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 568968530 515 FGQDFSQAALSTPDGVPFIVKKCVCEIERRALHTKGIYRVNGVKTRVEKLCQAFENGKELVELSQASPHDISNVLKLYLR 594
Cdd:cd04378    1 FGVDFSQVPRDFPDEVPFIIKKCTSEIENRALGVQGIYRVSGSKARVEKLCQAFENGKDLVELSELSPHDISSVLKLFLR 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968530 595 QLPEPLISFRFYHELVGLAKDSLKAEaeakaasrGRQGGSESEAATLAMVGRLRELMQDLPAENRATLLYLLKHLRRIVE 674
Cdd:cd04378   81 QLPEPLILFRLYNDFIALAKEIQRDT--------EEDKAPNTPIEVNRIIRKLKDLLRQLPASNYNTLQHLIAHLYRVAE 152

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|.
gi 568968530 675 MEQDNKMTPGNLGIVFGPTLLRPRPTDATVSLSSLVDYPHQARVIETLIVH 725
Cdd:cd04378  153 QFEENKMSPNNLGIVFGPTLIRPRPGDADVSLSSLVDYGYQARLVEFLITN 203

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968530  37 EGGVDAALQYAKDMARYMKDLISYLEKRTTLEMEFAKGLQKVVHNCRQSVTHEPHMPllSIYSLALEQDLEFGHGMVQAA 116
Cdd:cd07652    4 DVGLSTLLDRLKQSIASAKEFATFLKKRAAIEEEHARGLKKLARTTLDTYKRPDHKQ--GSFSNAYHSSLEFHEKLADNG 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968530 117 GTLQT--QTFMQPLTLRRLEHERRRKEIKESWHRAQRKLQEAEANLRKAKQGYKQRCEDHDKARLQvakaeEEQQGTG-- 192
Cdd:cd07652   82 LRFAKalNEMSDELSSLAKTVEKSRKSIKETGKRAEKKVQDAEAAAEKAKARYDSLADDLERVKTG-----DPGKKLKfg 156

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968530 193 -PGAGTAASKALDKRRRLEEEAKnkaeeamaTYRTCVADAKTQKQELEDT-KVTALRQIQEVIRQSDQTIKsatisyyql 270
Cdd:cd07652  157 lKGNKSAAQHEDELLRKVQAADQ--------DYASKVNAAQALRQELLSRhRPEAVKDLFDLILEIDAALR--------- 219

                        250
                 ....*....|....*...
gi 568968530 271 MHMQtaplpvNFQMLCES 288
Cdd:cd07652  220 LQYQ------KYALPNEL 231

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 568968530 515 FGQDFSQAALSTPDGVPFIVKKCVCEIERRALHTKGIYRVNGVKTRVEKLCQAFENGKELVELSQASPHDISNVLKLYLR 594
Cdd:cd04378    1 FGVDFSQVPRDFPDEVPFIIKKCTSEIENRALGVQGIYRVSGSKARVEKLCQAFENGKDLVELSELSPHDISSVLKLFLR 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968530 595 QLPEPLISFRFYHELVGLAKDSLKAEaeakaasrGRQGGSESEAATLAMVGRLRELMQDLPAENRATLLYLLKHLRRIVE 674
Cdd:cd04378   81 QLPEPLILFRLYNDFIALAKEIQRDT--------EEDKAPNTPIEVNRIIRKLKDLLRQLPASNYNTLQHLIAHLYRVAE 152

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|.
gi 568968530 675 MEQDNKMTPGNLGIVFGPTLLRPRPTDATVSLSSLVDYPHQARVIETLIVH 725
Cdd:cd04378  153 QFEENKMSPNNLGIVFGPTLIRPRPGDADVSLSSLVDYGYQARLVEFLITN 203

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968530  531 PFIVKKCVCEIERRALHTKGIYRVNGVKTRVEKLCQAFENGKELV-ELSQASPHDISNVLKLYLRQLPEPLISFRFYHEL 609
Cdd:pfam00620   1 PLIVRKCVEYLEKRGLDTEGIFRVSGSASRIKELREAFDRGPDVDlDLEEEDVHVVASLLKLFLRELPEPLLTFELYEEF 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968530  610 VGLAKDSlkaeaeakaasrgrqggSESEAatlamVGRLRELMQDLPAENRATLLYLLKHLRRIVEMEQDNKMTPGNLGIV 689
Cdd:pfam00620  81 IEAAKLP-----------------DEEER-----LEALRELLRKLPPANRDTLRYLLAHLNRVAQNSDVNKMNAHNLAIV 138

