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 55770848   17 SAFGCDLTEYLESSGQDVPYVLKSCAEFIETHGIVDGIYRLSGITSNIQRLRQEFGSDQCPDLTREVYLQDIHCVGSLCK 96
Cdd:cd04384    1 RVFGCDLTEHLLNSGQDVPQVLKSCTEFIEKHGIVDGIYRLSGIASNIQRLRHEFDSEQIPDLTKDVYIQDIHSVSSLCK 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55770848   97 LYFRELPNPLLTYELYEKFTEAVSHRPEEGQLARIQNVILELPPPHYRTLEYLIRHLAHIASFSSKTNMHARNLALVWAP 176
Cdd:cd04384   81 LYFRELPNPLLTYQLYEKFSEAVSAASDEERLEKIHDVIQQLPPPHYRTLEFLMRHLSRLAKYCSITNMHAKNLAIVWAP 160

                        170       180       190
                 ....*....|....*....|....*....|....*
gi 55770848  177 NLLRSKKIEATICNGDAAFLAVRVQQVVIEFILNH 211
Cdd:cd04384  161 NLLRSKQIESACFSGTAAFMEVRIQSVVVEFILNH 195

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 55770848   17 SAFGCDLTEYLESSGQDVPYVLKSCAEFIETHGIVDGIYRLSGITSNIQRLRQEFGSDQCPDLTREVYLQDIHCVGSLCK 96
Cdd:cd04384    1 RVFGCDLTEHLLNSGQDVPQVLKSCTEFIEKHGIVDGIYRLSGIASNIQRLRHEFDSEQIPDLTKDVYIQDIHSVSSLCK 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55770848   97 LYFRELPNPLLTYELYEKFTEAVSHRPEEGQLARIQNVILELPPPHYRTLEYLIRHLAHIASFSSKTNMHARNLALVWAP 176
Cdd:cd04384   81 LYFRELPNPLLTYQLYEKFSEAVSAASDEERLEKIHDVIQQLPPPHYRTLEFLMRHLSRLAKYCSITNMHAKNLAIVWAP 160

                        170       180       190
                 ....*....|....*....|....*....|....*
gi 55770848  177 NLLRSKKIEATICNGDAAFLAVRVQQVVIEFILNH 211
Cdd:cd04384  161 NLLRSKQIESACFSGTAAFMEVRIQSVVVEFILNH 195

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55770848     35 PYVLKSCAEFIETHGI-VDGIYRLSGITSNIQRLRQEFgsDQCPDLTREVYLQDIHCVGSLCKLYFRELPNPLLTYELYE 113
Cdd:pfam00620    1 PLIVRKCVEYLEKRGLdTEGIFRVSGSASRIKELREAF--DRGPDVDLDLEEEDVHVVASLLKLFLRELPEPLLTFELYE 78

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 55770848    114 KFTEAVSHRPEEGQLARIQNVILELPPPHYRTLEYLIRHLAHIASFSSKTNMHARNLALVWAPNLLRSK 182
Cdd:pfam00620   79 EFIEAAKLPDEEERLEALRELLRKLPPANRDTLRYLLAHLNRVAQNSDVNKMNAHNLAIVFGPTLLRPP 147

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 55770848   17 SAFGCDLTEYLESSGQDVPYVLKSCAEFIETHGIVDGIYRLSGITSNIQRLRQEFGSDQCPDLTREVYLQDIHCVGSLCK 96
Cdd:cd04384    1 RVFGCDLTEHLLNSGQDVPQVLKSCTEFIEKHGIVDGIYRLSGIASNIQRLRHEFDSEQIPDLTKDVYIQDIHSVSSLCK 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55770848   97 LYFRELPNPLLTYELYEKFTEAVSHRPEEGQLARIQNVILELPPPHYRTLEYLIRHLAHIASFSSKTNMHARNLALVWAP 176
Cdd:cd04384   81 LYFRELPNPLLTYQLYEKFSEAVSAASDEERLEKIHDVIQQLPPPHYRTLEFLMRHLSRLAKYCSITNMHAKNLAIVWAP 160

