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 1720396671 214 YSCDLTTLVKAHITKRPMVVDMCIREIESRGLNSEGLYRVSGFSDLIEDVKMAFDRDGEKADISVNMYEDINIITGALKL 293
Cdd:cd04372     1 YGCDLTTLVKAHNTQRPMVVDMCIREIEARGLQSEGLYRVSGFAEEIEDVKMAFDRDGEKADISATVYPDINVITGALKL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720396671 294 YFRDLPIPLITYDAYPKFIESAKIMDPDEQLETLHEALRSLPPAHCETLRYLMAHLKRVTLHEKENLMSAENLGIVFGPT 373
Cdd:cd04372    81 YFRDLPIPVITYDTYPKFIDAAKISNPDERLEAVHEALMLLPPAHYETLRYLMEHLKRVTLHEKDNKMNAENLGIVFGPT 160

                         170       180       190
                  ....*....|....*....|....*....|....
gi 1720396671 374 LMRSPELDPMAALNDIRYQRLVVELLIKNEDILF 407
Cdd:cd04372   161 LMRPPEDSALTTLNDMRYQILIVQLLITNEDVLF 194

Src homology 2 (SH2) domain; In general, SH2 domains are involved in signal transduction; they bind pTyr-containing polypeptide ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. They are present in a wide array of proteins including: adaptor proteins (Nck1, Crk, Grb2), scaffolds (Slp76, Shc, Dapp1), kinases (Src, Syk, Fps, Tec), phosphatases (Shp-1, Shp-2), transcription factors (STAT1), Ras signaling molecules (Ras-Gap), ubiquitination factors (c-Cbl), cytoskeleton regulators (Tensin), signal regulators (SAP), and phospholipid second messengers (PLCgamma), amongst others.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720396671   1 MISREETDQLLSVA-EGSYLIRESQRQPGTYTLALRFGSQTRNFRLYYDGK---HFVGEKRFESIHDLVTDGLITLYIET 76
Cdd:cd10352    12 LISREEAEQLLSGAsDGSYLIRESSRDDGYYTLSLRFNGKVKNYKLYYDGKnhyHYVGEKRFDTIHDLVADGLITLYMET 91

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 1720396671 214 YSCDLTTLVKAHITKRPMVVDMCIREIESRGLNSEGLYRVSGFSDLIEDVKMAFDRDGEKADISVNMYEDINIITGALKL 293
Cdd:cd04372     1 YGCDLTTLVKAHNTQRPMVVDMCIREIEARGLQSEGLYRVSGFAEEIEDVKMAFDRDGEKADISATVYPDINVITGALKL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720396671 294 YFRDLPIPLITYDAYPKFIESAKIMDPDEQLETLHEALRSLPPAHCETLRYLMAHLKRVTLHEKENLMSAENLGIVFGPT 373
Cdd:cd04372    81 YFRDLPIPVITYDTYPKFIDAAKISNPDERLEAVHEALMLLPPAHYETLRYLMEHLKRVTLHEKDNKMNAENLGIVFGPT 160

                         170       180       190
                  ....*....|....*....|....*....|....
gi 1720396671 374 LMRSPELDPMAALNDIRYQRLVVELLIKNEDILF 407
Cdd:cd04372   161 LMRPPEDSALTTLNDMRYQILIVQLLITNEDVLF 194

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720396671 230 PMVVDMCIREIESRGLNSEGLYRVSGFSDLIEDVKMAFDRDGEKADIsvNMYEDINIITGALKLYFRDLPIPLITYDAYP 309
Cdd:pfam00620   1 PLIVRKCVEYLEKRGLDTEGIFRVSGSASRIKELREAFDRGPDVDLD--LEEEDVHVVASLLKLFLRELPEPLLTFELYE 78

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1720396671 310 KFIESAKIMDPDEQLETLHEALRSLPPAHCETLRYLMAHLKRVTLHEKENLMSAENLGIVFGPTLMRSP 378
Cdd:pfam00620  79 EFIEAAKLPDEEERLEALRELLRKLPPANRDTLRYLLAHLNRVAQNSDVNKMNAHNLAIVFGPTLLRPP 147

