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 1846349849 1248 TFGVRLDDCPPAHTNKYIPLIVDICCKLVEERGLEYTGIYRVPGNNAAISSMQEELNKGMTDIDVHDDKWRDLNVISSLL 1327
Cdd:cd04395      1 TFGVPLDDCPPSSENPYVPLIVEVCCNIVEARGLETVGIYRVPGNNAAISALQEELNRGGFDIDLQDPRWRDVNVVSSLL 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1846349849 1328 KSFFRKLPEPLFTNDKYADFIDANRKEDPVERLKTLKRLIHDLPEHHYETLKFLSAHLKTVAENSEKNKMEPRNLAIVFG 1407
Cdd:cd04395     81 KSFFRKLPEPLFTNELYPDFIEANRIEDPVERLKELRRLIHSLPDHHYETLKHLIRHLKTVADNSEVNKMEPRNLAIVFG 160

                          170       180       190
                   ....*....|....*....|....*....|....*.
gi 1846349849 1408 PTLVRTSDDNMTHMVTHMPDQYKIVETLIQKHDWFF 1443
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 1846349849 1034 KEGWLHFRQLFTDKGKRVggSIRPWKQLYVVLRGHSLYLYKDKKEQVT----LSEEEQPISINACLIDISYCETKRKNVF 1109
Cdd:cd01253      2 REGWLHYKQIVTDKGKRV--SDRSWKQAWAVLRGHSLYLYKDKREQTPalsiELGSEQRISIRGCIVDIAYSYTKRKHVF 79

                           90       100       110
                   ....*....|....*....|....*....|....
gi 1846349849 1110 RLTTSDR-EYLFQAEDRDNMLAWIKAIQDNSNLN 1142
Cdd:cd01253     80 RLTTSDFsEYLFQAEDRDDMLGWIKAIQENSNAE 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 1846349849 1248 TFGVRLDDCPPAHTNKYIPLIVDICCKLVEERGLEYTGIYRVPGNNAAISSMQEELNKGMTDIDVHDDKWRDLNVISSLL 1327
Cdd:cd04395      1 TFGVPLDDCPPSSENPYVPLIVEVCCNIVEARGLETVGIYRVPGNNAAISALQEELNRGGFDIDLQDPRWRDVNVVSSLL 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1846349849 1328 KSFFRKLPEPLFTNDKYADFIDANRKEDPVERLKTLKRLIHDLPEHHYETLKFLSAHLKTVAENSEKNKMEPRNLAIVFG 1407
Cdd:cd04395     81 KSFFRKLPEPLFTNELYPDFIEANRIEDPVERLKELRRLIHSLPDHHYETLKHLIRHLKTVADNSEVNKMEPRNLAIVFG 160

                          170       180       190
                   ....*....|....*....|....*....|....*.
gi 1846349849 1408 PTLVRTSDDNMTHMVTHMPDQYKIVETLIQKHDWFF 1443
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 1846349849  1263 KYIPLIVDICCKLVEERGLEYTGIYRVPGNNAAISSMQEELNKGMtDIDVHDDKWrDLNVISSLLKSFFRKLPEPLFTND 1342
Cdd:smart00324    1 KPIPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGP-DPDLDLSEY-DVHDVAGLLKLFLRELPEPLITYE 78

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1846349849  1343 KYADFIDANRKEDPVERLKTLKRLIHDLPEHHYETLKFLSAHLKTVAENSEKNKMEPRNLAIVFGPTLVRTSDDNMThMV 1422
Cdd:smart00324   79 LYEEFIEAAKLEDETERLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEVA-SL 157

                           170
                    ....*....|....*..
gi 1846349849  1423 THMPDQYKIVETLIQKH 1439
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 1846349849 1034 KEGWLHFRQLFTDKGKRVggSIRPWKQLYVVLRGHSLYLYKDKKEQVT----LSEEEQPISINACLIDISYCETKRKNVF 1109
Cdd:cd01253      2 REGWLHYKQIVTDKGKRV--SDRSWKQAWAVLRGHSLYLYKDKREQTPalsiELGSEQRISIRGCIVDIAYSYTKRKHVF 79

                           90       100       110
                   ....*....|....*....|....*....|....
gi 1846349849 1110 RLTTSDR-EYLFQAEDRDNMLAWIKAIQDNSNLN 1142
Cdd:cd01253     80 RLTTSDFsEYLFQAEDRDDMLGWIKAIQENSNAE 113

