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 568912537 1149 TFGVRLDDCPPAHTNRYIPLIVDICCKLVEERGLEYTGIYRVPGNNAAISSMQEELNKGMADIDIQDDKWRDLNVISSLL 1228
Cdd:cd04395     1 TFGVPLDDCPPSSENPYVPLIVEVCCNIVEARGLETVGIYRVPGNNAAISALQEELNRGGFDIDLQDPRWRDVNVVSSLL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568912537 1229 KSFFRKLPEPLFTNDKYADFIEANRKEDPLDRLRTLKRLIHDLPEHHFETLKFLSAHLKTVAENSEKNKMEPRNLAIVFG 1308
Cdd:cd04395    81 KSFFRKLPEPLFTNELYPDFIEANRIEDPVERLKELRRLIHSLPDHHYETLKHLIRHLKTVADNSEVNKMEPRNLAIVFG 160

                         170       180       190
                  ....*....|....*....|....*....|....*.
gi 568912537 1309 PTLVRTSEDNMTHMVTHMPDQYKIVETLIQHHDWFF 1344
Cdd:cd04395   161 PTLVRTSDDNMETMVTHMPDQCKIVETLIQHYDWFF 196

ARHGAP21 and related proteins pleckstrin homology (PH) domain; ARHGAP family genes encode Rho/Rac/Cdc42-like GTPase activating proteins with a RhoGAP domain. These proteins functions as a GTPase-activating protein (GAP) for RHOA and CDC42. ARHGAP21 controls the Arp2/3 complex and F-actin dynamics at the Golgi complex by regulating the activity of the small GTPase Cdc42. It is recruited to the Golgi by to GTPase, ARF1, through its PH domain and its helical motif. It is also required for CTNNA1 recruitment to adherens junctions. ARHGAP21 and it related proteins all contains a PH domain and a RhoGAP domain. Some of the members have additional N-terminal domains including PDZ, SH3, and SPEC. The ARHGAP21 PH domain interacts with the GTPbound forms of both ARF1 and ARF6 ARF-binding domain/ArfBD. The members here include: ARHGAP15, ARHGAP21, and ARHGAP23. 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 568912537  937 AREGWLQFRPLVTDKGKRVggSIRPWKQMYVVLRGHSLYLYKDRREQTTP----SEEEQPISVNACLIDISYSETKRRNV 1012
Cdd:cd01253     1 AREGWLHYKQIVTDKGKRV--SDRSWKQAWAVLRGHSLYLYKDKREQTPAlsieLGSEQRISIRGCIVDIAYSYTKRKHV 78

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 568912537 1013 FRLTTSD-CECLFQAEDRDDMLSWIKTIQESSNLN 1046
Cdd:cd01253    79 FRLTTSDfSEYLFQAEDRDDMLGWIKAIQENSNAE 113

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 568912537 1149 TFGVRLDDCPPAHTNRYIPLIVDICCKLVEERGLEYTGIYRVPGNNAAISSMQEELNKGMADIDIQDDKWRDLNVISSLL 1228
Cdd:cd04395     1 TFGVPLDDCPPSSENPYVPLIVEVCCNIVEARGLETVGIYRVPGNNAAISALQEELNRGGFDIDLQDPRWRDVNVVSSLL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568912537 1229 KSFFRKLPEPLFTNDKYADFIEANRKEDPLDRLRTLKRLIHDLPEHHFETLKFLSAHLKTVAENSEKNKMEPRNLAIVFG 1308
Cdd:cd04395    81 KSFFRKLPEPLFTNELYPDFIEANRIEDPVERLKELRRLIHSLPDHHYETLKHLIRHLKTVADNSEVNKMEPRNLAIVFG 160

                         170       180       190
                  ....*....|....*....|....*....|....*.
gi 568912537 1309 PTLVRTSEDNMTHMVTHMPDQYKIVETLIQHHDWFF 1344
Cdd:cd04395   161 PTLVRTSDDNMETMVTHMPDQCKIVETLIQHYDWFF 196

GTPase-activator protein for Rho-like GTPases; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases. etter domain limits and outliers.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568912537   1164 RYIPLIVDICCKLVEERGLEYTGIYRVPGNNAAISSMQEELNKGMaDIDIQDDKWrDLNVISSLLKSFFRKLPEPLFTND 1243
Cdd:smart00324    1 KPIPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGP-DPDLDLSEY-DVHDVAGLLKLFLRELPEPLITYE 78

