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 203097667 1138 TFGVRLDDCPPAHTNRYIPLIVDICCKLVEERGLEYTGIYRVPGNNAAISSMQEELNKGMADIDIQDDKWRDLNVISSLL 1217
Cdd:cd04395     1 TFGVPLDDCPPSSENPYVPLIVEVCCNIVEARGLETVGIYRVPGNNAAISALQEELNRGGFDIDLQDPRWRDVNVVSSLL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 203097667 1218 KSFFRKLPEPLFTNDKYADFIEANRKEDPLDRLRTLKRLIHDLPEHHFETLKFLSAHLKTVAENSEKNKMEPRNLAIVFG 1297
Cdd:cd04395    81 KSFFRKLPEPLFTNELYPDFIEANRIEDPVERLKELRRLIHSLPDHHYETLKHLIRHLKTVADNSEVNKMEPRNLAIVFG 160

                         170       180       190
                  ....*....|....*....|....*....|....*.
gi 203097667 1298 PTLVRTSEDNMTHMVTHMPDQYKIVETLIQHHDWFF 1333
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 203097667  927 AREGWLQFRPLVTDKGKRVggSIRPWKQMYVVLRGHSLYLYKDRREQTTP----SEEEQPISVNACLIDISYSETKRRNV 1002
Cdd:cd01253     1 AREGWLHYKQIVTDKGKRV--SDRSWKQAWAVLRGHSLYLYKDKREQTPAlsieLGSEQRISIRGCIVDIAYSYTKRKHV 78

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 203097667 1003 FRLTTSD-CECLFQAEDRDDMLSWIKTIQESSNLN 1036
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 203097667 1138 TFGVRLDDCPPAHTNRYIPLIVDICCKLVEERGLEYTGIYRVPGNNAAISSMQEELNKGMADIDIQDDKWRDLNVISSLL 1217
Cdd:cd04395     1 TFGVPLDDCPPSSENPYVPLIVEVCCNIVEARGLETVGIYRVPGNNAAISALQEELNRGGFDIDLQDPRWRDVNVVSSLL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 203097667 1218 KSFFRKLPEPLFTNDKYADFIEANRKEDPLDRLRTLKRLIHDLPEHHFETLKFLSAHLKTVAENSEKNKMEPRNLAIVFG 1297
Cdd:cd04395    81 KSFFRKLPEPLFTNELYPDFIEANRIEDPVERLKELRRLIHSLPDHHYETLKHLIRHLKTVADNSEVNKMEPRNLAIVFG 160

                         170       180       190
                  ....*....|....*....|....*....|....*.
gi 203097667 1298 PTLVRTSEDNMTHMVTHMPDQYKIVETLIQHHDWFF 1333
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 203097667   1153 RYIPLIVDICCKLVEERGLEYTGIYRVPGNNAAISSMQEELNKGMaDIDIQDDKWrDLNVISSLLKSFFRKLPEPLFTND 1232
Cdd:smart00324    1 KPIPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGP-DPDLDLSEY-DVHDVAGLLKLFLRELPEPLITYE 78

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 203097667   1233 KYADFIEANRKEDPLDRLRTLKRLIHDLPEHHFETLKFLSAHLKTVAENSEKNKMEPRNLAIVFGPTLVRTSEDNMThMV 1312
Cdd:smart00324   79 LYEEFIEAAKLEDETERLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEVA-SL 157

                           170
                    ....*....|....*..
gi 203097667   1313 THMPDQYKIVETLIQHH 1329
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 203097667  927 AREGWLQFRPLVTDKGKRVggSIRPWKQMYVVLRGHSLYLYKDRREQTTP----SEEEQPISVNACLIDISYSETKRRNV 1002
Cdd:cd01253     1 AREGWLHYKQIVTDKGKRV--SDRSWKQAWAVLRGHSLYLYKDKREQTPAlsieLGSEQRISIRGCIVDIAYSYTKRKHV 78

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 203097667 1003 FRLTTSD-CECLFQAEDRDDMLSWIKTIQESSNLN 1036
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 203097667    928 REGWLQfrplvtdkgKRVGGSIRPWKQMYVVLRGHSLYLYKDrREQTTPSEEEQPISVNACLIDI--SYSETKRRNVFRL 1005
Cdd:smart00233    3 KEGWLY---------KKSGGGKKSWKKRYFVLFNSTLLYYKS-KKDKKSYKPKGSIDLSGCTVREapDPDSSKKPHCFEI 72