                        170       180       190
                 ....*....|....*....|....*....|....*
gi 55770848  177 NLLRSKKIEATICNGDAAFLAVRVQQVVIEFILNH 211
Cdd:cd04384  161 NLLRSKQIESACFSGTAAFMEVRIQSVVVEFILNH 195

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55770848     35 PYVLKSCAEFIETHGI-VDGIYRLSGITSNIQRLRQEFgsDQCPDLTREVYLQDIHCVGSLCKLYFRELPNPLLTYELYE 113
Cdd:pfam00620    1 PLIVRKCVEYLEKRGLdTEGIFRVSGSASRIKELREAF--DRGPDVDLDLEEEDVHVVASLLKLFLRELPEPLLTFELYE 78

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 55770848    114 KFTEAVSHRPEEGQLARIQNVILELPPPHYRTLEYLIRHLAHIASFSSKTNMHARNLALVWAPNLLRSK 182
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 55770848   19 FGCDLTEYLESSGQDVPYVLKSCAEFIETHGI-VDGIYRLSGITSNIQRLRQEFGSDqcPD----LTREVYLQDIHCVGS 93
Cdd:cd04398    1 FGVPLEDLILREGDNVPNIVYQCIQAIENFGLnLEGIYRLSGNVSRVNKLKELFDKD--PLnvllISPEDYESDIHSVAS 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55770848   94 LCKLYFRELPNPLLTYELYEKFTEAVSHRPEEGQLARIQNVILELPPPHYRTLEYLIRHLAHIASFSSKTNMHARNLALV 173
Cdd:cd04398   79 LLKLFFRELPEPLLTKALSREFIEAAKIEDESRRRDALHGLINDLPDANYATLRALMFHLARIKEHESVNRMSVNNLAII 158

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|...
gi 55770848  174 WAPNLLRSKKIEATicngDAAFlavrvQQVVIEFILNHADQIF 216
Cdd:cd04398  159 WGPTLMNAAPDNAA----DMSF-----QSRVIETLLDNAYQIF 192

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 55770848   17 SAFGCDLTEYLESSGQDVPYVLKSCAEFIETHGIVD-GIYRLSGITSNIQRLRQEFGSdQCPDLTREVYLQDIHCVGSLC 95
Cdd:cd04386    3 PVFGTPLEEHLKRTGREIALPIEACVMCLLETGMNEeGLFRVGGGASKLKRLKAALDA-GTFSLPLDEFYSDPHAVASAL 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55770848   96 KLYFRELPNPLLTYELYEKFTEAVSHRPEEGQLARIQNVILELPPPHYRTLEYLIRHLAHIASFSSKTNMHARNLALVWA 175
Cdd:cd04386   82 KSYLRELPDPLLTYNLYEDWVQAANKPDEDERLQAIWRILNKLPRENRDNLRYLIKFLSKLAQKSDENKMSPSNIAIVLA 161

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*
gi 55770848  176 PNLLRSkKIEATICNGDAAFLAVRVqqVVIEFILNHADQIFNGGA 220
Cdd:cd04386  162 PNLLWA-KNEGSLAEMAAGTSVHVV--AIVELIISHADWFFPGEV 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 55770848   19 FGCDLTEyLESSGQDVPYVLKSCAEFIETHGI-VDGIYRLSGITSNIQRLRQEFGSDqcPDltrEVYLQD--IHCVGSLC 95
Cdd:cd04377    1 FGVSLSS-LTSEDRSVPLVLEKLLEHIEMHGLyTEGIYRKSGSANKIKELRQGLDTD--PD---SVNLEDypIHVITSVL 74

