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 1372102860  66 EENVDKRKKKVEELTMAQNLREASVDLDyfQTSCLHRVINAYGTVLHAEVDEKVKLEMAMERRVYEELAPFSEYE-KNVN 144
Cdd:cd07595    47 GEDKDKRLKKLPEYGLAQSMLESSKELP--DDSLLGKVLKLCGEAQNTLARELVDHEMNVEEDVLSPLQNILEVEiPNIQ 124

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1372102860 145 KLKDKLNLVSTDLEIAQKDLEKENSMTHQ-----------ESLDAIQMKYEGMKDALVTDIFaSSVSKEFQLNEHMLTSM 213
Cdd:cd07595   125 KQKKRLSKLVLDMDSARSRYNAAHKSSGGqgaaakvdalkDEYEEAELKLEQCRDALATDMY-EFLAKEAEIASYLIDLI 203

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|.
gi 1372102860 214 NLKRDYFKKMYEMYEKAIPEVERMIATALPRPVFGVPLDEH 254
Cdd:cd07595   204 EAQREYHRTALSVLEAVLPELQEQIEQSPSKPVFGQPLEEH 244

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1372102860 265 VLTKCCDFLRQNGMNERGIFRVSGNASKIKRIRAALDAGQfDADEKHYNNDPHAVASTLKAYLRELPDPLTMDSLQSDWV 344
Cdd:pfam00620   3 IVRKCVEYLEKRGLDTEGIFRVSGSASRIKELREAFDRGP-DVDLDLEEEDVHVVASLLKLFLRELPEPLLTFELYEEFI 81

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1372102860 345 EAINLEGE-ERFSAIDRCLKKMTRGHRQNLIYLMKFLCDLEAKREETSMNASNLAIVFAPTM 405
Cdd:pfam00620  82 EAAKLPDEeERLEALRELLRKLPPANRDTLRYLLAHLNRVAQNSDVNKMNAHNLAIVFGPTL 143

The Bin/Amphiphysin/Rvs (BAR) domain of Rich-like Rho GTPase Activating Proteins; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. This subfamily is composed of Rho and Rac GTPase activating proteins (GAPs) with similarity to GAP interacting with CIP4 homologs proteins (Rich). Members contain an N-terminal BAR domain, followed by a Rho GAP domain, and a C-terminal prolin-rich region. Vertebrates harbor at least three Rho GAPs in this subfamily including Rich1, Rich2, and SH3-domain binding protein 1 (SH3BP1). Rich1 and Rich2 play complementary roles in the establishment and maintenance of cell polarity. Rich1 is a Cdc42- and Rac-specific GAP that binds to polarity proteins through the scaffold protein angiomotin and plays a role in maintaining the integrity of tight junctions. Rich2 is a Rac GAP that interacts with CD317 and plays a role in actin cytoskeleton organization and the maintenance of microvilli in polarized epithelial cells. SH3BP1 is a Rac GAP that inhibits Rac-mediated platelet-derived growth factor (PDGF)-induced membrane ruffling. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The BAR domain of Rich1 has been shown to form oligomers, bind membranes and induce membrane tubulation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1372102860  66 EENVDKRKKKVEELTMAQNLREASVDLDyfQTSCLHRVINAYGTVLHAEVDEKVKLEMAMERRVYEELAPFSEYE-KNVN 144
Cdd:cd07595    47 GEDKDKRLKKLPEYGLAQSMLESSKELP--DDSLLGKVLKLCGEAQNTLARELVDHEMNVEEDVLSPLQNILEVEiPNIQ 124

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1372102860 145 KLKDKLNLVSTDLEIAQKDLEKENSMTHQ-----------ESLDAIQMKYEGMKDALVTDIFaSSVSKEFQLNEHMLTSM 213
Cdd:cd07595   125 KQKKRLSKLVLDMDSARSRYNAAHKSSGGqgaaakvdalkDEYEEAELKLEQCRDALATDMY-EFLAKEAEIASYLIDLI 203

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|.
gi 1372102860 214 NLKRDYFKKMYEMYEKAIPEVERMIATALPRPVFGVPLDEH 254
Cdd:cd07595   204 EAQREYHRTALSVLEAVLPELQEQIEQSPSKPVFGQPLEEH 244

