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 767970799  342 RVFGCDLGEHLLNSGFEVPQVLQSCTAFIERYGIVDGIYRLSGVASNIQRLRHEFDSEHVPDLTKEPYVQDIHSVGSLCK 421
Cdd:cd04384     1 RVFGCDLTEHLLNSGQDVPQVLKSCTEFIEKHGIVDGIYRLSGIASNIQRLRHEFDSEQIPDLTKDVYIQDIHSVSSLCK 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767970799  422 LYFRELPNPLLTYQLYEKFSDAVSAATDEERLIKIHDVIQQLPPPHYRTLEFLMRHLSLLADYCSITNMHAKNLAIVWAP 501
Cdd:cd04384    81 LYFRELPNPLLTYQLYEKFSEAVSAASDEERLEKIHDVIQQLPPPHYRTLEFLMRHLSRLAKYCSITNMHAKNLAIVWAP 160

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 767970799  502 NLLRSKQIESACFSGTAAFMEVRIQSVVVEFILNH 536
Cdd:cd04384   161 NLLRSKQIESACFSGTAAFMEVRIQSVVVEFILNH 195

Src homology 3 domain of Rho GTPase-activating proteins 32 and 33, and similar proteins; Members of this family contain N-terminal PX and Src Homology 3 (SH3) domains, a central Rho GAP domain, and C-terminal extensions. RhoGAPs (or ARHGAPs) bind to Rho proteins and enhance the hydrolysis rates of bound GTP. ARHGAP32 is also called RICS, PX-RICS, p250GAP, or p200RhoGAP. It is a Rho GTPase-activating protein for Cdc42 and Rac1, and is implicated in the regulation of postsynaptic signaling and neurite outgrowth. PX-RICS, a variant of RICS that contain PX and SH3 domains, is the main isoform expressed during neural development. It is involved in neural functions including axon and dendrite extension, postnatal remodeling, and fine-tuning of neural circuits during early brain development. ARHGAP33, also called sorting nexin 26 or TCGAP (Tc10/CDC42 GTPase-activating protein), is widely expressed in the brain where it is involved in regulating the outgrowth of axons and dendrites and is regulated by the protein tyrosine kinase Fyn. It is translocated to the plasma membrane in adipocytes in response to insulin and may be involved in the regulation of insulin-stimulated glucose transport. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 767970799  237 AAHVIKRYTARAPDELTLEVGDIVSVIDMPPKVLSTWWRGKHGFQVGLFPGHCV 290
Cdd:cd11835     1 AAHVIKRYTAQAPDELSLEVGDIVSVIDMPPPEESTWWRGKKGFQVGFFPSECV 54

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 767970799  342 RVFGCDLGEHLLNSGFEVPQVLQSCTAFIERYGIVDGIYRLSGVASNIQRLRHEFDSEHVPDLTKEPYVQDIHSVGSLCK 421
Cdd:cd04384     1 RVFGCDLTEHLLNSGQDVPQVLKSCTEFIEKHGIVDGIYRLSGIASNIQRLRHEFDSEQIPDLTKDVYIQDIHSVSSLCK 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767970799  422 LYFRELPNPLLTYQLYEKFSDAVSAATDEERLIKIHDVIQQLPPPHYRTLEFLMRHLSLLADYCSITNMHAKNLAIVWAP 501
Cdd:cd04384    81 LYFRELPNPLLTYQLYEKFSEAVSAASDEERLEKIHDVIQQLPPPHYRTLEFLMRHLSRLAKYCSITNMHAKNLAIVWAP 160

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 767970799  502 NLLRSKQIESACFSGTAAFMEVRIQSVVVEFILNH 536
Cdd:cd04384   161 NLLRSKQIESACFSGTAAFMEVRIQSVVVEFILNH 195

RhoGAP domain; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767970799   360 PQVLQSCTAFIERYGI-VDGIYRLSGVASNIQRLRHEFDSEHVPDLtkEPYVQDIHSVGSLCKLYFRELPNPLLTYQLYE 438
Cdd:pfam00620    1 PLIVRKCVEYLEKRGLdTEGIFRVSGSASRIKELREAFDRGPDVDL--DLEEEDVHVVASLLKLFLRELPEPLLTFELYE 78

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767970799   439 KFSDAVSAATDEERLIKIHDVIQQLPPPHYRTLEFLMRHLSLLADYCSITNMHAKNLAIVWAPNLLRSKQ 508
Cdd:pfam00620   79 EFIEAAKLPDEEERLEALRELLRKLPPANRDTLRYLLAHLNRVAQNSDVNKMNAHNLAIVFGPTLLRPPD 148