Domain present in PSD-95, Dlg, and ZO-1/2; Also called DHR (Dlg homologous region) or GLGF (relatively well conserved tetrapeptide in these domains). Some PDZs have been shown to bind C-terminal polypeptides; others appear to bind internal (non-C-terminal) polypeptides. Different PDZs possess different binding specificities.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1846349849    49 PKTVVLRRTSQGFGFTLRhfivyppesaiqfSFKDEENGnrqgkqrnrlepmdtIFVKQVKEGGPAFEAGLCTGDRIIKV 128
Cdd:smart00228    2 PRLVELEKGGGGLGFSLV-------------GGKDEGGG---------------VVVSSVVPGSPAAKAGLRVGDVILEV 53

                            90       100       110
                    ....*....|....*....|....*....|..
gi 1846349849   129 NGESVIGKTYSQVIALIQNSDSVLELSVMPKD 160
Cdd:smart00228   54 NGTSVEGLTHLEAVDLLKKAGGKVTLTVLRGG 85

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

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1846349849  101 DTIFVKQVKEGGPAFEAGLCTGDRIIKVNGESVIGKTYSQVIALIQN-SDSVLELSVMPKDED 162
Cdd:COG0793     71 GKVVVVSVIPGSPAEKAGIKPGDIILAIDGKSVAGLTLDDAVKLLRGkAGTKVTLTIKRPGEG 133

sigma E protease regulator RseP;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1846349849   96 RLEPMdtifVKQVKEGGPAFEAGLCTGDRIIKVNGESvIGKTYSQVIALIQNSDSVLELSVmPKDEDILQLAYSQDAYLK 175
Cdd:PRK10779   220 QIEPV----LAEVQPNSAASKAGLQAGDRIVKVDGQP-LTQWQTFVTLVRDNPGKPLALEI-ERQGSPLSLTLTPDSKPG 293

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|
gi 1846349849  176 GNEAySGNAHNIPE--PPPICYP--RLTSTASVKAQAGDK 211
Cdd:PRK10779   294 NGKA-EGFAGVVPKviPLPDEYKtvRQYGPFSAIYEATDK 332

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 1846349849 1248 TFGVRLDDCPPAHTNKYIPLIVDICCKLVEERGLEYTGIYRVPGNNAAISSMQEELNKGMTDIDVHDDKWRDLNVISSLL 1327
Cdd:cd04395      1 TFGVPLDDCPPSSENPYVPLIVEVCCNIVEARGLETVGIYRVPGNNAAISALQEELNRGGFDIDLQDPRWRDVNVVSSLL 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1846349849 1328 KSFFRKLPEPLFTNDKYADFIDANRKEDPVERLKTLKRLIHDLPEHHYETLKFLSAHLKTVAENSEKNKMEPRNLAIVFG 1407
Cdd:cd04395     81 KSFFRKLPEPLFTNELYPDFIEANRIEDPVERLKELRRLIHSLPDHHYETLKHLIRHLKTVADNSEVNKMEPRNLAIVFG 160

                          170       180       190
                   ....*....|....*....|....*....|....*.
gi 1846349849 1408 PTLVRTSDDNMTHMVTHMPDQYKIVETLIQKHDWFF 1443
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 1846349849  1263 KYIPLIVDICCKLVEERGLEYTGIYRVPGNNAAISSMQEELNKGMtDIDVHDDKWrDLNVISSLLKSFFRKLPEPLFTND 1342
Cdd:smart00324    1 KPIPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGP-DPDLDLSEY-DVHDVAGLLKLFLRELPEPLITYE 78

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1846349849  1343 KYADFIDANRKEDPVERLKTLKRLIHDLPEHHYETLKFLSAHLKTVAENSEKNKMEPRNLAIVFGPTLVRTSDDNMThMV 1422
Cdd:smart00324   79 LYEEFIEAAKLEDETERLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEVA-SL 157

                           170
                    ....*....|....*..
gi 1846349849  1423 THMPDQYKIVETLIQKH 1439
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 1846349849 1266 PLIVDICCKLVEERGLEYTGIYRVPGNNAAISSMQEELNKGmtdIDVHDDKWRDLNVISSLLKSFFRKLPEPLFTNDKYA 1345
Cdd:cd00159      1 PLIIEKCIEYLEKNGLNTEGIFRVSGSASKIEELKKKFDRG---EDIDDLEDYDVHDVASLLKLYLRELPEPLIPFELYD 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1846349849 1346 DFIDANRKEDPVERLKTLKRLIHDLPEHHYETLKFLSAHLKTVAENSEKNKMEPRNLAIVFGPTLVRTSDDNMThMVTHM 1425
Cdd:cd00159     78 EFIELAKIEDEEERIEALKELLKSLPPENRDLLKYLLKLLHKISQNSEVNKMTASNLAIVFAPTLLRPPDSDDE-LLEDI 156