Src homology 2 (SH2) domain found in alpha2-chimerin and beta2-chimerin proteins; Chimerins are a family of phorbol ester- and diacylglycerol-responsive GTPase-activating proteins. Alpha1-chimerin (formerly known as n-chimerin) and alpha2-chimerin are alternatively spliced products of a single gene, as are beta1- and beta2-chimerin. alpha1- and beta1-chimerin have a relatively short N-terminal region that does not encode any recognizable domains, whereas alpha2- and beta2-chimerin both include a functional SH2 domain that can bind to phosphotyrosine motifs within receptors. All of the isoforms contain a GAP domain with specificity in vitro for Rac1 and a diacylglycerol (DAG)-binding C1 domain which allows them to translocate to membranes in response to DAG signaling and anchors them in close proximity to activated Rac. Other C1 domain-containing diacylglycerol receptors including: PKC, Munc-13 proteins, phorbol ester binding scaffolding proteins involved in Ca2+-stimulated exocytosis, and RasGRPs, diacylglycerol-activated guanine-nucleotide exchange factors (GEFs) for Ras and Rap1. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720396671   1 MISREETDQLLSVA-EGSYLIRESQRQPGTYTLALRFGSQTRNFRLYYDGK---HFVGEKRFESIHDLVTDGLITLYIET 76
Cdd:cd10352    12 LISREEAEQLLSGAsDGSYLIRESSRDDGYYTLSLRFNGKVKNYKLYYDGKnhyHYVGEKRFDTIHDLVADGLITLYMET 91

Protein kinase C conserved region 1 (C1) domains (Cysteine-rich domains); Some bind phorbol esters and diacylglycerol. Some bind RasGTP. Zinc-binding domains.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1720396671  154 HNFKVHTFRGPHWCEYCANFMWGLIAQGVKCADCGLNVHKQCSKMVPNDC 203
Cdd:smart00109   1 HKHVFRTFTKPTFCCVCRKSIWGSFKQGLRCSECKVKCHKKCADKVPKAC 50

SH2 domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720396671   2 ISREETDQLL--SVAEGSYLIRESQRQPGTYTLALRFGSQTRNFRLYY--DGKHFV-GEKRFESIHDLVT 66
Cdd:pfam00017   6 ISRQEAERLLlnGKPDGTFLVRESESTPGGYTLSVRDDGKVKHYKIQStdNGGYYIsGGVKFSSLAELVE 75

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 1720396671 214 YSCDLTTLVKAHITKRPMVVDMCIREIESRGLNSEGLYRVSGFSDLIEDVKMAFDRDGEKADISVNMYEDINIITGALKL 293
Cdd:cd04372     1 YGCDLTTLVKAHNTQRPMVVDMCIREIEARGLQSEGLYRVSGFAEEIEDVKMAFDRDGEKADISATVYPDINVITGALKL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720396671 294 YFRDLPIPLITYDAYPKFIESAKIMDPDEQLETLHEALRSLPPAHCETLRYLMAHLKRVTLHEKENLMSAENLGIVFGPT 373
Cdd:cd04372    81 YFRDLPIPVITYDTYPKFIDAAKISNPDERLEAVHEALMLLPPAHYETLRYLMEHLKRVTLHEKDNKMNAENLGIVFGPT 160

                         170       180       190
                  ....*....|....*....|....*....|....
gi 1720396671 374 LMRSPELDPMAALNDIRYQRLVVELLIKNEDILF 407
Cdd:cd04372   161 LMRPPEDSALTTLNDMRYQILIVQLLITNEDVLF 194

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720396671 230 PMVVDMCIREIESRGLNSEGLYRVSGFSDLIEDVKMAFDRDGEKADIsvNMYEDINIITGALKLYFRDLPIPLITYDAYP 309
Cdd:pfam00620   1 PLIVRKCVEYLEKRGLDTEGIFRVSGSASRIKELREAFDRGPDVDLD--LEEEDVHVVASLLKLFLRELPEPLLTFELYE 78