                         170
                  ....*....|
gi 568968530  690 FGPTLLRPRP 699
Cdd:pfam00620 139 FGPTLLRPPD 148

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 568968530  37 EGGVDAALQYAKDMARYMKDLISYLEKRTTLEMEFAKGLQKVVHNCRQSVTHEPHMPllSIYSLALEQDLEFGHGMVQAA 116
Cdd:cd07652    4 DVGLSTLLDRLKQSIASAKEFATFLKKRAAIEEEHARGLKKLARTTLDTYKRPDHKQ--GSFSNAYHSSLEFHEKLADNG 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968530 117 GTLQT--QTFMQPLTLRRLEHERRRKEIKESWHRAQRKLQEAEANLRKAKQGYKQRCEDHDKARLQvakaeEEQQGTG-- 192
Cdd:cd07652   82 LRFAKalNEMSDELSSLAKTVEKSRKSIKETGKRAEKKVQDAEAAAEKAKARYDSLADDLERVKTG-----DPGKKLKfg 156

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968530 193 -PGAGTAASKALDKRRRLEEEAKnkaeeamaTYRTCVADAKTQKQELEDT-KVTALRQIQEVIRQSDQTIKsatisyyql 270
Cdd:cd07652  157 lKGNKSAAQHEDELLRKVQAADQ--------DYASKVNAAQALRQELLSRhRPEAVKDLFDLILEIDAALR--------- 219

                        250
                 ....*....|....*...
gi 568968530 271 MHMQtaplpvNFQMLCES 288
Cdd:cd07652  220 LQYQ------KYALPNEL 231

Protein kinase C conserved region 1 (C1) domains (Cysteine-rich domains); Some bind phorbol esters and diacylglycerol. Some bind RasGTP. Zinc-binding domains.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 568968530   458 THRLRKLRTPAKCRECNSYVYF---QGAECEECCLACHKKCLETLAIQC 503
Cdd:smart00109   2 KHVFRTFTKPTFCCVCRKSIWGsfkQGLRCSECKVKCHKKCADKVPKAC 50

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 568968530 515 FGQDFSQAALSTPDGVPFIVKKCVCEIERRALHTKGIYRVNGVKTRVEKLCQAFENGKELVELSQASPHDISNVLKLYLR 594
Cdd:cd04378    1 FGVDFSQVPRDFPDEVPFIIKKCTSEIENRALGVQGIYRVSGSKARVEKLCQAFENGKDLVELSELSPHDISSVLKLFLR 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968530 595 QLPEPLISFRFYHELVGLAKDSLKAEaeakaasrGRQGGSESEAATLAMVGRLRELMQDLPAENRATLLYLLKHLRRIVE 674
Cdd:cd04378   81 QLPEPLILFRLYNDFIALAKEIQRDT--------EEDKAPNTPIEVNRIIRKLKDLLRQLPASNYNTLQHLIAHLYRVAE 152

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|.
gi 568968530 675 MEQDNKMTPGNLGIVFGPTLLRPRPTDATVSLSSLVDYPHQARVIETLIVH 725
Cdd:cd04378  153 QFEENKMSPNNLGIVFGPTLIRPRPGDADVSLSSLVDYGYQARLVEFLITN 203

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 568968530 515 FGQDFSQAALSTPDGVPFIVKKCVCEIERRALHTKGIYRVNGVKTRVEKLCQAFENGKELVELSQASPHDISNVLKLYLR 594
Cdd:cd04408    1 FGVDFSQLPRDFPEEVPFVVVRCTAEIENRALGVQGIYRISGSKARVEKLCQAFENGRDLVDLSGHSPHDITSVLKHFLK 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968530 595 QLPEPLISFRFYHELVGLAKDSLkaeaeakaasRGRQGGSESEAATLAMVGRLRELMQDLPAENRATLLYLLKHLRRIVE 674
Cdd:cd04408   81 ELPEPVLPFQLYDDFIALAKELQ----------RDSEKAAESPSIVENIIRSLKELLGRLPVSNYNTLRHLMAHLYRVAE 150

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|.
gi 568968530 675 MEQDNKMTPGNLGIVFGPTLLRPRPTDAtVSLSSLVDYPHQARVIETLIVH 725
Cdd:cd04408  151 RFEDNKMSPNNLGIVFGPTLLRPLVGGD-VSMICLLDTGYQAQLVEFLISN 200

