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 2024382834  337 RVFGCDLGEHLLNSGQDVPQVLKSCTEFIEKHGIVDGIYRLSGVASNIQKLRHEFDSEQIPDLTKDNYIHDIHSVSSLCK 416
Cdd:cd04384      1 RVFGCDLTEHLLNSGQDVPQVLKSCTEFIEKHGIVDGIYRLSGIASNIQRLRHEFDSEQIPDLTKDVYIQDIHSVSSLCK 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024382834  417 MYFRELPNPLLTYQLYEKFSDAVSAATDEERLVRIHDVIQQLPPPHYRTLEYLMRHLARLADYCTITNMHAKNLAIVWAP 496
Cdd:cd04384     81 LYFRELPNPLLTYQLYEKFSEAVSAASDEERLEKIHDVIQQLPPPHYRTLEFLMRHLSRLAKYCSITNMHAKNLAIVWAP 160

                          170       180       190
                   ....*....|....*....|....*....|....*
gi 2024382834  497 NLLRSKQIESACFSGTAAFMEVRIQSVVVEFILNH 531
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 2024382834  232 AAHVIKRYIAQAPDELSFEVGDIVSVIDMPPKELTTWWRGKHGFQVGFFPSECV 285
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 2024382834  337 RVFGCDLGEHLLNSGQDVPQVLKSCTEFIEKHGIVDGIYRLSGVASNIQKLRHEFDSEQIPDLTKDNYIHDIHSVSSLCK 416
Cdd:cd04384      1 RVFGCDLTEHLLNSGQDVPQVLKSCTEFIEKHGIVDGIYRLSGIASNIQRLRHEFDSEQIPDLTKDVYIQDIHSVSSLCK 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024382834  417 MYFRELPNPLLTYQLYEKFSDAVSAATDEERLVRIHDVIQQLPPPHYRTLEYLMRHLARLADYCTITNMHAKNLAIVWAP 496
Cdd:cd04384     81 LYFRELPNPLLTYQLYEKFSEAVSAASDEERLEKIHDVIQQLPPPHYRTLEFLMRHLSRLAKYCSITNMHAKNLAIVWAP 160

                          170       180       190
                   ....*....|....*....|....*....|....*
gi 2024382834  497 NLLRSKQIESACFSGTAAFMEVRIQSVVVEFILNH 531
Cdd:cd04384    161 NLLRSKQIESACFSGTAAFMEVRIQSVVVEFILNH 195

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 2024382834   352 QDVPQVLKSCTEFIEKHGI-VDGIYRLSGVASNIQKLRHEFDSEqiPDLTKDNYIHDIHSVSSLCKMYFRELPNPLLTYQ 430
Cdd:smart00324    1 KPIPIIVEKCIEYLEKRGLdTEGIYRVSGSKSRVKELRDAFDSG--PDPDLDLSEYDVHDVAGLLKLFLRELPEPLITYE 78

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024382834   431 LYEKFSDAVSAATDEERLVRIHDVIQQLPPPHYRTLEYLMRHLARLADYCTITNMHAKNLAIVWAPNLLRSKQIESacfs 510
Cdd:smart00324   79 LYEEFIEAAKLEDETERLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEV---- 154

                           170       180
                    ....*....|....*....|.
gi 2024382834   511 gtAAFMEVRIQSVVVEFILNH 531
Cdd:smart00324  155 --ASLKDIRHQNTVIEFLIEN 173

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 2024382834  232 AAHVIKRYIAQAPDELSFEVGDIVSVIDMPPKELTTWWRGKHGFQVGFFPSECV 285
Cdd:cd11835      1 AAHVIKRYTAQAPDELSLEVGDIVSVIDMPPPEESTWWRGKKGFQVGFFPSECV 54

Variant SH3 domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024382834  235 VIKRYIAQAPDELSFEVGDIVSVIDMPPKElttWWRGKHGFQVGFFPSECVE 286
Cdd:pfam14604    1 ALYPYEPKDDDELSLQRGDVITVIEESEDG---WWEGINTGRTGLVPANYVE 49

EBNA-3B; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024382834 1053 APDKLHLYTDLPEnqlHFQTSAPVEQDFQASSTAREQNHPPGA------PGSQDPQPLH----TSVPGDVPARRDAEQEQ 1122
Cdd:PHA03378   579 SPTTSQLASSAPS---YAQTPWPVPHPSQTPEPPTTQSHIPETsaprqwPMPLRPIPMRplrmQPITFNVLVFPTPHQPP 655