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 1372102860 265 VLTKCCDFLRQNGMNERGIFRVSGNASKIKRIRAALDAGQFDADEKHYnnDPHAVASTLKAYLRELPDPLTMDSLQSDWV 344
Cdd:cd00159     3 IIEKCIEYLEKNGLNTEGIFRVSGSASKIEELKKKFDRGEDIDDLEDY--DVHDVASLLKLYLRELPEPLIPFELYDEFI 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1372102860 345 EAINLE-GEERFSAIDRCLKKMTRGHRQNLIYLMKFLCDLEAKREETSMNASNLAIVFAPTM-----TGMIYDGMNTHGV 418
Cdd:cd00159    81 ELAKIEdEEERIEALKELLKSLPPENRDLLKYLLKLLHKISQNSEVNKMTASNLAIVFAPTLlrppdSDDELLEDIKKLN 160

                  ....*....
gi 1372102860 419 KLTEFMISN 427
Cdd:cd00159   161 EIVEFLIEN 169

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 1372102860  265 VLTKCCDFLRQNGMNERGIFRVSGNASKIKRIRAALDAGQfDADEKHYNNDPHAVASTLKAYLRELPDPLTMDSLQSDWV 344
Cdd:smart00324   6 IVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGP-DPDLDLSEYDVHDVAGLLKLFLRELPEPLITYELYEEFI 84

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1372102860  345 EAINLEGE-ERFSAIDRCLKKMTRGHRQNLIYLMKFLCDLEAKREETSMNASNLAIVFAPTMTGMIYDGM-----NTHGV 418
Cdd:smart00324  85 EAAKLEDEtERLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEVaslkdIRHQN 164

                   ....*....
gi 1372102860  419 KLTEFMISN 427
Cdd:smart00324 165 TVIEFLIEN 173

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 1372102860 265 VLTKCCDFLRQNGMNERGIFRVSGNASKIKRIRAAL--DAGQFDADEKHYNndPHAVASTLKAYLRELPDPLTMDSLQSD 342
Cdd:cd04385    18 IVDKCIDFITQHGLMSEGIYRKNGKNSSVKKLLEAFrkDARSVQLREGEYT--VHDVADVLKRFLRDLPDPLLTSELHAE 95

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1372102860 343 WVEAINLE-GEERFSAIDRCLKKMTRGHRQNLIYLMKFLCDLEAKREETSMNASNLAIVFAPTM--TGMIYDGMNTHGVK 419
Cdd:cd04385    96 WIEAAELEnKDERIARYKELIRRLPPINRATLKVLIGHLYRVQKHSDENQMSVHNLALVFGPTLfqTDEHSVGQTSHEVK 175

                  ....*...
gi 1372102860 420 LTEFMISN 427
Cdd:cd04385   176 VIEDLIDN 183

RhoGAP_ARHGAP20: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP20-like proteins. ArhGAP20, also known as KIAA1391 and RA-RhoGAP, contains a RhoGAP, a RA, and a PH domain, and ANXL repeats. ArhGAP20 is activated by Rap1 and induces inactivation of Rho, which in turn leads to neurite outgrowth. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1372102860 265 VLTKCCDFLRQNGMNERGIFRVSGNASKIKRIRAALDAGQfDADEKHYNndPHAVASTLKAYLRELPDPLTMDSLQSDWV 344
Cdd:cd04402    18 PILDMLSLLYQKGPSTEGIFRRSANAKACKELKEKLNSGV-EVDLKAEP--VLLLASVLKDFLRNIPGSLLSSDLYEEWM 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1372102860 345 EAINLE-GEERFSAIDRCLKKMTRGHRQNLIYLMKFLCDLEAKREETSMNASNLAIVFAPTM----TGMIYDGMNTHGV- 418
Cdd:cd04402    95 SALDQEnEEEKIAELQRLLDKLPRPNVLLLKHLICVLHNISQNSETNKMDAFNLAVCIAPSLlwppASSELQNEDLKKVt 174

                         170
                  ....*....|....
gi 1372102860 419 KLTEFMISNGVRIF 432
Cdd:cd04402   175 SLVQFLIENCQEIF 188

RhoGAP-p50rhoGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of p50RhoGAP-like proteins; p50RhoGAP, also known as RhoGAP-1, contains a C-terminal RhoGAP domain and an N-terminal Sec14 domain which binds phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3). It is ubiquitously expressed and preferentially active on Cdc42. This subgroup also contains closely related ARHGAP8. 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 1372102860 242 LPRPVFGVPLdEHL---SIQKERISGVLTKCCDFLRQNGMNERGIFRVSGNASKIKRIRAALDAGQfDADEKHYNnDPHA 318
Cdd:cd04404     1 LPTQQFGVSL-QFLkekNPEQEPIPPVVRETVEYLQAHALTTEGIFRRSANTQVVKEVQQKYNMGE-PVDFDQYE-DVHL 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1372102860 319 VASTLKAYLRELPDPLTMDSLQSDWVEAINLEGEERFSAIDRCLKKMTRGHRQNLIYLMKFLCDLEAKREETSMNASNLA 398
Cdd:cd04404    78 PAVILKTFLRELPEPLLTFDLYDDIVGFLNVDKEERVERVKQLLQTLPEENYQVLKYLIKFLVQVSAHSDQNKMTNSNLA 157