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968530  531 PFIVKKCVCEIERRALHTKGIYRVNGVKTRVEKLCQAFENGKELV-ELSQASPHDISNVLKLYLRQLPEPLISFRFYHEL 609
Cdd:pfam00620   1 PLIVRKCVEYLEKRGLDTEGIFRVSGSASRIKELREAFDRGPDVDlDLEEEDVHVVASLLKLFLRELPEPLLTFELYEEF 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968530  610 VGLAKDSlkaeaeakaasrgrqggSESEAatlamVGRLRELMQDLPAENRATLLYLLKHLRRIVEMEQDNKMTPGNLGIV 689
Cdd:pfam00620  81 IEAAKLP-----------------DEEER-----LEALRELLRKLPPANRDTLRYLLAHLNRVAQNSDVNKMNAHNLAIV 138

                         170
                  ....*....|
gi 568968530  690 FGPTLLRPRP 699
Cdd:pfam00620 139 FGPTLLRPPD 148

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 568968530 515 FGQDFSQAALSTPDGVPFIVKKCVCEIERRALHTKGIYRVNGVKTRVEKLCQAFE-NGKE-LVELSQASPHDISNVLKLY 592
Cdd:cd04387    1 FGVKISTVTKRERSKVPYIVRQCVEEVERRGMEEVGIYRISGVATDIQALKAAFDtNNKDvSVMLSEMDVNAIAGTLKLY 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968530 593 LRQLPEPLISFRFYHELV-GLAKdslkaeaeakaasrgrqggSESEAATLAMVgrlrELMQDLPAENRATLLYLLKHLRR 671
Cdd:cd04387   81 FRELPEPLFTDELYPNFAeGIAL-------------------SDPVAKESCML----NLLLSLPDPNLVTFLFLLHHLKR 137

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|
gi 568968530 672 IVEMEQDNKMTPGNLGIVFGPTLLRPRPTDATVSLSSLVD 711
Cdd:cd04387  138 VAEREEVNKMSLHNLATVFGPTLLRPSEKESKIPTNTMTD 177

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 568968530 526 TPDGVPFIVKKCVCEIERRALHTKGIYRVNGVKTRVEKLCQAFENGKELVEL--SQASPHDISNVLKLYLRQLPEPLISF 603
Cdd:cd04385   11 TDNDIPVIVDKCIDFITQHGLMSEGIYRKNGKNSSVKKLLEAFRKDARSVQLreGEYTVHDVADVLKRFLRDLPDPLLTS 90

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968530 604 RFYHELVGLAKdslkaeaeakaASRGRQGgseseaatlamVGRLRELMQDLPAENRATLLYLLKHLRRIVEMEQDNKMTP 683
Cdd:cd04385   91 ELHAEWIEAAE-----------LENKDER-----------IARYKELIRRLPPINRATLKVLIGHLYRVQKHSDENQMSV 148

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|...
gi 568968530 684 GNLGIVFGPTLLRprpTDATVSLSslvdYPHQARVIETLIVHY 726
Cdd:cd04385  149 HNLALVFGPTLFQ---TDEHSVGQ----TSHEVKVIEDLIDNY 184

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 568968530 530 VPFIVKKCVCEIERRALHTKGIYRVNGVKTRVEKL-CQAfeNGKELVELSQASPHDI---SNVLKLYLRQLPEPLISFRF 605
Cdd:cd04403   16 VPKFVRLCIEAVEKRGLDVDGIYRVSGNLAVIQKLrFAV--DHDEKLDLDDSKWEDIhviTGALKLFFRELPEPLFPYSL 93

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968530 606 YHELVGLAKDSlkaeaeakaASRGRqggseseaatlamVGRLRELMQDLPAENRATLLYLLKHLRRIVEMEQDNKMTPGN 685
Cdd:cd04403   94 FNDFVAAIKLS---------DYEQR-------------VSAVKDLIKSLPKPNHDTLKMLFRHLCRVIEHGEKNRMTTQN 151

                        170       180       190
                 ....*....|....*....|....*....|.
gi 568968530 686 LGIVFGPTLLRPRptDATVSLSSLVDYPHQA 716
Cdd:cd04403  152 LAIVFGPTLLRPE--QETGNIAVHMVYQNQI 180

