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
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1007377271   1 MYSFVAKEIDYANYFQTLIEVQAEYHRKSLTLLQAVLPQIKAQQEAWVEKPSFGKPLEEH 60
Cdd:cd07619   189 MYSFVAKEIDYANYFQTLIEVQAEYHRKSLELLQSVLPQIKAHQEAWVEKPSYGKPLEEH 248

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 1007377271   66 REIAFPIEACVTMLLECGMQEEGLFRVAPSASKLKKLKAALDCCVVDVQEYS-ADPHAIAGALKSYLRELPEPLMTFELY 144
Cdd:smart00324   1 KPIPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGPDPDLDLSeYDVHDVAGLLKLFLRELPEPLITYELY 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1007377271  145 DEWIQASNVQEQDKKLQALWNACEKLPKANHNNIRYLIKFLSKLSEYQDVNKMTPSNMAIVLGPNLLWPQAEGNITEMMT 224
Cdd:smart00324  81 EEFIEAAKLEDETERLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEVASLKDI 160

                          170
                   ....*....|....*..
gi 1007377271  225 TvslQIVGIIEPIIQHA 241
Cdd:smart00324 161 R---HQNTVIEFLIENA 174

The Bin/Amphiphysin/Rvs (BAR) domain of RhoGAP interacting with CIP4 homologs protein 2; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. RhoGAP interacting with CIP4 homologs protein 2 (Rich2) is a Rho GTPase activating protein that interacts with CD317, a lipid raft-associated integral membrane protein. It plays a role in actin cytoskeleton organization and the maintenance of microvilli in polarized epithelial cells. Rich2 contains an N-terminal BAR domain followed by a GAP domain for Rho and Rac GTPases and a C-terminal proline-rich domain. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1007377271   1 MYSFVAKEIDYANYFQTLIEVQAEYHRKSLTLLQAVLPQIKAQQEAWVEKPSFGKPLEEH 60
Cdd:cd07619   189 MYSFVAKEIDYANYFQTLIEVQAEYHRKSLELLQSVLPQIKAHQEAWVEKPSYGKPLEEH 248

BAR domain; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different protein families. A BAR domain with an additional N-terminal amphipathic helix (an N-BAR) can drive membrane curvature. These N-BAR domains are found in amphiphysin, endophilin, BRAP and Nadrin. BAR domains are also frequently found alongside domains that determine lipid specificity, like pfam00169 and pfam00787 domains in beta centaurins and sorting nexins respectively.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 1007377271   1 MYSFVAKEIDY-ANYFQTLIEVQAEYHRKSLTLLQAVLPQIKA 42
Cdd:pfam03114 193 LPNLLSLEVEFvVNQLVAFVEAQLDFHRQCYQLLEQLQQQLGK 235

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 1007377271   66 REIAFPIEACVTMLLECGMQEEGLFRVAPSASKLKKLKAALDCCVVDVQEYS-ADPHAIAGALKSYLRELPEPLMTFELY 144
Cdd:smart00324   1 KPIPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGPDPDLDLSeYDVHDVAGLLKLFLRELPEPLITYELY 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1007377271  145 DEWIQASNVQEQDKKLQALWNACEKLPKANHNNIRYLIKFLSKLSEYQDVNKMTPSNMAIVLGPNLLWPQAEGNITEMMT 224
Cdd:smart00324  81 EEFIEAAKLEDETERLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEVASLKDI 160

                          170
                   ....*....|....*..
gi 1007377271  225 TvslQIVGIIEPIIQHA 241
Cdd:smart00324 161 R---HQNTVIEFLIENA 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 1007377271  71 PIEACVTMLLECGMQEEGLFRVAPSASKLKKLKAALDCCVVDVQEYSADPHAIAGALKSYLRELPEPLMTFELYDEWIQA 150
Cdd:cd00159     3 IIEKCIEYLEKNGLNTEGIFRVSGSASKIEELKKKFDRGEDIDDLEDYDVHDVASLLKLYLRELPEPLIPFELYDEFIEL 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1007377271 151 SNVQEQDKKLQALWNACEKLPKANHNNIRYLIKFLSKLSEYQDVNKMTPSNMAIVLGPNLLWPQAEgniTEMMTTVSLQI 230
Cdd:cd00159    83 AKIEDEEERIEALKELLKSLPPENRDLLKYLLKLLHKISQNSEVNKMTASNLAIVFAPTLLRPPDS---DDELLEDIKKL 159

