protein kinase C conserved region 1 (C1 domain) found in the GEM-interacting protein (GMIP)-like family; The GMIP-like family includes GMIP, Rho GTPase-activating protein 29 (ARHGAP29) and Rho GTPase-activating protein 45 (ARHGAP45). GMIP is a RhoA-specific GTPase-activating protein that acts as a key factor in saltatory neuronal migration. It associates with the Rab27a effector JFC1 and modulates vesicular transport and exocytosis. ARHGAP29, also called PTPL1-associated RhoGAP protein 1 (PARG1) or Rho-type GTPase-activating protein 29, is a GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state. It has strong activity toward RHOA, and weaker activity toward RAC1 and CDC42. ARHGAP29 may act as a specific effector of RAP2A to regulate Rho. In concert with RASIP1, ARHGAP29 suppresses RhoA signaling and dampens ROCK and MYH9 activities in endothelial cells and plays an essential role in blood vessel tubulogenesis. ARHGAP45, also called minor histocompatibility antigen HA-1 (mHag HA-1), is a Rac-GAP (GTPase-Activating Protein) in endothelial cells. It acts as a novel regulator of endothelial integrity. ARHGAP45 contains a GTPase activator for the Rho-type GTPases (RhoGAP) domain that would be able to negatively regulate the actin cytoskeleton as well as cell spreading. However, it also contains N-terminally a BAR-domin which can play an autoinhibitory effect on this RhoGAP activity. Members of this family contain a zinc-binding C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 47834348  701 RTHRLRKLRTPAKCRECNSYVYFQGAECEECCLACHKKCLETLAIQCGHKK 751
Cdd:cd20816    1 QTHRFRRLRTPSKCRECDSYVYFNGAECEECGLACHKKCLETLAIQCGHKR 51

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 47834348     774 VPFIVKKCVCEIERRALRTKGIYRVNGVKTRVEKLCQAFENGKELV-ELSQASPHDISNVLKLYLRQLPEPLISFRLYHE 852
Cdd:smart00324    3 IPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGPDPDlDLSEYDVHDVAGLLKLFLRELPEPLITYELYEE 82

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47834348     853 LVGLAKDSlkaeaeakaasrgrqdgSESEAVAvalagRLRELLRDLPPENRASLQYLLRHLRRIVEVEQDNKMTPGNLGI 932
Cdd:smart00324   83 FIEAAKLE-----------------DETERLR-----ALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAI 140

                           170       180       190
                    ....*....|....*....|....*....|....*...
gi 47834348     933 VFGPTLLRPRPTEATvslsSLVDYPHQARVIETLIVHY 970
Cdd:smart00324  141 VFGPTLLRPPDGEVA----SLKDIRHQNTVIEFLIENA 174

protein kinase C conserved region 1 (C1 domain) found in the GEM-interacting protein (GMIP)-like family; The GMIP-like family includes GMIP, Rho GTPase-activating protein 29 (ARHGAP29) and Rho GTPase-activating protein 45 (ARHGAP45). GMIP is a RhoA-specific GTPase-activating protein that acts as a key factor in saltatory neuronal migration. It associates with the Rab27a effector JFC1 and modulates vesicular transport and exocytosis. ARHGAP29, also called PTPL1-associated RhoGAP protein 1 (PARG1) or Rho-type GTPase-activating protein 29, is a GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state. It has strong activity toward RHOA, and weaker activity toward RAC1 and CDC42. ARHGAP29 may act as a specific effector of RAP2A to regulate Rho. In concert with RASIP1, ARHGAP29 suppresses RhoA signaling and dampens ROCK and MYH9 activities in endothelial cells and plays an essential role in blood vessel tubulogenesis. ARHGAP45, also called minor histocompatibility antigen HA-1 (mHag HA-1), is a Rac-GAP (GTPase-Activating Protein) in endothelial cells. It acts as a novel regulator of endothelial integrity. ARHGAP45 contains a GTPase activator for the Rho-type GTPases (RhoGAP) domain that would be able to negatively regulate the actin cytoskeleton as well as cell spreading. However, it also contains N-terminally a BAR-domin which can play an autoinhibitory effect on this RhoGAP activity. Members of this family contain a zinc-binding C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 47834348  701 RTHRLRKLRTPAKCRECNSYVYFQGAECEECCLACHKKCLETLAIQCGHKK 751
Cdd:cd20816    1 QTHRFRRLRTPSKCRECDSYVYFNGAECEECGLACHKKCLETLAIQCGHKR 51

