protein kinase C conserved region 1 (C1 domain) found in the GEM-interacting protein (GMIP)-like family; The GMIP-like family includes GMIP, Rho GTPase-activating protein 29 (ARHGAP29) and Rho GTPase-activating protein 45 (ARHGAP45). GMIP is a RhoA-specific GTPase-activating protein that acts as a key factor in saltatory neuronal migration. It associates with the Rab27a effector JFC1 and modulates vesicular transport and exocytosis. ARHGAP29, also called PTPL1-associated RhoGAP protein 1 (PARG1) or Rho-type GTPase-activating protein 29, is a GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state. It has strong activity toward RHOA, and weaker activity toward RAC1 and CDC42. ARHGAP29 may act as a specific effector of RAP2A to regulate Rho. In concert with RASIP1, ARHGAP29 suppresses RhoA signaling and dampens ROCK and MYH9 activities in endothelial cells and plays an essential role in blood vessel tubulogenesis. ARHGAP45, also called minor histocompatibility antigen HA-1 (mHag HA-1), is a Rac-GAP (GTPase-Activating Protein) in endothelial cells. It acts as a novel regulator of endothelial integrity. ARHGAP45 contains a GTPase activator for the Rho-type GTPases (RhoGAP) domain that would be able to negatively regulate the actin cytoskeleton as well as cell spreading. However, it also contains N-terminally a BAR-domin which can play an autoinhibitory effect on this RhoGAP activity. Members of this family contain a zinc-binding 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 37674214 491 QTHRLRRLRGPAKCRECEAFMV-SGTECEECFLTCHKRCLETLLILCGHRR 540
Cdd:cd20816   1 QTHRFRRLRTPSKCRECDSYVYfNGAECEECGLACHKKCLETLAIQCGHKR 51

GTPase-activator protein for Rho-like GTPases; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases. etter domain limits and outliers.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 37674214    562 EVPFVITRCTAEIEHRALGLQGIYRVSGSRVRVERLCQAFENG-RALVELSGNSPHDITSVLKRFLQELTDPVVPFHLYD 640
Cdd:smart00324   2 PIPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGpDPDLDLSEYDVHDVAGLLKLFLRELPEPLITYELYE 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 37674214    641 AFISLAKTlhadpgddpgtpNPSPEIIRSLKTLLVQLPDSNYSTLRHLVAHLFRVAARFEENKMSANNLGIVFGPTLLRP 720
Cdd:smart00324  82 EFIEAAKL------------EDETERLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRP 149

                          170       180       190
                   ....*....|....*....|....*....|..
gi 37674214    721 PDGPRATgaspvacLLDSGHQAQLVEFLIVHY 752
Cdd:smart00324 150 PDGEVAS-------LKDIRHQNTVIEFLIENA 174

protein kinase C conserved region 1 (C1 domain) found in the GEM-interacting protein (GMIP)-like family; The GMIP-like family includes GMIP, Rho GTPase-activating protein 29 (ARHGAP29) and Rho GTPase-activating protein 45 (ARHGAP45). GMIP is a RhoA-specific GTPase-activating protein that acts as a key factor in saltatory neuronal migration. It associates with the Rab27a effector JFC1 and modulates vesicular transport and exocytosis. ARHGAP29, also called PTPL1-associated RhoGAP protein 1 (PARG1) or Rho-type GTPase-activating protein 29, is a GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state. It has strong activity toward RHOA, and weaker activity toward RAC1 and CDC42. ARHGAP29 may act as a specific effector of RAP2A to regulate Rho. In concert with RASIP1, ARHGAP29 suppresses RhoA signaling and dampens ROCK and MYH9 activities in endothelial cells and plays an essential role in blood vessel tubulogenesis. ARHGAP45, also called minor histocompatibility antigen HA-1 (mHag HA-1), is a Rac-GAP (GTPase-Activating Protein) in endothelial cells. It acts as a novel regulator of endothelial integrity. ARHGAP45 contains a GTPase activator for the Rho-type GTPases (RhoGAP) domain that would be able to negatively regulate the actin cytoskeleton as well as cell spreading. However, it also contains N-terminally a BAR-domin which can play an autoinhibitory effect on this RhoGAP activity. Members of this family contain a zinc-binding 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 37674214 491 QTHRLRRLRGPAKCRECEAFMV-SGTECEECFLTCHKRCLETLLILCGHRR 540
Cdd:cd20816   1 QTHRFRRLRTPSKCRECDSYVYfNGAECEECGLACHKKCLETLAIQCGHKR 51

