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 767918874 201 FGSHLHKVCERENSTVPWFVKQCIEAVEKRGLDVDGIYRVSGNLATIQKLRFIVNQEEKLNLDDSQWEDIHVVTGALKMF 280
Cdd:cd04403    1 FGCHLEALCQRENSTVPKFVRLCIEAVEKRGLDVDGIYRVSGNLAVIQKLRFAVDHDEKLDLDDSKWEDIHVITGALKLF 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767918874 281 FRELPEPLFPYSFFEQFVEAIKKQDNNTRIEAVKSLVQKLPPPNRDTMKVLFGHLTKIVAKASKNLMSTQSLGIVFGPTL 360
Cdd:cd04403   81 FRELPEPLFPYSLFNDFVAAIKLSDYEQRVSAVKDLIKSLPKPNHDTLKMLFRHLCRVIEHGEKNRMTTQNLAIVFGPTL 160

                        170       180
                 ....*....|....*....|....*..
gi 767918874 361 LRAENETGNMAIHMVYQNQIAELMLSE 387
Cdd:cd04403  161 LRPEQETGNIAVHMVYQNQIVELILLE 187

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 767918874 201 FGSHLHKVCERENSTVPWFVKQCIEAVEKRGLDVDGIYRVSGNLATIQKLRFIVNQEEKLNLDDSQWEDIHVVTGALKMF 280
Cdd:cd04403    1 FGCHLEALCQRENSTVPKFVRLCIEAVEKRGLDVDGIYRVSGNLAVIQKLRFAVDHDEKLDLDDSKWEDIHVITGALKLF 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767918874 281 FRELPEPLFPYSFFEQFVEAIKKQDNNTRIEAVKSLVQKLPPPNRDTMKVLFGHLTKIVAKASKNLMSTQSLGIVFGPTL 360
Cdd:cd04403   81 FRELPEPLFPYSLFNDFVAAIKLSDYEQRVSAVKDLIKSLPKPNHDTLKMLFRHLCRVIEHGEKNRMTTQNLAIVFGPTL 160

                        170       180
                 ....*....|....*....|....*..
gi 767918874 361 LRAENETGNMAIHMVYQNQIAELMLSE 387
Cdd:cd04403  161 LRPEQETGNIAVHMVYQNQIVELILLE 187

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 767918874   214 STVPWFVKQCIEAVEKRGLDVDGIYRVSGNLATIQKLRFIVNQEEKLNLDDSQWeDIHVVTGALKMFFRELPEPLFPYSF 293
Cdd:smart00324   1 KPIPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGPDPDLDLSEY-DVHDVAGLLKLFLRELPEPLITYEL 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767918874   294 FEQFVEAIKKQDNNTRIEAVKSLVQKLPPPNRDTMKVLFGHLTKIVAKASKNLMSTQSLGIVFGPTLLRAENETGNMAIH 373
Cdd:smart00324  80 YEEFIEAAKLEDETERLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEVASLKD 159

                          170
                   ....*....|....*
gi 767918874   374 MVYQNQIAELMLSEY 388
Cdd:smart00324 160 IRHQNTVIEFLIENA 174

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 767918874 201 FGSHLHKVCERENSTVPWFVKQCIEAVEKRGLDVDGIYRVSGNLATIQKLRFIVNQEEKLNLDDSQWEDIHVVTGALKMF 280
Cdd:cd04403    1 FGCHLEALCQRENSTVPKFVRLCIEAVEKRGLDVDGIYRVSGNLAVIQKLRFAVDHDEKLDLDDSKWEDIHVITGALKLF 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767918874 281 FRELPEPLFPYSFFEQFVEAIKKQDNNTRIEAVKSLVQKLPPPNRDTMKVLFGHLTKIVAKASKNLMSTQSLGIVFGPTL 360
Cdd:cd04403   81 FRELPEPLFPYSLFNDFVAAIKLSDYEQRVSAVKDLIKSLPKPNHDTLKMLFRHLCRVIEHGEKNRMTTQNLAIVFGPTL 160

                        170       180
                 ....*....|....*....|....*..
gi 767918874 361 LRAENETGNMAIHMVYQNQIAELMLSE 387
Cdd:cd04403  161 LRPEQETGNIAVHMVYQNQIVELILLE 187

