEKCAEFILE-HGRNEEGIFRLPGQDNLVKQLRDAFDAGERPSFDRDtDVHTVASL 209
Cdd:cd04389     1 FGSSLEEIMDRQKEKYPELkLPWILTFLSEKVLAlGGFQTEGIFRVPGDIDEVNELKLRVDQWDYPLSGLE-DPHVPASL 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1423310317 210 LKLYLRDLPEPVVPWSQYEGfllCgqLTNADEAKAQQELMKQLSILprdNYSLLSYICRFLHE--IQLNCAVNKMSVDNL 287
Cdd:cd04389    80 LKLWLRELEEPLIPDALYQQ---C--ISASEDPDKAVEIVQKLPII---NRLVLCYLINFLQVfaQPENVAHTKMDVSNL 151

                         170       180       190
                  ....*....|....*....|....*....|....
gi 1423310317 288 ATVIGVNLIRSKVEDPAVIMRGTPQIQRVMTMMI 321
Cdd:cd04389   152 AMVFAPNILRCTSDDPRVIFENTRKEMSFLRTLI 185

RhoGAP_CdGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of CdGAP-like proteins; CdGAP contains an N-terminal RhoGAP domain and a C-terminal proline-rich region, and it is active on both Cdc42 and Rac1 but not RhoA. CdGAP is recruited to focal adhesions via the interaction with the scaffold protein actopaxin (alpha-parvin). 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 1423310317 151 VPILVEKCAEFILEHGRnEEGIFRLPGQDNLVKQLRDAFDAGERPSFDRDT---DVHTVASLLKLYLRDLPEPVVPWSQY 227
Cdd:cd04384    18 VPQVLKSCTEFIEKHGI-VDGIYRLSGIASNIQRLRHEFDSEQIPDLTKDVyiqDIHSVSSLCKLYFRELPNPLLTYQLY 96

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1423310317 228 EGFLlcgQLTNADEAKAQQELMKQ-LSILPRDNYSLLSYICRFLHEIQLNCAVNKMSVDNLATVIGVNLIRSK 299
Cdd:cd04384    97 EKFS---EAVSAASDEERLEKIHDvIQQLPPPHYRTLEFLMRHLSRLAKYCSITNMHAKNLAIVWAPNLLRSK 166

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 1423310317 132 FGQRLDETVAYEqkfgpHLVPILVEKCAEFILEHGRNEEGIFRLPGQDNLVKQLRDAFDAGERPSFDRDTDVHTVASLLK 211
Cdd:cd04377     1 FGVSLSSLTSED-----RSVPLVLEKLLEHIEMHGLYTEGIYRKSGSANKIKELRQGLDTDPDSVNLEDYPIHVITSVLK 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1423310317 212 LYLRDLPEPVVPWSQYEGFLlcgqltNADEAKAQQELMKQLSI----LPRDNYSLLSYICRFLHEIQLNCAVNKMSVDNL 287
Cdd:cd04377    76 QWLRELPEPLMTFELYENFL------RAMELEEKQERVRALYSvleqLPRANLNTLERLIFHLVRVALQEEVNRMSANAL 149

                         170       180       190
                  ....*....|....*....|....*....|....*..
gi 1423310317 288 ATVIGVNLIRS-KVEDPAVIMRGTPQIQRVMTMMIRD 323
Cdd:cd04377   150 AIVFAPCILRCpDTADPLQSLQDVSKTTTCVETLIKE 186

RhoGAP_srGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in srGAPs. srGAPs are components of the intracellular part of Slit-Robo signalling pathway that is important for axon guidance and cell migration. srGAPs contain an N-terminal FCH domain, a central RhoGAP domain and a C-terminal SH3 domain; this SH3 domain interacts with the intracellular proline-rich-tail of the Roundabout receptor (Robo). This interaction with Robo then activates the rhoGAP domain which in turn inhibits Cdc42 activity. 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 1423310317 132 FGQRLDETVayeqKFGPHLVPILVEKCAEFILEHGRNEEGIFRLPGQDNLVKQLRDAFDAGERPSFD--RDTDVHTVASL 209
Cdd:cd04383     3 FNGSLEEYI----QDSGQAIPLVVESCIRFINLYGLQHQGIFRVSGSQVEVNDIKNAFERGEDPLADdqNDHDINSVAGV 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1423310317 210 LKLYLRDLPEPVVPWSQYEGFLLCGQLTNADEaKAQQeLMKQLSILPRDNYSLLSYICRFLHEIQLNCAVNKMSVDNLAT 289
Cdd:cd04383    79 LKLYFRGLENPLFPKERFEDLMSCVKLENPTE-RVHQ-IREILSTLPRSVIIVMRYLFAFLNHLSQFSDENMMDPYNLAI 156