Src homology 3 domain of Rho GTPase-activating proteins 32 and 33, and similar proteins; Members of this family contain N-terminal PX and Src Homology 3 (SH3) domains, a central Rho GAP domain, and C-terminal extensions. RhoGAPs (or ARHGAPs) bind to Rho proteins and enhance the hydrolysis rates of bound GTP. ARHGAP32 is also called RICS, PX-RICS, p250GAP, or p200RhoGAP. It is a Rho GTPase-activating protein for Cdc42 and Rac1, and is implicated in the regulation of postsynaptic signaling and neurite outgrowth. PX-RICS, a variant of RICS that contain PX and SH3 domains, is the main isoform expressed during neural development. It is involved in neural functions including axon and dendrite extension, postnatal remodeling, and fine-tuning of neural circuits during early brain development. ARHGAP33, also called sorting nexin 26 or TCGAP (Tc10/CDC42 GTPase-activating protein), is widely expressed in the brain where it is involved in regulating the outgrowth of axons and dendrites and is regulated by the protein tyrosine kinase Fyn. It is translocated to the plasma membrane in adipocytes in response to insulin and may be involved in the regulation of insulin-stimulated glucose transport. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 767970799  237 AAHVIKRYTARAPDELTLEVGDIVSVIDMPPKVLSTWWRGKHGFQVGLFPGHCV 290
Cdd:cd11835     1 AAHVIKRYTAQAPDELSLEVGDIVSVIDMPPPEESTWWRGKKGFQVGFFPSECV 54

Variant SH3 domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 767970799   240 VIKRYTARAPDELTLEVGDIVSVIDMPPkvlSTWWRGKHGFQVGLFPGHCVE 291
Cdd:pfam14604    1 ALYPYEPKDDDELSLQRGDVITVIEESE---DGWWEGINTGRTGLVPANYVE 49

Family of unknown function (DUF5585); This is a family of unknown function found in chordata.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767970799   683 SLTSLHAVDGDSKLFrprrprsssdALSASFNGemLGNRCNSYDNLPH-DNESEEEGGLLHIPALMSP------------ 749
Cdd:pfam17823   14 PLSESHAAPADPRHF----------VLNKMWNG--AGKQNASGDAVPRaDNKSSEQ*NFCAATAAPAPvtltkgtsaahl 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767970799   750 --------HSAEDVDLSPPDI------GVASLDfdPMSFQCSPPKAESECLESGASFLDSPGYSKDKPSANKKDAETGSS 815
Cdd:pfam17823   82 nstevtaeHTPHGTDLSEPATregaadGAASRA--LAAAASSSPSSAAQSLPAAIAALPSEAFSAPRAAACRANASAAPR 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767970799   816 qcqTPGSTASSEPVSPLQEKLSPFFTLDLSPTEDKSSKPSSFTEKVVYAFSPKIGRKLSK----SPSMSISE---PISVT 888
Cdd:pfam17823  160 ---AAIAAASAPHAASPAPRTAASSTTAASSTTAASSAPTTAASSAPATLTPARGISTAAtatgHPAAGTALaavGNSSP 236

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767970799   889 LPPRVSEVIGTVSNTT-------AQNASSSTWDKCVEERDATNRSPTQivKMKTNETVAQEAYESEVQ---PLDQVAAEE 958
Cdd:pfam17823  237 AAGTVTAAVGTVTPAAlatlaaaAGTVASAAGTINMGDPHARRLSPAK--HMPSDTMARNPAAPMGAQaqgPIIQVSTDQ 314

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767970799   959 V-------ELPGKEDQSVSSSQSKAVASGQ----TQTGAVTHDPPQDSVPVSSVSLIPPPPPPKNVARMLALALAESA-- 1025
Cdd:pfam17823  315 PvhntagePTPSPSNTTLEPNTPKSVASTNlavvTTTKAQAKEPSASPVPVLHTSMIPEVEATSPTTQPSPLLPTQGAag 394

                          410       420       430
                   ....*....|....*....|....*....|....*....
gi 767970799  1026 -------QQASTQSlkRPGTSQAGYT--NYGDIAVATTE 1055
Cdd:pfam17823  395 pgillapEQVATEA--TAGTASAGPTprSSGDPKTLAMA 431

