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 755498504 348 YSCDLTTLVKAHITKRPMVVDMCIREIESRGLNSEGLYRVSGFSDLIEDVKMAFDRDGEKADISVNMYEDINIITGALKL 427
Cdd:cd04372    1 YGCDLTTLVKAHNTQRPMVVDMCIREIEARGLQSEGLYRVSGFAEEIEDVKMAFDRDGEKADISATVYPDINVITGALKL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755498504 428 YFRDLPIPLITYDAYPKFIESAKIMDPDEQLETLHEALRSLPPAHCETLRYLMAHLKRVTLHEKENLMSAENLGIVFGPT 507
Cdd:cd04372   81 YFRDLPIPVITYDTYPKFIDAAKISNPDERLEAVHEALMLLPPAHYETLRYLMEHLKRVTLHEKDNKMNAENLGIVFGPT 160

                        170       180       190
                 ....*....|....*....|....*....|....
gi 755498504 508 LMRSPELDPMAALNDIRYQRLVVELLIKNEDILF 541
Cdd:cd04372  161 LMRPPEDSALTTLNDMRYQILIVQLLITNEDVLF 194

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
                 ....*....|....*....|....*....|....*....|....*....
gi 755498504 291 RVHTFRGPHWCEYCANFMWGLIAQGVKCADCGLNVHKQCSKMVPNDCKP 339
Cdd:cd20806    5 KVHTFKGPHWCDYCGNFMWGLIAQGVKCEDCGFNAHKQCSKLVPHDCQP 53

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 755498504 348 YSCDLTTLVKAHITKRPMVVDMCIREIESRGLNSEGLYRVSGFSDLIEDVKMAFDRDGEKADISVNMYEDINIITGALKL 427
Cdd:cd04372    1 YGCDLTTLVKAHNTQRPMVVDMCIREIEARGLQSEGLYRVSGFAEEIEDVKMAFDRDGEKADISATVYPDINVITGALKL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755498504 428 YFRDLPIPLITYDAYPKFIESAKIMDPDEQLETLHEALRSLPPAHCETLRYLMAHLKRVTLHEKENLMSAENLGIVFGPT 507
Cdd:cd04372   81 YFRDLPIPVITYDTYPKFIDAAKISNPDERLEAVHEALMLLPPAHYETLRYLMEHLKRVTLHEKDNKMNAENLGIVFGPT 160

                        170       180       190
                 ....*....|....*....|....*....|....
gi 755498504 508 LMRSPELDPMAALNDIRYQRLVVELLIKNEDILF 541
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 755498504  364 PMVVDMCIREIESRGLNSEGLYRVSGFSDLIEDVKMAFDRDGEKADIsvNMYEDINIITGALKLYFRDLPIPLITYDAYP 443
Cdd:pfam00620   1 PLIVRKCVEYLEKRGLDTEGIFRVSGSASRIKELREAFDRGPDVDLD--LEEEDVHVVASLLKLFLRELPEPLLTFELYE 78

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 755498504  444 KFIESAKIMDPDEQLETLHEALRSLPPAHCETLRYLMAHLKRVTLHEKENLMSAENLGIVFGPTLMRSP 512
Cdd:pfam00620  79 EFIEAAKLPDEEERLEALRELLRKLPPANRDTLRYLLAHLNRVAQNSDVNKMNAHNLAIVFGPTLLRPP 147

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
                 ....*....|....*....|....*....|....*....|....*....
gi 755498504 291 RVHTFRGPHWCEYCANFMWGLIAQGVKCADCGLNVHKQCSKMVPNDCKP 339
Cdd:cd20806    5 KVHTFKGPHWCDYCGNFMWGLIAQGVKCEDCGFNAHKQCSKLVPHDCQP 53

Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides via 2 surface pockets. Specificity is provided via interaction with residues that are distinct from the phosphotyrosine. Only a single occurrence of a SH2 domain has been found in S. cerevisiae.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 755498504   158 YHGMISREETDQLL-SVAEGSYLIRESQRQPGTYTLALRFGSQTRNFRLYYDGK---HFVGEKRFESIHDLV 225
Cdd:smart00252   4 YHGFISREEAEKLLkNEGDGDFLVRDSESSPGDYVLSVRVKGKVKHYRIRRNEDgkfYLEGGRKFPSLVELV 75

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
                   ....*....|....*....|....*....|....*....|....*..
gi 755498504   291 RVHTFRGPHWCEYCANFMWGLIAQGVKCADCGLNVHKQCSKMVPNDC 337
Cdd:smart00109   4 VFRTFTKPTFCCVCRKSIWGSFKQGLRCSECKVKCHKKCADKVPKAC 50

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 755498504 348 YSCDLTTLVKAHITKRPMVVDMCIREIESRGLNSEGLYRVSGFSDLIEDVKMAFDRDGEKADISVNMYEDINIITGALKL 427
Cdd:cd04372    1 YGCDLTTLVKAHNTQRPMVVDMCIREIEARGLQSEGLYRVSGFAEEIEDVKMAFDRDGEKADISATVYPDINVITGALKL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755498504 428 YFRDLPIPLITYDAYPKFIESAKIMDPDEQLETLHEALRSLPPAHCETLRYLMAHLKRVTLHEKENLMSAENLGIVFGPT 507
Cdd:cd04372   81 YFRDLPIPVITYDTYPKFIDAAKISNPDERLEAVHEALMLLPPAHYETLRYLMEHLKRVTLHEKDNKMNAENLGIVFGPT 160

                        170       180       190
                 ....*....|....*....|....*....|....
gi 755498504 508 LMRSPELDPMAALNDIRYQRLVVELLIKNEDILF 541
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 755498504  364 PMVVDMCIREIESRGLNSEGLYRVSGFSDLIEDVKMAFDRDGEKADIsvNMYEDINIITGALKLYFRDLPIPLITYDAYP 443
Cdd:pfam00620   1 PLIVRKCVEYLEKRGLDTEGIFRVSGSASRIKELREAFDRGPDVDLD--LEEEDVHVVASLLKLFLRELPEPLLTFELYE 78

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 755498504  444 KFIESAKIMDPDEQLETLHEALRSLPPAHCETLRYLMAHLKRVTLHEKENLMSAENLGIVFGPTLMRSP 512
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 755498504 348 YSCDLTTLVKAHITKRPMVVDMCIREIESRGLNSEGLYRVSGFSDLIEDVKMAFDRDgEKADISVNMYEDINIITGALKL 427
Cdd:cd04403    1 FGCHLEALCQRENSTVPKFVRLCIEAVEKRGLDVDGIYRVSGNLAVIQKLRFAVDHD-EKLDLDDSKWEDIHVITGALKL 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755498504 428 YFRDLPIPLITYDAYPKFIESAKIMDPDEQLETLHEALRSLPPAHCETLRYLMAHLKRVTLHEKENLMSAENLGIVFGPT 507
Cdd:cd04403   80 FFRELPEPLFPYSLFNDFVAAIKLSDYEQRVSAVKDLIKSLPKPNHDTLKMLFRHLCRVIEHGEKNRMTTQNLAIVFGPT 159

                        170       180
                 ....*....|....*....|....*....
gi 755498504 508 LMRsPELDPMAALNDIRYQRLVVELLIKN 536
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 755498504 364 PMVVDMCIREIESRGLNSEGLYRVSGFSDLIEDVKMAFDRDGEKADISVNMYEDINIITGALKLYFRDLPIPLITYDAYP 443
Cdd:cd04395   19 PLIVEVCCNIVEARGLETVGIYRVPGNNAAISALQEELNRGGFDIDLQDPRWRDVNVVSSLLKSFFRKLPEPLFTNELYP 98

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755498504 444 KFIESAKIMDPDEQLETLHEALRSLPPAHCETLRYLMAHLKRVTLHEKENLMSAENLGIVFGPTLMRSPElDPMA-ALND 522
Cdd:cd04395   99 DFIEANRIEDPVERLKELRRLIHSLPDHHYETLKHLIRHLKTVADNSEVNKMEPRNLAIVFGPTLVRTSD-DNMEtMVTH 177

