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 261399907  45 ERPIKMGWLKKQRSIVKNWQQRYFVLRAQQLYYYKDEEDTKPQGCMYLPGCTIKEIATNPEEAGKFVFEIIPASW-DQNR 123
Cdd:cd13263    1 ERPIKSGWLKKQGSIVKNWQQRWFVLRGDQLYYYKDEDDTKPQGTIPLPGNKVKEVPFNPEEPGKFLFEIIPGGGgDRMT 80

                         90       100       110
                 ....*....|....*....|....*....|....
gi 261399907 124 MGQDSYVLMASSQAEMEEWVKFLRRVAGTPCGAV 157
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 261399907  45 ERPIKMGWLKKQRSIVKNWQQRYFVLRAQQLYYYKDEEDTKPQGCMYLPGCTIKEIATNPEEAGKFVFEIIPASW-DQNR 123
Cdd:cd13263    1 ERPIKSGWLKKQGSIVKNWQQRWFVLRGDQLYYYKDEDDTKPQGTIPLPGNKVKEVPFNPEEPGKFLFEIIPGGGgDRMT 80

                         90       100       110
                 ....*....|....*....|....*....|....
gi 261399907 124 MGQDSYVLMASSQAEMEEWVKFLRRVAGTPCGAV 157
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 261399907  178 PILVEKCAEFILEHGRNEEGIFRLPGQDNLVKQLRDAFDAGERPSFD-RDTDVHTVASLLKLYLRDLPEPVVPWSQYEGF 256
Cdd:pfam00620   1 PLIVRKCVEYLEKRGLDTEGIFRVSGSASRIKELREAFDRGPDVDLDlEEEDVHVVASLLKLFLRELPEPLLTFELYEEF 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 261399907  257 LLCGQLTNADEakaQQELMKQL-SILPRDNYSLLSYICRFLHEIQLNCAVNKMSVDNLATVIGVNLIRSKV 326
Cdd:pfam00620  81 IEAAKLPDEEE---RLEALRELlRKLPPANRDTLRYLLAHLNRVAQNSDVNKMNAHNLAIVFGPTLLRPPD 148

PH domain; PH stands for pleckstrin homology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 261399907   47 PIKMGWLKKQRSIVK-NWQQRYFVLRAQQLYYYKDE---EDTKPQGCMYLPGCTIKEIATNPEEAGKFVFEIIPASWDQN 122
Cdd:pfam00169   1 VVKEGWLLKKGGGKKkSWKKRYFVLFDGSLLYYKDDksgKSKEPKGSISLSGCEVVEVVASDSPKRKFCFELRTGERTGK 80

                          90       100
                  ....*....|....*....|....*..
gi 261399907  123 RmgqdSYVLMASSQAEMEEWVKFLRRV 149
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 261399907  548 EEEIDSLQRMVQELRKEIETQKQMYE---EQIKNLEKENYDVWAKVVRLNEELEKEKKKSAALEISLRNMERSREDVEK- 623
Cdd:TIGR04523 411 DEQIKKLQQEKELLEKEIERLKETIIknnSEIKDLTNQDSVKELIIKNLDNTRESLETQLKVLSRSINKIKQNLEQKQKe 490

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 261399907  624 -------------RNKALEEEVKEFVKSMKEPKTE 645
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 261399907  45 ERPIKMGWLKKQRSIVKNWQQRYFVLRAQQLYYYKDEEDTKPQGCMYLPGCTIKEIATNPEEAGKFVFEIIPASW-DQNR 123
Cdd:cd13263    1 ERPIKSGWLKKQGSIVKNWQQRWFVLRGDQLYYYKDEDDTKPQGTIPLPGNKVKEVPFNPEEPGKFLFEIIPGGGgDRMT 80