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1720396671 310 KFIESAKIMDPDEQLETLHEALRSLPPAHCETLRYLMAHLKRVTLHEKENLMSAENLGIVFGPTLMRSP 378
Cdd:pfam00620  79 EFIEAAKLPDEEERLEALRELLRKLPPANRDTLRYLLAHLNRVAQNSDVNKMNAHNLAIVFGPTLLRPP 147

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 1720396671 214 YSCDLTTLVKAHITKRPMVVDMCIREIESRGLNSEGLYRVSGFSDLIEDVKMAFDRDgEKADISVNMYEDINIITGALKL 293
Cdd:cd04403     1 FGCHLEALCQRENSTVPKFVRLCIEAVEKRGLDVDGIYRVSGNLAVIQKLRFAVDHD-EKLDLDDSKWEDIHVITGALKL 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720396671 294 YFRDLPIPLITYDAYPKFIESAKIMDPDEQLETLHEALRSLPPAHCETLRYLMAHLKRVTLHEKENLMSAENLGIVFGPT 373
Cdd:cd04403    80 FFRELPEPLFPYSLFNDFVAAIKLSDYEQRVSAVKDLIKSLPKPNHDTLKMLFRHLCRVIEHGEKNRMTTQNLAIVFGPT 159

                         170       180
                  ....*....|....*....|....*....
gi 1720396671 374 LMRsPELDPMAALNDIRYQRLVVELLIKN 402
Cdd:cd04403   160 LLR-PEQETGNIAVHMVYQNQIVELILLE 187

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 1720396671 230 PMVVDMCIREIESRGLNSEGLYRVSGFSDLIEDVKMAFDRDGEKADISVNMYEDINIITGALKLYFRDLPIPLITYDAYP 309
Cdd:cd04395    19 PLIVEVCCNIVEARGLETVGIYRVPGNNAAISALQEELNRGGFDIDLQDPRWRDVNVVSSLLKSFFRKLPEPLFTNELYP 98

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720396671 310 KFIESAKIMDPDEQLETLHEALRSLPPAHCETLRYLMAHLKRVTLHEKENLMSAENLGIVFGPTLMRSPElDPMA-ALND 388
Cdd:cd04395    99 DFIEANRIEDPVERLKELRRLIHSLPDHHYETLKHLIRHLKTVADNSEVNKMEPRNLAIVFGPTLVRTSD-DNMEtMVTH 177

                         170
                  ....*....|....*....
gi 1720396671 389 IRYQRLVVELLIKNEDILF 407
Cdd:cd04395   178 MPDQCKIVETLIQHYDWFF 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 1720396671 230 PMVVDMCIREIESRGLNSEGLYRVSGFSDLIEDVKMAFDRDGEKADISVNMYEDIniiTGALKLYFRDLPIPLITYDAYP 309
Cdd:cd04378    17 PFIIKKCTSEIENRALGVQGIYRVSGSKARVEKLCQAFENGKDLVELSELSPHDI---SSVLKLFLRQLPEPLILFRLYN 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720396671 310 KFI----ESAKIMDPDEQLET----------LHEALRSLPPAHCETLRYLMAHLKRVTLHEKENLMSAENLGIVFGPTLM 375
Cdd:cd04378    94 DFIalakEIQRDTEEDKAPNTpievnriirkLKDLLRQLPASNYNTLQHLIAHLYRVAEQFEENKMSPNNLGIVFGPTLI 173

                         170       180       190
                  ....*....|....*....|....*....|
gi 1720396671 376 RSPELD---PMAALNDIRYQRLVVELLIKN 402
Cdd:cd04378   174 RPRPGDadvSLSSLVDYGYQARLVEFLITN 203

