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 7661882   38 ERPIKMGWLKKQRSIVKNWQQRYFVLRAQQLYYYKDEEDTKPQGCMYLPGCTIKEIATNPEEAGKFVFEIIPASW-DQNR 116
Cdd:cd13263   1 ERPIKSGWLKKQGSIVKNWQQRWFVLRGDQLYYYKDEDDTKPQGTIPLPGNKVKEVPFNPEEPGKFLFEIIPGGGgDRMT 80

                        90       100       110
                ....*....|....*....|....*....|..
gi 7661882  117 MGQDSYVLMASSQAEMEEWVKFLRRVAGTPCG 148
Cdd:cd13263  81 SNHDSYLLMANSQAEMEEWVKVIRRVIGSPFG 112

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 7661882   38 ERPIKMGWLKKQRSIVKNWQQRYFVLRAQQLYYYKDEEDTKPQGCMYLPGCTIKEIATNPEEAGKFVFEIIPASW-DQNR 116
Cdd:cd13263   1 ERPIKSGWLKKQGSIVKNWQQRWFVLRGDQLYYYKDEDDTKPQGTIPLPGNKVKEVPFNPEEPGKFLFEIIPGGGgDRMT 80

                        90       100       110
                ....*....|....*....|....*....|..
gi 7661882  117 MGQDSYVLMASSQAEMEEWVKFLRRVAGTPCG 148
Cdd:cd13263  81 SNHDSYLLMANSQAEMEEWVKVIRRVIGSPFG 112

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661882    170 PILVEKCAEFILEHGRNEEGIFRLPGQDNLVKQLRDAFDAGERPSFD-RDTDVHTVASLLKLYLRDLPEPVVPWSQYEGF 248
Cdd:pfam00620   1 PLIVRKCVEYLEKRGLDTEGIFRVSGSASRIKELREAFDRGPDVDLDlEEEDVHVVASLLKLFLRELPEPLLTFELYEEF 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 7661882    249 LLCGQLTNADEakaQQELMKQL-SILPRDNYSLLSYICRFLHEIQLNCAVNKMSVDNLATVIGVNLIRSKV 318
Cdd:pfam00620  81 IEAAKLPDEEE---RLEALRELlRKLPPANRDTLRYLLAHLNRVAQNSDVNKMNAHNLAIVFGPTLLRPPD 148

PH domain; PH stands for pleckstrin homology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661882     40 PIKMGWLKKQRSIVK-NWQQRYFVLRAQQLYYYKDE---EDTKPQGCMYLPGCTIKEIATNPEEAGKFVFEIIPASWDQN 115
Cdd:pfam00169   1 VVKEGWLLKKGGGKKkSWKKRYFVLFDGSLLYYKDDksgKSKEPKGSISLSGCEVVEVVASDSPKRKFCFELRTGERTGK 80

                          90       100
                  ....*....|....*....|....*..
gi 7661882    116 RmgqdSYVLMASSQAEMEEWVKFLRRV 142
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 7661882    540 EEEIDSLQRMVQELRKEIETQKQMYE---EQIKNLEKENYDVWAKVVRLNEELEKEKKKSAALEISLRNMERSREDVEK- 615
Cdd:TIGR04523 411 DEQIKKLQQEKELLEKEIERLKETIIknnSEIKDLTNQDSVKELIIKNLDNTRESLETQLKVLSRSINKIKQNLEQKQKe 490

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 7661882    616 -------------RNKALEEEVKEFVKSMKEPKTE 637
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 7661882   38 ERPIKMGWLKKQRSIVKNWQQRYFVLRAQQLYYYKDEEDTKPQGCMYLPGCTIKEIATNPEEAGKFVFEIIPASW-DQNR 116
Cdd:cd13263   1 ERPIKSGWLKKQGSIVKNWQQRWFVLRGDQLYYYKDEDDTKPQGTIPLPGNKVKEVPFNPEEPGKFLFEIIPGGGgDRMT 80

                        90       100       110
                ....*....|....*....|....*....|..
gi 7661882  117 MGQDSYVLMASSQAEMEEWVKFLRRVAGTPCG 148
Cdd:cd13263  81 SNHDSYLLMANSQAEMEEWVKVIRRVIGSPFG 112