                          170
                   ....*....|..
gi 1846349849 1426 PDQYKIVETLIQ 1437
Cdd:cd00159    157 KKLNEIVEFLIE 168

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 1846349849 1249 FGVRLDDC-PPAHTNkyIPLIVDICCKLVEERGLEYTGIYRVPGNNAAISSMQEELNK--GMTDIDVHDDKWRDLNVISS 1325
Cdd:cd04398      1 FGVPLEDLiLREGDN--VPNIVYQCIQAIENFGLNLEGIYRLSGNVSRVNKLKELFDKdpLNVLLISPEDYESDIHSVAS 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1846349849 1326 LLKSFFRKLPEPLFTNDKYADFIDANRKEDPVERLKTLKRLIHDLPEHHYETLKFLSAHLKTVAENSEKNKMEPRNLAIV 1405
Cdd:cd04398     79 LLKLFFRELPEPLLTKALSREFIEAAKIEDESRRRDALHGLINDLPDANYATLRALMFHLARIKEHESVNRMSVNNLAII 158

                          170       180       190
                   ....*....|....*....|....*....|....*...
gi 1846349849 1406 FGPTLVRTSDDNmthmVTHMPDQYKIVETLIQKHDWFF 1443
Cdd:cd04398    159 WGPTLMNAAPDN----AADMSFQSRVIETLLDNAYQIF 192

RhoGAP_chimaerin: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of chimaerins. Chimaerins are a family of phorbolester- and diacylglycerol-responsive GAPs specific for the Rho-like GTPase Rac. Chimaerins exist in two alternative splice forms that each contain a C-terminal GAP domain, and a central C1 domain which binds phorbol esters, inducing a conformational change that activates the protein; one splice form is lacking the N-terminal Src homology-2 (SH2) 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 1846349849 1249 FGVRLDDCPPAHtNKYIPLIVDICCKLVEERGLEYTGIYRVPGNNAAISSMQEELNKGMTDIDVHDDKWRDLNVISSLLK 1328
Cdd:cd04372      1 YGCDLTTLVKAH-NTQRPMVVDMCIREIEARGLQSEGLYRVSGFAEEIEDVKMAFDRDGEKADISATVYPDINVITGALK 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1846349849 1329 SFFRKLPEPLFTNDKYADFIDANRKEDPVERLKTLKRLIHDLPEHHYETLKFLSAHLKTVAENSEKNKMEPRNLAIVFGP 1408
Cdd:cd04372     80 LYFRDLPIPVITYDTYPKFIDAAKISNPDERLEAVHEALMLLPPAHYETLRYLMEHLKRVTLHEKDNKMNAENLGIVFGP 159

                          170       180       190
                   ....*....|....*....|....*....|....*
gi 1846349849 1409 TLVRTSDDNMTHMVTHMPDQYKIVETLIQKHDWFF 1443
Cdd:cd04372    160 TLMRPPEDSALTTLNDMRYQILIVQLLITNEDVLF 194

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 1846349849 1265 IPLIVDICCKLVEERGLEYTGIYRVPGNNAAISSMQEELNKgmtdiDVHDDKWR--DLNV--ISSLLKSFFRKLPEPLFT 1340
Cdd:cd04385     15 IPVIVDKCIDFITQHGLMSEGIYRKNGKNSSVKKLLEAFRK-----DARSVQLRegEYTVhdVADVLKRFLRDLPDPLLT 89

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1846349849 1341 NDKYADFIDANRKEDPVERLKTLKRLIHDLPEHHYETLKFLSAHLKTVAENSEKNKMEPRNLAIVFGPTLVRTSDdnmtH 1420
Cdd:cd04385     90 SELHAEWIEAAELENKDERIARYKELIRRLPPINRATLKVLIGHLYRVQKHSDENQMSVHNLALVFGPTLFQTDE----H 165

                          170
                   ....*....|....*..
gi 1846349849 1421 MVTHMPDQYKIVETLIQ 1437
Cdd:cd04385    166 SVGQTSHEVKVIEDLID 182

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 1846349849 1259 AHTNKYIPLIVDICCKLVEERGLEYTGIYRVPGNNaaiSSMQEELNKGM-------TDIDVHDDKWrDLNVISSLLKSFF 1331
Cdd:cd04374     22 AQLDDIGFKFVRKCIEAVETRGINEQGLYRVVGVN---SKVQKLLSLGLdpktstpGDVDLDNSEW-EIKTITSALKTYL 97

