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 573014822 463 QTHQLRRLRGPAKCRECEAFMV-SGTECEECFLTCHKRCLETLLILCGHRR 512
Cdd:cd20816    1 QTHRFRRLRTPSKCRECDSYVYfNGAECEECGLACHKKCLETLAIQCGHKR 51

The Bin/Amphiphysin/Rvs (BAR) domain, a dimerization module that binds membranes and detects membrane curvature; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions including organelle biogenesis, membrane trafficking or remodeling, and cell division and migration. Mutations in BAR containing proteins have been linked to diseases and their inactivation in cells leads to altered membrane dynamics. A BAR domain with an additional N-terminal amphipathic helix (an N-BAR) can drive membrane curvature. These N-BAR domains are found in amphiphysins and endophilins, among others. BAR domains are also frequently found alongside domains that determine lipid specificity, such as the Pleckstrin Homology (PH) and Phox Homology (PX) domains which are present in beta centaurins (ACAPs and ASAPs) and sorting nexins, respectively. A FES-CIP4 Homology (FCH) domain together with a coiled coil region is called the F-BAR domain and is present in Pombe/Cdc15 homology (PCH) family proteins, which include Fes/Fes tyrosine kinases, PACSIN or syndapin, CIP4-like proteins, and srGAPs, among others. The Inverse (I)-BAR or IRSp53/MIM homology Domain (IMD) is found in multi-domain proteins, such as IRSp53 and MIM, that act as scaffolding proteins and transducers of a variety of signaling pathways that link membrane dynamics and the underlying actin cytoskeleton. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The I-BAR domain induces membrane protrusions in the opposite direction compared to classical BAR and F-BAR domains, which produce membrane invaginations. BAR domains that also serve as protein interaction domains include those of arfaptin and OPHN1-like proteins, among others, which bind to Rac and Rho GAP domains, respectively.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 573014822    93 GVDAALEYAKTWSRYAKELLAWTEKRASYELEFAKSTMKIA-EAGKVSIQQQSHMPLQYIYTLFLEHDLSLGT 164
Cdd:smart00055  10 GFEALLSRLKNGLRLLEDLKKFMRERAKIEEEYAKKLQKLSkKLRAVRDTEPEYGSLSKAWEVLLSETDALAK 82

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 573014822   534 EVPFVVTKCTAEIEHRALDVQGIYRVSGSRVRVERLCQAFENG-RALVELSGNSPHDVSSVLKRFLQELTEPVIPFHLYD 612
Cdd:smart00324   2 PIPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGpDPDLDLSEYDVHDVAGLLKLFLRELPEPLITYELYE 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 573014822   613 AFISLAKTLHADpgddpgtpspspEVIRSLKTLLVQLPDSNYNTLRHLVAHLFRVAARFMENKMSANNLGIVFGPTLLRP 692
Cdd:smart00324  82 EFIEAAKLEDET------------ERLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRP 149

                          170       180       190
                   ....*....|....*....|....*....|..
gi 573014822   693 PDGPRAASAipvtcllDSGHQAQLVEFLIVHY 724
Cdd:smart00324 150 PDGEVASLK-------DIRHQNTVIEFLIENA 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 573014822 463 QTHQLRRLRGPAKCRECEAFMV-SGTECEECFLTCHKRCLETLLILCGHRR 512
Cdd:cd20816    1 QTHRFRRLRTPSKCRECDSYVYfNGAECEECGLACHKKCLETLAIQCGHKR 51

envelope glycoprotein C; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 573014822 731 DELPQATEPPPQDSSPAPGPLTTSSQPPPPHLDPDSQP---------PVLASDPGPDPQHHSTLEQHPTATPTEIPTPQS 801
Cdd:PHA03269  41 DPAPAPHQAASRAPDPAVAPTSAASRKPDLAQAPTPAAsekfdpapaPHQAASRAPDPAVAPQLAAAPKPDAAEAFTSAA 120

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 573014822 802 DQREDVAedtkDGGGEVSSQGPeDSLLGTQSrghfSRQPVKYPR 845
Cdd:PHA03269 121 QAHEAPA----DAGTSAASKKP-DPAAHTQH----SPPPFAYTR 155