The F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs) domain of Saccharomyces cerevisiae Rho GTPase activating protein Rgd1 and similar proteins; F-BAR domains are dimerization modules that bind and bend membranes and are found in proteins involved in membrane dynamics and actin reorganization. Saccharomyces cerevisiae Rgd1 is a GTPase activating protein (GAP) with activity towards Rho3p and Rho4p, which are involved in bud growth and cytokinesis, respectively. At low pH, S. cerevisiae Rgd1 is required for cell survival and the activation of the protein kinase C pathway, which is important in cell integrity and the maintenance of cell shape. It contains an N-terminal F-BAR domain and a C-terminal Rho GAP domain. The F-BAR domain of S. cerevisiae Rgd1 binds to phosphoinositides and plays an important role in the localization of the protein to the bud tip/neck during the cell cycle. F-BAR domains form banana-shaped dimers with a positively-charged concave surface that binds to negatively-charged lipid membranes. They can induce membrane deformation in the form of long tubules.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 37674214 112 AKELLAWTDKRANYELEFAKSIMKLA----EAGKVSILQQSQMPLQYIYTLFLEHDLSLGALALETVAQQKRDYYQPLAA 187
Cdd:cd07652  21 AKEFATFLKKRAAIEEEHARGLKKLArttlDTYKRPDHKQGSFSNAYHSSLEFHEKLADNGLRFAKALNEMSDELSSLAK 100

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 37674214 188 krmEIEKWRKEFKEQWLKEQKRMNEAVQALRRSELQYIQRREDL-RARSQgspedPPSQASPGSNKQQERRRRSREEAQA 266
Cdd:cd07652 101 ---TVEKSRKSIKETGKRAEKKVQDAEAAAEKAKARYDSLADDLeRVKTG-----DPGKKLKFGLKGNKSAAQHEDELLR 172

                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*..
gi 37674214 267 KAHEAEALYQACVREANS-RQQDLETTKRRIVSHVRKLVLQGDEVLR 312
Cdd:cd07652 173 KVQAADQDYASKVNAAQAlRQELLSRHRPEAVKDLFDLILEIDAALR 219

Fes/CIP4 homology domain; Alignment extended from original report. Highly alpha-helical. Also known as the RAEYL motif or the S. pombe Cdc15 N-terminal domain.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 37674214     97 GVDAALEYAKAWSRYAKELLAWTDKRANYELEFAKSIMKLAEAGKVSILQQSQM-PLQYIYTLFLEHDLSLG 167
Cdd:smart00055  10 GFEALLSRLKNGLRLLEDLKKFMRERAKIEEEYAKKLQKLSKKLRAVRDTEPEYgSLSKAWEVLLSETDALA 81

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 37674214 548 FGVDFLQLPRDFPEEVPFVITRCTAEIEHRALGLQGIYRVSGSRVRVERLCQAFENGRALVELSGNSPHDITSVLKRFLQ 627
Cdd:cd04378   1 FGVDFSQVPRDFPDEVPFIIKKCTSEIENRALGVQGIYRVSGSKARVEKLCQAFENGKDLVELSELSPHDISSVLKLFLR 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 37674214 628 ELTDPVVPFHLYDAFISLAKTLHADPGDD--PGTPNPSPEIIRSLKTLLVQLPDSNYSTLRHLVAHLFRVAARFEENKMS 705
Cdd:cd04378  81 QLPEPLILFRLYNDFIALAKEIQRDTEEDkaPNTPIEVNRIIRKLKDLLRQLPASNYNTLQHLIAHLYRVAEQFEENKMS 160

                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*.
gi 37674214 706 ANNLGIVFGPTLLRPPDGPratGASPVACLLDSGHQAQLVEFLIVH 751
Cdd:cd04378 161 PNNLGIVFGPTLIRPRPGD---ADVSLSSLVDYGYQARLVEFLITN 203

GTPase-activator protein for Rho-like GTPases; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases. etter domain limits and outliers.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 37674214    562 EVPFVITRCTAEIEHRALGLQGIYRVSGSRVRVERLCQAFENG-RALVELSGNSPHDITSVLKRFLQELTDPVVPFHLYD 640
Cdd:smart00324   2 PIPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGpDPDLDLSEYDVHDVAGLLKLFLRELPEPLITYELYE 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 37674214    641 AFISLAKTlhadpgddpgtpNPSPEIIRSLKTLLVQLPDSNYSTLRHLVAHLFRVAARFEENKMSANNLGIVFGPTLLRP 720
Cdd:smart00324  82 EFIEAAKL------------EDETERLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRP 149

