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 641386920 240 YCCDLTTLVKAHNTQRPMVVDICIREIEARGLKSEGLYRVSGFTEHIEDVKMAFDRDGEKADISANVYPDINIITGALKL 319
Cdd:cd04372    1 YGCDLTTLVKAHNTQRPMVVDMCIREIEARGLQSEGLYRVSGFAEEIEDVKMAFDRDGEKADISATVYPDINVITGALKL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641386920 320 YFRDLPIPVITYDTYSKFIDAAKISNADERLEAVHEVLMLLPPAHYETLRYLMIHLKKVTMNEKDNFMNAENLGIVFGPT 399
Cdd:cd04372   81 YFRDLPIPVITYDTYPKFIDAAKISNPDERLEAVHEALMLLPPAHYETLRYLMEHLKRVTLHEKDNKMNAENLGIVFGPT 160

                        170       180       190
                 ....*....|....*....|....*....|....
gi 641386920 400 LMRPPEDSTLTTLHDMRYQKLIVQILIENEDVLF 433
Cdd:cd04372  161 LMRPPEDSALTTLNDMRYQILIVQLLITNEDVLF 194

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 641386920 175 NYEKTHNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDCQPDLKR 235
Cdd:cd20857    1 NYEKAHNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDCQPDLKR 61

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 641386920 240 YCCDLTTLVKAHNTQRPMVVDICIREIEARGLKSEGLYRVSGFTEHIEDVKMAFDRDGEKADISANVYPDINIITGALKL 319
Cdd:cd04372    1 YGCDLTTLVKAHNTQRPMVVDMCIREIEARGLQSEGLYRVSGFAEEIEDVKMAFDRDGEKADISATVYPDINVITGALKL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641386920 320 YFRDLPIPVITYDTYSKFIDAAKISNADERLEAVHEVLMLLPPAHYETLRYLMIHLKKVTMNEKDNFMNAENLGIVFGPT 399
Cdd:cd04372   81 YFRDLPIPVITYDTYPKFIDAAKISNPDERLEAVHEALMLLPPAHYETLRYLMEHLKRVTLHEKDNKMNAENLGIVFGPT 160

                        170       180       190
                 ....*....|....*....|....*....|....
gi 641386920 400 LMRPPEDSTLTTLHDMRYQKLIVQILIENEDVLF 433
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 641386920  256 PMVVDICIREIEARGLKSEGLYRVSGFTEHIEDVKMAFDRDGEKADISANVypDINIITGALKLYFRDLPIPVITYDTYS 335
Cdd:pfam00620   1 PLIVRKCVEYLEKRGLDTEGIFRVSGSASRIKELREAFDRGPDVDLDLEEE--DVHVVASLLKLFLRELPEPLLTFELYE 78

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 641386920  336 KFIDAAKISNADERLEAVHEVLMLLPPAHYETLRYLMIHLKKVTMNEKDNFMNAENLGIVFGPTLMRPP 404
Cdd:pfam00620  79 EFIEAAKLPDEEERLEALRELLRKLPPANRDTLRYLLAHLNRVAQNSDVNKMNAHNLAIVFGPTLLRPP 147

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 641386920 175 NYEKTHNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDCQPDLKR 235
Cdd:cd20857    1 NYEKAHNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDCQPDLKR 61