The F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs) domain of Saccharomyces cerevisiae Rho GTPase activating protein Rgd1 and similar proteins; F-BAR domains are dimerization modules that bind and bend membranes and are found in proteins involved in membrane dynamics and actin reorganization. Saccharomyces cerevisiae Rgd1 is a GTPase activating protein (GAP) with activity towards Rho3p and Rho4p, which are involved in bud growth and cytokinesis, respectively. At low pH, S. cerevisiae Rgd1 is required for cell survival and the activation of the protein kinase C pathway, which is important in cell integrity and the maintenance of cell shape. It contains an N-terminal F-BAR domain and a C-terminal Rho GAP domain. The F-BAR domain of S. cerevisiae Rgd1 binds to phosphoinositides and plays an important role in the localization of the protein to the bud tip/neck during the cell cycle. F-BAR domains form banana-shaped dimers with a positively-charged concave surface that binds to negatively-charged lipid membranes. They can induce membrane deformation in the form of long tubules.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47834348  296 MKDLISYLEKRTTLEMEFAKGLQKIAHNCRQsVMQEPHMpLLSIYSLALEQDLEFGHSMVQAVGTLQT--QTFMQPLTLR 373
Cdd:cd07652   21 AKEFATFLKKRAAIEEEHARGLKKLARTTLD-TYKRPDH-KQGSFSNAYHSSLEFHEKLADNGLRFAKalNEMSDELSSL 98

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47834348  374 RLEHEKRRKEIKEAWHRAQRKLQEAESNLRKAKQGYVQRCEDHDKarflvAKAEEEQAGSapGAGSTATKTL-----DKR 448
Cdd:cd07652   99 AKTVEKSRKSIKETGKRAEKKVQDAEAAAEKAKARYDSLADDLER-----VKTGDPGKKL--KFGLKGNKSAaqhedELL 171

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47834348  449 RRLEEEAKnkaeeamaTYRTCVADAKTQKQELEDT-KVTALRQIQEVIRQSDQTIKsatisyyqmMHMQtaplpvHFQML 527
Cdd:cd07652  172 RKVQAADQ--------DYASKVNAAQALRQELLSRhRPEAVKDLFDLILEIDAALR---------LQYQ------KYALP 228

                 ...
gi 47834348  528 CES 530
Cdd:cd07652  229 NEL 231

Phorbol esters/diacylglycerol binding domain (C1 domain); This domain is also known as the Protein kinase C conserved region 1 (C1) domain.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 47834348    706 RKLRTPAKCRECNSYVYF---QGAECEECCLACHKKCLETLAIQCG 748
Cdd:pfam00130    6 RNFKQPTFCDHCGEFLWGlgkQGLKCSWCKLNVHKRCHEKVPPECG 51

RhoGAP_PARG1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of PARG1 (PTPL1-associated RhoGAP1). PARG1 was originally cloned as an interaction partner of PTPL1, an intracellular protein-tyrosine phosphatase. PARG1 interacts with Rap2, also a member of the Ras small GTPase superfamily whose exact function is unknown, and shows strong preference for Rho. 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 47834348  759 FGQDFSHAARSAPDGVPFIVKKCVCEIERRALRTKGIYRVNGVKTRVEKLCQAFENGKELVELSQASPHDISNVLKLYLR 838
Cdd:cd04409    1 FGADFAQVAKKSPDGIPFIIKKCTSEIESRALCLKGIYRVNGAKSRVEKLCQAFENGKDLVELSELSPHDISNVLKLYLR 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47834348  839 QLPEPLISFRLYHELVGLAKDSLK--AEAEAKAASRGRQDGSESEAVAVALagRLRELLRDLPPENRASLQYLLRHLRRI 916
Cdd:cd04409   81 QLPEPLILFRLYNEFIGLAKESQHvnETQEAKKNSDKKWPNMCTELNRILL--KSKDLLRQLPAPNYNTLQFLIVHLHRV 158