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 7661882  170 PILVEKCAEFILEHGRNEEGIFRLPGQDNLVKQLRDAFDAGERPSFDRDTDVHTVASLLKLYLRDLPEPVVPWSQYEGFL 249
Cdd:cd00159   1 PLIIEKCIEYLEKNGLNTEGIFRVSGSASKIEELKKKFDRGEDIDDLEDYDVHDVASLLKLYLRELPEPLIPFELYDEFI 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661882  250 LCgqLTNADEAKAQQELMKQLSILPRDNYSLLSYICRFLHEIQLNCAVNKMSVDNLATVIGVNLIRSKVEDPAVIMRgTP 329
Cdd:cd00159  81 EL--AKIEDEEERIEALKELLKSLPPENRDLLKYLLKLLHKISQNSEVNKMTASNLAIVFAPTLLRPPDSDDELLED-IK 157

                       170
                ....*....|..
gi 7661882  330 QIQRVMTMMIRD 341
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 7661882   38 ERPIKMGWLKKQRSIVKNWQQRYFVLRAQQLYYYKDEEDTKPQGCMYLPGCTIKEIATNPEEAGKFVFEIIPASW---DQ 114
Cdd:cd13378   1 EGVLKAGWLKKQRSIMKNWQQRWFVLRGDQLFYYKDEEETKPQGCISLQGSQVNELPPNPEEPGKHLFEILPGGAgdrEK 80

                        90       100       110
                ....*....|....*....|....*....|....
gi 7661882  115 NRMGQDSYVLMASSQAEMEEWVKFLRRVAGTPCG 148
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 7661882  149 VFGQRLDETvayeQKFG--PHLVPILVEKCAEFILEHGRNEEGIFRLPGQDNLVKQLRDAFDAGERPSFDRDTDVHTVAS 226
Cdd:cd04393   2 VFGVPLQEL----QQAGqpENGVPAVVRHIVEYLEQHGLEQEGLFRVNGNAETVEWLRQRLDSGEEVDLSKEADVCSAAS 77

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661882  227 LLKLYLRDLPEPVVPWSQYEGFLLCGQLTNADEAKAqQELMKQLSILPRDNYSLLSYICRFLHEIQLNCAVNKMSVDNLA 306
Cdd:cd04393  78 LLRLFLQELPEGLIPASLQIRLMQLYQDYNGEDEFG-RKLRDLLQQLPPVNYSLLKFLCHFLSNVASQHHENRMTAENLA 156

                       170
                ....*....|....*.
gi 7661882  307 TVIGVNL--IRSKVED 320
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 7661882  169 VPILVEKCAEFILEHGRNEEGIFRLPGQDNLVKQLRDAFDAGERPSFDRDTDVHTVASLLKLYLRDLPEPVVPWSQYEGF 248
Cdd:cd04376   9 VPRLVESCCQHLEKHGLQTVGIFRVGSSKKRVRQLREEFDRGIDVVLDENHSVHDVAALLKEFFRDMPDPLLPRELYTAF 88

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661882  249 LLCGQLTNADEAKAQQELmkqLSILPRDNYSLLSYICRFLHEIQLNCAV-----------NKMSVDNLATVIGVNLIR-- 315
Cdd:cd04376  89 IGTALLEPDEQLEALQLL---IYLLPPCNCDTLHRLLKFLHTVAEHAADsidedgqevsgNKMTSLNLATIFGPNLLHkq 165

                       170       180       190       200
                ....*....|....*....|....*....|....*....|.
gi 7661882  316 ----SKVEDPAVIMRGTPQIQRVMTMMIRDHEVLFPKSKDI 352
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 7661882  165 GPHLVPILVEKCAEFILEHGRNEEGIFRLPGQDNLVKQLRDAFDAGERPSFDRDTDVHTVASLLKLYLRDLPEPVVPWSQ 244
Cdd:cd04404  19 EQEPIPPVVRETVEYLQAHALTTEGIFRRSANTQVVKEVQQKYNMGEPVDFDQYEDVHLPAVILKTFLRELPEPLLTFDL 98