                          170       180       190
                   ....*....|....*....|....*....|..
gi 37674214    721 PDGPRATgaspvacLLDSGHQAQLVEFLIVHY 752
Cdd:smart00324 150 PDGEVAS-------LKDIRHQNTVIEFLIENA 174

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 37674214   564 PFVITRCTAEIEHRALGLQGIYRVSGSRVRVERLCQAFENGRALV-ELSGNSPHDITSVLKRFLQELTDPVVPFHLYDAF 642
Cdd:pfam00620   1 PLIVRKCVEYLEKRGLDTEGIFRVSGSASRIKELREAFDRGPDVDlDLEEEDVHVVASLLKLFLRELPEPLLTFELYEEF 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 37674214   643 ISLAKTlhadpgddpgtpNPSPEIIRSLKTLLVQLPDSNYSTLRHLVAHLFRVAARFEENKMSANNLGIVFGPTLLRPPD 722
Cdd:pfam00620  81 IEAAKL------------PDEEERLEALRELLRKLPPANRDTLRYLLAHLNRVAQNSDVNKMNAHNLAIVFGPTLLRPPD 148

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 37674214 548 FGVDFLQLPRDFPEEVPFVITRCTAEIEHRALGLQGIYRVSGSRVRVERLCQAFENGRALVELSGNSPHD---ITSVLKR 624
Cdd:cd04372   1 YGCDLTTLVKAHNTQRPMVVDMCIREIEARGLQSEGLYRVSGFAEEIEDVKMAFDRDGEKADISATVYPDinvITGALKL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 37674214 625 FLQELTDPVVPFHLYDAFISLAKTLHADpgddpgtpnpspEIIRSLKTLLVQLPDSNYSTLRHLVAHLFRVAARFEENKM 704
Cdd:cd04372  81 YFRDLPIPVITYDTYPKFIDAAKISNPD------------ERLEAVHEALMLLPPAHYETLRYLMEHLKRVTLHEKDNKM 148

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|..
gi 37674214 705 SANNLGIVFGPTLLRPPDgpratgASPVACLLDSGHQAQLVEFLIVHYEQIF 756
Cdd:cd04372 149 NAENLGIVFGPTLMRPPE------DSALTTLNDMRYQILIVQLLITNEDVLF 194

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 37674214 548 FGVDFLQ-LPRDFPEEVPFVITRCTAEIEHRALGLQGIYRVSGSRVRVERLCQAFENGRALVELSGNSPHD---ITSVLK 623
Cdd:cd04395   2 FGVPLDDcPPSSENPYVPLIVEVCCNIVEARGLETVGIYRVPGNNAAISALQEELNRGGFDIDLQDPRWRDvnvVSSLLK 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 37674214 624 RFLQELTDPVVPFHLYDAFISlaktlhADPGDDPgtpnpsPEIIRSLKTLLVQLPDSNYSTLRHLVAHLFRVAARFEENK 703
Cdd:cd04395  82 SFFRKLPEPLFTNELYPDFIE------ANRIEDP------VERLKELRRLIHSLPDHHYETLKHLIRHLKTVADNSEVNK 149

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|...
gi 37674214 704 MSANNLGIVFGPTLLRPPDGPRATGASpvacllDSGHQAQLVEFLIVHYEQIF 756
Cdd:cd04395 150 MEPRNLAIVFGPTLVRTSDDNMETMVT------HMPDQCKIVETLIQHYDWFF 196

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 37674214 563 VPFVITRCTAEIEHRALGLQGIYRVSGSRVRVERL-CQA-FENGRALVELSGNSPHDITSVLKRFLQELTDPVVPFHLYD 640
Cdd:cd04403  16 VPKFVRLCIEAVEKRGLDVDGIYRVSGNLAVIQKLrFAVdHDEKLDLDDSKWEDIHVITGALKLFFRELPEPLFPYSLFN 95

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 37674214 641 AFISLAKTlhadpgddpgtPNPSpEIIRSLKTLLVQLPDSNYSTLRHLVAHLFRVAARFEENKMSANNLGIVFGPTLLRP 720
Cdd:cd04403  96 DFVAAIKL-----------SDYE-QRVSAVKDLIKSLPKPNHDTLKMLFRHLCRVIEHGEKNRMTTQNLAIVFGPTLLRP 163

                       170       180
                ....*....|....*....|....*....
gi 37674214 721 PDGpraTGASPVACLldsgHQAQLVEFLI 749
Cdd:cd04403 164 EQE---TGNIAVHMV----YQNQIVELIL 185