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 767970799  342 RVFGCDLGEHLLNSGFEVPQVLQSCTAFIERYGIVDGIYRLSGVASNIQRLRHEFDSEHVPDLTKEPYVQDIHSVGSLCK 421
Cdd:cd04384     1 RVFGCDLTEHLLNSGQDVPQVLKSCTEFIEKHGIVDGIYRLSGIASNIQRLRHEFDSEQIPDLTKDVYIQDIHSVSSLCK 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767970799  422 LYFRELPNPLLTYQLYEKFSDAVSAATDEERLIKIHDVIQQLPPPHYRTLEFLMRHLSLLADYCSITNMHAKNLAIVWAP 501
Cdd:cd04384    81 LYFRELPNPLLTYQLYEKFSEAVSAASDEERLEKIHDVIQQLPPPHYRTLEFLMRHLSRLAKYCSITNMHAKNLAIVWAP 160

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 767970799  502 NLLRSKQIESACFSGTAAFMEVRIQSVVVEFILNH 536
Cdd:cd04384   161 NLLRSKQIESACFSGTAAFMEVRIQSVVVEFILNH 195

The phosphoinositide binding Phox Homology domain of PX-RICS-like proteins; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. Members of this family include PX-RICS, TCGAP (Tc10/Cdc42 GTPase-activating protein), and similar proteins. They contain N-terminal PX and Src Homology 3 (SH3) domains, a central Rho GAP domain, and C-terminal extensions. They act as Rho GTPase-activating proteins. PX-RICS is the main isoform expressed during neural development. It is involved in neural functions including axon and dendrite extension, postnatal remodeling, and fine-tuning of neural circuits during early brain development. The PX domain of PX-RICS specifically binds phosphatidylinositol 3-phosphate (PI3P), PI4P, and PI5P. TCGAP is widely expressed in the brain where it is involved in regulating the outgrowth of axons and dendrites and is regulated by the protein tyrosine kinase Fyn. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767970799  101 NVEFGSIQLSLSEEQNEVmKNGCESKELVYLVQIACQGKSWIVKRSYEDFRVLDKHLHLCIYDRRFSQLSELPRSDTLKD 180
Cdd:cd07278     1 NVDIGSLQVVLSDDGSLK-SYKNSGKELVYLVQVQCQGKSWLVKRSYDDFRMLDKHLHQCIYDRKFSQLTELPEECIEKR 79

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 767970799  181 SPESVTQMLMAYLSRLSAIAGNKINCGPALTWMEI 215
Cdd:cd07278    80 EQQNLHQVLSDYLKRLSSIAGNLLNCGPVLNWLEL 114

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 767970799    358 EVPQVLQSCTAFIERYGI-VDGIYRLSGVASNIQRLRHEFDSEHVPDLTKEPYvqDIHSVGSLCKLYFRELPNPLLTYQL 436
Cdd:smart00324    2 PIPIIVEKCIEYLEKRGLdTEGIYRVSGSKSRVKELRDAFDSGPDPDLDLSEY--DVHDVAGLLKLFLRELPEPLITYEL 79

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767970799    437 YEKFSDAVSAATDEERLIKIHDVIQQLPPPHYRTLEFLMRHLSLLADYCSITNMHAKNLAIVWAPNLLRSKQIESacfsg 516
Cdd:smart00324   80 YEEFIEAAKLEDETERLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEV----- 154

                           170       180
                    ....*....|....*....|.
gi 767970799    517 tAAFMEVRIQSVVVEFILNHV 537
Cdd:smart00324  155 -ASLKDIRHQNTVIEFLIENA 174

The phosphoinositide binding Phox Homology domain of Tc10/Cdc42 GTPase-activating protein; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. TCGAP (Tc10/Cdc42 GTPase-activating protein) contains N-terminal PX and Src Homology 3 (SH3) domains, a central Rho GAP domain, and C-terminal proline-rich regions. It is widely expressed in the brain where it is involved in regulating the outgrowth of axons and dendrites and is regulated by the protein tyrosine kinase Fyn. It interacts with cdc42 and TC10beta through its GAP domain and with phosphatidylinositol-(4,5)-bisphosphate [PI(4,5)P2] through its PX domain. It is translocated to the plasma membrane in adipocytes in response to insulin and may be involved in the regulation of insulin-stimulated glucose transport. TCGAP has also been named sorting nexins 26 (SNX26). SNXs make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. It is unknown whether TCGAP also functions as a SNX.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767970799  101 NVEFGSIQLSLSEEQNEvmKNGCESKELVYLVQIACQGKSWIVKRSYEDFRVLDKHLHLCIYDRRFSQLSELPRSDTLKD 180
Cdd:cd07299     1 NVDFGSIQLQLSNERSD--WTSSSEKDLVFLVQVTCQGRSWMVLRSYEDFRTLDAHLHRCIFDRRFSQLLELPPLCEIGD 78