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568912537   1244 KYADFIEANRKEDPLDRLRTLKRLIHDLPEHHFETLKFLSAHLKTVAENSEKNKMEPRNLAIVFGPTLVRTSEDNMThMV 1323
Cdd:smart00324   79 LYEEFIEAAKLEDETERLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEVA-SL 157

                           170
                    ....*....|....*..
gi 568912537   1324 THMPDQYKIVETLIQHH 1340
Cdd:smart00324  158 KDIRHQNTVIEFLIENA 174

ARHGAP21 and related proteins pleckstrin homology (PH) domain; ARHGAP family genes encode Rho/Rac/Cdc42-like GTPase activating proteins with a RhoGAP domain. These proteins functions as a GTPase-activating protein (GAP) for RHOA and CDC42. ARHGAP21 controls the Arp2/3 complex and F-actin dynamics at the Golgi complex by regulating the activity of the small GTPase Cdc42. It is recruited to the Golgi by to GTPase, ARF1, through its PH domain and its helical motif. It is also required for CTNNA1 recruitment to adherens junctions. ARHGAP21 and it related proteins all contains a PH domain and a RhoGAP domain. Some of the members have additional N-terminal domains including PDZ, SH3, and SPEC. The ARHGAP21 PH domain interacts with the GTPbound forms of both ARF1 and ARF6 ARF-binding domain/ArfBD. The members here include: ARHGAP15, ARHGAP21, and ARHGAP23. 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 568912537  937 AREGWLQFRPLVTDKGKRVggSIRPWKQMYVVLRGHSLYLYKDRREQTTP----SEEEQPISVNACLIDISYSETKRRNV 1012
Cdd:cd01253     1 AREGWLHYKQIVTDKGKRV--SDRSWKQAWAVLRGHSLYLYKDKREQTPAlsieLGSEQRISIRGCIVDIAYSYTKRKHV 78

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 568912537 1013 FRLTTSD-CECLFQAEDRDDMLSWIKTIQESSNLN 1046
Cdd:cd01253    79 FRLTTSDfSEYLFQAEDRDDMLGWIKAIQENSNAE 113

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 568912537    938 REGWLQfrplvtdkgKRVGGSIRPWKQMYVVLRGHSLYLYKDrREQTTPSEEEQPISVNACLIDI--SYSETKRRNVFRL 1015
Cdd:smart00233    3 KEGWLY---------KKSGGGKKSWKKRYFVLFNSTLLYYKS-KKDKKSYKPKGSIDLSGCTVREapDPDSSKKPHCFEI 72

                            90       100       110
                    ....*....|....*....|....*....|
gi 568912537   1016 TTSDCECL-FQAEDRDDMLSWIKTIQESSN 1044
Cdd:smart00233   73 KTSDRKTLlLQAESEEEREKWVEALRKAIA 102

C-terminal processing protease CtpA/Prc, contains a PDZ domain [Posttranslational modification, protein turnover, chaperones];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568912537  106 DTIFVKQVKEGGPAFEAGLCTGDRIIKVNGESVIGKTYSQVIALIQN-SDTTLELSVMPKDEDILQVLQFTKDVTALAYS 184
Cdd:COG0793    71 GKVVVVSVIPGSPAEKAGIKPGDIILAIDGKSVAGLTLDDAVKLLRGkAGTKVTLTIKRPGEGEPITVTLTRAEIKLPSV 150

                          90
                  ....*....|.
gi 568912537  185 QDAYLKGNEAY 195
Cdd:COG0793   151 EAKLLEGKIGY 161

sigma E protease regulator RseP;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 568912537  101 RLEPMdtifVKQVKEGGPAFEAGLCTGDRIIKVNGESvIGKTYSQVIALIQNSDTTLELSV 161
Cdd:PRK10779  220 QIEPV----LAEVQPNSAASKAGLQAGDRIVKVDGQP-LTQWQTFVTLVRDNPGKPLALEI 275