                  ....*...
gi 1372102860 399 IVFAPTMT 406
Cdd:cd04404   158 VVFGPNLL 165

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 1372102860 245 PVFGVPLDE--HLSIQKERISGVLTKCCDFLRQNGMNERGIFRVSGNASKIKRIRAALDAGQFDADEKhyNNDPHAVAST 322
Cdd:cd04393     1 KVFGVPLQElqQAGQPENGVPAVVRHIVEYLEQHGLEQEGLFRVNGNAETVEWLRQRLDSGEEVDLSK--EADVCSAASL 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1372102860 323 LKAYLRELPDPLTMDSLQSDWVEAI-NLEGEERF-SAIDRCLKKMTRGHRQNLIYLMKFLCDLEAKREETSMNASNLAIV 400
Cdd:cd04393    79 LRLFLQELPEGLIPASLQIRLMQLYqDYNGEDEFgRKLRDLLQQLPPVNYSLLKFLCHFLSNVASQHHENRMTAENLAAV 158

                  ...
gi 1372102860 401 FAP 403
Cdd:cd04393   159 FGP 161

RhoGAP_myosin_IX: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in class IX myosins. Class IX myosins contain a characteristic head domain, a neck domain, a tail domain which contains a C6H2-zinc binding motif and a RhoGAP domain. Class IX myosins are single-headed, processive myosins that are partly cytoplasmic, and partly associated with membranes and the actin cytoskeleton. Class IX myosins are implicated in the regulation of neuronal morphogenesis and function of sensory systems, like the inner ear. There are two major isoforms, myosin IXA and IXB with several splice variants, which are both expressed in developing neurons. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1372102860 247 FGVPLDEhLSIQKERISGVLTKCCDFLRQNGMNERGIFRVSGNASKIKRIRAALDAgqfDADEKHYNNDP-HAVASTLKA 325
Cdd:cd04377     1 FGVSLSS-LTSEDRSVPLVLEKLLEHIEMHGLYTEGIYRKSGSANKIKELRQGLDT---DPDSVNLEDYPiHVITSVLKQ 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1372102860 326 YLRELPDPLTMDSLQSDWVEAINL-EGEERFSAIDRCLKKMTRGHRQNLIYLMKFLCDLeAKREETS-MNASNLAIVFAP 403
Cdd:cd04377    77 WLRELPEPLMTFELYENFLRAMELeEKQERVRALYSVLEQLPRANLNTLERLIFHLVRV-ALQEEVNrMSANALAIVFAP 155

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 1372102860 247 FGVPLDEHLSIQKERISGVLTKCCDFLRQNGMNERGIFRVSGNASKIKRIRAALDAGQFDADEKHYNNDPHAVASTLKAY 326
Cdd:cd04403     1 FGCHLEALCQRENSTVPKFVRLCIEAVEKRGLDVDGIYRVSGNLAVIQKLRFAVDHDEKLDLDDSKWEDIHVITGALKLF 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1372102860 327 LRELPDPLTMDSLQSDWVEAINLEG-EERFSAIDRCLKKMTRGHRQNLIYLMKFLCDLEAKREETSMNASNLAIVFAPTM 405
Cdd:cd04403    81 FRELPEPLFPYSLFNDFVAAIKLSDyEQRVSAVKDLIKSLPKPNHDTLKMLFRHLCRVIEHGEKNRMTTQNLAIVFGPTL 160

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 1372102860 247 FGVPLdeHLSIQKER------ISGVLTKCCDFLRQNGMNERGIFRVSGNASKIKRIRAALDAGQFDADEKHynnDPHAVA 320
Cdd:cd04381     1 FGASL--SLAVERSRchdgidLPLVFRECIDYVEKHGMKCEGIYKVSGIKSKVDELKAAYNRRESPNLEEY---EPPTVA 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1372102860 321 STLKAYLRELPDPLTMDSLQSDWVEAINLEGE-ERFSAIDRCLKKMTRGHRQNLIYLMKFLCDLEAKREETSMNASNLAI 399
Cdd:cd04381    76 SLLKQYLRELPEPLLTKELMPRFEEACGRPTEaEREQELQRLLKELPECNRLLLAWLIVHMDHVIAQELETKMNIQNISI 155