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 37674214 548 FGVDFLQLPRDfPEEVPFVITRCTAEIEHRALGLQGIYRVSGSRVRVERLCQAFENGRALVELSGNSPHDITSVLKRFLQ 627
Cdd:cd04407   1 FGVRVGSLTSN-KTSVPIVLEKLLEHVEMHGLYTEGIYRKSGSANRMKELHQLLQADPENVKLENYPIHAITGLLKQWLR 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 37674214 628 ELTDPVVPFHLYDAFISLAKtlhadpgddpgTPNPSpEIIRSLKTLLVQLPDSNYSTLRHLVAHLFRVAARFEENKMSAN 707
Cdd:cd04407  80 ELPEPLMTFAQYNDFLRAVE-----------LPEKQ-EQLQAIYRVLEQLPTANHNTLERLIFHLVKVALEEDVNRMSPN 147

                       170       180       190       200
                ....*....|....*....|....*....|....*....|...
gi 37674214 708 NLGIVFGPTLLRPPDgpratGASPVACLLDSGHQAQLVEFLIV 750
Cdd:cd04407 148 ALAIVFAPCLLRCPD-----SSDPLTSMKDVAKTTTCVEMLIK 185

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 37674214 563 VPFVITRCTAEIEHRALGLQGIYRVSGSRVRVERLCQAFENGRALVELSGNSPHDITSVLKRFLQELTDPVVPFHLYDAF 642
Cdd:cd04382  17 IPALIVHCVNEIEARGLTEEGLYRVSGSEREVKALKEKFLRGKTVPNLSKVDIHVICGCLKDFLRSLKEPLITFALWKEF 96

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 37674214 643 ISLAKtlHADPgddpgtpnpsPEIIRSLKTLLVQLPDSNYSTLRHLVAHLFRVaARFEENKMSANNLGIVFGPTLLrppd 722
Cdd:cd04382  97 MEAAE--ILDE----------DNSRAALYQAISELPQPNRDTLAFLILHLQRV-AQSPECKMDINNLARVFGPTIV---- 159

                       170       180
                ....*....|....*....|....*.
gi 37674214 723 GPRATGASPVACLLDSGHQAQLVEFL 748
Cdd:cd04382 160 GYSVPNPDPMTILQDTVRQPRVVERL 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 37674214 548 FGVDFLQLPRDFPEEVPFVITRCTAEIEHRALGLQGIYRVSGSRVRVERLCQAFE--NGRALVELSGNSPHDITSVLKRF 625
Cdd:cd04387   1 FGVKISTVTKRERSKVPYIVRQCVEEVERRGMEEVGIYRISGVATDIQALKAAFDtnNKDVSVMLSEMDVNAIAGTLKLY 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 37674214 626 LQELTDPVVPFHLYDAFISLAKTlhADPGDDPGtpnpspeiirSLKTLLVQLPDSNYSTLRHLVAHLFRVAARFEENKMS 705
Cdd:cd04387  81 FRELPEPLFTDELYPNFAEGIAL--SDPVAKES----------CMLNLLLSLPDPNLVTFLFLLHHLKRVAEREEVNKMS 148

                       170
                ....*....|....*..
gi 37674214 706 ANNLGIVFGPTLLRPPD 722
Cdd:cd04387 149 LHNLATVFGPTLLRPSE 165

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 37674214 546 SLFGVDFLQLPRDFPEEVPFVITRCTAEIEHRALgLQGIYRVSGSRVRVERLCQAFENGRALVELSGNSPHDITSV---L 622
Cdd:cd04384   1 RVFGCDLTEHLLNSGQDVPQVLKSCTEFIEKHGI-VDGIYRLSGIASNIQRLRHEFDSEQIPDLTKDVYIQDIHSVsslC 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 37674214 623 KRFLQELTDPVVPFHLYDAFIslaKTLHADPGDdpgtpnpspEIIRSLKTLLVQLPDSNYSTLRHLVAHLFRVAARFEEN 702
Cdd:cd04384  80 KLYFRELPNPLLTYQLYEKFS---EAVSAASDE---------ERLEKIHDVIQQLPPPHYRTLEFLMRHLSRLAKYCSIT 147

                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*....
gi 37674214 703 KMSANNLGIVFGPTLLRPPDgPRATGASPVACLLDSGHQAQLVEFLIVH 751
Cdd:cd04384 148 NMHAKNLAIVWAPNLLRSKQ-IESACFSGTAAFMEVRIQSVVVEFILNH 195