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 568912537 1149 TFGVRLDDCPPAHTNRYIPLIVDICCKLVEERGLEYTGIYRVPGNNAAISSMQEELNKGMADIDIQDDKWRDLNVISSLL 1228
Cdd:cd04395     1 TFGVPLDDCPPSSENPYVPLIVEVCCNIVEARGLETVGIYRVPGNNAAISALQEELNRGGFDIDLQDPRWRDVNVVSSLL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568912537 1229 KSFFRKLPEPLFTNDKYADFIEANRKEDPLDRLRTLKRLIHDLPEHHFETLKFLSAHLKTVAENSEKNKMEPRNLAIVFG 1308
Cdd:cd04395    81 KSFFRKLPEPLFTNELYPDFIEANRIEDPVERLKELRRLIHSLPDHHYETLKHLIRHLKTVADNSEVNKMEPRNLAIVFG 160

                         170       180       190
                  ....*....|....*....|....*....|....*.
gi 568912537 1309 PTLVRTSEDNMTHMVTHMPDQYKIVETLIQHHDWFF 1344
Cdd:cd04395   161 PTLVRTSDDNMETMVTHMPDQCKIVETLIQHYDWFF 196

GTPase-activator protein for Rho-like GTPases; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases. etter domain limits and outliers.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568912537   1164 RYIPLIVDICCKLVEERGLEYTGIYRVPGNNAAISSMQEELNKGMaDIDIQDDKWrDLNVISSLLKSFFRKLPEPLFTND 1243
Cdd:smart00324    1 KPIPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGP-DPDLDLSEY-DVHDVAGLLKLFLRELPEPLITYE 78

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568912537   1244 KYADFIEANRKEDPLDRLRTLKRLIHDLPEHHFETLKFLSAHLKTVAENSEKNKMEPRNLAIVFGPTLVRTSEDNMThMV 1323
Cdd:smart00324   79 LYEEFIEAAKLEDETERLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEVA-SL 157

                           170
                    ....*....|....*..
gi 568912537   1324 THMPDQYKIVETLIQHH 1340
Cdd:smart00324  158 KDIRHQNTVIEFLIENA 174

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 568912537 1167 PLIVDICCKLVEERGLEYTGIYRVPGNNAAISSMQEELNKGmadIDIQDDKWRDLNVISSLLKSFFRKLPEPLFTNDKYA 1246
Cdd:cd00159     1 PLIIEKCIEYLEKNGLNTEGIFRVSGSASKIEELKKKFDRG---EDIDDLEDYDVHDVASLLKLYLRELPEPLIPFELYD 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568912537 1247 DFIEANRKEDPLDRLRTLKRLIHDLPEHHFETLKFLSAHLKTVAENSEKNKMEPRNLAIVFGPTLVRTSEDNMThMVTHM 1326
Cdd:cd00159    78 EFIELAKIEDEEERIEALKELLKSLPPENRDLLKYLLKLLHKISQNSEVNKMTASNLAIVFAPTLLRPPDSDDE-LLEDI 156

                         170
                  ....*....|...
gi 568912537 1327 PDQYKIVETLIQH 1339
Cdd:cd00159   157 KKLNEIVEFLIEN 169

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 568912537 1161 HTNRYIPLIVDICCKLVEERGLEYTGIYRVPGNNAAISSMQEELNKGMAdIDIQDDKWRDLNVISSLLKSFFRKLPEPLF 1240
Cdd:cd04403    11 RENSTVPKFVRLCIEAVEKRGLDVDGIYRVSGNLAVIQKLRFAVDHDEK-LDLDDSKWEDIHVITGALKLFFRELPEPLF 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568912537 1241 TNDKYADFIEANRKEDPLDRLRTLKRLIHDLPEHHFETLKFLSAHLKTVAENSEKNKMEPRNLAIVFGPTLVRtSEDNMT 1320
Cdd:cd04403    90 PYSLFNDFVAAIKLSDYEQRVSAVKDLIKSLPKPNHDTLKMLFRHLCRVIEHGEKNRMTTQNLAIVFGPTLLR-PEQETG 168

                         170
                  ....*....|....*...
gi 568912537 1321 HMVTHMPDQYKIVETLIQ 1338
Cdd:cd04403   169 NIAVHMVYQNQIVELILL 186