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024382834 1123 SSYLAGQTENKEQfPAHAEDWEQTRQHAPGALPDWEPPTTNLPMDKPHVRACTSGDKQLTSTCAADDKLETPVTAGEKST 1202
Cdd:PHA03378   656 QVEITPYKPTWTQ-IGHIPYQPSPTGANTMLPIQWAPGTMQPPPRAPTPMRPPAAPPGRAQRPAAATGRARPPAAAPGRA 734

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2024382834 1203 PVPVPYLTTIQTAAAEPTRAPTCQHAAGPAIIQADVTGTSAQRTPTGSQPAPPQR 1257
Cdd:PHA03378   735 RPPAAAPGRARPPAAAPGRARPPAAAPGRARPPAAAPGAPTPQPPPQAPPAPQQR 789

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 2024382834  337 RVFGCDLGEHLLNSGQDVPQVLKSCTEFIEKHGIVDGIYRLSGVASNIQKLRHEFDSEQIPDLTKDNYIHDIHSVSSLCK 416
Cdd:cd04384      1 RVFGCDLTEHLLNSGQDVPQVLKSCTEFIEKHGIVDGIYRLSGIASNIQRLRHEFDSEQIPDLTKDVYIQDIHSVSSLCK 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024382834  417 MYFRELPNPLLTYQLYEKFSDAVSAATDEERLVRIHDVIQQLPPPHYRTLEYLMRHLARLADYCTITNMHAKNLAIVWAP 496
Cdd:cd04384     81 LYFRELPNPLLTYQLYEKFSEAVSAASDEERLEKIHDVIQQLPPPHYRTLEFLMRHLSRLAKYCSITNMHAKNLAIVWAP 160

                          170       180       190
                   ....*....|....*....|....*....|....*
gi 2024382834  497 NLLRSKQIESACFSGTAAFMEVRIQSVVVEFILNH 531
Cdd:cd04384    161 NLLRSKQIESACFSGTAAFMEVRIQSVVVEFILNH 195

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 2024382834   352 QDVPQVLKSCTEFIEKHGI-VDGIYRLSGVASNIQKLRHEFDSEqiPDLTKDNYIHDIHSVSSLCKMYFRELPNPLLTYQ 430
Cdd:smart00324    1 KPIPIIVEKCIEYLEKRGLdTEGIYRVSGSKSRVKELRDAFDSG--PDPDLDLSEYDVHDVAGLLKLFLRELPEPLITYE 78

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024382834   431 LYEKFSDAVSAATDEERLVRIHDVIQQLPPPHYRTLEYLMRHLARLADYCTITNMHAKNLAIVWAPNLLRSKQIESacfs 510
Cdd:smart00324   79 LYEEFIEAAKLEDETERLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEV---- 154

                           170       180
                    ....*....|....*....|.
gi 2024382834   511 gtAAFMEVRIQSVVVEFILNH 531
Cdd:smart00324  155 --ASLKDIRHQNTVIEFLIEN 173

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 2024382834   96 NVDFGNIQLSLPEEQSEVmRNGCESKELVYLVQISCQGKSWIVKRSYEDFRVLDKHLHLCIYDRRFSQLAELPRSDVLRD 175
Cdd:cd07278      1 NVDIGSLQVVLSDDGSLK-SYKNSGKELVYLVQVQCQGKSWLVKRSYDDFRMLDKHLHQCIYDRKFSQLTELPEECIEKR 79

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 2024382834  176 SPELVTHTLMAYLSRLSAIACNKINCGPALTWMEI 210
Cdd:cd07278     80 EQQNLHQVLSDYLKRLSSIAGNLLNCGPVLNWLEL 114

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 2024382834  339 FGCDLGEHLLNSGQDVPQVLKSCTEFIEKHGI-VDGIYRLSGVASNIQKLRHEFDSE--QIPDLTKDNYIHDIHSVSSLC 415
Cdd:cd04398      1 FGVPLEDLILREGDNVPNIVYQCIQAIENFGLnLEGIYRLSGNVSRVNKLKELFDKDplNVLLISPEDYESDIHSVASLL 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024382834  416 KMYFRELPNPLLTYQLYEKFSDAVSAATDEERLVRIHDVIQQLPPPHYRTLEYLMRHLARLADYCTITNMHAKNLAIVWA 495
Cdd:cd04398     81 KLFFRELPEPLLTKALSREFIEAAKIEDESRRRDALHGLINDLPDANYATLRALMFHLARIKEHESVNRMSVNNLAIIWG 160