                         90       100       110
                 ....*....|....*....|....*....|....
gi 261399907 124 MGQDSYVLMASSQAEMEEWVKFLRRVAGTPCGAV 157
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 261399907 178 PILVEKCAEFILEHGRNEEGIFRLPGQDNLVKQLRDAFDAGERPSFDRDTDVHTVASLLKLYLRDLPEPVVPWSQYEGFL 257
Cdd:cd00159    1 PLIIEKCIEYLEKNGLNTEGIFRVSGSASKIEELKKKFDRGEDIDDLEDYDVHDVASLLKLYLRELPEPLIPFELYDEFI 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 261399907 258 LCgqLTNADEAKAQQELMKQLSILPRDNYSLLSYICRFLHEIQLNCAVNKMSVDNLATVIGVNLIRSKVEDPAVIMRgTP 337
Cdd:cd00159   81 EL--AKIEDEEERIEALKELLKSLPPENRDLLKYLLKLLHKISQNSEVNKMTASNLAIVFAPTLLRPPDSDDELLED-IK 157

                        170
                 ....*....|..
gi 261399907 338 QIQRVMTMMIRD 349
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 261399907  45 ERPIKMGWLKKQRSIVKNWQQRYFVLRAQQLYYYKDEEDTKPQGCMYLPGCTIKEIATNPEEAGKFVFEIIPASW---DQ 121
Cdd:cd13378    1 EGVLKAGWLKKQRSIMKNWQQRWFVLRGDQLFYYKDEEETKPQGCISLQGSQVNELPPNPEEPGKHLFEILPGGAgdrEK 80

                         90       100       110
                 ....*....|....*....|....*....|....
gi 261399907 122 NRMGQDSYVLMASSQAEMEEWVKFLRRVAGTPCG 155
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 261399907 157 VFGQRLDETvayeQKFG--PHLVPILVEKCAEFILEHGRNEEGIFRLPGQDNLVKQLRDAFDAGERPSFDRDTDVHTVAS 234
Cdd:cd04393    2 VFGVPLQEL----QQAGqpENGVPAVVRHIVEYLEQHGLEQEGLFRVNGNAETVEWLRQRLDSGEEVDLSKEADVCSAAS 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 261399907 235 LLKLYLRDLPEPVVPWSQYEGFLLCGQLTNADEAKAqQELMKQLSILPRDNYSLLSYICRFLHEIQLNCAVNKMSVDNLA 314
Cdd:cd04393   78 LLRLFLQELPEGLIPASLQIRLMQLYQDYNGEDEFG-RKLRDLLQQLPPVNYSLLKFLCHFLSNVASQHHENRMTAENLA 156

                        170
                 ....*....|....*.
gi 261399907 315 TVIGVNL--IRSKVED 328
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 261399907 177 VPILVEKCAEFILEHGRNEEGIFRLPGQDNLVKQLRDAFDAGERPSFDRDTDVHTVASLLKLYLRDLPEPVVPWSQYEGF 256
Cdd:cd04376    9 VPRLVESCCQHLEKHGLQTVGIFRVGSSKKRVRQLREEFDRGIDVVLDENHSVHDVAALLKEFFRDMPDPLLPRELYTAF 88

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 261399907 257 LLCGQLTNADEAKAQQELmkqLSILPRDNYSLLSYICRFLHEIQLNCAV-----------NKMSVDNLATVIGVNLIR-- 323
Cdd:cd04376   89 IGTALLEPDEQLEALQLL---IYLLPPCNCDTLHRLLKFLHTVAEHAADsidedgqevsgNKMTSLNLATIFGPNLLHkq 165

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|.
gi 261399907 324 ----SKVEDPAVIMRGTPQIQRVMTMMIRDHEVLFPKSKDI 360
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 261399907 173 GPHLVPILVEKCAEFILEHGRNEEGIFRLPGQDNLVKQLRDAFDAGERPSFDRDTDVHTVASLLKLYLRDLPEPVVPWSQ 252
Cdd:cd04404   19 EQEPIPPVVRETVEYLQAHALTTEGIFRRSANTQVVKEVQQKYNMGEPVDFDQYEDVHLPAVILKTFLRELPEPLLTFDL 98