                            90       100       110
                    ....*....|....*....|....*....|
gi 203097667   1006 TTSDCECL-FQAEDRDDMLSWIKTIQESSN 1034
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
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 203097667  106 DTIFVKQVKEGGPAFEAGLCTGDRIIKVNGESVIGKTYSQVIALIQN-SDTTLELSVMPKDED 167
Cdd:COG0793    71 GKVVVVSVIPGSPAEKAGIKPGDIILAIDGKSVAGLTLDDAVKLLRGkAGTKVTLTIKRPGEG 133

sigma E protease regulator RseP;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 203097667  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 203097667 1138 TFGVRLDDCPPAHTNRYIPLIVDICCKLVEERGLEYTGIYRVPGNNAAISSMQEELNKGMADIDIQDDKWRDLNVISSLL 1217
Cdd:cd04395     1 TFGVPLDDCPPSSENPYVPLIVEVCCNIVEARGLETVGIYRVPGNNAAISALQEELNRGGFDIDLQDPRWRDVNVVSSLL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 203097667 1218 KSFFRKLPEPLFTNDKYADFIEANRKEDPLDRLRTLKRLIHDLPEHHFETLKFLSAHLKTVAENSEKNKMEPRNLAIVFG 1297
Cdd:cd04395    81 KSFFRKLPEPLFTNELYPDFIEANRIEDPVERLKELRRLIHSLPDHHYETLKHLIRHLKTVADNSEVNKMEPRNLAIVFG 160

                         170       180       190
                  ....*....|....*....|....*....|....*.
gi 203097667 1298 PTLVRTSEDNMTHMVTHMPDQYKIVETLIQHHDWFF 1333
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 203097667   1153 RYIPLIVDICCKLVEERGLEYTGIYRVPGNNAAISSMQEELNKGMaDIDIQDDKWrDLNVISSLLKSFFRKLPEPLFTND 1232
Cdd:smart00324    1 KPIPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGP-DPDLDLSEY-DVHDVAGLLKLFLRELPEPLITYE 78

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 203097667   1233 KYADFIEANRKEDPLDRLRTLKRLIHDLPEHHFETLKFLSAHLKTVAENSEKNKMEPRNLAIVFGPTLVRTSEDNMThMV 1312
Cdd:smart00324   79 LYEEFIEAAKLEDETERLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEVA-SL 157

                           170
                    ....*....|....*..
gi 203097667   1313 THMPDQYKIVETLIQHH 1329
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 203097667 1156 PLIVDICCKLVEERGLEYTGIYRVPGNNAAISSMQEELNKGmadIDIQDDKWRDLNVISSLLKSFFRKLPEPLFTNDKYA 1235
Cdd:cd00159     1 PLIIEKCIEYLEKNGLNTEGIFRVSGSASKIEELKKKFDRG---EDIDDLEDYDVHDVASLLKLYLRELPEPLIPFELYD 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 203097667 1236 DFIEANRKEDPLDRLRTLKRLIHDLPEHHFETLKFLSAHLKTVAENSEKNKMEPRNLAIVFGPTLVRTSEDNMThMVTHM 1315
Cdd:cd00159    78 EFIELAKIEDEEERIEALKELLKSLPPENRDLLKYLLKLLHKISQNSEVNKMTASNLAIVFAPTLLRPPDSDDE-LLEDI 156

                         170
                  ....*....|...
gi 203097667 1316 PDQYKIVETLIQH 1328
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 203097667 1150 HTNRYIPLIVDICCKLVEERGLEYTGIYRVPGNNAAISSMQEELNKGMAdIDIQDDKWRDLNVISSLLKSFFRKLPEPLF 1229
Cdd:cd04403    11 RENSTVPKFVRLCIEAVEKRGLDVDGIYRVSGNLAVIQKLRFAVDHDEK-LDLDDSKWEDIHVITGALKLFFRELPEPLF 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 203097667 1230 TNDKYADFIEANRKEDPLDRLRTLKRLIHDLPEHHFETLKFLSAHLKTVAENSEKNKMEPRNLAIVFGPTLVRtSEDNMT 1309
Cdd:cd04403    90 PYSLFNDFVAAIKLSDYEQRVSAVKDLIKSLPKPNHDTLKMLFRHLCRVIEHGEKNRMTTQNLAIVFGPTLLR-PEQETG 168

                         170
                  ....*....|....*...
gi 203097667 1310 HMVTHMPDQYKIVETLIQ 1327
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 203097667 1139 FGVRLDDC-PPAHTNryIPLIVDICCKLVEERGLEYTGIYRVPGNNAAISSMQEELNKGMADIDI--QDDKWRDLNVISS 1215
Cdd:cd04398     1 FGVPLEDLiLREGDN--VPNIVYQCIQAIENFGLNLEGIYRLSGNVSRVNKLKELFDKDPLNVLLisPEDYESDIHSVAS 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 203097667 1216 LLKSFFRKLPEPLFTNDKYADFIEANRKEDPLDRLRTLKRLIHDLPEHHFETLKFLSAHLKTVAENSEKNKMEPRNLAIV 1295
Cdd:cd04398    79 LLKLFFRELPEPLLTKALSREFIEAAKIEDESRRRDALHGLINDLPDANYATLRALMFHLARIKEHESVNRMSVNNLAII 158