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|.
gi 2024382834  496 PNLLRSKqiesacfSGTAAfmEVRIQSVVVEFILNHTDVLF 536
Cdd:cd04398    161 PTLMNAA-------PDNAA--DMSFQSRVIETLLDNAYQIF 192

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 2024382834  339 FGCDLGEHLLNSGQDVPQVLKSCTEFIEKHGI-VDGIYRLSGVASNIQKLRHEFDSEQIPDLTkDNYIHDIHSVSSLCKM 417
Cdd:cd04403      1 FGCHLEALCQRENSTVPKFVRLCIEAVEKRGLdVDGIYRVSGNLAVIQKLRFAVDHDEKLDLD-DSKWEDIHVITGALKL 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024382834  418 YFRELPNPLLTYQLYEKFSDAVSAATDEERLVRIHDVIQQLPPPHYRTLEYLMRHLARLADYCTITNMHAKNLAIVWAPN 497
Cdd:cd04403     80 FFRELPEPLFPYSLFNDFVAAIKLSDYEQRVSAVKDLIKSLPKPNHDTLKMLFRHLCRVIEHGEKNRMTTQNLAIVFGPT 159

                          170       180       190
                   ....*....|....*....|....*....|..
gi 2024382834  498 LLRSKQiesacFSGTAAFMEVrIQSVVVEFIL 529
Cdd:cd04403    160 LLRPEQ-----ETGNIAVHMV-YQNQIVELIL 185

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 2024382834  339 FGCDLGEHLLNSGQDVPQVLKSCTEFIEKHGIV-DGIYRLSGVASNIQKLRHEFDSE-QIPDLTKDNYiHDIHSVSSLCK 416
Cdd:cd04372      1 YGCDLTTLVKAHNTQRPMVVDMCIREIEARGLQsEGLYRVSGFAEEIEDVKMAFDRDgEKADISATVY-PDINVITGALK 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024382834  417 MYFRELPNPLLTYQLYEKFSDAVSAATDEERLVRIHDVIQQLPPPHYRTLEYLMRHLARLADYCTITNMHAKNLAIVWAP 496
Cdd:cd04372     80 LYFRDLPIPVITYDTYPKFIDAAKISNPDERLEAVHEALMLLPPAHYETLRYLMEHLKRVTLHEKDNKMNAENLGIVFGP 159

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|
gi 2024382834  497 NLLRSKQIesacfSGTAAFMEVRIQSVVVEFILNHTDVLF 536
Cdd:cd04372    160 TLMRPPED-----SALTTLNDMRYQILIVQLLITNEDVLF 194

RhoGAP_ARHGAP21: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP21-like proteins. ArhGAP21 is a multi-domain protein, containing RhoGAP, PH and PDZ domains, and is believed to play a role in the organization of the cell-cell junction complex. It has been shown to function as a GAP of Cdc42 and RhoA, and to interact with alpha-catenin and Arf6. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024382834  354 VPQVLKSCTEFIEKHGI-VDGIYRLSGVASNIQKLRHEFDS--EQIpDLTKDNYiHDIHSVSSLCKMYFRELPNPLLTYQ 430
Cdd:cd04395     18 VPLIVEVCCNIVEARGLeTVGIYRVPGNNAAISALQEELNRggFDI-DLQDPRW-RDVNVVSSLLKSFFRKLPEPLFTNE 95

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024382834  431 LYEKFSDAVSAATDEERLVRIHDVIQQLPPPHYRTLEYLMRHLARLADYCTITNMHAKNLAIVWAPNLLRSKQIesacfS 510
Cdd:cd04395     96 LYPDFIEANRIEDPVERLKELRRLIHSLPDHHYETLKHLIRHLKTVADNSEVNKMEPRNLAIVFGPTLVRTSDD-----N 170

                          170       180
                   ....*....|....*....|....*.
gi 2024382834  511 GTAAFMEVRIQSVVVEFILNHTDVLF 536
Cdd:cd04395    171 METMVTHMPDQCKIVETLIQHYDWFF 196