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 261399907 253 YEGFLLCGQLTNADEAKAQQELMKQlsiLPRDNYSLLSYICRFLHEIQLNCAVNKMSVDNLATVIGVNLIRSKveDPAVI 332
Cdd:cd04404   99 YDDIVGFLNVDKEERVERVKQLLQT---LPEENYQVLKYLIKFLVQVSAHSDQNKMTNSNLAVVFGPNLLWAK--DASMS 173

                        170       180
                 ....*....|....*....|..
gi 261399907 333 MRGTPQIQRVMTMMIRDHEVLF 354
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 261399907 157 VFGQRLDET-VAYEQKFgphlVPILVEKCAEFILEHGRNEEGIFRLPGQDNLVKQLRDAFDAG--ERPSFD-RDTDVHTV 232
Cdd:cd04395    1 TFGVPLDDCpPSSENPY----VPLIVEVCCNIVEARGLETVGIYRVPGNNAAISALQEELNRGgfDIDLQDpRWRDVNVV 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 261399907 233 ASLLKLYLRDLPEPVVPWSQYEGFLLCGQLTNADEAkaQQELMKQLSILPRDNYSLLSYICRFLHEIQLNCAVNKMSVDN 312
Cdd:cd04395   77 SSLLKSFFRKLPEPLFTNELYPDFIEANRIEDPVER--LKELRRLIHSLPDHHYETLKHLIRHLKTVADNSEVNKMEPRN 154

                        170
                 ....*....|..
gi 261399907 313 LATVIGVNLIRS 324
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 261399907 158 FGQRLDETVAYEQKFGPHL-VPILVEKCAEFILE-HGRNEEGIFRLPGQDNLVKQLRDAFDAGERPSFDRDtDVHTVASL 235
Cdd:cd04389    1 FGSSLEEIMDRQKEKYPELkLPWILTFLSEKVLAlGGFQTEGIFRVPGDIDEVNELKLRVDQWDYPLSGLE-DPHVPASL 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 261399907 236 LKLYLRDLPEPVVPWSQYEGfllCgqLTNADEAKAQQELMKQLSILprdNYSLLSYICRFLHE--IQLNCAVNKMSVDNL 313
Cdd:cd04389   80 LKLWLRELEEPLIPDALYQQ---C--ISASEDPDKAVEIVQKLPII---NRLVLCYLINFLQVfaQPENVAHTKMDVSNL 151

                        170       180       190
                 ....*....|....*....|....*....|....
gi 261399907 314 ATVIGVNLIRSKVEDPAVIMRGTPQIQRVMTMMI 347
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 261399907 177 VPILVEKCAEFILEHGRnEEGIFRLPGQDNLVKQLRDAFDAGERPSFDRDT---DVHTVASLLKLYLRDLPEPVVPWSQY 253
Cdd:cd04384   18 VPQVLKSCTEFIEKHGI-VDGIYRLSGIASNIQRLRHEFDSEQIPDLTKDVyiqDIHSVSSLCKLYFRELPNPLLTYQLY 96

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 261399907 254 EGFLlcgQLTNADEAKAQQELMKQ-LSILPRDNYSLLSYICRFLHEIQLNCAVNKMSVDNLATVIGVNLIRSK 325
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 261399907 158 FGQRLDETVAYEqkfgpHLVPILVEKCAEFILEHGRNEEGIFRLPGQDNLVKQLRDAFDAGERPSFDRDTDVHTVASLLK 237
Cdd:cd04377    1 FGVSLSSLTSED-----RSVPLVLEKLLEHIEMHGLYTEGIYRKSGSANKIKELRQGLDTDPDSVNLEDYPIHVITSVLK 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 261399907 238 LYLRDLPEPVVPWSQYEGFLlcgqltNADEAKAQQELMKQLSI----LPRDNYSLLSYICRFLHEIQLNCAVNKMSVDNL 313
Cdd:cd04377   76 QWLRELPEPLMTFELYENFL------RAMELEEKQERVRALYSvleqLPRANLNTLERLIFHLVRVALQEEVNRMSANAL 149