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 568968530 525 STPDGVPFIVKKCVCEIERRALHTKGIYRVNGVKTRVEKLCQAFENGKELVELSQASPHDISNVLKLYLRQLPEPLISFR 604
Cdd:cd04382   12 STSPMIPALIVHCVNEIEARGLTEEGLYRVSGSEREVKALKEKFLRGKTVPNLSKVDIHVICGCLKDFLRSLKEPLITFA 91

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968530 605 FYHELVglakdslkaeaeakaasrgrqggsesEAATLA----MVGRLRELMQDLPAENRATLLYLLKHLRRIVEMEqDNK 680
Cdd:cd04382   92 LWKEFM--------------------------EAAEILdednSRAALYQAISELPQPNRDTLAFLILHLQRVAQSP-ECK 144

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*
gi 568968530 681 MTPGNLGIVFGPTL---LRPRPTDATvslsSLVDYPHQARVIETL 722
Cdd:cd04382  145 MDINNLARVFGPTIvgySVPNPDPMT----ILQDTVRQPRVVERL 185

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 568968530 515 FGQDFSQAALSTPDGVPFIVKKCVCEIERRALHTKGIYRVNGVKTRVEKLCQAFENGKELVEL--SQASPHDISNV---L 589
Cdd:cd04398    1 FGVPLEDLILREGDNVPNIVYQCIQAIENFGLNLEGIYRLSGNVSRVNKLKELFDKDPLNVLLisPEDYESDIHSVaslL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968530 590 KLYLRQLPEPLISFRFYHELVGLAKdslkaeaeakaasrgrqggseSEAATLAMVgRLRELMQDLPAENRATLLYLLKHL 669
Cdd:cd04398   81 KLFFRELPEPLLTKALSREFIEAAK---------------------IEDESRRRD-ALHGLINDLPDANYATLRALMFHL 138

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 568968530 670 RRIVEMEQDNKMTPGNLGIVFGPTLLRPRPTDATvslsslvDYPHQARVIETLIVHYGLVF 730
Cdd:cd04398  139 ARIKEHESVNRMSVNNLAIIWGPTLMNAAPDNAA-------DMSFQSRVIETLLDNAYQIF 192

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 568968530 457 RTHRLRKLRTPAKCRECNSYVYFQGAECEECCLACHKKCLETLAIQCGHKK 507
Cdd:cd20816    1 QTHRFRRLRTPSKCRECDSYVYFNGAECEECGLACHKKCLETLAIQCGHKR 51

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 568968530 525 STPDGVPFIVKKCVCEIERRALHTKGIYRVNGVKTRVEKLCQAFENGKELVELSQASPHD---ISNVLKLYLRQLPEPLI 601
Cdd:cd04379   13 GESRDVPIVLQKCVQEIERRGLDVIGLYRLCGSAAKKKELRDAFERNSAAVELSEELYPDinvITGVLKDYLRELPEPLI 92

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968530 602 SFRFYHELVglakdslkaeaeakaasrgrqggsesEAATLAMVGR-------LRELMQDLPAENRATLLYLLKHLRRIVE 674
Cdd:cd04379   93 TPQLYEMVL--------------------------EALAVALPNDvqtnthlTLSIIDCLPLSAKATLLLLLDHLSLVLS 146

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 568968530 675 MEQDNKMTPGNLGIVFGPTLLRPRPTDATVSLS--------SLVDYPHQARVIETLI 723
Cdd:cd04379  147 NSERNKMTPQNLAVCFGPVLMFCSQEFSRYGISptskmaavSTVDFKQHIEVLHYLL 203

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 568968530 530 VPFIVKKCVCEIERRALHTKGIYRVNGVKTRVEKLCQAFENGKELVELSQASPHDISNVLKLYLRQLPEPLISFRFYHEL 609
Cdd:cd04407   15 VPIVLEKLLEHVEMHGLYTEGIYRKSGSANRMKELHQLLQADPENVKLENYPIHAITGLLKQWLRELPEPLMTFAQYNDF 94

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968530 610 VglakdslkaeaeakaasRGRQGGSESEaaTLAMVGRlreLMQDLPAENRATLLYLLKHLRRIVEMEQDNKMTPGNLGIV 689
Cdd:cd04407   95 L-----------------RAVELPEKQE--QLQAIYR---VLEQLPTANHNTLERLIFHLVKVALEEDVNRMSPNALAIV 152