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 641386920    25 FHGIISREQADELL-GGVEGAYILRESQRQPGCYTLALRFGNQTLNYRLFHDGK---HFVGEKRFESIHDLV 92
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        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 641386920   180 HNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDC 229
Cdd:smart00109   1 HKHVFRTFTKPTFCCVCRKSIWGSFKQGLRCSECKVKCHKKCADKVPKAC 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 641386920 240 YCCDLTTLVKAHNTQRPMVVDICIREIEARGLKSEGLYRVSGFTEHIEDVKMAFDRDGEKADISANVYPDINIITGALKL 319
Cdd:cd04372    1 YGCDLTTLVKAHNTQRPMVVDMCIREIEARGLQSEGLYRVSGFAEEIEDVKMAFDRDGEKADISATVYPDINVITGALKL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641386920 320 YFRDLPIPVITYDTYSKFIDAAKISNADERLEAVHEVLMLLPPAHYETLRYLMIHLKKVTMNEKDNFMNAENLGIVFGPT 399
Cdd:cd04372   81 YFRDLPIPVITYDTYPKFIDAAKISNPDERLEAVHEALMLLPPAHYETLRYLMEHLKRVTLHEKDNKMNAENLGIVFGPT 160

                        170       180       190
                 ....*....|....*....|....*....|....
gi 641386920 400 LMRPPEDSTLTTLHDMRYQKLIVQILIENEDVLF 433
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 641386920  256 PMVVDICIREIEARGLKSEGLYRVSGFTEHIEDVKMAFDRDGEKADISANVypDINIITGALKLYFRDLPIPVITYDTYS 335
Cdd:pfam00620   1 PLIVRKCVEYLEKRGLDTEGIFRVSGSASRIKELREAFDRGPDVDLDLEEE--DVHVVASLLKLFLRELPEPLLTFELYE 78

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 641386920  336 KFIDAAKISNADERLEAVHEVLMLLPPAHYETLRYLMIHLKKVTMNEKDNFMNAENLGIVFGPTLMRPP 404
Cdd:pfam00620  79 EFIEAAKLPDEEERLEALRELLRKLPPANRDTLRYLLAHLNRVAQNSDVNKMNAHNLAIVFGPTLLRPP 147

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 641386920 256 PMVVDICIREIEARGLKSEGLYRVSGFTEHIEDVKMAFDRDGEKAD-ISANVY-PDINIITGALKLYFRDLPIPVITYDT 333
Cdd:cd04398   17 PNIVYQCIQAIENFGLNLEGIYRLSGNVSRVNKLKELFDKDPLNVLlISPEDYeSDIHSVASLLKLFFRELPEPLLTKAL 96

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641386920 334 YSKFIDAAKISNADERLEAVHEVLMLLPPAHYETLRYLMIHLKKVTMNEKDNFMNAENLGIVFGPTLMRPPEDStlttLH 413
Cdd:cd04398   97 SREFIEAAKIEDESRRRDALHGLINDLPDANYATLRALMFHLARIKEHESVNRMSVNNLAIIWGPTLMNAAPDN----AA 172

                        170       180
                 ....*....|....*....|
gi 641386920 414 DMRYQKLIVQILIENEDVLF 433
Cdd:cd04398  173 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 641386920 242 CDLTTLVKAHNTQRPMVVDICIREIEARGLKSEGLYRVSGFTEHIEDVKMAFDRDgEKADISANVYPDINIITGALKLYF 321
Cdd:cd04403    3 CHLEALCQRENSTVPKFVRLCIEAVEKRGLDVDGIYRVSGNLAVIQKLRFAVDHD-EKLDLDDSKWEDIHVITGALKLFF 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641386920 322 RDLPIPVITYDTYSKFIDAAKISNADERLEAVHEVLMLLPPAHYETLRYLMIHLKKVTMNEKDNFMNAENLGIVFGPTLM 401
Cdd:cd04403   82 RELPEPLFPYSLFNDFVAAIKLSDYEQRVSAVKDLIKSLPKPNHDTLKMLFRHLCRVIEHGEKNRMTTQNLAIVFGPTLL 161

                        170       180
                 ....*....|....*....|....*..
gi 641386920 402 RPPEDSTLTTLHdMRYQKLIVQILIEN 428
Cdd:cd04403  162 RPEQETGNIAVH-MVYQNQIVELILLE 187