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 573014822    93 GVDAALEYAKTWSRYAKELLAWTEKRASYELEFAKSTMKIA-EAGKVSIQQQSHMPLQYIYTLFLEHDLSLGT 164
Cdd:smart00055  10 GFEALLSRLKNGLRLLEDLKKFMRERAKIEEEYAKKLQKLSkKLRAVRDTEPEYGSLSKAWEVLLSETDALAK 82

The Extended FES-CIP4 Homology (FCH) or F-BAR (FCH and Bin/Amphiphysin/Rvs) domain, a dimerization module that binds and bends membranes; F-BAR domains are dimerization modules that bind and bend membranes and are found in proteins involved in membrane dynamics and actin reorganization. F-BAR domain containing proteins, also known as Pombe Cdc15 homology (PCH) family proteins, include Fes and Fer tyrosine kinases, PACSINs/Syndapins, FCHO, PSTPIP, CIP4-like proteins and srGAPs. Many members also contain an SH3 domain and play roles in endocytosis. 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. These tubules have diameters larger than those observed with N-BARs. The F-BAR domains of some members such as NOSTRIN and Rgd1 are important for the subcellular localization of the protein.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 573014822 108 AKELLAWTEKRASYELEFAKSTMKIAEagKVSIQQQSHMPlqyiYTLFLEHDLSLGTLAMETVAQQ-----KRDYYQPLA 182
Cdd:cd07610   16 LKDLREFLKKRAAIEEEYAKNLQKLAK--KFSKKPESGKT----SLGTSWNSLREETESAATVHEElseklSQLIREPLE 89

                         90       100       110
                 ....*....|....*....|....*....|.
gi 573014822 183 AKRTEIEKWRKEFKEQWMKEQKRMNEAVQAL 213
Cdd:cd07610   90 KVKEDKEQARKKELAEGEKLKKKLQELWAKL 120

flagellar export protein FliJ; Members of this family are the FliJ protein found, in nearly every case, in the midst of other flagellar biosynthesis genes in bacgterial genomes. Typically the fliJ gene is found adjacent to the gene for the flagellum-specific ATPase FliI. Sequence scoring in the gray zone between trusted and noise cutoffs include both probable FliJ proteins and components of bacterial type III secretion systems.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 573014822   83 LDLRLIRTKggvDAALEYAK---TWSRYAKELLAWTEKRASYELEFAKSTMKIaeagkVSIQQQSHMPlQYIYTL----- 154
Cdd:TIGR02473   8 LDLREKEEE---QAKLELAKaqaEFERLETQLQQLIKYREEYEQQALEKVGAG-----TSALELSNYQ-RFIRQLdqriq 78

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 573014822  155 FLEHDLSLgtlaMETVAQQKRDYYQPLAAKR----TEIEKWRKEF-KEQWMKEQKRMNEAVQAL 213
Cdd:TIGR02473  79 QQQQELAL----LQQEVEAKRERLLEARRELkaleKLKEKKQKEYrAEEAKREQKEMDELATQR 138

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 573014822 520 FGVDFLQLPRDFPEEVPFVVTKCTAEIEHRALDVQGIYRVSGSRVRVERLCQAFENGRALVELSGNSPHDVSSVLKRFLQ 599
Cdd:cd04408    1 FGVDFSQLPRDFPEEVPFVVVRCTAEIENRALGVQGIYRISGSKARVEKLCQAFENGRDLVDLSGHSPHDITSVLKHFLK 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 573014822 600 ELTEPVIPFHLYDAFISLAKTLHADPGDDPGTPSPSPEVIRSLKTLLVQLPDSNYNTLRHLVAHLFRVAARFMENKMSAN 679
Cdd:cd04408   81 ELPEPVLPFQLYDDFIALAKELQRDSEKAAESPSIVENIIRSLKELLGRLPVSNYNTLRHLMAHLYRVAERFEDNKMSPN 160

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....
gi 573014822 680 NLGIVFGPTLLRPPDGPraasAIPVTCLLDSGHQAQLVEFLIVH 723
Cdd:cd04408  161 NLGIVFGPTLLRPLVGG----DVSMICLLDTGYQAQLVEFLISN 200