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|...
gi 47834348  917 VEVEQDNKMTPGNLGIVFGPTLLRPRPTEATVSLSSLVDYPHQARVIETLIVH 969
Cdd:cd04409  159 SEQAEENKMSASNLGIIFGPTLIRPRPTDATVSLSSLVDYPHQARLVELLITY 211

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 47834348     774 VPFIVKKCVCEIERRALRTKGIYRVNGVKTRVEKLCQAFENGKELV-ELSQASPHDISNVLKLYLRQLPEPLISFRLYHE 852
Cdd:smart00324    3 IPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGPDPDlDLSEYDVHDVAGLLKLFLRELPEPLITYELYEE 82

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47834348     853 LVGLAKDSlkaeaeakaasrgrqdgSESEAVAvalagRLRELLRDLPPENRASLQYLLRHLRRIVEVEQDNKMTPGNLGI 932
Cdd:smart00324   83 FIEAAKLE-----------------DETERLR-----ALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAI 140

                           170       180       190
                    ....*....|....*....|....*....|....*...
gi 47834348     933 VFGPTLLRPRPTEATvslsSLVDYPHQARVIETLIVHY 970
Cdd:smart00324  141 VFGPTLLRPPDGEVA----SLKDIRHQNTVIEFLIENA 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 47834348  775 PFIVKKCVCEIERRALRTKGIYRVNGVKTRVEKLCQAFENGKELVELSQASPHDISNVLKLYLRQLPEPLISFRLYHELV 854
Cdd:cd00159    1 PLIIEKCIEYLEKNGLNTEGIFRVSGSASKIEELKKKFDRGEDIDDLEDYDVHDVASLLKLYLRELPEPLIPFELYDEFI 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47834348  855 GLAKDSlkaeaeakaasrgrqdgSESEAVAvalagRLRELLRDLPPENRASLQYLLRHLRRIVEVEQDNKMTPGNLGIVF 934
Cdd:cd00159   81 ELAKIE-----------------DEEERIE-----ALKELLKSLPPENRDLLKYLLKLLHKISQNSEVNKMTASNLAIVF 138

                        170       180       190
                 ....*....|....*....|....*....|....*
gi 47834348  935 GPTLLRPRPTeatvSLSSLVDYPHQARVIETLIVH 969
Cdd:cd00159  139 APTLLRPPDS----DDELLEDIKKLNEIVEFLIEN 169

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 47834348  759 FGQDFSHAARSAPDGVPFIVKKCVCEIERRALRTKGIYRVNGVKTRVEKLCQAFENGKELVELSQASPHD---ISNVLKL 835
Cdd:cd04372    1 YGCDLTTLVKAHNTQRPMVVDMCIREIEARGLQSEGLYRVSGFAEEIEDVKMAFDRDGEKADISATVYPDinvITGALKL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47834348  836 YLRQLPEPLISFRLYHELVGLAKdslkaeaeakaasRGRQDgSESEAVAvalagrlrELLRDLPPENRASLQYLLRHLRR 915
Cdd:cd04372   81 YFRDLPIPVITYDTYPKFIDAAK-------------ISNPD-ERLEAVH--------EALMLLPPAHYETLRYLMEHLKR 138

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 47834348  916 IVEVEQDNKMTPGNLGIVFGPTLLRPrPTEATvsLSSLVDYPHQARVIETLIVHYGLVF 974
Cdd:cd04372  139 VTLHEKDNKMNAENLGIVFGPTLMRP-PEDSA--LTTLNDMRYQILIVQLLITNEDVLF 194

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 47834348  774 VPFIVKKCVCEIERRALRTKGIYRVNGVKTRVEKLCQAFE-NGKE-LVELSQASPHDISNVLKLYLRQLPEPLISFRLYH 851
Cdd:cd04387   16 VPYIVRQCVEEVERRGMEEVGIYRISGVATDIQALKAAFDtNNKDvSVMLSEMDVNAIAGTLKLYFRELPEPLFTDELYP 95