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 767918874 217 PWFVKQCIEAVEKRGLDVDGIYRVSGNLATIQKLRFIVNQEEklNLDDSQWEDIHVVTGALKMFFRELPEPLFPYSFFEQ 296
Cdd:cd00159    1 PLIIEKCIEYLEKNGLNTEGIFRVSGSASKIEELKKKFDRGE--DIDDLEDYDVHDVASLLKLYLRELPEPLIPFELYDE 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767918874 297 FVEAIKKQDNNTRIEAVKSLVQKLPPPNRDTMKVLFGHLTKIVAKASKNLMSTQSLGIVFGPTLLRAENETGNMAIHMVY 376
Cdd:cd00159   79 FIELAKIEDEEERIEALKELLKSLPPENRDLLKYLLKLLHKISQNSEVNKMTASNLAIVFAPTLLRPPDSDDELLEDIKK 158

                        170
                 ....*....|.
gi 767918874 377 QNQIAELMLSE 387
Cdd:cd00159  159 LNEIVEFLIEN 169

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 767918874 201 FGSHLHKVCERENSTVPWFVKQCIEAVEKRGLDVDGIYRVSGNLATIQKLR--FIVNQEEKLNLDDSQWE-DIHVVTGAL 277
Cdd:cd04398    1 FGVPLEDLILREGDNVPNIVYQCIQAIENFGLNLEGIYRLSGNVSRVNKLKelFDKDPLNVLLISPEDYEsDIHSVASLL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767918874 278 KMFFRELPEPLFPYSFFEQFVEAIKKQDNNTRIEAVKSLVQKLPPPNRDTMKVLFGHLTKIVAKASKNLMSTQSLGIVFG 357
Cdd:cd04398   81 KLFFRELPEPLLTKALSREFIEAAKIEDESRRRDALHGLINDLPDANYATLRALMFHLARIKEHESVNRMSVNNLAIIWG 160

                        170       180       190
                 ....*....|....*....|....*....|....*
gi 767918874 358 PTLLRAenETGNMAiHMVYQNQIAELMLSEYSKIF 392
Cdd:cd04398  161 PTLMNA--APDNAA-DMSFQSRVIETLLDNAYQIF 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 767918874 219 FVKQCIEAVEKRGLDVDGIYRVSGNLATIQKLRFIVNQEEK-----LNLDDSQWEdIHVVTGALKMFFRELPEPLFPYSF 293
Cdd:cd04374   31 FVRKCIEAVETRGINEQGLYRVVGVNSKVQKLLSLGLDPKTstpgdVDLDNSEWE-IKTITSALKTYLRNLPEPLMTYEL 109

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767918874 294 FEQFVEAIKKQDNNTRIEAVKSLVQKLPPPNRDTMKVLFGHLTKIVAKASKNLMSTQSLGIVFGPTLLRAENETGNMAIH 373
Cdd:cd04374  110 HNDFINAAKSENLESRVNAIHSLVHKLPEKNREMLELLIKHLTNVSDHSKKNLMTVSNLGVVFGPTLLRPQEETVAAIMD 189

                        170
                 ....*....|...
gi 767918874 374 MVYQNQIAELMLS 386
Cdd:cd04374  190 IKFQNIVVEILIE 202

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 767918874 201 FGSHLHKVCERENSTVPWFVKQCIEAVEKRGLDVDGIYRVSGNLATIQKLR--FIVNQEEKLNLDDSQweDIHVVTGALK 278
Cdd:cd04387    1 FGVKISTVTKRERSKVPYIVRQCVEEVERRGMEEVGIYRISGVATDIQALKaaFDTNNKDVSVMLSEM--DVNAIAGTLK 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767918874 279 MFFRELPEPLFPYSFFEQFVEAIKKQDNNTRIEAVKSLVQKLPPPNRDTMKVLFGHLTKIVAKASKNLMSTQSLGIVFGP 358
Cdd:cd04387   79 LYFRELPEPLFTDELYPNFAEGIALSDPVAKESCMLNLLLSLPDPNLVTFLFLLHHLKRVAEREEVNKMSLHNLATVFGP 158

                 ....
gi 767918874 359 TLLR 362
Cdd:cd04387  159 TLLR 162

RhoGAP_GMIP_PARG1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of GMIP (Gem interacting protein) and PARG1 (PTPL1-associated RhoGAP1). 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. 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 767918874 201 FGSHLHKVCERENSTVPWFVKQCIEAVEKRGLDVDGIYRVSGNLATIQKL-RFIVNQEEKLNLDDSQWEDIhvvTGALKM 279
Cdd:cd04378    1 FGVDFSQVPRDFPDEVPFIIKKCTSEIENRALGVQGIYRVSGSKARVEKLcQAFENGKDLVELSELSPHDI---SSVLKL 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767918874 280 FFRELPEPLFPYSFFEQFV----------EAIKKQDNNTRIEAV----KSLVQKLPPPNRDTMKVLFGHLTKIVAKASKN 345
Cdd:cd04378   78 FLRQLPEPLILFRLYNDFIalakeiqrdtEEDKAPNTPIEVNRIirklKDLLRQLPASNYNTLQHLIAHLYRVAEQFEEN 157