RhoGAP_fRGD1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of fungal RGD1-like proteins. Yeast Rgd1 is a GAP protein for Rho3 and Rho4 and plays a role in low-pH response. 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 568912537 1150 FGVRLDDC-PPAHTNryIPLIVDICCKLVEERGLEYTGIYRVPGNNAAISSMQEELNKGMADIDI--QDDKWRDLNVISS 1226
Cdd:cd04398     1 FGVPLEDLiLREGDN--VPNIVYQCIQAIENFGLNLEGIYRLSGNVSRVNKLKELFDKDPLNVLLisPEDYESDIHSVAS 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568912537 1227 LLKSFFRKLPEPLFTNDKYADFIEANRKEDPLDRLRTLKRLIHDLPEHHFETLKFLSAHLKTVAENSEKNKMEPRNLAIV 1306
Cdd:cd04398    79 LLKLFFRELPEPLLTKALSREFIEAAKIEDESRRRDALHGLINDLPDANYATLRALMFHLARIKEHESVNRMSVNNLAII 158

                         170       180       190
                  ....*....|....*....|....*....|....*...
gi 568912537 1307 FGPTLVRTSEDNmthmVTHMPDQYKIVETLIQHHDWFF 1344
Cdd:cd04398   159 WGPTLMNAAPDN----AADMSFQSRVIETLLDNAYQIF 192

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568912537 1169 IVDICCKLVEERGLEYTGIYRVPGNNaaiSSMQEELNKGM-------ADIDIQDDKWrDLNVISSLLKSFFRKLPEPLFT 1241
Cdd:cd04374    31 FVRKCIEAVETRGINEQGLYRVVGVN---SKVQKLLSLGLdpktstpGDVDLDNSEW-EIKTITSALKTYLRNLPEPLMT 106

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568912537 1242 NDKYADFIEANRKEDPLDRLRTLKRLIHDLPEHHFETLKFLSAHLKTVAENSEKNKMEPRNLAIVFGPTLVRTSEDNmth 1321
Cdd:cd04374   107 YELHNDFINAAKSENLESRVNAIHSLVHKLPEKNREMLELLIKHLTNVSDHSKKNLMTVSNLGVVFGPTLLRPQEET--- 183

                         170       180
                  ....*....|....*....|.
gi 568912537 1322 mVTHMPD---QYKIVETLIQH 1339
Cdd:cd04374   184 -VAAIMDikfQNIVVEILIEN 203

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568912537 1166 IPLIVDICCKLVEERGLEYTGIYRVPGNNAAISSMQEELNKgmadiDIQDDKWR--DLNV--ISSLLKSFFRKLPEPLFT 1241
Cdd:cd04385    15 IPVIVDKCIDFITQHGLMSEGIYRKNGKNSSVKKLLEAFRK-----DARSVQLRegEYTVhdVADVLKRFLRDLPDPLLT 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568912537 1242 NDKYADFIEANRKEDPLDRLRTLKRLIHDLPEHHFETLKFLSAHLKTVAENSEKNKMEPRNLAIVFGPTLVRTSEdnmtH 1321
Cdd:cd04385    90 SELHAEWIEAAELENKDERIARYKELIRRLPPINRATLKVLIGHLYRVQKHSDENQMSVHNLALVFGPTLFQTDE----H 165

                         170
                  ....*....|....*...
gi 568912537 1322 MVTHMPDQYKIVETLIQH 1339
Cdd:cd04385   166 SVGQTSHEVKVIEDLIDN 183

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568912537 1166 IPLIVDICCKLVEERGLEYTGIYRVPGNNAAISSMQEELNKG-----MADIDIqddkwrdlNVISSLLKSFFRKLPEPLF 1240
Cdd:cd04382    17 IPALIVHCVNEIEARGLTEEGLYRVSGSEREVKALKEKFLRGktvpnLSKVDI--------HVICGCLKDFLRSLKEPLI 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568912537 1241 TNDKYADFIEANRKEDPLDRLRTLKRLIHDLPEHHFETLKFLSAHLKTVAEnSEKNKMEPRNLAIVFGPTLV--RTSEDN 1318
Cdd:cd04382    89 TFALWKEFMEAAEILDEDNSRAALYQAISELPQPNRDTLAFLILHLQRVAQ-SPECKMDINNLARVFGPTIVgySVPNPD 167

                         170
                  ....*....|....*...
gi 568912537 1319 MTHMVTHMPDQYKIVETL 1336
Cdd:cd04382   168 PMTILQDTVRQPRVVERL 185