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 2024382834  339 FGCDLGEHLLNSGQDVPQVLKSCTEFIEKHG-IVDGIYRLSGVASNIQKLRHEFDS-EQIPDLTkDNYIHDIhsvSSLCK 416
Cdd:cd04378      1 FGVDFSQVPRDFPDEVPFIIKKCTSEIENRAlGVQGIYRVSGSKARVEKLCQAFENgKDLVELS-ELSPHDI---SSVLK 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024382834  417 MYFRELPNPLLTYQLYEKFSD-------------AVSAATDEERLVR-IHDVIQQLPPPHYRTLEYLMRHLARLADYCTI 482
Cdd:cd04378     77 LFLRQLPEPLILFRLYNDFIAlakeiqrdteedkAPNTPIEVNRIIRkLKDLLRQLPASNYNTLQHLIAHLYRVAEQFEE 156

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*....
gi 2024382834  483 TNMHAKNLAIVWAPNLLRSKQIESACfsGTAAFMEVRIQSVVVEFILNH 531
Cdd:cd04378    157 NKMSPNNLGIVFGPTLIRPRPGDADV--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 2024382834  356 QVLKSCTEFIEKHGIVD-GIYRLSGVASNIQKLRHE-FDSEQIP--DLTKDNYIHDIHSVSSLCKMYFRELPNPLLTYQL 431
Cdd:cd04374     30 KFVRKCIEAVETRGINEqGLYRVVGVNSKVQKLLSLgLDPKTSTpgDVDLDNSEWEIKTITSALKTYLRNLPEPLMTYEL 109

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024382834  432 YEKFSDAVSAATDEERLVRIHDVIQQLPPPHYRTLEYLMRHLARLADYCTITNMHAKNLAIVWAPNLLRSKQiESacfsg 511
Cdd:cd04374    110 HNDFINAAKSENLESRVNAIHSLVHKLPEKNREMLELLIKHLTNVSDHSKKNLMTVSNLGVVFGPTLLRPQE-ET----- 183

                          170       180
                   ....*....|....*....|
gi 2024382834  512 TAAFMEVRIQSVVVEFILNH 531
Cdd:cd04374    184 VAAIMDIKFQNIVVEILIEN 203

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 2024382834  339 FGCDLgEHLL--NSGQD-VPQVLKSCTEFIEKHGI-VDGIYRLSGVASNIQKLRHEFDSEQipDLTKDNYiHDIHSVSSL 414
Cdd:cd04404      6 FGVSL-QFLKekNPEQEpIPPVVRETVEYLQAHALtTEGIFRRSANTQVVKEVQQKYNMGE--PVDFDQY-EDVHLPAVI 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024382834  415 CKMYFRELPNPLLTYQLYEKFSdAVSAATDEERLVRIHDVIQQLPPPHYRTLEYLMRHLARLADYCTITNMHAKNLAIVW 494
Cdd:cd04404     82 LKTFLRELPEPLLTFDLYDDIV-GFLNVDKEERVERVKQLLQTLPEENYQVLKYLIKFLVQVSAHSDQNKMTNSNLAVVF 160

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|..
gi 2024382834  495 APNLLRSKqiesacfSGTAAFMEVRIQSVVVEFILNHTDVLF 536
Cdd:cd04404    161 GPNLLWAK-------DASMSLSAINPINTFTKFLLDHQDEIF 195

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 2024382834  354 VPQVLKSCTEFIEKHGI-VDGIYRLSGVASNIQKLRHEFDSEQIPDLTKDnyiHDIHSVSSLCKMYFRELPNPLLTYQLY 432
Cdd:cd04376      9 VPRLVESCCQHLEKHGLqTVGIFRVGSSKKRVRQLREEFDRGIDVVLDEN---HSVHDVAALLKEFFRDMPDPLLPRELY 85

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024382834  433 EKFSDAVSAATDeERLVRIHDVIQQLPPPHYRTLEYLMRHLARLADYCTIT-----------NMHAKNLAIVWAPNLLRS 501
Cdd:cd04376     86 TAFIGTALLEPD-EQLEALQLLIYLLPPCNCDTLHRLLKFLHTVAEHAADSidedgqevsgnKMTSLNLATIFGPNLLHK 164

                          170       180       190
                   ....*....|....*....|....*....|....*.
gi 2024382834  502 KQIESACFSGTAAFMEVRIQSV-VVEFILNHTDVLF 536
Cdd:cd04376    165 QKSGEREFVQASLRIEESTAIInVVQTMIDNYEELF 200