                        170
                 ....*....|....*....
gi 755498504 523 IRYQRLVVELLIKNEDILF 541
Cdd:cd04395  178 MPDQCKIVETLIQHYDWFF 196

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 755498504 150 RPKYYGREYHGMISREETDQLLSVA-EGSYLIRESQRQPGTYTLALRFGSQTRNFRLYYDGK---HFVGEKRFESIHDLV 225
Cdd:cd10352    1 RPRFYGREYHGLISREEAEQLLSGAsDGSYLIRESSRDDGYYTLSLRFNGKVKNYKLYYDGKnhyHYVGEKRFDTIHDLV 80

                         90
                 ....*....|.
gi 755498504 226 TDGLITLYIET 236
Cdd:cd10352   81 ADGLITLYMET 91

RhoGAP_p190: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of p190-like proteins. p190, also named RhoGAP5, plays a role in neuritogenesis and axon branch stability. p190 shows a preference for Rho, over Rac and Cdc42, and consists of an N-terminal GTPase domain and a C-terminal GAP domain. The central portion of p190 contains important regulatory phosphorylation sites. 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 755498504 364 PMVVDMCIREIESRGLNSEGLYRVSGFSDLIEDVKMAFDRDGEkADIsVNMYEDINIITGALKLYFRDLPIPLITYDAYP 443
Cdd:cd04373   16 PIFLEKCVEFIEATGLETEGIYRVSGNKTHLDSLQKQFDQDHN-LDL-VSKDFTVNAVAGALKSFFSELPDPLIPYSMHL 93

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755498504 444 KFIESAKIMDPDEQLETLHEALRSLPPAHCETLRYLMAHLKRVTLHEKENLMSAENLGIVFGPTLMRsPELDPMAALNDI 523
Cdd:cd04373   94 ELVEAAKINDREQRLHALKELLKKFPPENFDVFKYVITHLNKVSQNSKVNLMTSENLSICFWPTLMR-PDFTSMEALSAT 172

                        170
                 ....*....|...
gi 755498504 524 RYQRLVVELLIKN 536
Cdd:cd04373  173 RIYQTIIETFIQQ 185

RhoGAP_Bcr: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of Bcr (breakpoint cluster region protein)-like proteins. Bcr is a multidomain protein with a variety of enzymatic functions. It contains a RhoGAP and a Rho GEF domain, a Ser/Thr kinase domain, an N-terminal oligomerization domain, and a C-terminal PDZ binding domain, in addition to PH and C2 domains. Bcr is a negative regulator of: i) RacGTPase, via the Rho GAP domain, ii) the Ras-Raf-MEK-ERK pathway, via phosphorylation of the Ras binding protein AF-6, and iii) the Wnt signaling pathway through binding beta-catenin. Bcr can form a complex with beta-catenin and Tcf1. The Wnt signaling pathway is involved in cell proliferation, differentiation, and cell renewal. Bcr was discovered as a fusion partner of Abl. The Bcr-Abl fusion is characteristic for a large majority of chronic myelogenous leukemias (CML). Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755498504 352 LTTLVKAHITKRPMVVDMCIREIESRGLNSEGLYRVSGFSDLIEDVKMAFDRDGEkaDISVNMYE-DINIITGALKLYFR 430
Cdd:cd04387    5 ISTVTKRERSKVPYIVRQCVEEVERRGMEEVGIYRISGVATDIQALKAAFDTNNK--DVSVMLSEmDVNAIAGTLKLYFR 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755498504 431 DLPIPLITYDAYPKFIESAKIMDPDEQLETLHEALRSLPPAHCETLRYLMAHLKRVTLHEKENLMSAENLGIVFGPTLMR 510
Cdd:cd04387   83 ELPEPLFTDELYPNFAEGIALSDPVAKESCMLNLLLSLPDPNLVTFLFLLHHLKRVAEREEVNKMSLHNLATVFGPTLLR 162