RhoGAP_Bcr: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of Bcr (breakpoint cluster region protein)-like proteins. Bcr is a multidomain protein with a variety of enzymatic functions. It contains a RhoGAP and a Rho GEF domain, a Ser/Thr kinase domain, an N-terminal oligomerization domain, and a C-terminal PDZ binding domain, in addition to PH and C2 domains. Bcr is a negative regulator of: i) RacGTPase, via the Rho GAP domain, ii) the Ras-Raf-MEK-ERK pathway, via phosphorylation of the Ras binding protein AF-6, and iii) the Wnt signaling pathway through binding beta-catenin. Bcr can form a complex with beta-catenin and Tcf1. The Wnt signaling pathway is involved in cell proliferation, differentiation, and cell renewal. Bcr was discovered as a fusion partner of Abl. The Bcr-Abl fusion is characteristic for a large majority of chronic myelogenous leukemias (CML). 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 568912537 1166 IPLIVDICCKLVEERGLEYTGIYRVPGNNAAISSMQEELNKGMADIDIQDDKwRDLNVISSLLKSFFRKLPEPLFTNDKY 1245
Cdd:cd04387    16 VPYIVRQCVEEVERRGMEEVGIYRISGVATDIQALKAAFDTNNKDVSVMLSE-MDVNAIAGTLKLYFRELPEPLFTDELY 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568912537 1246 ADFIEANRKEDPLDRLRTLKRLIHDLPEHHFETLKFLSAHLKTVAENSEKNKMEPRNLAIVFGPTLVRTSEDNMTHMVTH 1325
Cdd:cd04387    95 PNFAEGIALSDPVAKESCMLNLLLSLPDPNLVTFLFLLHHLKRVAEREEVNKMSLHNLATVFGPTLLRPSEKESKIPTNT 174

                         170
                  ....*....|...
gi 568912537 1326 MPDQYKiVETLIQ 1338
Cdd:cd04387   175 MTDSWS-LEVMSQ 186

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 568912537 1164 RYIPLIVDICCKLVEERGLEYTGIYRVPGNNAAISSMQEELNKGmadIDIQDDKWRDLNVISSLLKSFFRKLPEPLFTND 1243
Cdd:cd04376     7 RQVPRLVESCCQHLEKHGLQTVGIFRVGSSKKRVRQLREEFDRG---IDVVLDENHSVHDVAALLKEFFRDMPDPLLPRE 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568912537 1244 KYADFIEANrKEDPLDRLRTLKRLIHDLPEHHFETLKFLSAHLKTVAENSEK-----------NKMEPRNLAIVFGPTLV 1312
Cdd:cd04376    84 LYTAFIGTA-LLEPDEQLEALQLLIYLLPPCNCDTLHRLLKFLHTVAEHAADsidedgqevsgNKMTSLNLATIFGPNLL 162

                         170       180       190
                  ....*....|....*....|....*....|....*....
gi 568912537 1313 RTSEDNMTHMVT------HMPDQYKIVETLIQHHDWFFT 1345
Cdd:cd04376   163 HKQKSGEREFVQaslrieESTAIINVVQTMIDNYEELFM 201

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568912537 1159 PAHTNRYIPLIVDICCKLVEERGLEYTGIYRVPGNNAAISSMQEELNKGMADIDIQDDKWRDlnvISSLLKSFFRKLPEP 1238
Cdd:cd04408     9 PRDFPEEVPFVVVRCTAEIENRALGVQGIYRISGSKARVEKLCQAFENGRDLVDLSGHSPHD---ITSVLKHFLKELPEP 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568912537 1239 LFTNDKYADFIEANR--KEDPLDR----------LRTLKRLIHDLPEHHFETLKFLSAHLKTVAENSEKNKMEPRNLAIV 1306
Cdd:cd04408    86 VLPFQLYDDFIALAKelQRDSEKAaespsiveniIRSLKELLGRLPVSNYNTLRHLMAHLYRVAERFEDNKMSPNNLGIV 165

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 568912537 1307 FGPTLVRTSEDNMTHMVTHMPDQYK--IVETLIQH 1339
Cdd:cd04408   166 FGPTLLRPLVGGDVSMICLLDTGYQaqLVEFLISN 200