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1846349849 1332 RKLPEPLFTNDKYADFIDANRKEDPVERLKTLKRLIHDLPEHHYETLKFLSAHLKTVAENSEKNKMEPRNLAIVFGPTLV 1411
Cdd:cd04374     98 RNLPEPLMTYELHNDFINAAKSENLESRVNAIHSLVHKLPEKNREMLELLIKHLTNVSDHSKKNLMTVSNLGVVFGPTLL 177

                          170       180
                   ....*....|....*....|....*....
gi 1846349849 1412 RTSDDNmthmVTHMPD---QYKIVETLIQ 1437
Cdd:cd04374    178 RPQEET----VAAIMDikfQNIVVEILIE 202

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 1846349849 1265 IPLIVDICCKLVEERGLEYTGIYRVPGNNAAISSMQEELNKGMTDIDVHDdkwRDLNVISSLLKSFFRKLPEPLFTNDKY 1344
Cdd:cd04382     17 IPALIVHCVNEIEARGLTEEGLYRVSGSEREVKALKEKFLRGKTVPNLSK---VDIHVICGCLKDFLRSLKEPLITFALW 93

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1846349849 1345 ADFIDANRKEDPVERLKTLKRLIHDLPEHHYETLKFLSAHLKTVAEnSEKNKMEPRNLAIVFGPTLVRTSDDN--MTHMV 1422
Cdd:cd04382     94 KEFMEAAEILDEDNSRAALYQAISELPQPNRDTLAFLILHLQRVAQ-SPECKMDINNLARVFGPTIVGYSVPNpdPMTIL 172

                          170
                   ....*....|...
gi 1846349849 1423 THMPDQYKIVETL 1435
Cdd:cd04382    173 QDTVRQPRVVERL 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 1846349849 1265 IPLIVDICCKLVEERGLEYTGIYRVPGNNAAISSMQEELNKGMTDIDVHDDKwRDLNVISSLLKSFFRKLPEPLFTNDKY 1344
Cdd:cd04387     16 VPYIVRQCVEEVERRGMEEVGIYRISGVATDIQALKAAFDTNNKDVSVMLSE-MDVNAIAGTLKLYFRELPEPLFTDELY 94

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1846349849 1345 ADFIDANRKEDPVERLKTLKRLIHDLPEHHYETLKFLSAHLKTVAENSEKNKMEPRNLAIVFGPTLVRTSDDNMTHMVTH 1424
Cdd:cd04387     95 PNFAEGIALSDPVAKESCMLNLLLSLPDPNLVTFLFLLHHLKRVAEREEVNKMSLHNLATVFGPTLLRPSEKESKIPTNT 174

                          170
                   ....*....|...
gi 1846349849 1425 MPDQYKiVETLIQ 1437
Cdd:cd04387    175 MTDSWS-LEVMSQ 186

RhoGAP_srGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in srGAPs. srGAPs are components of the intracellular part of Slit-Robo signalling pathway that is important for axon guidance and cell migration. srGAPs contain an N-terminal FCH domain, a central RhoGAP domain and a C-terminal SH3 domain; this SH3 domain interacts with the intracellular proline-rich-tail of the Roundabout receptor (Robo). This interaction with Robo then activates the rhoGAP domain which in turn inhibits Cdc42 activity. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1846349849 1261 TNKYIPLIVDICCKLVEERGLEYTGIYRVPGNNAAISSMQEELNKGmTDIDVHDDKWRDLNVISSLLKSFFRKLPEPLFT 1340
Cdd:cd04383     14 SGQAIPLVVESCIRFINLYGLQHQGIFRVSGSQVEVNDIKNAFERG-EDPLADDQNDHDINSVAGVLKLYFRGLENPLFP 92

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1846349849 1341 NDKYADFIDANRKEDPVERLKTLKRLIHDLPEHHYETLKFLSAHLKTVAENSEKNKMEPRNLAIVFGPTLVRTSDD 1416
Cdd:cd04383     93 KERFEDLMSCVKLENPTERVHQIREILSTLPRSVIIVMRYLFAFLNHLSQFSDENMMDPYNLAICFGPTLMPVPEG 168

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 1846349849 1261 TNKYIPLIVDICCKLVEERGLeYTGIYRVPGNNAAISSMQEELNKGMTDiDVHDDKW-RDLNVISSLLKSFFRKLPEPLF 1339
Cdd:cd04384     14 SGQDVPQVLKSCTEFIEKHGI-VDGIYRLSGIASNIQRLRHEFDSEQIP-DLTKDVYiQDIHSVSSLCKLYFRELPNPLL 91