                         170       180       190
                  ....*....|....*....|....*....|....*...
gi 203097667 1296 FGPTLVRTSEDNmthmVTHMPDQYKIVETLIQHHDWFF 1333
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 203097667 1158 IVDICCKLVEERGLEYTGIYRVPGNNaaiSSMQEELNKGM-------ADIDIQDDKWrDLNVISSLLKSFFRKLPEPLFT 1230
Cdd:cd04374    31 FVRKCIEAVETRGINEQGLYRVVGVN---SKVQKLLSLGLdpktstpGDVDLDNSEW-EIKTITSALKTYLRNLPEPLMT 106

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 203097667 1231 NDKYADFIEANRKEDPLDRLRTLKRLIHDLPEHHFETLKFLSAHLKTVAENSEKNKMEPRNLAIVFGPTLVRTSEDNmth 1310
Cdd:cd04374   107 YELHNDFINAAKSENLESRVNAIHSLVHKLPEKNREMLELLIKHLTNVSDHSKKNLMTVSNLGVVFGPTLLRPQEET--- 183

                         170       180
                  ....*....|....*....|.
gi 203097667 1311 mVTHMPD---QYKIVETLIQH 1328
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 203097667 1155 IPLIVDICCKLVEERGLEYTGIYRVPGNNAAISSMQEELNKgmadiDIQDDKWR--DLNV--ISSLLKSFFRKLPEPLFT 1230
Cdd:cd04385    15 IPVIVDKCIDFITQHGLMSEGIYRKNGKNSSVKKLLEAFRK-----DARSVQLRegEYTVhdVADVLKRFLRDLPDPLLT 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 203097667 1231 NDKYADFIEANRKEDPLDRLRTLKRLIHDLPEHHFETLKFLSAHLKTVAENSEKNKMEPRNLAIVFGPTLVRTSEdnmtH 1310
Cdd:cd04385    90 SELHAEWIEAAELENKDERIARYKELIRRLPPINRATLKVLIGHLYRVQKHSDENQMSVHNLALVFGPTLFQTDE----H 165

                         170
                  ....*....|....*...
gi 203097667 1311 MVTHMPDQYKIVETLIQH 1328
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 203097667 1155 IPLIVDICCKLVEERGLEYTGIYRVPGNNAAISSMQEELNKG-----MADIDIqddkwrdlNVISSLLKSFFRKLPEPLF 1229
Cdd:cd04382    17 IPALIVHCVNEIEARGLTEEGLYRVSGSEREVKALKEKFLRGktvpnLSKVDI--------HVICGCLKDFLRSLKEPLI 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 203097667 1230 TNDKYADFIEANRKEDPLDRLRTLKRLIHDLPEHHFETLKFLSAHLKTVAEnSEKNKMEPRNLAIVFGPTLV--RTSEDN 1307
Cdd:cd04382    89 TFALWKEFMEAAEILDEDNSRAALYQAISELPQPNRDTLAFLILHLQRVAQ-SPECKMDINNLARVFGPTIVgySVPNPD 167

                         170
                  ....*....|....*...
gi 203097667 1308 MTHMVTHMPDQYKIVETL 1325
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 203097667 1155 IPLIVDICCKLVEERGLEYTGIYRVPGNNAAISSMQEELNKGMADIDIQDDKwRDLNVISSLLKSFFRKLPEPLFTNDKY 1234
Cdd:cd04387    16 VPYIVRQCVEEVERRGMEEVGIYRISGVATDIQALKAAFDTNNKDVSVMLSE-MDVNAIAGTLKLYFRELPEPLFTDELY 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 203097667 1235 ADFIEANRKEDPLDRLRTLKRLIHDLPEHHFETLKFLSAHLKTVAENSEKNKMEPRNLAIVFGPTLVRTSEDNMTHMVTH 1314
Cdd:cd04387    95 PNFAEGIALSDPVAKESCMLNLLLSLPDPNLVTFLFLLHHLKRVAEREEVNKMSLHNLATVFGPTLLRPSEKESKIPTNT 174

                         170
                  ....*....|...
gi 203097667 1315 MPDQYKiVETLIQ 1327
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 203097667 1153 RYIPLIVDICCKLVEERGLEYTGIYRVPGNNAAISSMQEELNKGmadIDIQDDKWRDLNVISSLLKSFFRKLPEPLFTND 1232
Cdd:cd04376     7 RQVPRLVESCCQHLEKHGLQTVGIFRVGSSKKRVRQLREEFDRG---IDVVLDENHSVHDVAALLKEFFRDMPDPLLPRE 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 203097667 1233 KYADFIEANrKEDPLDRLRTLKRLIHDLPEHHFETLKFLSAHLKTVAENSEK-----------NKMEPRNLAIVFGPTLV 1301
Cdd:cd04376    84 LYTAFIGTA-LLEPDEQLEALQLLIYLLPPCNCDTLHRLLKFLHTVAEHAADsidedgqevsgNKMTSLNLATIFGPNLL 162