RhoGAP_fBEM3: RhoGAP (GTPase-activator [GAP] protein for Rho-like small GTPases) domain of fungal BEM3-like proteins. Bem3 is a GAP protein of Cdc42, and is specifically involved in the control of the initial assembly of the septin ring in yeast bud formation. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568912537 1150 FGVRLDDC----PPAHTNRYIPLIVDICCKLVEERGLEYT-GIYRVPGNNAAISSMQEELNKGMaDIDI-QDDKWRDLNV 1223
Cdd:cd04400     2 FGSPLEEAvelsSHKYNGRDLPSVVYRCIEYLDKNRAIYEeGIFRLSGSASVIKQLKERFNTEY-DVDLfSSSLYPDVHT 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568912537 1224 ISSLLKSFFRKLPEPLFTNDKYADFIEANRK-EDPLDRLRTLKRLIHDLPEHHFETLKFLSAHLKTVAENSEKNKMEPRN 1302
Cdd:cd04400    81 VAGLLKLYLRELPTLILGGELHNDFKRLVEEnHDRSQRALELKDLVSQLPQANYDLLYVLFSFLRKIIEHSDVNKMNLRN 160

                  ....*....
gi 568912537 1303 LAIVFGPTL 1311
Cdd:cd04400   161 VCIVFSPTL 169

RhoGAP_SYD1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in SYD-1_like proteins. Syd-1, first identified and best studied in C.elegans, has been shown to play an important role in neuronal development by specifying axonal properties. 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 568912537 1162 TNRYIPLIVDICCKLVEERGLEYTGIYRVPGNNAAISSMQEELNKGMADIDIQDDKWRDLNVISSLLKSFFRKLPEPLFT 1241
Cdd:cd04379    14 ESRDVPIVLQKCVQEIERRGLDVIGLYRLCGSAAKKKELRDAFERNSAAVELSEELYPDINVITGVLKDYLRELPEPLIT 93

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 568912537 1242 NDKYADFIEANRKEDPLDRLRTLK---RLIHDLPEHHFETLKFLSAHLKTVAENSEKNKMEPRNLAIVFGPTL 1311
Cdd:cd04379    94 PQLYEMVLEALAVALPNDVQTNTHltlSIIDCLPLSAKATLLLLLDHLSLVLSNSERNKMTPQNLAVCFGPVL 166

Beta-spectrin pleckstrin homology (PH) domain; Beta spectrin binds actin and functions as a major component of the cytoskeleton underlying cellular membranes. Beta spectrin consists of multiple spectrin repeats followed by a PH domain, which binds to inositol-1,4,5-trisphosphate. The PH domain of beta-spectrin is thought to play a role in the association of spectrin with the plasma membrane of cells. 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 568912537  939 EGWLQfRPLVTD-KGKRvgGSIRPWKQMYVVLRGHSLYLYKDRR--EQTTPSEEEQPISVNACLIDISYSETKRRNVFRL 1015
Cdd:cd10571     2 EGFLE-RKHEWEsGGKK--ASNRSWKNVYTVLRGQELSFYKDQKaaKSGITYAAEPPLNLYNAVCEVASDYTKKKHVFRL 78

                          90       100
                  ....*....|....*....|....*...
gi 568912537 1016 TTSD-CECLFQAEDRDDMLSWIKTIQES 1042
Cdd:cd10571    79 KLSDgAEFLFQAKDEEEMNQWVKKISFA 106

RhoGAP_ARHGAP18: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP18-like proteins. The function of ArhGAP18 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 568912537 1166 IPLIVDICCKLVEERGLEYTGIYRVPGNNAAISSMQEELNkgmADIDIQDDKWRDLNV--ISSLLKSFFRKLPEPLFTND 1243
Cdd:cd04391    22 VPLIFQKLINKLEERGLETEGILRIPGSAQRVKFLCQELE---AKFYEGTFLWDQVKQhdAASLLKLFIRELPQPLLTVE 98

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568912537 1244 KYADFIEANRKEDPLDRLRTLKRLIHDLPEHHFETLKFLSAHLKTVAENSEKNKMEPRNLAIVFGPTLV-------RTSE 1316
Cdd:cd04391    99 YLPAFYSVQGLPSKKDQLQALNLLVLLLPEANRDTLKALLEFLQKVVDHEEKNKMNLWNVAMIMAPNLFpprgkhsKDNE 178

                         170       180
                  ....*....|....*....|....*....
gi 568912537 1317 DNMTHMVTHMPDQYkIVETLIQHHDWFFT 1345
Cdd:cd04391   179 SLQEEVNMAAGCAN-IMRLLIRYQDLLWT 206