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*
gi 767918874 346 LMSTQSLGIVFGPTLLRAENETGNMAIHMV----YQNQIAELMLS 386
Cdd:cd04378  158 KMSPNNLGIVFGPTLIRPRPGDADVSLSSLvdygYQARLVEFLIT 202

RhoGAP_nadrin: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of Nadrin-like proteins. Nadrin, also named Rich-1, has been shown to be involved in the regulation of Ca2+-dependent exocytosis in neurons and recently has been implicated in tight junction maintenance in mammalian epithelium. 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 767918874 199 QIFGSHLHKVCERENSTVPWFVKQCIEAVEKRGLDVDGIYRVSGNLATIQKLRFIVN-QEEKLNLDDsQWEDIHVVTGAL 277
Cdd:cd04386    3 PVFGTPLEEHLKRTGREIALPIEACVMCLLETGMNEEGLFRVGGGASKLKRLKAALDaGTFSLPLDE-FYSDPHAVASAL 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767918874 278 KMFFRELPEPLFPYSFFEQFVEAIKKQDNNTRIEAVKSLVQKLPPPNRDTMKVLFGHLTKIVAKASKNLMSTQSLGIVFG 357
Cdd:cd04386   82 KSYLRELPDPLLTYNLYEDWVQAANKPDEDERLQAIWRILNKLPRENRDNLRYLIKFLSKLAQKSDENKMSPSNIAIVLA 161

                        170       180       190
                 ....*....|....*....|....*....|....*...
gi 767918874 358 PTLLRAENETGN--MAIHM-VYQNQIAELMLSEYSKIF 392
Cdd:cd04386  162 PNLLWAKNEGSLaeMAAGTsVHVVAIVELIISHADWFF 199

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 767918874 199 QIFGSHLHKVCER--ENSTVPWFVKQCIEAVEKRGLDVDGIYRVSGNLATIQKLRFIVNQEEKLNLDdsQWEDIHVVTGA 276
Cdd:cd04404    4 QQFGVSLQFLKEKnpEQEPIPPVVRETVEYLQAHALTTEGIFRRSANTQVVKEVQQKYNMGEPVDFD--QYEDVHLPAVI 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767918874 277 LKMFFRELPEPLFPYSFFEqFVEAIKKQDNNTRIEAVKSLVQKLPPPNRDTMKVLFGHLTKIVAKASKNLMSTQSLGIVF 356
Cdd:cd04404   82 LKTFLRELPEPLLTFDLYD-DIVGFLNVDKEERVERVKQLLQTLPEENYQVLKYLIKFLVQVSAHSDQNKMTNSNLAVVF 160

                        170       180       190
                 ....*....|....*....|....*....|....*..
gi 767918874 357 GPTLLRAENETGNM-AIHMVyqNQIAELMLSEYSKIF 392
Cdd:cd04404  161 GPNLLWAKDASMSLsAINPI--NTFTKFLLDHQDEIF 195

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 767918874 216 VPWFVKQCIEAVEKRGLDVDGIYRVSGNLATIQKLRfivnqeEKLNLD--DSQW----EDIHVVTGALKMFFRELPEPLF 289
Cdd:cd04385   15 IPVIVDKCIDFITQHGLMSEGIYRKNGKNSSVKKLL------EAFRKDarSVQLregeYTVHDVADVLKRFLRDLPDPLL 88

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 767918874 290 PYSFFEQFVEAIKKQDNNTRIEAVKSLVQKLPPPNRDTMKVLFGHLTKIVAKASKNLMSTQSLGIVFGPTLLRAE 364
Cdd:cd04385   89 TSELHAEWIEAAELENKDERIARYKELIRRLPPINRATLKVLIGHLYRVQKHSDENQMSVHNLALVFGPTLFQTD 163