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55770848   96 KLYFRELPNPLLTYELYEKFTEAVSHRPEEGQLARIQNVILELPPPHYRTLEYLIRHLAHIASFSSKTNMHARNLALVWA 175
Cdd:cd04377   75 KQWLRELPEPLMTFELYENFLRAMELEEKQERVRALYSVLEQLPRANLNTLERLIFHLVRVALQEEVNRMSANALAIVFA 154

                 ....*
gi 55770848  176 PNLLR 180
Cdd:cd04377  155 PCILR 159

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 55770848   30 SGQDVPYVLKSCAEFIETHGI-VDGIYRLSGITSNIQRLRQEFGSDqcpdlTREVYL----QDIHCVGSLCKLYFRELPN 104
Cdd:cd04385   11 TDNDIPVIVDKCIDFITQHGLmSEGIYRKNGKNSSVKKLLEAFRKD-----ARSVQLregeYTVHDVADVLKRFLRDLPD 85

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 55770848  105 PLLTYELYEKFTEAVSHRPEEGQLARIQNVILELPPPHYRTLEYLIRHLAHIASFSSKTNMHARNLALVWAPNLLRSK 182
Cdd:cd04385   86 PLLTSELHAEWIEAAELENKDERIARYKELIRRLPPINRATLKVLIGHLYRVQKHSDENQMSVHNLALVFGPTLFQTD 163

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 55770848   34 VPYVLKSCAEFIETHGI-VDGIYRLSGITSNIQRLRQEFgsdQCPDLTREVYLQDIHCVGSLCKLYFRELPNPLLTYELY 112
Cdd:cd04376    9 VPRLVESCCQHLEKHGLqTVGIFRVGSSKKRVRQLREEF---DRGIDVVLDENHSVHDVAALLKEFFRDMPDPLLPRELY 85

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55770848  113 EKFTEAVSHRPEEgQLARIQNVILELPPPHYRTLEYLIRHLAHIASFSSKT-----------NMHARNLALVWAPNLLRS 181
Cdd:cd04376   86 TAFIGTALLEPDE-QLEALQLLIYLLPPCNCDTLHRLLKFLHTVAEHAADSidedgqevsgnKMTSLNLATIFGPNLLHK 164

                        170       180       190
                 ....*....|....*....|....*....|....*.
gi 55770848  182 KKIEATICNGDAAFLAVRVQQV-VIEFILNHADQIF 216
Cdd:cd04376  165 QKSGEREFVQASLRIEESTAIInVVQTMIDNYEELF 200

RhoGAP_srGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in srGAPs. srGAPs are components of the intracellular part of Slit-Robo signalling pathway that is important for axon guidance and cell migration. srGAPs contain an N-terminal FCH domain, a central RhoGAP domain and a C-terminal SH3 domain; this SH3 domain interacts with the intracellular proline-rich-tail of the Roundabout receptor (Robo). This interaction with Robo then activates the rhoGAP domain which in turn inhibits Cdc42 activity. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55770848   19 FGCDLTEYLESSGQDVPYVLKSCAEFIETHGIV-DGIYRLSGITSNIQRLRQEF--GSDQCPDLTREvylQDIHCVGSLC 95
Cdd:cd04383    3 FNGSLEEYIQDSGQAIPLVVESCIRFINLYGLQhQGIFRVSGSQVEVNDIKNAFerGEDPLADDQND---HDINSVAGVL 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55770848   96 KLYFRELPNPLLTYELYEKFTEAVSHRPEEGQLARIQNVILELPPPHYRTLEYLIRHLAHIASFSSKTNMHARNLALVWA 175
Cdd:cd04383   80 KLYFRGLENPLFPKERFEDLMSCVKLENPTERVHQIREILSTLPRSVIIVMRYLFAFLNHLSQFSDENMMDPYNLAICFG 159

                        170       180       190
                 ....*....|....*....|....*....|....*
gi 55770848  176 PNLLRSKKieaticNGDAAFLAVRVQQVVIEFILN 210
Cdd:cd04383  160 PTLMPVPE------GQDQVSCQAHVNELIKTIIIH 188