RhoGAP_myosin_IX: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in class IX myosins. Class IX myosins contain a characteristic head domain, a neck domain, a tail domain which contains a C6H2-zinc binding motif and a RhoGAP 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 1720396671 230 PMVVDMCIREIESRGLNSEGLYRVSGFSDLIEDVKMAFDRDGEkadiSVNMyEDINI--ITGALKLYFRDLPIPLITYDA 307
Cdd:cd04377    16 PLVLEKLLEHIEMHGLYTEGIYRKSGSANKIKELRQGLDTDPD----SVNL-EDYPIhvITSVLKQWLRELPEPLMTFEL 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720396671 308 YPKFIESAKIMDPDEQLETLHEALRSLPPAHCETLRYLMAHLKRVTLHEKENLMSAENLGIVFGPTLMRSPE-LDPMAAL 386
Cdd:cd04377    91 YENFLRAMELEEKQERVRALYSVLEQLPRANLNTLERLIFHLVRVALQEEVNRMSANALAIVFAPCILRCPDtADPLQSL 170

                         170
                  ....*....|....*
gi 1720396671 387 NDIRYQRLVVELLIK 401
Cdd:cd04377   171 QDVSKTTTCVETLIK 185

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 1720396671 212 KVYSCDLTTLVKAHITKRPMVVDMCIREIESRGLnSEGLYRVSGFSDLIEDVKMAFDRDGEKADISVNMYEDINIITGAL 291
Cdd:cd04384     1 RVFGCDLTEHLLNSGQDVPQVLKSCTEFIEKHGI-VDGIYRLSGIASNIQRLRHEFDSEQIPDLTKDVYIQDIHSVSSLC 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720396671 292 KLYFRDLPIPLITYDAYPKFIESAKIMDPDEQLETLHEALRSLPPAHCETLRYLMAHLKRVTLHEKENLMSAENLGIVFG 371
Cdd:cd04384    80 KLYFRELPNPLLTYQLYEKFSEAVSAASDEERLEKIHDVIQQLPPPHYRTLEFLMRHLSRLAKYCSITNMHAKNLAIVWA 159

                         170       180       190
                  ....*....|....*....|....*....|....*.
gi 1720396671 372 PTLMRSPELD-----PMAALNDIRYQRLVVELLIKN 402
Cdd:cd04384   160 PNLLRSKQIEsacfsGTAAFMEVRIQSVVVEFILNH 195

protein kinase C conserved region 1 (C1 domain) found in beta-chimaerin and similar proteins; Beta-chimaerin, also called beta-chimerin (BCH) or Rho GTPase-activating protein 3 (ARHGAP3), is a GTPase-activating protein (GAP) for p21-rac. Insufficient expression of beta-2 chimaerin is expected to lead to higher Rac activity and could therefore play a role in the progression from low-grade to high-grade tumors. Beta-chimaerin contains a functional SH2 domain that can bind to phosphotyrosine motifs within receptors, a GAP domain with specificity in vitro for Rac1 and a diacylglycerol (DAG)-binding C1 domain which allows them to translocate to membranes in response to DAG signaling and anchors them in close proximity to activated Rac. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1720396671 150 YEKVHNFKVHTFRGPHWCEYCANFMWGLIAQGVKCADCGLNVHKQCSKMVPNDCKPDLK 208
Cdd:cd20857     2 YEKAHNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDCQPDLK 60

protein kinase C conserved region 1 (C1 domain) found in the chimaerin family; Chimaerins are a family of phorbolester- and diacylglycerol-responsive GTPase activating proteins (GAPs) specific for the Rho-like GTPase Rac. Alpha1-chimerin (formerly known as N-chimerin) and alpha2-chimerin are alternatively spliced products of a single gene, as are beta1- and beta2-chimerin. Alpha1- and beta1-chimerin have a relatively short N-terminal region that does not encode any recognizable domains, whereas alpha2- and beta2-chimerin both include a functional SH2 domain that can bind to phosphotyrosine motifs within receptors. All the isoforms contain a GAP domain with specificity in vitro for Rac1 and a diacylglycerol (DAG)-binding C1 domain which allows them to translocate to membranes in response to DAG signaling and anchors them in close proximity to activated Rac. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1720396671 154 HNFKVHTFRGPHWCEYCANFMWGLIAQGVKCADCGLNVHKQCSKMVPNDCKP 205
Cdd:cd20806     2 HNFKVHTFKGPHWCDYCGNFMWGLIAQGVKCEDCGFNAHKQCSKLVPHDCQP 53