                  ....*.
gi 1372102860 400 VFAPTM 405
Cdd:cd04381   156 VLSPTV 161

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 1372102860 247 FGVPLDEHLSIQKERISGVLTKCCDFLRQNGMNERGIFRVSGNASKIKRIRAALDAGQFDAD--EKHYNnDPHAVASTLK 324
Cdd:cd04372     1 YGCDLTTLVKAHNTQRPMVVDMCIREIEARGLQSEGLYRVSGFAEEIEDVKMAFDRDGEKADisATVYP-DINVITGALK 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1372102860 325 AYLRELPDPLTMDSLQSDWVEAINLEG-EERFSAIDRCLKKMTRGHRQNLIYLMKFLCDLEAKREETSMNASNLAIVFAP 403
Cdd:cd04372    80 LYFRDLPIPVITYDTYPKFIDAAKISNpDERLEAVHEALMLLPPAHYETLRYLMEHLKRVTLHEKDNKMNAENLGIVFGP 159

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 1372102860 404 TMTG----MIYDGMN--THGVKLTEFMISNGVRIF 432
Cdd:cd04372   160 TLMRppedSALTTLNdmRYQILIVQLLITNEDVLF 194

RhoGAP_KIAA1688: GTPase-activator protein (GAP) domain for Rho-like GTPases found in KIAA1688-like proteins; KIAA1688 is a protein of unknown function that contains a RhoGAP domain and a myosin tail homology 4 (MyTH4) 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 1372102860 247 FGVPLDEHLSIQKE-----RISGVLTKCCDFLRQ-NGMNERGIFRVSGNASKIKRIRAALDAGQFDADEKHynnDPHAVA 320
Cdd:cd04389     1 FGSSLEEIMDRQKEkypelKLPWILTFLSEKVLAlGGFQTEGIFRVPGDIDEVNELKLRVDQWDYPLSGLE---DPHVPA 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1372102860 321 STLKAYLRELPDPLTMDSLQSDWVEAinlegEERFSAIDRCLKKMTRGHRQNLIYLMKFL--CDLEAKREETSMNASNLA 398
Cdd:cd04389    78 SLLKLWLRELEEPLIPDALYQQCISA-----SEDPDKAVEIVQKLPIINRLVLCYLINFLqvFAQPENVAHTKMDVSNLA 152

                  ....*
gi 1372102860 399 IVFAP 403
Cdd:cd04389   153 MVFAP 157

The Bin/Amphiphysin/Rvs (BAR) domain of Rich-like Rho GTPase Activating Proteins; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. This subfamily is composed of Rho and Rac GTPase activating proteins (GAPs) with similarity to GAP interacting with CIP4 homologs proteins (Rich). Members contain an N-terminal BAR domain, followed by a Rho GAP domain, and a C-terminal prolin-rich region. Vertebrates harbor at least three Rho GAPs in this subfamily including Rich1, Rich2, and SH3-domain binding protein 1 (SH3BP1). Rich1 and Rich2 play complementary roles in the establishment and maintenance of cell polarity. Rich1 is a Cdc42- and Rac-specific GAP that binds to polarity proteins through the scaffold protein angiomotin and plays a role in maintaining the integrity of tight junctions. Rich2 is a Rac GAP that interacts with CD317 and plays a role in actin cytoskeleton organization and the maintenance of microvilli in polarized epithelial cells. SH3BP1 is a Rac GAP that inhibits Rac-mediated platelet-derived growth factor (PDGF)-induced membrane ruffling. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The BAR domain of Rich1 has been shown to form oligomers, bind membranes and induce membrane tubulation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1372102860  66 EENVDKRKKKVEELTMAQNLREASVDLDyfQTSCLHRVINAYGTVLHAEVDEKVKLEMAMERRVYEELAPFSEYE-KNVN 144
Cdd:cd07595    47 GEDKDKRLKKLPEYGLAQSMLESSKELP--DDSLLGKVLKLCGEAQNTLARELVDHEMNVEEDVLSPLQNILEVEiPNIQ 124

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1372102860 145 KLKDKLNLVSTDLEIAQKDLEKENSMTHQ-----------ESLDAIQMKYEGMKDALVTDIFaSSVSKEFQLNEHMLTSM 213
Cdd:cd07595   125 KQKKRLSKLVLDMDSARSRYNAAHKSSGGqgaaakvdalkDEYEEAELKLEQCRDALATDMY-EFLAKEAEIASYLIDLI 203