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 767970799  181 SPESVTQMLMAYLSRLSAIAGNKINCGPALTWMEI 215
Cdd:cd07299    79 RLQILTPLLSEYLNRLTGIVDSNLNCGPVLTWMEI 113

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 767970799  342 RVFGCDLGEHLLNSGFEVPQVLQSCTAFIERYGIVD-GIYRLSGVASNIQRLRHEFDSEHVpDLTKEPYVQDIHSVGSLC 420
Cdd:cd04386     3 PVFGTPLEEHLKRTGREIALPIEACVMCLLETGMNEeGLFRVGGGASKLKRLKAALDAGTF-SLPLDEFYSDPHAVASAL 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767970799  421 KLYFRELPNPLLTYQLYEKFSDAVSAATDEERLIKIHDVIQQLPPPHYRTLEFLMRHLSLLADYCSITNMHAKNLAIVWA 500
Cdd:cd04386    82 KSYLRELPDPLLTYNLYEDWVQAANKPDEDERLQAIWRILNKLPRENRDNLRYLIKFLSKLAQKSDENKMSPSNIAIVLA 161

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|...
gi 767970799  501 PNLLRSKqIESACFSGTAAfMEVRIqSVVVEFILNHVDVLFSG 543
Cdd:cd04386   162 PNLLWAK-NEGSLAEMAAG-TSVHV-VAIVELIISHADWFFPG 201

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 767970799  344 FGCDLGEHLLNSGFEVPQVLQSCTAFIERYGI-VDGIYRLSGVASNIQRLRHEFDSEHVPDLTKEPYvQDIHSVGSLCKL 422
Cdd:cd04403     1 FGCHLEALCQRENSTVPKFVRLCIEAVEKRGLdVDGIYRVSGNLAVIQKLRFAVDHDEKLDLDDSKW-EDIHVITGALKL 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767970799  423 YFRELPNPLLTYQLYEKFSDAVSAATDEERLIKIHDVIQQLPPPHYRTLEFLMRHLSLLADYCSITNMHAKNLAIVWAPN 502
Cdd:cd04403    80 FFRELPEPLFPYSLFNDFVAAIKLSDYEQRVSAVKDLIKSLPKPNHDTLKMLFRHLCRVIEHGEKNRMTTQNLAIVFGPT 159

                         170       180       190
                  ....*....|....*....|....*....|..
gi 767970799  503 LLRSKQiesacFSGTAAFMEVrIQSVVVEFIL 534
Cdd:cd04403   160 LLRPEQ-----ETGNIAVHMV-YQNQIVELIL 185

Src homology 3 domain of Rho GTPase-activating proteins 32 and 33, and similar proteins; Members of this family contain N-terminal PX and Src Homology 3 (SH3) domains, a central Rho GAP domain, and C-terminal extensions. RhoGAPs (or ARHGAPs) bind to Rho proteins and enhance the hydrolysis rates of bound GTP. ARHGAP32 is also called RICS, PX-RICS, p250GAP, or p200RhoGAP. It is a Rho GTPase-activating protein for Cdc42 and Rac1, and is implicated in the regulation of postsynaptic signaling and neurite outgrowth. PX-RICS, a variant of RICS that contain PX and SH3 domains, is the main isoform expressed during neural development. It is involved in neural functions including axon and dendrite extension, postnatal remodeling, and fine-tuning of neural circuits during early brain development. ARHGAP33, also called sorting nexin 26 or TCGAP (Tc10/CDC42 GTPase-activating protein), is widely expressed in the brain where it is involved in regulating the outgrowth of axons and dendrites and is regulated by the protein tyrosine kinase Fyn. It is translocated to the plasma membrane in adipocytes in response to insulin and may be involved in the regulation of insulin-stimulated glucose transport. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 767970799  237 AAHVIKRYTARAPDELTLEVGDIVSVIDMPPKVLSTWWRGKHGFQVGLFPGHCV 290
Cdd:cd11835     1 AAHVIKRYTAQAPDELSLEVGDIVSVIDMPPPEESTWWRGKKGFQVGFFPSECV 54