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661882  245 YEGFLLCGQLTNADEAKAQQELMKQlsiLPRDNYSLLSYICRFLHEIQLNCAVNKMSVDNLATVIGVNLIRSKveDPAVI 324
Cdd:cd04404  99 YDDIVGFLNVDKEERVERVKQLLQT---LPEENYQVLKYLIKFLVQVSAHSDQNKMTNSNLAVVFGPNLLWAK--DASMS 173

                       170       180
                ....*....|....*....|..
gi 7661882  325 MRGTPQIQRVMTMMIRDHEVLF 346
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 7661882  149 VFGQRLDET-VAYEQKFgphlVPILVEKCAEFILEHGRNEEGIFRLPGQDNLVKQLRDAFDAG--ERPSFD-RDTDVHTV 224
Cdd:cd04395   1 TFGVPLDDCpPSSENPY----VPLIVEVCCNIVEARGLETVGIYRVPGNNAAISALQEELNRGgfDIDLQDpRWRDVNVV 76

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661882  225 ASLLKLYLRDLPEPVVPWSQYEGFLLCGQLTNADEAkaQQELMKQLSILPRDNYSLLSYICRFLHEIQLNCAVNKMSVDN 304
Cdd:cd04395  77 SSLLKSFFRKLPEPLFTNELYPDFIEANRIEDPVER--LKELRRLIHSLPDHHYETLKHLIRHLKTVADNSEVNKMEPRN 154

                       170
                ....*....|..
gi 7661882  305 LATVIGVNLIRS 316
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 7661882  150 FGQRLDETVAYEQKFGPHL-VPILVEKCAEFILE-HGRNEEGIFRLPGQDNLVKQLRDAFDAGERPSFDRDtDVHTVASL 227
Cdd:cd04389   1 FGSSLEEIMDRQKEKYPELkLPWILTFLSEKVLAlGGFQTEGIFRVPGDIDEVNELKLRVDQWDYPLSGLE-DPHVPASL 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661882  228 LKLYLRDLPEPVVPWSQYEGfllCgqLTNADEAKAQQELMKQLSILprdNYSLLSYICRFLHE--IQLNCAVNKMSVDNL 305
Cdd:cd04389  80 LKLWLRELEEPLIPDALYQQ---C--ISASEDPDKAVEIVQKLPII---NRLVLCYLINFLQVfaQPENVAHTKMDVSNL 151

                       170       180       190
                ....*....|....*....|....*....|....
gi 7661882  306 ATVIGVNLIRSKVEDPAVIMRGTPQIQRVMTMMI 339
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 7661882  169 VPILVEKCAEFILEHGRnEEGIFRLPGQDNLVKQLRDAFDAGERPSFDRDT---DVHTVASLLKLYLRDLPEPVVPWSQY 245
Cdd:cd04384  18 VPQVLKSCTEFIEKHGI-VDGIYRLSGIASNIQRLRHEFDSEQIPDLTKDVyiqDIHSVSSLCKLYFRELPNPLLTYQLY 96

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 7661882  246 EGFLlcgQLTNADEAKAQQELMKQ-LSILPRDNYSLLSYICRFLHEIQLNCAVNKMSVDNLATVIGVNLIRSK 317
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 7661882  150 FGQRLDETVAYEqkfgpHLVPILVEKCAEFILEHGRNEEGIFRLPGQDNLVKQLRDAFDAGERPSFDRDTDVHTVASLLK 229
Cdd:cd04377   1 FGVSLSSLTSED-----RSVPLVLEKLLEHIEMHGLYTEGIYRKSGSANKIKELRQGLDTDPDSVNLEDYPIHVITSVLK 75

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661882  230 LYLRDLPEPVVPWSQYEGFLlcgqltNADEAKAQQELMKQLSI----LPRDNYSLLSYICRFLHEIQLNCAVNKMSVDNL 305
Cdd:cd04377  76 QWLRELPEPLMTFELYENFL------RAMELEEKQERVRALYSvleqLPRANLNTLERLIFHLVRVALQEEVNRMSANAL 149

                       170       180       190
                ....*....|....*....|....*....|....*..
gi 7661882  306 ATVIGVNLIRS-KVEDPAVIMRGTPQIQRVMTMMIRD 341
Cdd:cd04377 150 AIVFAPCILRCpDTADPLQSLQDVSKTTTCVETLIKE 186