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 37674214 548 FGVDFLQLPRDFPE--EVPFVITRCTAEIEHRALGLQGIYRVSGSRVRVERLCQAFENGRALVELSGNSPHD---ITSVL 622
Cdd:cd04379   1 FGVPLSRLVEREGEsrDVPIVLQKCVQEIERRGLDVIGLYRLCGSAAKKKELRDAFERNSAAVELSEELYPDinvITGVL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 37674214 623 KRFLQELTDPVVPFHLYDafislaKTLHADPGDDPGTPNPSPEIIRSlktLLVQLPDSNYSTLRHLVAHLFRVAARFEEN 702
Cdd:cd04379  81 KDYLRELPEPLITPQLYE------MVLEALAVALPNDVQTNTHLTLS---IIDCLPLSAKATLLLLLDHLSLVLSNSERN 151

                       170       180
                ....*....|....*....|....*....
gi 37674214 703 KMSANNLGIVFGPTLLRPPDGPRATGASP 731
Cdd:cd04379 152 KMTPQNLAVCFGPVLMFCSQEFSRYGISP 180

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 37674214 560 PEEVPFVITRCTAEIEHRALGLQGIYRVSGSRVRVERLCQAFENGRALVELSGNSPHDITSVLKRFLQELTDPVVPFHLY 639
Cdd:cd04390  19 PRLVPILVEQCVDFIREHGLKEEGLFRLPGQANLVKQLQDAFDAGERPSFDSDTDVHTVASLLKLYLRELPEPVIPWAQY 98

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 37674214 640 DAFISLAKTLHADPGDDPGtpnpspeiirSLKTLLVQLPDSNYSTLRHLVAHLFRVAARFEENKMSANNLGIVFGPTLLR 719
Cdd:cd04390  99 EDFLSCAQLLSKDEEKGLG----------ELMKQVSILPKVNYNLLSYICRFLDEVQSNSSVNKMSVQNLATVFGPNILR 168

                       170       180       190
                ....*....|....*....|....*....|....*..
gi 37674214 720 PpdgpraTGASPVACLLDSGHQAQLVEFLIVHYEQIF 756
Cdd:cd04390 169 P------KVEDPATIMEGTPQIQQLMTVMISKHEPLF 199

protein kinase C conserved region 1 (C1 domain) found in the GEM-interacting protein (GMIP)-like family; The GMIP-like family includes GMIP, Rho GTPase-activating protein 29 (ARHGAP29) and Rho GTPase-activating protein 45 (ARHGAP45). GMIP is a RhoA-specific GTPase-activating protein that acts as a key factor in saltatory neuronal migration. It associates with the Rab27a effector JFC1 and modulates vesicular transport and exocytosis. ARHGAP29, also called PTPL1-associated RhoGAP protein 1 (PARG1) or Rho-type GTPase-activating protein 29, is a GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state. It has strong activity toward RHOA, and weaker activity toward RAC1 and CDC42. ARHGAP29 may act as a specific effector of RAP2A to regulate Rho. In concert with RASIP1, ARHGAP29 suppresses RhoA signaling and dampens ROCK and MYH9 activities in endothelial cells and plays an essential role in blood vessel tubulogenesis. ARHGAP45, also called minor histocompatibility antigen HA-1 (mHag HA-1), is a Rac-GAP (GTPase-Activating Protein) in endothelial cells. It acts as a novel regulator of endothelial integrity. ARHGAP45 contains a GTPase activator for the Rho-type GTPases (RhoGAP) domain that would be able to negatively regulate the actin cytoskeleton as well as cell spreading. However, it also contains N-terminally a BAR-domin which can play an autoinhibitory effect on this RhoGAP activity. Members of this family contain a zinc-binding 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 37674214 491 QTHRLRRLRGPAKCRECEAFMV-SGTECEECFLTCHKRCLETLLILCGHRR 540
Cdd:cd20816   1 QTHRFRRLRTPSKCRECDSYVYfNGAECEECGLACHKKCLETLAIQCGHKR 51

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 37674214 548 FGVDFLQLPRDfPEEVPFVITRCTAEIEHRALGLQGIYRVSGSRVRVERLCQAFENGRALVELSGNSPHDITSVLKRFLQ 627
Cdd:cd04406   1 FGVELSRLTSE-DRSVPLVVEKLINYIEMHGLYTEGIYRKSGSTNKIKELRQGLDTDANSVNLDDYNIHVIASVFKQWLR 79