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 573014822   534 EVPFVVTKCTAEIEHRALDVQGIYRVSGSRVRVERLCQAFENG-RALVELSGNSPHDVSSVLKRFLQELTEPVIPFHLYD 612
Cdd:smart00324   2 PIPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGpDPDLDLSEYDVHDVAGLLKLFLRELPEPLITYELYE 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 573014822   613 AFISLAKTLHADpgddpgtpspspEVIRSLKTLLVQLPDSNYNTLRHLVAHLFRVAARFMENKMSANNLGIVFGPTLLRP 692
Cdd:smart00324  82 EFIEAAKLEDET------------ERLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRP 149

                          170       180       190
                   ....*....|....*....|....*....|..
gi 573014822   693 PDGPRAASAipvtcllDSGHQAQLVEFLIVHY 724
Cdd:smart00324 150 PDGEVASLK-------DIRHQNTVIEFLIENA 174

RhoGAP: GTPase-activator protein (GAP) for Rho-like GTPases; GAPs towards Rho/Rac/Cdc42-like small GTPases. Small GTPases (G proteins) cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when bound to GDP. The Rho family of small G proteins, which includes Cdc42Hs, activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. G proteins 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. The RhoGAPs are one of the major classes of regulators of Rho G proteins.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 573014822 536 PFVVTKCTAEIEHRALDVQGIYRVSGSRVRVERLCQAFENGRALVELSGNSPHDVSSVLKRFLQELTEPVIPFHLYDAFI 615
Cdd:cd00159    1 PLIIEKCIEYLEKNGLNTEGIFRVSGSASKIEELKKKFDRGEDIDDLEDYDVHDVASLLKLYLRELPEPLIPFELYDEFI 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 573014822 616 SLAKTlhadpgddpgtpSPSPEVIRSLKTLLVQLPDSNYNTLRHLVAHLFRVAARFMENKMSANNLGIVFGPTLLRPPDG 695
Cdd:cd00159   81 ELAKI------------EDEEERIEALKELLKSLPPENRDLLKYLLKLLHKISQNSEVNKMTASNLAIVFAPTLLRPPDS 148

                        170       180
                 ....*....|....*....|....*...
gi 573014822 696 praasaiPVTCLLDSGHQAQLVEFLIVH 723
Cdd:cd00159  149 -------DDELLEDIKKLNEIVEFLIEN 169

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 573014822 520 FGVDFLQLPRDFPEEVPFVVTKCTAEIEHRALDVQGIYRVSGSRVRVERLCQAFENGRALVELSGNSPHDV---SSVLKR 596
Cdd:cd04372    1 YGCDLTTLVKAHNTQRPMVVDMCIREIEARGLQSEGLYRVSGFAEEIEDVKMAFDRDGEKADISATVYPDInviTGALKL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 573014822 597 FLQELTEPVIPFHLYDAFISLAKTLHADpgddpgtpspspEVIRSLKTLLVQLPDSNYNTLRHLVAHLFRVAARFMENKM 676
Cdd:cd04372   81 YFRDLPIPVITYDTYPKFIDAAKISNPD------------ERLEAVHEALMLLPPAHYETLRYLMEHLKRVTLHEKDNKM 148

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|..
gi 573014822 677 SANNLGIVFGPTLLRPPDGPraasaiPVTCLLDSGHQAQLVEFLIVHYEQIF 728
Cdd:cd04372  149 NAENLGIVFGPTLMRPPEDS------ALTTLNDMRYQILIVQLLITNEDVLF 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 573014822 520 FGVDFLQ-LPRDFPEEVPFVVTKCTAEIEHRALDVQGIYRVSGSRVRVERLCQAFENGRALVELSGNSPHD---VSSVLK 595
Cdd:cd04395    2 FGVPLDDcPPSSENPYVPLIVEVCCNIVEARGLETVGIYRVPGNNAAISALQEELNRGGFDIDLQDPRWRDvnvVSSLLK 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 573014822 596 RFLQELTEPVIPFHLYDAFISlaktlhADPGDDPgtpspsPEVIRSLKTLLVQLPDSNYNTLRHLVAHLFRVAARFMENK 675
Cdd:cd04395   82 SFFRKLPEPLFTNELYPDFIE------ANRIEDP------VERLKELRRLIHSLPDHHYETLKHLIRHLKTVADNSEVNK 149