                         170       180       190
                  ....*....|....*....|....*....|....*....
gi 203097667 1302 RTSEDNMTHMVT------HMPDQYKIVETLIQHHDWFFT 1334
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 203097667 1148 PAHTNRYIPLIVDICCKLVEERGLEYTGIYRVPGNNAAISSMQEELNKGMADIDIQDDKWRDlnvISSLLKSFFRKLPEP 1227
Cdd:cd04408     9 PRDFPEEVPFVVVRCTAEIENRALGVQGIYRISGSKARVEKLCQAFENGRDLVDLSGHSPHD---ITSVLKHFLKELPEP 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 203097667 1228 LFTNDKYADFIEANR--KEDPLDR----------LRTLKRLIHDLPEHHFETLKFLSAHLKTVAENSEKNKMEPRNLAIV 1295
Cdd:cd04408    86 VLPFQLYDDFIALAKelQRDSEKAaespsiveniIRSLKELLGRLPVSNYNTLRHLMAHLYRVAERFEDNKMSPNNLGIV 165

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 203097667 1296 FGPTLVRTSEDNMTHMVTHMPDQYK--IVETLIQH 1328
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 203097667 1139 FGVRLDDC----PPAHTNRYIPLIVDICCKLVEERGLEYT-GIYRVPGNNAAISSMQEELNKGMaDIDI-QDDKWRDLNV 1212
Cdd:cd04400     2 FGSPLEEAvelsSHKYNGRDLPSVVYRCIEYLDKNRAIYEeGIFRLSGSASVIKQLKERFNTEY-DVDLfSSSLYPDVHT 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 203097667 1213 ISSLLKSFFRKLPEPLFTNDKYADFIEANRK-EDPLDRLRTLKRLIHDLPEHHFETLKFLSAHLKTVAENSEKNKMEPRN 1291
Cdd:cd04400    81 VAGLLKLYLRELPTLILGGELHNDFKRLVEEnHDRSQRALELKDLVSQLPQANYDLLYVLFSFLRKIIEHSDVNKMNLRN 160

                  ....*....
gi 203097667 1292 LAIVFGPTL 1300
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 203097667 1151 TNRYIPLIVDICCKLVEERGLEYTGIYRVPGNNAAISSMQEELNKGMADIDIQDDKWRDLNVISSLLKSFFRKLPEPLFT 1230
Cdd:cd04379    14 ESRDVPIVLQKCVQEIERRGLDVIGLYRLCGSAAKKKELRDAFERNSAAVELSEELYPDINVITGVLKDYLRELPEPLIT 93

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 203097667 1231 NDKYADFIEANRKEDPLDRLRTLK---RLIHDLPEHHFETLKFLSAHLKTVAENSEKNKMEPRNLAIVFGPTL 1300
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 203097667  929 EGWLQfRPLVTD-KGKRvgGSIRPWKQMYVVLRGHSLYLYKDRR--EQTTPSEEEQPISVNACLIDISYSETKRRNVFRL 1005
Cdd:cd10571     2 EGFLE-RKHEWEsGGKK--ASNRSWKNVYTVLRGQELSFYKDQKaaKSGITYAAEPPLNLYNAVCEVASDYTKKKHVFRL 78

                          90       100
                  ....*....|....*....|....*...
gi 203097667 1006 TTSD-CECLFQAEDRDDMLSWIKTIQES 1032
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 203097667 1155 IPLIVDICCKLVEERGLEYTGIYRVPGNNAAISSMQEELNkgmADIDIQDDKWRDLNV--ISSLLKSFFRKLPEPLFTND 1232
Cdd:cd04391    22 VPLIFQKLINKLEERGLETEGILRIPGSAQRVKFLCQELE---AKFYEGTFLWDQVKQhdAASLLKLFIRELPQPLLTVE 98

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 203097667 1233 KYADFIEANRKEDPLDRLRTLKRLIHDLPEHHFETLKFLSAHLKTVAENSEKNKMEPRNLAIVFGPTLV-------RTSE 1305
Cdd:cd04391    99 YLPAFYSVQGLPSKKDQLQALNLLVLLLPEANRDTLKALLEFLQKVVDHEEKNKMNLWNVAMIMAPNLFpprgkhsKDNE 178

                         170       180
                  ....*....|....*....|....*....
gi 203097667 1306 DNMTHMVTHMPDQYkIVETLIQHHDWFFT 1334
Cdd:cd04391   179 SLQEEVNMAAGCAN-IMRLLIRYQDLLWT 206