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47834348  852 ELvglakdslkaeaeakaasrgrqdgSESEAVA--VALAGRLRELLRDLPPENRASLQYLLRHLRRIVEVEQDNKMTPGN 929
Cdd:cd04387   96 NF------------------------AEGIALSdpVAKESCMLNLLLSLPDPNLVTFLFLLHHLKRVAEREEVNKMSLHN 151

                        170       180
                 ....*....|....*....|....*.
gi 47834348  930 LGIVFGPTLLRPRPTEATVSLSSLVD 955
Cdd:cd04387  152 LATVFGPTLLRPSEKESKIPTNTMTD 177

RhoGAP-p50rhoGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of p50RhoGAP-like proteins; p50RhoGAP, also known as RhoGAP-1, contains a C-terminal RhoGAP domain and an N-terminal Sec14 domain which binds phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3). It is ubiquitously expressed and preferentially active on Cdc42. This subgroup also contains closely related ARHGAP8. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47834348  757 QLFGQDFSHAARSAP--DGVPFIVKKCVCEIERRALRTKGIYRVNGVKTRVEKLCQAFENGKELVELSQASPHDISNVLK 834
Cdd:cd04404    4 QQFGVSLQFLKEKNPeqEPIPPVVRETVEYLQAHALTTEGIFRRSANTQVVKEVQQKYNMGEPVDFDQYEDVHLPAVILK 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47834348  835 LYLRQLPEPLISFRLYHELVGLakdslkaeaeakaasrgrQDGSESEAVAvalagRLRELLRDLPPENRASLQYLLRHLR 914
Cdd:cd04404   84 TFLRELPEPLLTFDLYDDIVGF------------------LNVDKEERVE-----RVKQLLQTLPEENYQVLKYLIKFLV 140

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 47834348  915 RIVEVEQDNKMTPGNLGIVFGPTLLRPRPTEATVSLSSLVDyphqaRVIETLIVHYGLVF 974
Cdd:cd04404  141 QVSAHSDQNKMTNSNLAVVFGPNLLWAKDASMSLSAINPIN-----TFTKFLLDHQDEIF 195

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 47834348  759 FGQDFSHAARSAPDGVPFIVKKCVCEIERRALRTKGIYRVNGVKTRVEKLCQAFENGKELVEL--SQASPHDISNV---L 833
Cdd:cd04398    1 FGVPLEDLILREGDNVPNIVYQCIQAIENFGLNLEGIYRLSGNVSRVNKLKELFDKDPLNVLLisPEDYESDIHSVaslL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47834348  834 KLYLRQLPEPLISFRLYHELVGLAKdslkaeaeakaasrgrqdgSESEavaVALAGRLRELLRDLPPENRASLQYLLRHL 913
Cdd:cd04398   81 KLFFRELPEPLLTKALSREFIEAAK-------------------IEDE---SRRRDALHGLINDLPDANYATLRALMFHL 138

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 47834348  914 RRIVEVEQDNKMTPGNLGIVFGPTLLRPRPTeatvslsSLVDYPHQARVIETLIVHYGLVF 974
Cdd:cd04398  139 ARIKEHESVNRMSVNNLAIIWGPTLMNAAPD-------NAADMSFQSRVIETLLDNAYQIF 192