                 ....*
gi 755498504 511 SPELD 515
Cdd:cd04387  163 PSEKE 167

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 755498504 361 TKRPMV---VDMCIREIESRGLNSEGLYRVSGFSDLIEDVKMAFDRDGEKADISVnmyEDINIITGALKLYFRDLPIPLI 437
Cdd:cd04382   12 STSPMIpalIVHCVNEIEARGLTEEGLYRVSGSEREVKALKEKFLRGKTVPNLSK---VDIHVICGCLKDFLRSLKEPLI 88

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755498504 438 TYDAYPKFIESAKIMDPDEQLETLHEALRSLPPAHCETLRYLMAHLKRVTlHEKENLMSAENLGIVFGPTLM--RSPELD 515
Cdd:cd04382   89 TFALWKEFMEAAEILDEDNSRAALYQAISELPQPNRDTLAFLILHLQRVA-QSPECKMDINNLARVFGPTIVgySVPNPD 167

                        170       180
                 ....*....|....*....|
gi 755498504 516 PMAALNDIRYQRLVVELLIK 535
Cdd:cd04382  168 PMTILQDTVRQPRVVERLLE 187

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 755498504 364 PMVVDMCIREIESRGLNSEGLYRVSGFSDLIEDVKMAFDRDGEKADISVNMYEDIniiTGALKLYFRDLPIPLITYDAYP 443
Cdd:cd04408   17 PFVVVRCTAEIENRALGVQGIYRISGSKARVEKLCQAFENGRDLVDLSGHSPHDI---TSVLKHFLKELPEPVLPFQLYD 93

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755498504 444 KFIESAKIM--DPDEQLET---LHEALRS-------LPPAHCETLRYLMAHLKRVTLHEKENLMSAENLGIVFGPTLMRS 511
Cdd:cd04408   94 DFIALAKELqrDSEKAAESpsiVENIIRSlkellgrLPVSNYNTLRHLMAHLYRVAERFEDNKMSPNNLGIVFGPTLLRP 173

                        170       180
                 ....*....|....*....|....*..
gi 755498504 512 PELD--PMAALNDIRYQRLVVELLIKN 536
Cdd:cd04408  174 LVGGdvSMICLLDTGYQAQLVEFLISN 200

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
                 ....*....|....*....|....*....|....*....|....*....
gi 755498504 291 RVHTFRGPHWCEYCANFMWGLIAQGVKCADCGLNVHKQCSKMVPNDCKP 339
Cdd:cd20806    5 KVHTFKGPHWCDYCGNFMWGLIAQGVKCEDCGFNAHKQCSKLVPHDCQP 53

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 755498504 291 RVHTFRGPHWCEYCANFMWGLIAQGVKCADCGLNVHKQCSKMVPNDCKPDLK 342
Cdd:cd20857    9 KVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDCQPDLK 60

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 755498504 344 VKKVYSCDLTTLVKAHITKRPMVVDMCIREIESRGLNSEGLYRVSGFSDLIEDVKMAFDRDGEKADISvNMYEDINIITG 423
Cdd:cd04386    1 EKPVFGTPLEEHLKRTGREIALPIEACVMCLLETGMNEEGLFRVGGGASKLKRLKAALDAGTFSLPLD-EFYSDPHAVAS 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755498504 424 ALKLYFRDLPIPLITYDAYPKFIESAKIMDPDEQLETLHEALRSLPPAHCETLRYLMAHLKRVTLHEKENLMSAENLGIV 503
Cdd:cd04386   80 ALKSYLRELPDPLLTYNLYEDWVQAANKPDEDERLQAIWRILNKLPRENRDNLRYLIKFLSKLAQKSDENKMSPSNIAIV 159

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|
gi 755498504 504 FGPTL--MRSPELDPMAALNDIRYQRLVVELLIKNEDILF 541
Cdd:cd04386  160 LAPNLlwAKNEGSLAEMAAGTSVHVVAIVELIISHADWFF 199