RhoGAP_GMIP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of GMIP (Gem interacting protein). 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. 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 1720396671 230 PMVVDMCIREIESRGLNSEGLYRVSGFSDLIEDVKMAFDRDGEKADISVNMYEDIniiTGALKLYFRDLPIPLITYDAYP 309
Cdd:cd04408    17 PFVVVRCTAEIENRALGVQGIYRISGSKARVEKLCQAFENGRDLVDLSGHSPHDI---TSVLKHFLKELPEPVLPFQLYD 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720396671 310 KFIESAKIM--DPDEQLET---LHEALRS-------LPPAHCETLRYLMAHLKRVTLHEKENLMSAENLGIVFGPTLMRS 377
Cdd:cd04408    94 DFIALAKELqrDSEKAAESpsiVENIIRSlkellgrLPVSNYNTLRHLMAHLYRVAERFEDNKMSPNNLGIVFGPTLLRP 173

                         170       180
                  ....*....|....*....|....*..
gi 1720396671 378 PELD--PMAALNDIRYQRLVVELLIKN 402
Cdd:cd04408   174 LVGGdvSMICLLDTGYQAQLVEFLISN 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 1720396671 230 PMVVDMCIREIESRGLNSEGLYRVSGFSDLIEDVKMAFDRDGEKADISVNMYEDIniiTGALKLYFRDLPIPLITYDAYP 309
Cdd:cd04409    17 PFIIKKCTSEIESRALCLKGIYRVNGAKSRVEKLCQAFENGKDLVELSELSPHDI---SNVLKLYLRQLPEPLILFRLYN 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720396671 310 KFIESAK-IMDPDEQLET---------------------LHEALRSLPPAHCETLRYLMAHLKRVTLHEKENLMSAENLG 367
Cdd:cd04409    94 EFIGLAKeSQHVNETQEAkknsdkkwpnmctelnrillkSKDLLRQLPAPNYNTLQFLIVHLHRVSEQAEENKMSASNLG 173

                         170       180       190
                  ....*....|....*....|....*....|....*..
gi 1720396671 368 IVFGPTLMRSPELDP---MAALNDIRYQRLVVELLIK 401
Cdd:cd04409   174 IIFGPTLIRPRPTDAtvsLSSLVDYPHQARLVELLIT 210

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 1720396671 230 PMVVDMCIREIESRGLNSEGLYRVSGFSDLIEDVKMAFDRDGEKADIsvnmyED--INIITGALKLYFRDLPIPLITYDA 307
Cdd:cd04407    16 PIVLEKLLEHVEMHGLYTEGIYRKSGSANRMKELHQLLQADPENVKL-----ENypIHAITGLLKQWLRELPEPLMTFAQ 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720396671 308 YPKFIESAKIMDPDEQLETLHEALRSLPPAHCETLRYLMAHLKRVTLHEKENLMSAENLGIVFGPTLMRSPE-LDPMAAL 386
Cdd:cd04407    91 YNDFLRAVELPEKQEQLQAIYRVLEQLPTANHNTLERLIFHLVKVALEEDVNRMSPNALAIVFAPCLLRCPDsSDPLTSM 170