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 55770848   19 FGCDLTEYLESSGQDVPYVLKSCAEFIETHG-IVDGIYRLSGITSNIQRLRQEF--GSDQcpdltreVYLQDI--HCVGS 93
Cdd:cd04378    1 FGVDFSQVPRDFPDEVPFIIKKCTSEIENRAlGVQGIYRVSGSKARVEKLCQAFenGKDL-------VELSELspHDISS 73

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55770848   94 LCKLYFRELPNPLLTYELYEKF---TEAVSHRPEEGQ-----------LARIQNVILELPPPHYRTLEYLIRHLAHIASF 159
Cdd:cd04378   74 VLKLFLRQLPEPLILFRLYNDFialAKEIQRDTEEDKapntpievnriIRKLKDLLRQLPASNYNTLQHLIAHLYRVAEQ 153

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 55770848  160 SSKTNMHARNLALVWAPNLLRSKKIEATI---CNGDAAFlavrvQQVVIEFILNH 211
Cdd:cd04378  154 FEENKMSPNNLGIVFGPTLIRPRPGDADVslsSLVDYGY-----QARLVEFLITN 203

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 55770848   34 VPYVLKSCAEFIETHGIVD-GIYRLSGITSNIQRLRQEFGSDQcPDLTREVYLQDIHCVGSLCKLYFRELPNPLLTYELY 112
Cdd:cd04387   16 VPYIVRQCVEEVERRGMEEvGIYRISGVATDIQALKAAFDTNN-KDVSVMLSEMDVNAIAGTLKLYFRELPEPLFTDELY 94

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55770848  113 EKFTEAVSHRPEEGQLARIQNVILELPPPHYRTLEYLIRHLAHIASFSSKTNMHARNLALVWAPNLLRSKKIEA---TIC 189
Cdd:cd04387   95 PNFAEGIALSDPVAKESCMLNLLLSLPDPNLVTFLFLLHHLKRVAEREEVNKMSLHNLATVFGPTLLRPSEKESkipTNT 174

                        170       180
                 ....*....|....*....|..
gi 55770848  190 NGDAAFLAVRVQQVVIEFILNH 211
Cdd:cd04387  175 MTDSWSLEVMSQVQVLLYFLQL 196

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 55770848   19 FGCDLTEyLESSGQDVPYVLKSCAEFIETHGI-VDGIYRLSGITSNIQRLRQEFGSDqcpdlTREVYLQD--IHCVGSLC 95
Cdd:cd04406    1 FGVELSR-LTSEDRSVPLVVEKLINYIEMHGLyTEGIYRKSGSTNKIKELRQGLDTD-----ANSVNLDDynIHVIASVF 74

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55770848   96 KLYFRELPNPLLTYELYEKFTEAVSHRPEEGQLARIQNVILELPPPHYRTLEYLIRHLAHIASFSSKTNMHARNLALVWA 175
Cdd:cd04406   75 KQWLRDLPNPLMTFELYEEFLRAMGLQERRETVRGVYSVIDQLSRTHLNTLERLIFHLVRIALQEETNRMSANALAIVFA 154

                 ....*
gi 55770848  176 PNLLR 180
Cdd:cd04406  155 PCILR 159

RhoGAP_FAM13A1a: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of FAM13A1, isoform a-like proteins. The function of FAM13A1a is unknown. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by up several orders of magnitude.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55770848   19 FGCDLTEyLESSGQ---DVPYVLKSCAEFIETHGIV-DGIYRLSGITSNIQRLRQEFGSDQCPDLTREvylQDIHCVGSL 94
Cdd:cd04393    3 FGVPLQE-LQQAGQpenGVPAVVRHIVEYLEQHGLEqEGLFRVNGNAETVEWLRQRLDSGEEVDLSKE---ADVCSAASL 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55770848   95 CKLYFRELPNPLLTYELYEKFTEaVSH--RPEEGQLARIQNVILELPPPHYRTLEYLIRHLAHIASFSSKTNMHARNLAL 172
Cdd:cd04393   79 LRLFLQELPEGLIPASLQIRLMQ-LYQdyNGEDEFGRKLRDLLQQLPPVNYSLLKFLCHFLSNVASQHHENRMTAENLAA 157