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 641386920 257 MVVDICIREIEARGLKSEGLYRVSGFTEHIEDVKMAF--DRDGEKADIS-ANVYPDINIITGALKLYFRDLPIPVITYDT 333
Cdd:cd04374   30 KFVRKCIEAVETRGINEQGLYRVVGVNSKVQKLLSLGldPKTSTPGDVDlDNSEWEIKTITSALKTYLRNLPEPLMTYEL 109

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641386920 334 YSKFIDAAKISNADERLEAVHEVLMLLPPAHYETLRYLMIHLKKVTMNEKDNFMNAENLGIVFGPTLMRPPEDsTLTTLH 413
Cdd:cd04374  110 HNDFINAAKSENLESRVNAIHSLVHKLPEKNREMLELLIKHLTNVSDHSKKNLMTVSNLGVVFGPTLLRPQEE-TVAAIM 188

                        170
                 ....*....|....*
gi 641386920 414 DMRYQKLIVQILIEN 428
Cdd:cd04374  189 DIKFQNIVVEILIEN 203

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 641386920 175 NYEKTHNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDCQPDLKR 235
Cdd:cd20857    1 NYEKAHNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDCQPDLKR 61

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 641386920 243 DLTTLVKAHNTQRPMVVDICIREIEARGLKSEGLYRVSGFTEHIEDVKMAFDRDGEKADISANVYPDIniiTGALKLYFR 322
Cdd:cd04408    4 DFSQLPRDFPEEVPFVVVRCTAEIENRALGVQGIYRISGSKARVEKLCQAFENGRDLVDLSGHSPHDI---TSVLKHFLK 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641386920 323 DLPIPVITYDTYSKFIDAAKISNAD------------ERLEAVHEVLMLLPPAHYETLRYLMIHLKKVTMNEKDNFMNAE 390
Cdd:cd04408   81 ELPEPVLPFQLYDDFIALAKELQRDsekaaespsiveNIIRSLKELLGRLPVSNYNTLRHLMAHLYRVAERFEDNKMSPN 160

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|
gi 641386920 391 NLGIVFGPTLMRPP--EDSTLTTLHDMRYQKLIVQILIEN 428
Cdd:cd04408  161 NLGIVFGPTLLRPLvgGDVSMICLLDTGYQAQLVEFLISN 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        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 641386920 180 HNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDCQP 231
Cdd:cd20806    2 HNFKVHTFKGPHWCDYCGNFMWGLIAQGVKCEDCGFNAHKQCSKLVPHDCQP 53

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 641386920 244 LTTLVKAHNTQRPMVVDICIREIEARGLKSEGLYRVSGFTEHIEDVKMAFDRDGEkaDISANVYP-DINIITGALKLYFR 322
Cdd:cd04387    5 ISTVTKRERSKVPYIVRQCVEEVERRGMEEVGIYRISGVATDIQALKAAFDTNNK--DVSVMLSEmDVNAIAGTLKLYFR 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641386920 323 DLPIPVITYDTYSKFIDAAKISNADERLEAVHEVLMLLPPAHYETLRYLMIHLKKVTMNEKDNFMNAENLGIVFGPTLMR 402
Cdd:cd04387   83 ELPEPLFTDELYPNFAEGIALSDPVAKESCMLNLLLSLPDPNLVTFLFLLHHLKRVAEREEVNKMSLHNLATVFGPTLLR 162

                        170       180
                 ....*....|....*....|....*..
gi 641386920 403 PPE---DSTLTTLHDMRYQKLIVQILI 426
Cdd:cd04387  163 PSEkesKIPTNTMTDSWSLEVMSQVQV 189

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641386920 256 PMVVDICIREIEARGLKSEGLYRVSGFTEHIEDVKMAFDRDgekadiSANVYPDIN-----IITGALKLYFRDLPIPVIT 330
Cdd:cd04385   16 PVIVDKCIDFITQHGLMSEGIYRKNGKNSSVKKLLEAFRKD------ARSVQLREGeytvhDVADVLKRFLRDLPDPLLT 89