protein kinase C conserved region 1 (C1 domain) found in the GEM-interacting protein (GMIP)-like family; The GMIP-like family includes GMIP, Rho GTPase-activating protein 29 (ARHGAP29) and Rho GTPase-activating protein 45 (ARHGAP45). GMIP is a RhoA-specific GTPase-activating protein that acts as a key factor in saltatory neuronal migration. It associates with the Rab27a effector JFC1 and modulates vesicular transport and exocytosis. ARHGAP29, also called PTPL1-associated RhoGAP protein 1 (PARG1) or Rho-type GTPase-activating protein 29, is a GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state. It has strong activity toward RHOA, and weaker activity toward RAC1 and CDC42. ARHGAP29 may act as a specific effector of RAP2A to regulate Rho. In concert with RASIP1, ARHGAP29 suppresses RhoA signaling and dampens ROCK and MYH9 activities in endothelial cells and plays an essential role in blood vessel tubulogenesis. ARHGAP45, also called minor histocompatibility antigen HA-1 (mHag HA-1), is a Rac-GAP (GTPase-Activating Protein) in endothelial cells. It acts as a novel regulator of endothelial integrity. ARHGAP45 contains a GTPase activator for the Rho-type GTPases (RhoGAP) domain that would be able to negatively regulate the actin cytoskeleton as well as cell spreading. However, it also contains N-terminally a BAR-domin which can play an autoinhibitory effect on this RhoGAP activity. Members of this family contain a zinc-binding C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 47834348  701 RTHRLRKLRTPAKCRECNSYVYFQGAECEECCLACHKKCLETLAIQCGHKK 751
Cdd:cd20816    1 QTHRFRRLRTPSKCRECDSYVYFNGAECEECGLACHKKCLETLAIQCGHKR 51

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 47834348  774 VPFIVKKCVCEIERRALRTKGIYRVNGVKTRVEKLCQAFENGKELVELSQASPHD---ISNVLKLYLRQLPEPLISFRLY 850
Cdd:cd04379   18 VPIVLQKCVQEIERRGLDVIGLYRLCGSAAKKKELRDAFERNSAAVELSEELYPDinvITGVLKDYLRELPEPLITPQLY 97

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47834348  851 HELVglakdslkaeaeakaasrgrqdgsesEAVAVALAGR-------LRELLRDLPPENRASLQYLLRHLRRIVEVEQDN 923
Cdd:cd04379   98 EMVL--------------------------EALAVALPNDvqtnthlTLSIIDCLPLSAKATLLLLLDHLSLVLSNSERN 151

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|..
gi 47834348  924 KMTPGNLGIVFGPTLLRPR--PTEATVSLS------SLVDYPHQARVIETLI 967
Cdd:cd04379  152 KMTPQNLAVCFGPVLMFCSqeFSRYGISPTskmaavSTVDFKQHIEVLHYLL 203

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 47834348  774 VPFIVKKCVCEIERRALRTKGIYRVNGVKTRVEKLCQAFENGKELVELSQASPHDISNVLKLYLRQLPEPLISFRLYHEL 853
Cdd:cd04376    9 VPRLVESCCQHLEKHGLQTVGIFRVGSSKKRVRQLREEFDRGIDVVLDENHSVHDVAALLKEFFRDMPDPLLPRELYTAF 88

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47834348  854 VGLAKDSLkaeaeakaasrgrQDGSESeavavalagrLRELLRDLPPENRASLQYLLRHLRRIVEVEQD----------- 922
Cdd:cd04376   89 IGTALLEP-------------DEQLEA----------LQLLIYLLPPCNCDTLHRLLKFLHTVAEHAADsidedgqevsg 145

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 47834348  923 NKMTPGNLGIVFGPTLLR-PRPTEATVSLSSL--VDYPHQARVIETLIVHYGLVF 974
Cdd:cd04376  146 NKMTSLNLATIFGPNLLHkQKSGEREFVQASLriEESTAIINVVQTMIDNYEELF 200

RhoGAP_myosin_IXB: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in myosins IXB. Class IX myosins contain a characteristic head domain, a neck domain and a tail domain which contains a C6H2-zinc binding motif and a Rho-GAP domain. Class IX myosins are single-headed, processive myosins that are partly cytoplasmic, and partly associated with membranes and the actin cytoskeleton. Class IX myosins are implicated in the regulation of neuronal morphogenesis and function of sensory systems, like the inner ear. There are two major isoforms, myosin IXA and IXB with several splice variants, which are both expressed in developing neurons Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47834348  774 VPFIVKKCVCEIERRALRTKGIYRVNGVKTRVEKLCQAFENGKELVELSQASPHDISNVLKLYLRQLPEPLISFRLYHEL 853
Cdd:cd04407   15 VPIVLEKLLEHVEMHGLYTEGIYRKSGSANRMKELHQLLQADPENVKLENYPIHAITGLLKQWLRELPEPLMTFAQYNDF 94