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1846349849 1340 TNDKYADFIDANRKEDPVERLKTLKRLIHDLPEHHYETLKFLSAHLKTVAENSEKNKMEPRNLAIVFGPTLVRT 1413
Cdd:cd04384     92 TYQLYEKFSEAVSAASDEERLEKIHDVIQQLPPPHYRTLEFLMRHLSRLAKYCSITNMHAKNLAIVWAPNLLRS 165

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 1846349849 1249 FGVRLDDCPPAHTNKY----IPLIVDICCKLVEERGLEYT-GIYRVPGNNAAISSMQEELNKGMtDID-VHDDKWRDLNV 1322
Cdd:cd04400      2 FGSPLEEAVELSSHKYngrdLPSVVYRCIEYLDKNRAIYEeGIFRLSGSASVIKQLKERFNTEY-DVDlFSSSLYPDVHT 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1846349849 1323 ISSLLKSFFRKLPEPLFTNDKYADFIDANRK-EDPVERLKTLKRLIHDLPEHHYETLKFLSAHLKTVAENSEKNKMEPRN 1401
Cdd:cd04400     81 VAGLLKLYLRELPTLILGGELHNDFKRLVEEnHDRSQRALELKDLVSQLPQANYDLLYVLFSFLRKIIEHSDVNKMNLRN 160

                   ....*....
gi 1846349849 1402 LAIVFGPTL 1410
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 1846349849 1265 IPLIVDICCKLVEERGLEYTGIYRVPGNNAAISSMQEELNKGMTDIDVHDDKWRDLNVISSLLKSFFRKLPEPLFTNDKY 1344
Cdd:cd04379     18 VPIVLQKCVQEIERRGLDVIGLYRLCGSAAKKKELRDAFERNSAAVELSEELYPDINVITGVLKDYLRELPEPLITPQLY 97

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1846349849 1345 ADFIDA---NRKEDPVERLKTLKRLIHDLPEHHYETLKFLSAHLKTVAENSEKNKMEPRNLAIVFGPTLVRTSD 1415
Cdd:cd04379     98 EMVLEAlavALPNDVQTNTHLTLSIIDCLPLSAKATLLLLLDHLSLVLSNSERNKMTPQNLAVCFGPVLMFCSQ 171

RhoGAP_ARHGAP22_24_25: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ARHGAP22, 24 and 25-like proteins; longer isoforms of these proteins contain an additional N-terminal pleckstrin homology (PH) domain. ARHGAP25 (KIA0053) has been identified as a GAP for Rac1 and Cdc42. Short isoforms (without the PH domain) of ARHGAP24, called RC-GAP72 and p73RhoGAP, and of ARHGAP22, called p68RacGAP, has been shown to be involved in angiogenesis and endothelial cell capillary 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 1846349849 1247 GTFGVRLDDCPpAHTNKY----IPLIVDICCKLVEERGLEYTGIYRVPGNNAAISSMQEELNKGM-----TDIDVHddkw 1317
Cdd:cd04390      1 GVFGQRLEDTV-AYERKFgprlVPILVEQCVDFIREHGLKEEGLFRLPGQANLVKQLQDAFDAGErpsfdSDTDVH---- 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1846349849 1318 rdlnVISSLLKSFFRKLPEPLFTNDKYADFIDANRKEDPVER--LKTLKRLIHDLPEHHYETLKFLSAHLKTVAENSEKN 1395
Cdd:cd04390     76 ----TVASLLKLYLRELPEPVIPWAQYEDFLSCAQLLSKDEEkgLGELMKQVSILPKVNYNLLSYICRFLDEVQSNSSVN 151

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*...
gi 1846349849 1396 KMEPRNLAIVFGPTLVRTSDDNMTHMVTHMPDQYKIVETLIQKHDWFF 1443
Cdd:cd04390    152 KMSVQNLATVFGPNILRPKVEDPATIMEGTPQIQQLMTVMISKHEPLF 199

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 1846349849 1265 IPLIVDICCKLVEERGLEYTGIYRVPGNNAAISSMQEEL----NKGMTDID---VHDdkwrdlnvISSLLKSFFRKLPEP 1337
Cdd:cd04391     22 VPLIFQKLINKLEERGLETEGILRIPGSAQRVKFLCQELeakfYEGTFLWDqvkQHD--------AASLLKLFIRELPQP 93

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1846349849 1338 LFTNDKYADFIDANRKEDPVERLKTLKRLIHDLPEHHYETLKFLSAHLKTVAENSEKNKMEPRNLAIVFGPTL 1410
Cdd:cd04391     94 LLTVEYLPAFYSVQGLPSKKDQLQALNLLVLLLPEANRDTLKALLEFLQKVVDHEEKNKMNLWNVAMIMAPNL 166