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755498504 364 PMVVDMCIREIESRGLNSEGLYRVSGFSDLIEDVKMAFDRdGEkaDISVNMYEDINIITGALKLYFRDLPIPLITYDAYP 443
Cdd:cd04404   24 PPVVRETVEYLQAHALTTEGIFRRSANTQVVKEVQQKYNM-GE--PVDFDQYEDVHLPAVILKTFLRELPEPLLTFDLYD 100

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755498504 444 KFIESAKImDPDEQLETLHEALRSLPPAHCETLRYLMAHLKRVTLHEKENLMSAENLGIVFGPTLMRSPELD-PMAALND 522
Cdd:cd04404  101 DIVGFLNV-DKEERVERVKQLLQTLPEENYQVLKYLIKFLVQVSAHSDQNKMTNSNLAVVFGPNLLWAKDASmSLSAINP 179

                        170
                 ....*....|....*....
gi 755498504 523 IryqRLVVELLIKNEDILF 541
Cdd:cd04404  180 I---NTFTKFLLDHQDEIF 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 755498504 364 PMVVDMCIREIESRGLNSEGLYRVSGFSDLIEDVKMAFDRDGEkadiSVNMYE-DINIITGALKLYFRDLPIPLITYDAY 442
Cdd:cd04406   16 PLVVEKLINYIEMHGLYTEGIYRKSGSTNKIKELRQGLDTDAN----SVNLDDyNIHVIASVFKQWLRDLPNPLMTFELY 91

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755498504 443 PKFIESAKIMDPDEQLETLHEALRSLPPAHCETLRYLMAHLKRVTLHEKENLMSAENLGIVFGPTLMRSPE-LDPMAALN 521
Cdd:cd04406   92 EEFLRAMGLQERRETVRGVYSVIDQLSRTHLNTLERLIFHLVRIALQEETNRMSANALAIVFAPCILRCPDtTDPLQSVQ 171

                        170
                 ....*....|...
gi 755498504 522 DIRYQRLVVELLI 534
Cdd:cd04406  172 DISKTTTCVELIV 184

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 755498504 364 PMVVDMCIREIESRGLNSEGLYRVSGFSDLIEDVKMAFDRdGEKADISVNMyeDINIITGALKLYFRDLPIPLITYDAYP 443
Cdd:cd04390   23 PILVEQCVDFIREHGLKEEGLFRLPGQANLVKQLQDAFDA-GERPSFDSDT--DVHTVASLLKLYLRELPEPVIPWAQYE 99

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755498504 444 KFIESAKIMDPDEQ--LETLHEALRSLPPAHCETLRYLMAHLKRVTLHEKENLMSAENLGIVFGPTLMRSPELDPMAALN 521
Cdd:cd04390  100 DFLSCAQLLSKDEEkgLGELMKQVSILPKVNYNLLSYICRFLDEVQSNSSVNKMSVQNLATVFGPNILRPKVEDPATIME 179

                        170       180
                 ....*....|....*....|
gi 755498504 522 DIRYQRLVVELLIKNEDILF 541
Cdd:cd04390  180 GTPQIQQLMTVMISKHEPLF 199

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 755498504 364 PMVVDMCIREIESRGLNSEGLYRVSGFSDLIEDVKMAFDRDGekadiSVNMYE-DINIITGALKLYFRDLPIPLITYDAY 442
Cdd:cd04381   21 PLVFRECIDYVEKHGMKCEGIYKVSGIKSKVDELKAAYNRRE-----SPNLEEyEPPTVASLLKQYLRELPEPLLTKELM 95

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 755498504 443 PKFIESAKIMDPDEQLETLHEALRSLPPAHCETLRYLMAHLKRVTLHEKENLMSAENLGIVFGPTLMRSPEL 514
Cdd:cd04381   96 PRFEEACGRPTEAEREQELQRLLKELPECNRLLLAWLIVHMDHVIAQELETKMNIQNISIVLSPTVQISNRL 167