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641386920 331 YDTYSKFIDAAKISNADERLEAVHEVLMLLPPAHYETLRYLMIHLKKVTMNEKDNFMNAENLGIVFGPTLMRPPEDSTLT 410
Cdd:cd04385   90 SELHAEWIEAAELENKDERIARYKELIRRLPPINRATLKVLIGHLYRVQKHSDENQMSVHNLALVFGPTLFQTDEHSVGQ 169

                        170
                 ....*....|....*...
gi 641386920 411 TLHDMRyqklIVQILIEN 428
Cdd:cd04385  170 TSHEVK----VIEDLIDN 183

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 641386920 243 DLTTLVKAHNTQRPMVVDICIREIEARGLKSEGLYRVSGFTEHIEDVKMAFDRDGEKADISaNVYPdiNIITGALKLYFR 322
Cdd:cd04409    4 DFAQVAKKSPDGIPFIIKKCTSEIESRALCLKGIYRVNGAKSRVEKLCQAFENGKDLVELS-ELSP--HDISNVLKLYLR 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641386920 323 DLPIPVITYDTYSKFIDAAK-ISNADERLEA---------------------VHEVLMLLPPAHYETLRYLMIHLKKVTM 380
Cdd:cd04409   81 QLPEPLILFRLYNEFIGLAKeSQHVNETQEAkknsdkkwpnmctelnrillkSKDLLRQLPAPNYNTLQFLIVHLHRVSE 160

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 641386920 381 NEKDNFMNAENLGIVFGPTLMRP-PEDST--LTTLHDMRYQKLIVQILI 426
Cdd:cd04409  161 QAEENKMSASNLGIIFGPTLIRPrPTDATvsLSSLVDYPHQARLVELLI 209

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 641386920 256 PMVVDICIREIEARGLKSEGLYRVSGFTEHIEDVKMAFDRDGEKADISAnvYPdINIITGALKLYFRDLPIPVITYDTYS 335
Cdd:cd04407   16 PIVLEKLLEHVEMHGLYTEGIYRKSGSANRMKELHQLLQADPENVKLEN--YP-IHAITGLLKQWLRELPEPLMTFAQYN 92

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641386920 336 KFIDAAKISNADERLEAVHEVLMLLPPAHYETLRYLMIHLKKVTMNEKDNFMNAENLGIVFGPTLMRPPEDST-LTTLHD 414
Cdd:cd04407   93 DFLRAVELPEKQEQLQAIYRVLEQLPTANHNTLERLIFHLVKVALEEDVNRMSPNALAIVFAPCLLRCPDSSDpLTSMKD 172

                        170
                 ....*....|..
gi 641386920 415 MRYQKLIVQILI 426
Cdd:cd04407  173 VAKTTTCVEMLI 184

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 641386920 243 DLTTLVKAHNTQR--PMVVDICIREIEARGLKSEGLYRVSGFTEHIEDVKMAFDRDGEKADISANVYPDINIITGALKLY 320
Cdd:cd04379    4 PLSRLVEREGESRdvPIVLQKCVQEIERRGLDVIGLYRLCGSAAKKKELRDAFERNSAAVELSEELYPDINVITGVLKDY 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641386920 321 FRDLPIPVITYDTYSKFIDAAKISNADERLEAVHEVLML---LPPAHYETLRYLMIHLKKVTMNEKDNFMNAENLGIVFG 397
Cdd:cd04379   84 LRELPEPLITPQLYEMVLEALAVALPNDVQTNTHLTLSIidcLPLSAKATLLLLLDHLSLVLSNSERNKMTPQNLAVCFG 163

                        170       180
                 ....*....|....*....|..
gi 641386920 398 PTLMRP---PEDSTLTTLHDMR 416
Cdd:cd04379  164 PVLMFCsqeFSRYGISPTSKMA 185