Beta-spectrin pleckstrin homology (PH) domain; ARHGAP family genes encode Rho/Rac/Cdc42-like GTPase activating proteins with RhoGAP domain. The ARHGAP members here all have a PH domain upstream of their C-terminal RhoGAP domain. Some have additional N-terminal SH3 and WW domains. The members here include: ARHGAP9, ARHGAP12, ARHGAP15, and ARHGAP27. ARHGAP27 and ARHGAP12 shared the common-domain structure, consisting of SH3, WW, PH, and RhoGAP domains. The PH domain of ArhGAP9 employs a non-canonical phosphoinositide binding mechanism, a variation of the spectrin- Ins(4,5)P2-binding mode, that gives rise to a unique PI binding profile, namely a preference for both PI(4,5)P2 and the PI 3-kinase products PI(3,4,5)P3 and PI(3,4)P2. This lipid binding mechanism is also employed by the PH domain of Tiam1 and Slm1. 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 767918874  49 SPKTGHKPESVDLCGAHIEWAKEKSSRKNVFQITTVSGNEFLLQSDIDFIILDWFHAIKNAIDR 112
Cdd:cd13233   47 GNPYSKPESSVDLRGASIEWAKEKSSRKNVFQISTVTGTEFLLQSDNDTEIREWFDAIKAVIQR 110

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 767918874 200 IFGSHLHKVCEREN-----STVPWFVKQCIEAVEK-RGLDVDGIYRVSGNLATIQKLRFIVNQEEKLNL-DDSQWEDIHV 272
Cdd:cd04400    1 IFGSPLEEAVELSShkyngRDLPSVVYRCIEYLDKnRAIYEEGIFRLSGSASVIKQLKERFNTEYDVDLfSSSLYPDVHT 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767918874 273 VTGALKMFFRELPEPLFPYSFFEQFVEAIKKQDNNT-RIEAVKSLVQKLPPPNRDTMKVLFGHLTKIVAKASKNLMSTQS 351
Cdd:cd04400   81 VAGLLKLYLRELPTLILGGELHNDFKRLVEENHDRSqRALELKDLVSQLPQANYDLLYVLFSFLRKIIEHSDVNKMNLRN 160

                 ....*....
gi 767918874 352 LGIVFGPTL 360
Cdd:cd04400  161 VCIVFSPTL 169

RhoGap_RalBP1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in RalBP1 proteins, also known as RLIP, RLIP76 or cytocentrin. RalBP1 plays an important role in endocytosis during interphase. During mitosis, RalBP1 transiently associates with the centromere and has been shown to play an essential role in the proper assembly of the mitotic apparatus. RalBP1 is an effector of the Ral GTPase which itself is an effector of Ras. RalBP1 contains a RhoGAP domain, which shows weak activity towards Rac1 and Cdc42, but not towards Ral, and a Ral effector domain binding motif. 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 767918874 201 FGSHLHKVCER----ENSTVPWFVKQCIEAVEKRGLDVDGIYRVSGNLATIQKLRFIVNQEEKLNLDDSqweDIHVVTGA 276
Cdd:cd04381    1 FGASLSLAVERsrchDGIDLPLVFRECIDYVEKHGMKCEGIYKVSGIKSKVDELKAAYNRRESPNLEEY---EPPTVASL 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767918874 277 LKMFFRELPEPLFPYSFFEQFVEAIKKQDNNTRIEAVKSLVQKLPPPNRDTMKVLFGHLTKIVAKASKNLMSTQSLGIVF 356
Cdd:cd04381   78 LKQYLRELPEPLLTKELMPRFEEACGRPTEAEREQELQRLLKELPECNRLLLAWLIVHMDHVIAQELETKMNIQNISIVL 157

                 ....
gi 767918874 357 GPTL 360
Cdd:cd04381  158 SPTV 161

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 767918874 199 QIFGSHLHKVCERENSTVPWFVKQCIEAVEKRGLDVDGIYRVSGNLATIQKLRFIVNQEEKLNLDDSQWEDIHVVTGALK 278
Cdd:cd04383    1 KLFNGSLEEYIQDSGQAIPLVVESCIRFINLYGLQHQGIFRVSGSQVEVNDIKNAFERGEDPLADDQNDHDINSVAGVLK 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767918874 279 MFFRELPEPLFPYSFFEQFVEAIKKQDNNTRIEAVKSLVQKLPPPNRDTMKVLFGHLTKIVAKASKNLMSTQSLGIVFGP 358
Cdd:cd04383   81 LYFRGLENPLFPKERFEDLMSCVKLENPTERVHQIREILSTLPRSVIIVMRYLFAFLNHLSQFSDENMMDPYNLAICFGP 160

                        170       180
                 ....*....|....*....|....*.
gi 767918874 359 TLLRAENETGNMAihmvYQNQIAELM 384
Cdd:cd04383  161 TLMPVPEGQDQVS----CQAHVNELI 182