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47834348  854 VglakdslkaeaeakaasRGRQDGSESEAVAVALAgrlreLLRDLPPENRASLQYLLRHLRRIVEVEQDNKMTPGNLGIV 933
Cdd:cd04407   95 L-----------------RAVELPEKQEQLQAIYR-----VLEQLPTANHNTLERLIFHLVKVALEEDVNRMSPNALAIV 152

                        170       180       190
                 ....*....|....*....|....*....|....*.
gi 47834348  934 FGPTLLR-PRPTEatvSLSSLVDYPHQARVIETLIV 968
Cdd:cd04407  153 FAPCLLRcPDSSD---PLTSMKDVAKTTTCVEMLIK 185

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 47834348  774 VPFIVKKCVCEIERRALRTKGIYRVNGVKTRVEKLCQAFEN--GKELVELSQASPHDISNVLKLYLRQLPEPLisfrLYH 851
Cdd:cd04391   22 VPLIFQKLINKLEERGLETEGILRIPGSAQRVKFLCQELEAkfYEGTFLWDQVKQHDAASLLKLFIRELPQPL----LTV 97

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47834348  852 ELVGLAKDSlkaeaeakaasrgrQDGSESEAVAVALagRLRELLrdLPPENRASLQYLLRHLRRIVEVEQDNKMTPGNLG 931
Cdd:cd04391   98 EYLPAFYSV--------------QGLPSKKDQLQAL--NLLVLL--LPEANRDTLKALLEFLQKVVDHEEKNKMNLWNVA 159

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*.
gi 47834348  932 IVFGPTL---LRPRPTEATVSLSSLVDYPHQARVIETLIVHYGLVF 974
Cdd:cd04391  160 MIMAPNLfppRGKHSKDNESLQEEVNMAAGCANIMRLLIRYQDLLW 205

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 47834348  757 QLFGQDFSHAARSAPDGVPFIVKKCVCEIERRALRTKGIYRVNGVKTRVEKLCQAFENGKELVELSQaSPHDISN---VL 833
Cdd:cd04383    1 KLFNGSLEEYIQDSGQAIPLVVESCIRFINLYGLQHQGIFRVSGSQVEVNDIKNAFERGEDPLADDQ-NDHDINSvagVL 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47834348  834 KLYLRQLPEPLISFRLYHELVGLAKdslkaeaeakaasrgrqdgSESEAvavALAGRLRELLRDLPPENRASLQYLLRHL 913
Cdd:cd04383   80 KLYFRGLENPLFPKERFEDLMSCVK-------------------LENPT---ERVHQIREILSTLPRSVIIVMRYLFAFL 137

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 47834348  914 RRIVEVEQDNKMTPGNLGIVFGPTLLRPRPTEATVSLSSLVDyphqaRVIETLIVH 969
Cdd:cd04383  138 NHLSQFSDENMMDPYNLAICFGPTLMPVPEGQDQVSCQAHVN-----ELIKTIIIH 188

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 47834348  758 LFGQDFS----HAARSAPDGVPFIVKKCVCEIERRALRTKGIYRVNGVKTRVEKLCQAFENGKELVELSQASPHDISNVL 833
Cdd:cd04390    2 VFGQRLEdtvaYERKFGPRLVPILVEQCVDFIREHGLKEEGLFRLPGQANLVKQLQDAFDAGERPSFDSDTDVHTVASLL 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47834348  834 KLYLRQLPEPLISFRLYHELVGLAKdslkaeaeakaasrgRQDGSESEAVavalaGRLRELLRDLPPENRASLQYLLRHL 913
Cdd:cd04390   82 KLYLRELPEPVIPWAQYEDFLSCAQ---------------LLSKDEEKGL-----GELMKQVSILPKVNYNLLSYICRFL 141

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 47834348  914 RRIVEVEQDNKMTPGNLGIVFGPTLLRPRpTEATVSLssLVDYPHQARVIETLIVHYGLVF 974
Cdd:cd04390  142 DEVQSNSSVNKMSVQNLATVFGPNILRPK-VEDPATI--MEGTPQIQQLMTVMISKHEPLF 199