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 767970799  344 FGCDLGEHLLNSGFEVPQVLQSCTAFIE-RYGIVDGIYRLSGVASNIQRLRHEFD--------SEHVPdltkepyvqdiH 414
Cdd:cd04378     1 FGVDFSQVPRDFPDEVPFIIKKCTSEIEnRALGVQGIYRVSGSKARVEKLCQAFEngkdlvelSELSP-----------H 69

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767970799  415 SVGSLCKLYFRELPNPLLTYQLYEKFSD-------------AVSAATDEERLI-KIHDVIQQLPPPHYRTLEFLMRHLSL 480
Cdd:cd04378    70 DISSVLKLFLRQLPEPLILFRLYNDFIAlakeiqrdteedkAPNTPIEVNRIIrKLKDLLRQLPASNYNTLQHLIAHLYR 149

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 767970799  481 LADYCSITNMHAKNLAIVWAPNLLRSKQIESACfsGTAAFMEVRIQSVVVEFILNH 536
Cdd:cd04378   150 VAEQFEENKMSPNNLGIVFGPTLIRPRPGDADV--SLSSLVDYGYQARLVEFLITN 203

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 767970799  349 GEHLLNS-GFevpQVLQSCTAFIERYGIVD-GIYRLSGVASNIQRLRHE-FDSEHVP--DLTKEPYVQDIHSVGSLCKLY 423
Cdd:cd04374    20 GEAQLDDiGF---KFVRKCIEAVETRGINEqGLYRVVGVNSKVQKLLSLgLDPKTSTpgDVDLDNSEWEIKTITSALKTY 96

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767970799  424 FRELPNPLLTYQLYEKFSDAVSAATDEERLIKIHDVIQQLPPPHYRTLEFLMRHLSLLADYCSITNMHAKNLAIVWAPNL 503
Cdd:cd04374    97 LRNLPEPLMTYELHNDFINAAKSENLESRVNAIHSLVHKLPEKNREMLELLIKHLTNVSDHSKKNLMTVSNLGVVFGPTL 176

                         170       180       190
                  ....*....|....*....|....*....|...
gi 767970799  504 LRSKQiESacfsgTAAFMEVRIQSVVVEFILNH 536
Cdd:cd04374   177 LRPQE-ET-----VAAIMDIKFQNIVVEILIEN 203

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767970799  349 GEHLLN---SGFEVPQVLQSCTAFIERYGI-VDGIYRLSGVASNIQRLRHEF--DSEHVpDLTKEPYvqDIHSVGSLCKL 422
Cdd:cd04385     2 GPALEDqqlTDNDIPVIVDKCIDFITQHGLmSEGIYRKNGKNSSVKKLLEAFrkDARSV-QLREGEY--TVHDVADVLKR 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767970799  423 YFRELPNPLLTYQLYEKFSDAVSAATDEERLIKIHDVIQQLPPPHYRTLEFLMRHLSLLADYCSITNMHAKNLAIVWAPN 502
Cdd:cd04385    79 FLRDLPDPLLTSELHAEWIEAAELENKDERIARYKELIRRLPPINRATLKVLIGHLYRVQKHSDENQMSVHNLALVFGPT 158

                         170
                  ....*....|
gi 767970799  503 LLRSKQIESA 512
Cdd:cd04385   159 LFQTDEHSVG 168

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 767970799  344 FGCDLGEHLLNSGFEVPQVLQSCTAFIE-RYGIVDGIYRLSGVASNIQRLRHEFDS-EHVPDLTkEPYVQDIHSVgslCK 421
Cdd:cd04409     1 FGADFAQVAKKSPDGIPFIIKKCTSEIEsRALCLKGIYRVNGAKSRVEKLCQAFENgKDLVELS-ELSPHDISNV---LK 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767970799  422 LYFRELPNPLLTYQLYEKF------------SDAVSAATDEER----------LIKIHDVIQQLPPPHYRTLEFLMRHLS 479
Cdd:cd04409    77 LYLRQLPEPLILFRLYNEFiglakesqhvneTQEAKKNSDKKWpnmctelnriLLKSKDLLRQLPAPNYNTLQFLIVHLH 156

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 767970799  480 LLADYCSITNMHAKNLAIVWAPNLLRSKQIESACfsGTAAFMEVRIQSVVVEFILNH 536
Cdd:cd04409   157 RVSEQAEENKMSASNLGIIFGPTLIRPRPTDATV--SLSSLVDYPHQARLVELLITY 211