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 7661882      40 PIKMGWLKKQ-RSIVKNWQQRYFVLRAQQLYYYKDEE---DTKPQGCMYLPGCTIKEIATNPEEAGKFVFEIIPASwdqn 115
Cdd:smart00233   1 VIKEGWLYKKsGGGKKSWKKRYFVLFNSTLLYYKSKKdkkSYKPKGSIDLSGCTVREAPDPDSSKKPHCFEIKTSD---- 76

                           90       100
                   ....*....|....*....|....*...
gi 7661882     116 rmgQDSYVLMASSQAEMEEWVKFLRRVA 143
Cdd:smart00233  77 ---RKTLLLQAESEEEREKWVEALRKAI 101

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 7661882  164 FGPHL----------VPILVEKCAEFILEHGRNEEGIFRLPGQDNLVKQLRDAFDAGERPSFD--RDTDVHTVASLLKLY 231
Cdd:cd04403   1 FGCHLealcqrenstVPKFVRLCIEAVEKRGLDVDGIYRVSGNLAVIQKLRFAVDHDEKLDLDdsKWEDIHVITGALKLF 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661882  232 LRDLPEPVVPWSQYEGFLLCGQLTNA-DEAKAQQELMKQlsiLPRDNYSLLSYICRFLHEIQLNCAVNKMSVDNLATVIG 310
Cdd:cd04403  81 FRELPEPLFPYSLFNDFVAAIKLSDYeQRVSAVKDLIKS---LPKPNHDTLKMLFRHLCRVIEHGEKNRMTTQNLAIVFG 157

                       170       180
                ....*....|....*....|....*..
gi 7661882  311 VNLIRSKVE--DPAVIMRGTPQIQRVM 335
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 7661882  149 VFGQRLDETVAYEQ-------------KFGphLVPILVEKCAEFILEHGRNEEGIFRLPGQDNLVKQLRDAFDAGER--P 213
Cdd:cd04396   1 VFGVSLEESLKYASvaisivdedgeqyVYG--YIPVVVAKCGVYLKENATEVEGIFRVAGSSKRIRELQLIFSTPPDygK 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661882  214 SFDRDT-DVHTVASLLKLYLRDLPEPVVPWSQYEGF-------------LLCGQLTNADEAKAQQELMKQLSI--LPRDN 277
Cdd:cd04396  79 SFDWDGyTVHDAASVLRRYLNNLPEPLVPLDLYEEFrnplrkrprilqyMKGRINEPLNTDIDQAIKEYRDLItrLPNLN 158

                       170       180       190
                ....*....|....*....|....*....|.
gi 7661882  278 YSLLSYICRFLHEIQLNCAVNKMSVDNLATV 308
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 7661882  167 HLVPILVEKCaEFILEHgRNEEGIFRLPGQDNLVKQLRDAFDAGErpsfDRDTDVHT--VASLLKLYLRDLPEPVVPWSQ 244
Cdd:cd04394  19 NVPKFLVDAC-TFLLDH-LSTEGLFRKSGSVVRQKELKAKLEGGE----ACLSSALPcdVAGLLKQFFRELPEPLLPYDL 92

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 7661882  245 YEGFLLCGQLTNADEAKAQQELMKQLsiLPRDNYSLLSYICRFLHEIQLNCAVNKMSVDNLATVIGVNLIRS 316
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 7661882   34 PNPLERPIKMGWLKKQR-SIVKNWQQRYFVLRAQQLYYYKDEEDTKPQGCMYLPGCTIKEIATNPEEAGKFVFEIipasw 112
Cdd:cd13248   1 RDPNAPVVMSGWLHKQGgSGLKNWRKRWFVLKDNCLYYYKDPEEEKALGSILLPSYTISPAPPSDEISRKFAFKA----- 75

                        90       100       110
                ....*....|....*....|....*....|.
gi 7661882  113 dqNRMGQDSYVLMASSQAEMEEWVKFLRRVA 143
Cdd:cd13248  76 --EHANMRTYYFAADTAEEMEQWMNAMSLAA 104