                        170       180       190
                 ....*....|....*....|....*....|....*.
gi 568968530 690 FGPTLLR-PRPTDatvSLSSLVDYPHQARVIETLIV 724
Cdd:cd04407  153 FAPCLLRcPDSSD---PLTSMKDVAKTTTCVEMLIK 185

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968530 530 VPFIVKKCVCEIERRALHTKGIYRVNGVKTRVEKLCQAFEN--GKELVELSQASPHDISNVLKLYLRQLPEPLisfrFYH 607
Cdd:cd04391   22 VPLIFQKLINKLEERGLETEGILRIPGSAQRVKFLCQELEAkfYEGTFLWDQVKQHDAASLLKLFIRELPQPL----LTV 97

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968530 608 ELVGLAKDSlkaeaeakaasrgrQGGSESEAATLAmvgrLRELMQDLPAENRATLLYLLKHLRRIVEMEQDNKMTPGNLG 687
Cdd:cd04391   98 EYLPAFYSV--------------QGLPSKKDQLQA----LNLLVLLLPEANRDTLKALLEFLQKVVDHEEKNKMNLWNVA 159

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*.
gi 568968530 688 IVFGPTL---LRPRPTDATVSLSSLVDYPHQARVIETLIVHYGLVF 730
Cdd:cd04391  160 MIMAPNLfppRGKHSKDNESLQEEVNMAAGCANIMRLLIRYQDLLW 205

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 568968530 506 KKLQGRLQLFGQDFSQAalstpdgVPFIVKKCVCEIERRALHTKGIYRVNGVKTRVEKLCQAFENGKELVELSQaSPHDI 585
Cdd:cd04383    1 KLFNGSLEEYIQDSGQA-------IPLVVESCIRFINLYGLQHQGIFRVSGSQVEVNDIKNAFERGEDPLADDQ-NDHDI 72

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968530 586 SN---VLKLYLRQLPEPLISFRFYHELVGLAKdslkaeaeakaasrgrqggSESEAAtlaMVGRLRELMQDLPAENRATL 662
Cdd:cd04383   73 NSvagVLKLYFRGLENPLFPKERFEDLMSCVK-------------------LENPTE---RVHQIREILSTLPRSVIIVM 130

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 568968530 663 LYLLKHLRRIVEMEQDNKMTPGNLGIVFGPTLLR-PRPTDATVSLSslvdypHQARVIETLIVH 725
Cdd:cd04383  131 RYLFAFLNHLSQFSDENMMDPYNLAICFGPTLMPvPEGQDQVSCQA------HVNELIKTIIIH 188

RhoGap_RalBP1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in RalBP1 proteins, also known as RLIP, RLIP76 or cytocentrin. RalBP1 plays an important role in endocytosis during interphase. During mitosis, RalBP1 transiently associates with the centromere and has been shown to play an essential role in the proper assembly of the mitotic apparatus. RalBP1 is an effector of the Ral GTPase which itself is an effector of Ras. RalBP1 contains a RhoGAP domain, which shows weak activity towards Rac1 and Cdc42, but not towards Ral, and a Ral effector domain binding motif. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968530 515 FGQDFSQAALSTP--DGV--PFIVKKCVCEIERRALHTKGIYRVNGVKTRVEKLCQAFeNGKELVELSQASPHDISNVLK 590
Cdd:cd04381    1 FGASLSLAVERSRchDGIdlPLVFRECIDYVEKHGMKCEGIYKVSGIKSKVDELKAAY-NRRESPNLEEYEPPTVASLLK 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968530 591 LYLRQLPEPLisfrfyhelvgLAKDSLkaeaeakaaSRGRQGGSESEAATlaMVGRLRELMQDLPAENRATLLYLLKHLR 670
Cdd:cd04381   80 QYLRELPEPL-----------LTKELM---------PRFEEACGRPTEAE--REQELQRLLKELPECNRLLLAWLIVHMD 137

                        170       180
                 ....*....|....*....|....
gi 568968530 671 RIVEMEQDNKMTPGNLGIVFGPTL 694
Cdd:cd04381  138 HVIAQELETKMNIQNISIVLSPTV 161

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 568968530 513 QLFG---QDFSQAALsTPDGVPFIVKKCVCEIERRALHTKGIYRVNGVKTRVEKLCQAFENGkELVELSQ-ASPHDISNV 588
Cdd:cd04393    1 KVFGvplQELQQAGQ-PENGVPAVVRHIVEYLEQHGLEQEGLFRVNGNAETVEWLRQRLDSG-EEVDLSKeADVCSAASL 78