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 2024382834  339 FGCDLGEHLLNSGQDVPQVLKSCTEFIEKHG-IVDGIYRLSGVASNIQKLRHEFDS-EQIPDLTkDNYIHDIhsvSSLCK 416
Cdd:cd04409      1 FGADFAQVAKKSPDGIPFIIKKCTSEIESRAlCLKGIYRVNGAKSRVEKLCQAFENgKDLVELS-ELSPHDI---SNVLK 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024382834  417 MYFRELPNPLLTYQLYEKF------------SDAVSAATDEER----------LVRIHDVIQQLPPPHYRTLEYLMRHLA 474
Cdd:cd04409     77 LYLRQLPEPLILFRLYNEFiglakesqhvneTQEAKKNSDKKWpnmctelnriLLKSKDLLRQLPAPNYNTLQFLIVHLH 156

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2024382834  475 RLADYCTITNMHAKNLAIVWAPNLLRSKQIESACfsGTAAFMEVRIQSVVVEFILNH 531
Cdd:cd04409    157 RVSEQAEENKMSASNLGIIFGPTLIRPRPTDATV--SLSSLVDYPHQARLVELLITY 211

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 2024382834  333 ILKERVFGCDLgehllnsgqdVPQVLKSCTEFIEKHGIVD-GIYRLSGVASNIQKLRHEFDSEQIPDLTKDNyihDIHSV 411
Cdd:cd04390     11 VAYERKFGPRL----------VPILVEQCVDFIREHGLKEeGLFRLPGQANLVKQLQDAFDAGERPSFDSDT---DVHTV 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024382834  412 SSLCKMYFRELPNPLLTYQLYEKF--SDAVSAATDEERLVRIHDVIQQLPPPHYRTLEYLMRHLARLADYCTITNMHAKN 489
Cdd:cd04390     78 ASLLKLYLRELPEPVIPWAQYEDFlsCAQLLSKDEEKGLGELMKQVSILPKVNYNLLSYICRFLDEVQSNSSVNKMSVQN 157

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....
gi 2024382834  490 LAIVWAPNLLRSKqIESAcfsgtAAFME--VRIQSVVVEFILNH 531
Cdd:cd04390    158 LATVFGPNILRPK-VEDP-----ATIMEgtPQIQQLMTVMISKH 195

RhoGAP_myosin_IXA: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in myosins IXA. 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 2024382834  339 FGCDLGEhLLNSGQDVPQVLKSCTEFIEKHGI-VDGIYRLSGVASNIQKLRHEFDSEqIPDLTKDNYihDIHSVSSLCKM 417
Cdd:cd04406      1 FGVELSR-LTSEDRSVPLVVEKLINYIEMHGLyTEGIYRKSGSTNKIKELRQGLDTD-ANSVNLDDY--NIHVIASVFKQ 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024382834  418 YFRELPNPLLTYQLYEKFSDAVSAATDEERLVRIHDVIQQLPPPHYRTLEYLMRHLARLADYCTITNMHAKNLAIVWAPN 497
Cdd:cd04406     77 WLRDLPNPLMTFELYEEFLRAMGLQERRETVRGVYSVIDQLSRTHLNTLERLIFHLVRIALQEETNRMSANALAIVFAPC 156

                   ...
gi 2024382834  498 LLR 500
Cdd:cd04406    157 ILR 159

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 2024382834  337 RVFGCDLGEHLLNSGQDVPQVLKSCTEFIEKHGIV-DGIYRLSGVASNIQKLRHEFDSEQIPdLTKDNYIHDIHSVSSLC 415
Cdd:cd04383      1 KLFNGSLEEYIQDSGQAIPLVVESCIRFINLYGLQhQGIFRVSGSQVEVNDIKNAFERGEDP-LADDQNDHDINSVAGVL 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024382834  416 KMYFRELPNPLLTYQLYEKFSDAVSAATDEERLVRIHDVIQQLPPPHYRTLEYLMRHLARLADYCTITNMHAKNLAIVWA 495
Cdd:cd04383     80 KLYFRGLENPLFPKERFEDLMSCVKLENPTERVHQIREILSTLPRSVIIVMRYLFAFLNHLSQFSDENMMDPYNLAICFG 159

                   ....*
gi 2024382834  496 PNLLR 500
Cdd:cd04383    160 PTLMP 164

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 2024382834  354 VPQVLKSCTEFIEKHGIVD-GIYRLSGVASNIQKLRHEF-DSEQIPDLTKdnyiHDIHSVSSLCKMYFRELPNPLLTYQL 431
Cdd:cd04382     17 IPALIVHCVNEIEARGLTEeGLYRVSGSEREVKALKEKFlRGKTVPNLSK----VDIHVICGCLKDFLRSLKEPLITFAL 92