                  ....*...
gi 1423310317 290 VIGVNLIR 297
Cdd:cd04383   157 CFGPTLMP 164

RhoGAP_ARHGAP27_15_12_9: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ARHGAP27 (also called CAMGAP1), ARHGAP15, 12 and 9-like proteins; This subgroup of ARHGAPs are multidomain proteins that contain RhoGAP, PH, SH3 and WW domains. Most members that are studied show GAP activity towards Rac1, some additionally show activity towards Cdc42. 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 1423310317 146 FGPHL----------VPILVEKCAEFILEHGRNEEGIFRLPGQDNLVKQLRDAFDAGERPSFD--RDTDVHTVASLLKLY 213
Cdd:cd04403     1 FGCHLealcqrenstVPKFVRLCIEAVEKRGLDVDGIYRVSGNLAVIQKLRFAVDHDEKLDLDdsKWEDIHVITGALKLF 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1423310317 214 LRDLPEPVVPWSQYEGFLLCGQLTNA-DEAKAQQELMKQlsiLPRDNYSLLSYICRFLHEIQLNCAVNKMSVDNLATVIG 292
Cdd:cd04403    81 FRELPEPLFPYSLFNDFVAAIKLSDYeQRVSAVKDLIKS---LPKPNHDTLKMLFRHLCRVIEHGEKNRMTTQNLAIVFG 157

                         170       180
                  ....*....|....*....|....*..
gi 1423310317 293 VNLIRSKVE--DPAVIMRGTPQIQRVM 317
Cdd:cd04403   158 PTLLRPEQEtgNIAVHMVYQNQIVELI 184

RhoGAP_fSAC7_BAG7: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of fungal SAC7 and BAG7-like proteins. Both proteins are GTPase activating proteins of Rho1, but differ functionally in vivo: SAC7, but not BAG7, is involved in the control of Rho1-mediated activation of the PKC-MPK1 pathway. 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 1423310317 131 VFGQRLDETVAYEQ-------------KFGphLVPILVEKCAEFILEHGRNEEGIFRLPGQDNLVKQLRDAFDAGER--P 195
Cdd:cd04396     1 VFGVSLEESLKYASvaisivdedgeqyVYG--YIPVVVAKCGVYLKENATEVEGIFRVAGSSKRIRELQLIFSTPPDygK 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1423310317 196 SFDRDT-DVHTVASLLKLYLRDLPEPVVPWSQYEGF-------------LLCGQLTNADEAKAQQELMKQLSI--LPRDN 259
Cdd:cd04396    79 SFDWDGyTVHDAASVLRRYLNNLPEPLVPLDLYEEFrnplrkrprilqyMKGRINEPLNTDIDQAIKEYRDLItrLPNLN 158

                         170       180       190
                  ....*....|....*....|....*....|.
gi 1423310317 260 YSLLSYICRFLHEIQLNCAVNKMSVDNLATV 290
Cdd:cd04396   159 RQLLLYLLDLLAVFARNSDKNLMTASNLAAI 189

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 1423310317 149 HLVPILVEKCaEFILEHgRNEEGIFRLPGQDNLVKQLRDAFDAGErpsfDRDTDVHT--VASLLKLYLRDLPEPVVPWSQ 226
Cdd:cd04394    19 NVPKFLVDAC-TFLLDH-LSTEGLFRKSGSVVRQKELKAKLEGGE----ACLSSALPcdVAGLLKQFFRELPEPLLPYDL 92

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1423310317 227 YEGFLLCGQLTNADEAKAQQELMKQLsiLPRDNYSLLSYICRFLHEIQLNCAVNKMSVDNLATVIGVNLIRS 298
Cdd:cd04394    93 HEALLKAQELPTDEERKSATLLLTCL--LPDEHVNTLRYFFSFLYDVAQRCSENKMDSSNLAVIFAPNLFQS 162

Phosphoinositol 3-phosphate binding proteins 1, 2, and 3 pleckstrin homology (PH) domain; PEPP1 (also called PLEKHA4/PH domain-containing family A member 4 and RHOXF1/Rhox homeobox family member 1), and related homologs PEPP2 (also called PLEKHA5/PH domain-containing family A member 5) and PEPP3 (also called PLEKHA6/PH domain-containing family A member 6), have PH domains that interact specifically with PtdIns(3,4)P3. Other proteins that bind PtdIns(3,4)P3 specifically are: TAPP1 (tandem PH-domain-containing protein-1) and TAPP2], PtdIns3P AtPH1, and Ptd- Ins(3,5)P2 (centaurin-beta2). All of these proteins contain at least 5 of the 6 conserved amino acids that make up the putative phosphatidylinositol 3,4,5- trisphosphate-binding motif (PPBM) located at their N-terminus. 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 1423310317  15 PNPLERPIKMGWLKKQR-SIVKNWQQRYFVLRAQQLYYYKDEEDTKPQGCMYLPGCTIKEIATNPEEAGKFVFEIipasw 93
Cdd:cd13248     1 RDPNAPVVMSGWLHKQGgSGLKNWRKRWFVLKDNCLYYYKDPEEEKALGSILLPSYTISPAPPSDEISRKFAFKA----- 75

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1423310317  94 dqNRMGQDSYVLMASSQAEMEEWVKFLRRVA 124
Cdd:cd13248    76 --EHANMRTYYFAADTAEEMEQWMNAMSLAA 104