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|...
gi 573014822 676 MSANNLGIVFGPTLLRPPDGPRAasaipvTCLLDSGHQAQLVEFLIVHYEQIF 728
Cdd:cd04395  150 MEPRNLAIVFGPTLVRTSDDNME------TMVTHMPDQCKIVETLIQHYDWFF 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 573014822 535 VPFVVTKCTAEIEHRALDVQGIYRVSGSRVRVERL-CQA-FENGRALVELSGNSPHDVSSVLKRFLQELTEPVIPFHLYD 612
Cdd:cd04403   16 VPKFVRLCIEAVEKRGLDVDGIYRVSGNLAVIQKLrFAVdHDEKLDLDDSKWEDIHVITGALKLFFRELPEPLFPYSLFN 95

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 573014822 613 AFISLAKTlhadpgddpgtpSPSPEVIRSLKTLLVQLPDSNYNTLRHLVAHLFRVAARFMENKMSANNLGIVFGPTLLRP 692
Cdd:cd04403   96 DFVAAIKL------------SDYEQRVSAVKDLIKSLPKPNHDTLKMLFRHLCRVIEHGEKNRMTTQNLAIVFGPTLLRP 163

                        170       180
                 ....*....|....*....|....*....
gi 573014822 693 PDGpraASAIPVTCLldsgHQAQLVEFLI 721
Cdd:cd04403  164 EQE---TGNIAVHMV----YQNQIVELIL 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 573014822 520 FGVDFLQLPRDFPEEVPFVVTKCTAEIEHRALDVQGIYRVSGSRVRVERLCQAFE--NGRALVELSGNSPHDVSSVLKRF 597
Cdd:cd04387    1 FGVKISTVTKRERSKVPYIVRQCVEEVERRGMEEVGIYRISGVATDIQALKAAFDtnNKDVSVMLSEMDVNAIAGTLKLY 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 573014822 598 LQELTEPVIPFHLYDAFISLAKTlhADPgddpgtpspspeVIR--SLKTLLVQLPDSNYNTLRHLVAHLFRVAARFMENK 675
Cdd:cd04387   81 FRELPEPLFTDELYPNFAEGIAL--SDP------------VAKesCMLNLLLSLPDPNLVTFLFLLHHLKRVAEREEVNK 146

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 573014822 676 MSANNLGIVFGPTLLRPPDgprAASAIPVTCLLDSGHQAQLVEFLIVHY 724
Cdd:cd04387  147 MSLHNLATVFGPTLLRPSE---KESKIPTNTMTDSWSLEVMSQVQVLLY 192

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 573014822 533 EEVPFVVTKCTAEIEHRALDVQGIYRVSGSRVRVERLCQAFENGRALVELSGNSPHDVSSVLKRFLQELTEPVIPFHLYD 612
Cdd:cd04376    7 RQVPRLVESCCQHLEKHGLQTVGIFRVGSSKKRVRQLREEFDRGIDVVLDENHSVHDVAALLKEFFRDMPDPLLPRELYT 86

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 573014822 613 AFIsLAKTLHADpgddpgtpspspEVIRSLKTLLVQLPDSNYNTLRHLVAHLFRVAARFME-----------NKMSANNL 681
Cdd:cd04376   87 AFI-GTALLEPD------------EQLEALQLLIYLLPPCNCDTLHRLLKFLHTVAEHAADsidedgqevsgNKMTSLNL 153

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*..
gi 573014822 682 GIVFGPTLLRPPDGPRAASAIPVTCLLDSGHQAQLVEFLIVHYEQIF 728
Cdd:cd04376  154 ATIFGPNLLHKQKSGEREFVQASLRIEESTAIINVVQTMIDNYEELF 200