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|.
gi 1372102860 214 NLKRDYFKKMYEMYEKAIPEVERMIATALPRPVFGVPLDEH 254
Cdd:cd07595   204 EAQREYHRTALSVLEAVLPELQEQIEQSPSKPVFGQPLEEH 244

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 1372102860 247 FGVPLDEHLSIQKERISGVLTKCCDFLRQNGMNERGIFRVSGNASKIKRIRAALDAG--QFDADEKHynndPHAVASTLK 324
Cdd:cd04378     1 FGVDFSQVPRDFPDEVPFIIKKCTSEIENRALGVQGIYRVSGSKARVEKLCQAFENGkdLVELSELS----PHDISSVLK 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1372102860 325 AYLRELPDPLTMDSLQSDWV---------------EAINLEGEERFSAIDRCLKKMTRGHRQNLIYLMKFLCDLEAKREE 389
Cdd:cd04378    77 LFLRQLPEPLILFRLYNDFIalakeiqrdteedkaPNTPIEVNRIIRKLKDLLRQLPASNYNTLQHLIAHLYRVAEQFEE 156

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 1372102860 390 TSMNASNLAIVFAPT------------MTGMIYDGmntHGVKLTEFMISN 427
Cdd:cd04378   157 NKMSPNNLGIVFGPTlirprpgdadvsLSSLVDYG---YQARLVEFLITN 203

RhoGAP_fSAC7_BAG7: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of fungal SAC7 and BAG7-like proteins. Both proteins are GTPase activating proteins of Rho1, but differ functionally in vivo: SAC7, but not BAG7, is involved in the control of Rho1-mediated activation of the PKC-MPK1 pathway. 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 1372102860 246 VFGVPLDEHL-------SIQKE--------RISGVLTKCCDFLRQNGMNERGIFRVSGNASKIKRIRAALDAG-----QF 305
Cdd:cd04396     1 VFGVSLEESLkyasvaiSIVDEdgeqyvygYIPVVVAKCGVYLKENATEVEGIFRVAGSSKRIRELQLIFSTPpdygkSF 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1372102860 306 DADEkhYNndPHAVASTLKAYLRELPDPL------------------TMDSLQSDWVEAINLEGEERFSAIDRCLKKMTR 367
Cdd:cd04396    81 DWDG--YT--VHDAASVLRRYLNNLPEPLvpldlyeefrnplrkrprILQYMKGRINEPLNTDIDQAIKEYRDLITRLPN 156

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1372102860 368 GHRQNLIYLMKFLCDLEAKREETSMNASNLAIVFAPTMTGMIYDGMNTHGVKLT----EFMISN 427
Cdd:cd04396   157 LNRQLLLYLLDLLAVFARNSDKNLMTASNLAAIFQPGILSHPDHEMDPKEYKLSrlvvEFLIEH 220

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 1372102860 261 RISGVLTKCCDFLRQNGMNERGIFRVSGNASKIKRIRAALDAGQFDADekHYNNDPHAVASTLKAYLRELPDPLTMDSLQ 340
Cdd:cd04382    16 MIPALIVHCVNEIEARGLTEEGLYRVSGSEREVKALKEKFLRGKTVPN--LSKVDIHVICGCLKDFLRSLKEPLITFALW 93

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1372102860 341 SDWVEAINLEGEERF-SAIDRCLKKMTRGHRQNLIYLMKFLCDLeAKREETSMNASNLAIVFAPTMTG 407
Cdd:cd04382    94 KEFMEAAEILDEDNSrAALYQAISELPQPNRDTLAFLILHLQRV-AQSPECKMDINNLARVFGPTIVG 160

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 1372102860 246 VFGVPLDEHLSIQKERISG-----VLTKCCDFLRQNGMNERGIFRVSGNASKIKRIRAALDAGQFDADEKHYNNDPHAVA 320
Cdd:cd04391     1 LFGVPLSTLLERDQKKVPGskvplIFQKLINKLEERGLETEGILRIPGSAQRVKFLCQELEAKFYEGTFLWDQVKQHDAA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1372102860 321 STLKAYLRELPDPL-TMDSLQSdwveAINLEG----EERFSAIDRCLKKMTRGHRQNLIYLMKFLCDLEAKREETSMNAS 395
Cdd:cd04391    81 SLLKLFIRELPQPLlTVEYLPA----FYSVQGlpskKDQLQALNLLVLLLPEANRDTLKALLEFLQKVVDHEEKNKMNLW 156

                         170
                  ....*....|
gi 1372102860 396 NLAIVFAPTM 405
Cdd:cd04391   157 NVAMIMAPNL 166