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 641386920 251 HNTQRPMVVDICIREIEARGLKSEGLYRVSGFTEHIEDVKMAFDRDGekaDISANVYPDINIITGALKLYFRDLPIPVIT 330
Cdd:cd04376    5 IARQVPRLVESCCQHLEKHGLQTVGIFRVGSSKKRVRQLREEFDRGI---DVVLDENHSVHDVAALLKEFFRDMPDPLLP 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641386920 331 YDTYSKFIDAAKIsNADERLEAVHEVLMLLPPAHYETLRYLMIHLKKVTMNEKD-----------NFMNAENLGIVFGPT 399
Cdd:cd04376   82 RELYTAFIGTALL-EPDEQLEALQLLIYLLPPCNCDTLHRLLKFLHTVAEHAADsidedgqevsgNKMTSLNLATIFGPN 160

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|
gi 641386920 400 LMRPPEDSTLT------TLHDMRYQKLIVQILIENEDVLF 433
Cdd:cd04376  161 LLHKQKSGEREfvqaslRIEESTAIINVVQTMIDNYEELF 200

RhoGAP-ARHGAP11A: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP11A-like proteins. The mouse homolog of human ArhGAP11A has been detected as a gene exclusively expressed in immature ganglion cells, potentially playing a role in retinal development. The exact function of ArhGAP11A is unknown. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641386920 257 MVVDICiREIEARgLKSEGLYRVSGFTEHIEDVKMAFDrDGEKADISANvypdINIITGALKLYFRDLPIPVITYDTYSK 336
Cdd:cd04394   23 FLVDAC-TFLLDH-LSTEGLFRKSGSVVRQKELKAKLE-GGEACLSSAL----PCDVAGLLKQFFRELPEPLLPYDLHEA 95

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641386920 337 FIDAAKISNADERLEAVHEVLMLLPPAHYETLRYLMIHLKKVTMNEKDNFMNAENLGIVFGPTLMRPPED-STLTTLHDM 415
Cdd:cd04394   96 LLKAQELPTDEERKSATLLLTCLLPDEHVNTLRYFFSFLYDVAQRCSENKMDSSNLAVIFAPNLFQSEEGgEKMSSSTEK 175

                        170
                 ....*....|....*
gi 641386920 416 RYQKL--IVQILIEN 428
Cdd:cd04394  176 RLRLQaaVVQTLIDN 190

RhoGAP_fBEM3: RhoGAP (GTPase-activator [GAP] protein for Rho-like small GTPases) domain of fungal BEM3-like proteins. Bem3 is a GAP protein of Cdc42, and is specifically involved in the control of the initial assembly of the septin ring in yeast bud formation. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641386920 256 PMVVDICIREIEA-RGLKSEGLYRVSGFTEHIEDVKMAFDRDGEKADISANVYPDINIITGALKLYFRDLPIPVITYDTY 334
Cdd:cd04400   23 PSVVYRCIEYLDKnRAIYEEGIFRLSGSASVIKQLKERFNTEYDVDLFSSSLYPDVHTVAGLLKLYLRELPTLILGGELH 102

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 641386920 335 SKFIDAAKI-SNADERLEAVHEVLMLLPPAHYETLRYLMIHLKKVTMNEKDNFMNAENLGIVFGPTL 400
Cdd:cd04400  103 NDFKRLVEEnHDRSQRALELKDLVSQLPQANYDLLYVLFSFLRKIIEHSDVNKMNLRNVCIVFSPTL 169

RhoGAP_ARHGAP18: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP18-like proteins. The function of ArhGAP18 is unknown. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641386920 239 VYCCDLTTLV-----KAHNTQRPMVVDICIREIEARGLKSEGLYRVSGFTEHIEDVKMAFDRD-GEKADISANVYPdiNI 312
Cdd:cd04391    1 LFGVPLSTLLerdqkKVPGSKVPLIFQKLINKLEERGLETEGILRIPGSAQRVKFLCQELEAKfYEGTFLWDQVKQ--HD 78