                        170       180       190
                 ....*....|....*....|....*....|....*..
gi 261399907 314 ATVIGVNLIRS-KVEDPAVIMRGTPQIQRVMTMMIRD 349
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 261399907    47 PIKMGWLKKQ-RSIVKNWQQRYFVLRAQQLYYYKDEE---DTKPQGCMYLPGCTIKEIATNPEEAGKFVFEIIPASwdqn 122
Cdd:smart00233   1 VIKEGWLYKKsGGGKKSWKKRYFVLFNSTLLYYKSKKdkkSYKPKGSIDLSGCTVREAPDPDSSKKPHCFEIKTSD---- 76

                           90       100
                   ....*....|....*....|....*...
gi 261399907   123 rmgQDSYVLMASSQAEMEEWVKFLRRVA 150
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 261399907 172 FGPHL----------VPILVEKCAEFILEHGRNEEGIFRLPGQDNLVKQLRDAFDAGERPSFD--RDTDVHTVASLLKLY 239
Cdd:cd04403    1 FGCHLealcqrenstVPKFVRLCIEAVEKRGLDVDGIYRVSGNLAVIQKLRFAVDHDEKLDLDdsKWEDIHVITGALKLF 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 261399907 240 LRDLPEPVVPWSQYEGFLLCGQLTNA-DEAKAQQELMKQlsiLPRDNYSLLSYICRFLHEIQLNCAVNKMSVDNLATVIG 318
Cdd:cd04403   81 FRELPEPLFPYSLFNDFVAAIKLSDYeQRVSAVKDLIKS---LPKPNHDTLKMLFRHLCRVIEHGEKNRMTTQNLAIVFG 157

                        170       180
                 ....*....|....*....|....*..
gi 261399907 319 VNLIRSKVE--DPAVIMRGTPQIQRVM 343
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 261399907 157 VFGQRLDETVAYEQ-------------KFGphLVPILVEKCAEFILEHGRNEEGIFRLPGQDNLVKQLRDAFDAGER--P 221
Cdd:cd04396    1 VFGVSLEESLKYASvaisivdedgeqyVYG--YIPVVVAKCGVYLKENATEVEGIFRVAGSSKRIRELQLIFSTPPDygK 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 261399907 222 SFDRDT-DVHTVASLLKLYLRDLPEPVVPWSQYEGF-------------LLCGQLTNADEAKAQQELMKQLSI--LPRDN 285
Cdd:cd04396   79 SFDWDGyTVHDAASVLRRYLNNLPEPLVPLDLYEEFrnplrkrprilqyMKGRINEPLNTDIDQAIKEYRDLItrLPNLN 158

                        170       180       190
                 ....*....|....*....|....*....|.
gi 261399907 286 YSLLSYICRFLHEIQLNCAVNKMSVDNLATV 316
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 261399907 175 HLVPILVEKCaEFILEHgRNEEGIFRLPGQDNLVKQLRDAFDAGErpsfDRDTDVHT--VASLLKLYLRDLPEPVVPWSQ 252
Cdd:cd04394   19 NVPKFLVDAC-TFLLDH-LSTEGLFRKSGSVVRQKELKAKLEGGE----ACLSSALPcdVAGLLKQFFRELPEPLLPYDL 92

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 261399907 253 YEGFLLCGQLTNADEAKAQQELMKQLsiLPRDNYSLLSYICRFLHEIQLNCAVNKMSVDNLATVIGVNLIRS 324
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 261399907  41 PNPLERPIKMGWLKKQR-SIVKNWQQRYFVLRAQQLYYYKDEEDTKPQGCMYLPGCTIKEIATNPEEAGKFVFEIipasw 119
Cdd:cd13248    1 RDPNAPVVMSGWLHKQGgSGLKNWRKRWFVLKDNCLYYYKDPEEEKALGSILLPSYTISPAPPSDEISRKFAFKA----- 75

                         90       100       110
                 ....*....|....*....|....*....|.
gi 261399907 120 dqNRMGQDSYVLMASSQAEMEEWVKFLRRVA 150
Cdd:cd13248   76 --EHANMRTYYFAADTAEEMEQWMNAMSLAA 104