                        170       180
                 ....*....|....*....|...
gi 55770848  173 VWAPNLLR-----SKKIEATICN 190
Cdd:cd04393  158 VFGPDVFHvytdvEDMKEQEICS 180

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 55770848   19 FGCDLTEYLESSGQDVPYVLKSCAEFIETHG-IVDGIYRLSGITSNIQRLRQEFGSDQCPDLTREVYLQDIHCVgslCKL 97
Cdd:cd04409    1 FGADFAQVAKKSPDGIPFIIKKCTSEIESRAlCLKGIYRVNGAKSRVEKLCQAFENGKDLVELSELSPHDISNV---LKL 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55770848   98 YFRELPNPLLTYELYEKF---TEAVSHRPEEGQ-------------------LARIQNVILELPPPHYRTLEYLIRHLAH 155
Cdd:cd04409   78 YLRQLPEPLILFRLYNEFiglAKESQHVNETQEakknsdkkwpnmctelnriLLKSKDLLRQLPAPNYNTLQFLIVHLHR 157

                        170       180       190
                 ....*....|....*....|....*....|...
gi 55770848  156 IASFSSKTNMHARNLALVWAPNLLRSKKIEATI 188
Cdd:cd04409  158 VSEQAEENKMSASNLGIIFGPTLIRPRPTDATV 190

RhoGAP_ARHGAP20: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP20-like proteins. ArhGAP20, also known as KIAA1391 and RA-RhoGAP, contains a RhoGAP, a RA, and a PH domain, and ANXL repeats. ArhGAP20 is activated by Rap1 and induces inactivation of Rho, which in turn leads to neurite outgrowth. 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 55770848   52 DGIYRLSGITSNIQRLRQEFGSDQCPDLTREvylqDIHCVGSLCKLYFRELPNPLLTYELYEKFTEAVSHRPEEGQLARI 131
Cdd:cd04402   34 EGIFRRSANAKACKELKEKLNSGVEVDLKAE----PVLLLASVLKDFLRNIPGSLLSSDLYEEWMSALDQENEEEKIAEL 109

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55770848  132 QNVILELPPPHYRTLEYLIRHLAHIaSFSSKTN-MHARNLALVWAPNLLRSKkieaTICNGDAAFLavRVQQVVIEFILN 210
Cdd:cd04402  110 QRLLDKLPRPNVLLLKHLICVLHNI-SQNSETNkMDAFNLAVCIAPSLLWPP----ASSELQNEDL--KKVTSLVQFLIE 182

                 ....*.
gi 55770848  211 HADQIF 216
Cdd:cd04402  183 NCQEIF 188

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 55770848   34 VPYVLKSCAEFIETHGIVD-GIYRLSGITSNIQRLRQEF-GSDQCPDLTrevyLQDIHCVGSLCKLYFRELPNPLLTYEL 111
Cdd:cd04382   17 IPALIVHCVNEIEARGLTEeGLYRVSGSEREVKALKEKFlRGKTVPNLS----KVDIHVICGCLKDFLRSLKEPLITFAL 92

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 55770848  112 YEKFTEAVSHRPEEGQLARIQNVILELPPPHYRTLEYLIRHLAHIASfSSKTNMHARNLALVWAPNL 178
Cdd:cd04382   93 WKEFMEAAEILDEDNSRAALYQAISELPQPNRDTLAFLILHLQRVAQ-SPECKMDINNLARVFGPTI 158

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.