RhoGAP_ARHGAP20: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP20-like proteins. ArhGAP20, also known as KIAA1391 and RA-RhoGAP, contains a RhoGAP, a RA, and a PH domain, and ANXL repeats. ArhGAP20 is activated by Rap1 and induces inactivation of Rho, which in turn leads to neurite outgrowth. 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 767918874 200 IFGSHLHKVCEreNSTVPWFVKQCIEAVEKRGLDVDGIYRVSGNLATIQKLRFIVNQEEKLNLDDsqwEDIHVVTGALKM 279
Cdd:cd04402    1 LFGQPLSNICE--DDNLPKPILDMLSLLYQKGPSTEGIFRRSANAKACKELKEKLNSGVEVDLKA---EPVLLLASVLKD 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767918874 280 FFRELPEPLFPYSFFEQFVEAIKKQDNNTRIEAVKSLVQKLPPPNRDTMKVLFGHLTKIVAKASKNLMSTQSLGIVFGPT 359
Cdd:cd04402   76 FLRNIPGSLLSSDLYEEWMSALDQENEEEKIAELQRLLDKLPRPNVLLLKHLICVLHNISQNSETNKMDAFNLAVCIAPS 155

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 767918874 360 LLR------AENETGNMAIHMVyqnqiaELMLSEYSKIFGSE 395
Cdd:cd04402  156 LLWppasseLQNEDLKKVTSLV------QFLIENCQEIFGED 191

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 767918874 200 IFGSHLHKVCER-----ENSTVPWFVKQCIEAVEKRGLDVDGIYRVSGnlaTIQKLRFIVNQ-EEKLNLDDSQWEDIHV- 272
Cdd:cd04391    1 LFGVPLSTLLERdqkkvPGSKVPLIFQKLINKLEERGLETEGILRIPG---SAQRVKFLCQElEAKFYEGTFLWDQVKQh 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767918874 273 -VTGALKMFFRELPEPLFPYSFFEQFVEAIKKQDNNTRIEAVKSLVQKLPPPNRDTMKVLFGHLTKIVAKASKNLMSTQS 351
Cdd:cd04391   78 dAASLLKLFIRELPQPLLTVEYLPAFYSVQGLPSKKDQLQALNLLVLLLPEANRDTLKALLEFLQKVVDHEEKNKMNLWN 157

                 ....*....
gi 767918874 352 LGIVFGPTL 360
Cdd:cd04391  158 VAMIMAPNL 166

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 767918874 200 IFGSHLHKVCERE----NSTVPWFVKQCIEAVEKRGLDVDGIYRVSGNLATIQKLRFIVNQEEKLNLDDSQweDIHVVTG 275
Cdd:cd04390    2 VFGQRLEDTVAYErkfgPRLVPILVEQCVDFIREHGLKEEGLFRLPGQANLVKQLQDAFDAGERPSFDSDT--DVHTVAS 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767918874 276 ALKMFFRELPEPLFPYSFFEQFVEAIKKQDNNTR--IEAVKSLVQKLPPPNRDTMKVLFGHLTKIVAKASKNLMSTQSLG 353
Cdd:cd04390   80 LLKLYLRELPEPVIPWAQYEDFLSCAQLLSKDEEkgLGELMKQVSILPKVNYNLLSYICRFLDEVQSNSSVNKMSVQNLA 159

                        170       180       190
                 ....*....|....*....|....*....|.
gi 767918874 354 IVFGPTLLRAENEtgNMAIHMVYQNQIAELM 384
Cdd:cd04390  160 TVFGPNILRPKVE--DPATIMEGTPQIQQLM 188

RhoGAP_KIAA1688: GTPase-activator protein (GAP) domain for Rho-like GTPases found in KIAA1688-like proteins; KIAA1688 is a protein of unknown function that contains a RhoGAP domain and a myosin tail homology 4 (MyTH4) domain. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767918874 201 FGSHLHKVCERENST-----VPWFVKQCIEAVEKRGLDV-DGIYRVSGNLATIQKLRfivNQEEKLNLDDSQWEDIHVVT 274
Cdd:cd04389    1 FGSSLEEIMDRQKEKypelkLPWILTFLSEKVLALGGFQtEGIFRVPGDIDEVNELK---LRVDQWDYPLSGLEDPHVPA 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767918874 275 GALKMFFRELPEPLFPYSFFEQFVEAIKKQDnntrieAVKSLVQKLPPPNRDTMKVLFgHLTKIVAK---ASKNLMSTQS 351
Cdd:cd04389   78 SLLKLWLRELEEPLIPDALYQQCISASEDPD------KAVEIVQKLPIINRLVLCYLI-NFLQVFAQpenVAHTKMDVSN 150

                        170
                 ....*....|....*
gi 767918874 352 LGIVFGPTLLRAENE 366
Cdd:cd04389  151 LAMVFAPNILRCTSD 165