RhoGAP_FAM13A1a: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of FAM13A1, isoform a-like proteins. The function of FAM13A1a 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 up several orders of magnitude.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767970799  342 RVFGCDLGEhLLNSGF---EVPQVLQSCTAFIERYGIV-DGIYRLSGVASNIQRLRHEFDS-EHVpDLTKEpyvQDIHSV 416
Cdd:cd04393     1 KVFGVPLQE-LQQAGQpenGVPAVVRHIVEYLEQHGLEqEGLFRVNGNAETVEWLRQRLDSgEEV-DLSKE---ADVCSA 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767970799  417 GSLCKLYFRELPNPLLT-------YQLYEKFSDavsaatDEERLIKIHDVIQQLPPPHYRTLEFLMRHLSLLADYCSITN 489
Cdd:cd04393    76 ASLLRLFLQELPEGLIPaslqirlMQLYQDYNG------EDEFGRKLRDLLQQLPPVNYSLLKFLCHFLSNVASQHHENR 149

                         170
                  ....*....|....
gi 767970799  490 MHAKNLAIVWAPNL 503
Cdd:cd04393   150 MTAENLAAVFGPDV 163

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 767970799  344 FGCDLgEHLLNSGFE---VPQVLQSCTAFIERYGI-VDGIYRLSGVASNIQRLRHEFDSEHVPDLTKepyVQDIHSVGSL 419
Cdd:cd04404     6 FGVSL-QFLKEKNPEqepIPPVVRETVEYLQAHALtTEGIFRRSANTQVVKEVQQKYNMGEPVDFDQ---YEDVHLPAVI 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767970799  420 CKLYFRELPNPLLTYQLYEKFSdAVSAATDEERLIKIHDVIQQLPPPHYRTLEFLMRHLSLLADYCSITNMHAKNLAIVW 499
Cdd:cd04404    82 LKTFLRELPEPLLTFDLYDDIV-GFLNVDKEERVERVKQLLQTLPEENYQVLKYLIKFLVQVSAHSDQNKMTNSNLAVVF 160

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|..
gi 767970799  500 APNLLRSKqiesacfSGTAAFMEVRIQSVVVEFILNHVDVLF 541
Cdd:cd04404   161 GPNLLWAK-------DASMSLSAINPINTFTKFLLDHQDEIF 195

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 767970799  344 FGCDLGEhLLNSGFEVPQVLQSCTAFIERYGI-VDGIYRLSGVASNIQRLRHEFDSEhvPDLTK-EPYvqDIHSVGSLCK 421
Cdd:cd04407     1 FGVRVGS-LTSNKTSVPIVLEKLLEHVEMHGLyTEGIYRKSGSANRMKELHQLLQAD--PENVKlENY--PIHAITGLLK 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767970799  422 LYFRELPNPLLTYQLYEKFSDAVSAATDEERLIKIHDVIQQLPPPHYRTLEFLMRHLSLLADYCSITNMHAKNLAIVWAP 501
Cdd:cd04407    76 QWLRELPEPLMTFAQYNDFLRAVELPEKQEQLQAIYRVLEQLPTANHNTLERLIFHLVKVALEEDVNRMSPNALAIVFAP 155

                  ....
gi 767970799  502 NLLR 505
Cdd:cd04407   156 CLLR 159

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 767970799  359 VPQVLQSCTAFIERYGIVD-GIYRLSGVASNIQRLRHEF-DSEHVPDLTKepyvQDIHSVGSLCKLYFRELPNPLLTYQL 436
Cdd:cd04382    17 IPALIVHCVNEIEARGLTEeGLYRVSGSEREVKALKEKFlRGKTVPNLSK----VDIHVICGCLKDFLRSLKEPLITFAL 92

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767970799  437 YEKFSDAVSAAtDEERLIK-IHDVIQQLPPPHYRTLEFLMRHLSLLADyCSITNMHAKNLAIVWAPNLLRSKQIESacfS 515
Cdd:cd04382    93 WKEFMEAAEIL-DEDNSRAaLYQAISELPQPNRDTLAFLILHLQRVAQ-SPECKMDINNLARVFGPTIVGYSVPNP---D 167

                         170       180
                  ....*....|....*....|
gi 767970799  516 GTAAFMEVRIQSVVVEFILN 535
Cdd:cd04382   168 PMTILQDTVRQPRVVERLLE 187