                         170
                  ....*....|....*
gi 1720396671 387 NDIRYQRLVVELLIK 401
Cdd:cd04407   171 KDVAKTTTCVEMLIK 185

RhoGAP_SYD1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in SYD-1_like proteins. Syd-1, first identified and best studied in C.elegans, has been shown to play an important role in neuronal development by specifying axonal properties. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720396671 217 DLTTLVKAHITKR--PMVVDMCIREIESRGLNSEGLYRVSGFSDLIEDVKMAFDRDGEKADISVNMYEDINIITGALKLY 294
Cdd:cd04379     4 PLSRLVEREGESRdvPIVLQKCVQEIERRGLDVIGLYRLCGSAAKKKELRDAFERNSAAVELSEELYPDINVITGVLKDY 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720396671 295 FRDLPIPLITYDAYPKFIESAKIMDPDEQLETLHEALR---SLPPAHCETLRYLMAHLKRVTLHEKENLMSAENLGIVFG 371
Cdd:cd04379    84 LRELPEPLITPQLYEMVLEALAVALPNDVQTNTHLTLSiidCLPLSAKATLLLLLDHLSLVLSNSERNKMTPQNLAVCFG 163

                  ....
gi 1720396671 372 PTLM 375
Cdd:cd04379   164 PVLM 167

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 1720396671 230 PMVVDMCIREIESRGLNSEGLYRVSGFSDLIEDVKMAFDRDGEkadiSVNMYE-DINIITGALKLYFRDLPIPLITYDAY 308
Cdd:cd04406    16 PLVVEKLINYIEMHGLYTEGIYRKSGSTNKIKELRQGLDTDAN----SVNLDDyNIHVIASVFKQWLRDLPNPLMTFELY 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720396671 309 PKFIESAKIMDPDEQLETLHEALRSLPPAHCETLRYLMAHLKRVTLHEKENLMSAENLGIVFGPTLMRSPE-LDPMAALN 387
Cdd:cd04406    92 EEFLRAMGLQERRETVRGVYSVIDQLSRTHLNTLERLIFHLVRIALQEETNRMSANALAIVFAPCILRCPDtTDPLQSVQ 171

                         170
                  ....*....|...
gi 1720396671 388 DIRYQRLVVELLI 400
Cdd:cd04406   172 DISKTTTCVELIV 184

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 1720396671 230 PMVVDMCIREIESRGLNSEGLYRVSGFSDLIEDVKMAFDRDGEkadisVNMYEDINI--ITGALKLYFRDLPIPLITYDA 307
Cdd:cd04376    10 PRLVESCCQHLEKHGLQTVGIFRVGSSKKRVRQLREEFDRGID-----VVLDENHSVhdVAALLKEFFRDMPDPLLPREL 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720396671 308 YPKFIESAKiMDPDEQLETLHEALRSLPPAHCETLRYLMAHLKRVTLHEKE-----------NLMSAENLGIVFGPTLMR 376
Cdd:cd04376    85 YTAFIGTAL-LEPDEQLEALQLLIYLLPPCNCDTLHRLLKFLHTVAEHAADsidedgqevsgNKMTSLNLATIFGPNLLH 163

                         170       180       190
                  ....*....|....*....|....*....|....*..
gi 1720396671 377 -----SPELDPMAA-LNDIRYQRLVVELLIKNEDILF 407
Cdd:cd04376   164 kqksgEREFVQASLrIEESTAIINVVQTMIDNYEELF 200

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 1720396671 230 PMVVDMCIREIESRGLNSEGLYRVSGFSDLIEDVKMAFDRDGekadiSVNMYE-DINIITGALKLYFRDLPIPLITYDAY 308
Cdd:cd04381    21 PLVFRECIDYVEKHGMKCEGIYKVSGIKSKVDELKAAYNRRE-----SPNLEEyEPPTVASLLKQYLRELPEPLLTKELM 95

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1720396671 309 PKFIESAKIMDPDEQLETLHEALRSLPPAHCETLRYLMAHLKRVTLHEKENLMSAENLGIVFGPTLMRSPEL 380
Cdd:cd04381    96 PRFEEACGRPTEAEREQELQRLLKELPECNRLLLAWLIVHMDHVIAQELETKMNIQNISIVLSPTVQISNRL 167

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1720396671 154 HNFKVHTFRGPHWCEYCANFMWGLIAQGVKCADCGLNVHKQCSKMVPNDCKPD 206
Cdd:pfam00130   1 HHFVHRNFKQPTFCDHCGEFLWGLGKQGLKCSWCKLNVHKRCHEKVPPECGCD 53