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 573014822 518 PLFGVDFLQLPRDFPEEVPFVVTKCTAEIEHRALdVQGIYRVSGSRVRVERLCQAFENGRA--LVELSG-NSPHDVSSVL 594
Cdd:cd04384    1 RVFGCDLTEHLLNSGQDVPQVLKSCTEFIEKHGI-VDGIYRLSGIASNIQRLRHEFDSEQIpdLTKDVYiQDIHSVSSLC 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 573014822 595 KRFLQELTEPVIPFHLYDAFIslaKTLHADPGDdpgtpspspEVIRSLKTLLVQLPDSNYNTLRHLVAHLFRVAARFMEN 674
Cdd:cd04384   80 KLYFRELPNPLLTYQLYEKFS---EAVSAASDE---------ERLEKIHDVIQQLPPPHYRTLEFLMRHLSRLAKYCSIT 147

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 573014822 675 KMSANNLGIVFGPTLLRPPDgPRAASAIPVTCLLDSGHQAQLVEFLIVH 723
Cdd:cd04384  148 NMHAKNLAIVWAPNLLRSKQ-IESACFSGTAAFMEVRIQSVVVEFILNH 195

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 573014822 535 VPFVVTKCTAEIEHRALDVQGIYRVSGSRVRVERLCQAFENGRALVELSGNSPHDVSSVLKRFLQELTEPVIPFHLYDAF 614
Cdd:cd04382   17 IPALIVHCVNEIEARGLTEEGLYRVSGSEREVKALKEKFLRGKTVPNLSKVDIHVICGCLKDFLRSLKEPLITFALWKEF 96

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 573014822 615 ISLAKtlHADPgddpgtpspsPEVIRSLKTLLVQLPDSNYNTLRHLVAHLFRVaARFMENKMSANNLGIVFGPTL 689
Cdd:cd04382   97 MEAAE--ILDE----------DNSRAALYQAISELPQPNRDTLAFLILHLQRV-AQSPECKMDINNLARVFGPTI 158

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 573014822 518 PLFGVDFLQLPRDFPEEVPFVVTKCTAEIEHRALDVQGIYRVSGSRVRVERLCQAFENG--RALVELSGNSPHDVSSVLK 595
Cdd:cd04386    3 PVFGTPLEEHLKRTGREIALPIEACVMCLLETGMNEEGLFRVGGGASKLKRLKAALDAGtfSLPLDEFYSDPHAVASALK 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 573014822 596 RFLQELTEPVIPFHLYDAFISLAKTlhadPGDDpgtpspspEVIRSLKTLLVQLPDSNYNTLRHLVAHLFRVAARFMENK 675
Cdd:cd04386   83 SYLRELPDPLLTYNLYEDWVQAANK----PDED--------ERLQAIWRILNKLPRENRDNLRYLIKFLSKLAQKSDENK 150

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|...
gi 573014822 676 MSANNLGIVFGPTLLRPPDGPRAASAIPVTCLldsgHQAQLVEFLIVHYEQIF 728
Cdd:cd04386  151 MSPSNIAIVLAPNLLWAKNEGSLAEMAAGTSV----HVVAIVELIISHADWFF 199

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 573014822 519 LFGVDFLQLPRDF-PEE--VP-FVVTKCTAEIEHraLDVQGIYRVSGSRVRVERLCQAFENGRALveLSGNSPHDVSSVL 594
Cdd:cd04394    1 VFGVPLHSLPHSTvPEYgnVPkFLVDACTFLLDH--LSTEGLFRKSGSVVRQKELKAKLEGGEAC--LSSALPCDVAGLL 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 573014822 595 KRFLQELTEPVIPFHLYDAFISLAKTlhadpgddpgtpsPSPEViRSLKTLLVQ--LPDSNYNTLRHLVAHLFRVAARFM 672
Cdd:cd04394   77 KQFFRELPEPLLPYDLHEALLKAQEL-------------PTDEE-RKSATLLLTclLPDEHVNTLRYFFSFLYDVAQRCS 142

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 573014822 673 ENKMSANNLGIVFGPTLLRPPDGpraASAIPVTCLLDSGHQAQLVEFLI 721
Cdd:cd04394  143 ENKMDSSNLAVIFAPNLFQSEEG---GEKMSSSTEKRLRLQAAVVQTLI 188