                         170
                  ....*....|
gi 1007377271 231 VGIIEPIIQH 240
Cdd:cd00159   160 NEIVEFLIEN 169

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 1007377271  53 FGKPLEeHLTISGRE---IAFPIEACVTMLLECGMQEEGLFRVAPSASKLKKLKAALDCCV-VDVQEYSaDPHAIAGALK 128
Cdd:cd04404     6 FGVSLQ-FLKEKNPEqepIPPVVRETVEYLQAHALTTEGIFRRSANTQVVKEVQQKYNMGEpVDFDQYE-DVHLPAVILK 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1007377271 129 SYLRELPEPLMTFELYDEWIQASNVQEQDKkLQALWNACEKLPKANHNNIRYLIKFLSKLSEYQDVNKMTPSNMAIVLGP 208
Cdd:cd04404    84 TFLRELPEPLLTFDLYDDIVGFLNVDKEER-VERVKQLLQTLPEENYQVLKYLIKFLVQVSAHSDQNKMTNSNLAVVFGP 162

                  ....*.
gi 1007377271 209 NLLWPQ 214
Cdd:cd04404   163 NLLWAK 168

RhoGAP_ARHGAP22_24_25: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ARHGAP22, 24 and 25-like proteins; longer isoforms of these proteins contain an additional N-terminal pleckstrin homology (PH) domain. ARHGAP25 (KIA0053) has been identified as a GAP for Rac1 and Cdc42. Short isoforms (without the PH domain) of ARHGAP24, called RC-GAP72 and p73RhoGAP, and of ARHGAP22, called p68RacGAP, has been shown to be involved in angiogenesis and endothelial cell capillary formation. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1007377271  53 FGKPLEEHLTIS---GREIAfPI--EACVTMLLECGMQEEGLFRVAPSASKLKKLKAALDCCVVDVQEYSADPHAIAGAL 127
Cdd:cd04390     3 FGQRLEDTVAYErkfGPRLV-PIlvEQCVDFIREHGLKEEGLFRLPGQANLVKQLQDAFDAGERPSFDSDTDVHTVASLL 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1007377271 128 KSYLRELPEPLMTFELYDEWIQASNV--QEQDKKLQALWNACEKLPKANHNNIRYLIKFLSKLSEYQDVNKMTPSNMAIV 205
Cdd:cd04390    82 KLYLRELPEPVIPWAQYEDFLSCAQLlsKDEEKGLGELMKQVSILPKVNYNLLSYICRFLDEVQSNSSVNKMSVQNLATV 161

                         170       180       190
                  ....*....|....*....|....*....|....*....
gi 1007377271 206 LGPNLLWPQAEGNITEMMTTVSLQIVGIIEpIIQHADWF 244
Cdd:cd04390   162 FGPNILRPKVEDPATIMEGTPQIQQLMTVM-ISKHEPLF 199

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 1007377271  53 FGKPLEEHLTISGREIAFPIEACVTMLLECGMQEEGLFRVAPSASKLKKLKAALDCCVVDV-----QEYSADPHAIAGAL 127
Cdd:cd04398     1 FGVPLEDLILREGDNVPNIVYQCIQAIENFGLNLEGIYRLSGNVSRVNKLKELFDKDPLNVllispEDYESDIHSVASLL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1007377271 128 KSYLRELPEPLMTFELYDEWIQASNVQEQDKKLQALWNACEKLPKANHNNIRYLIKFLSKLSEYQDVNKMTPSNMAIVLG 207
Cdd:cd04398    81 KLFFRELPEPLLTKALSREFIEAAKIEDESRRRDALHGLINDLPDANYATLRALMFHLARIKEHESVNRMSVNNLAIIWG 160

                         170       180       190
                  ....*....|....*....|....*....|....*...
gi 1007377271 208 PNLLwPQAEGNITEMmttvSLQIVgIIEPIIQHADWFF 245
Cdd:cd04398   161 PTLM-NAAPDNAADM----SFQSR-VIETLLDNAYQIF 192

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 1007377271  53 FGKPLEEHLTISGREIAFPIEACVTMLLECGMQEEGLFRVAPSASKLKKLKAALD--CCVVDV-QEYSADPHAIAGALKS 129
Cdd:cd04372     1 YGCDLTTLVKAHNTQRPMVVDMCIREIEARGLQSEGLYRVSGFAEEIEDVKMAFDrdGEKADIsATVYPDINVITGALKL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1007377271 130 YLRELPEPLMTFELYDEWIQASNVQEQDKKLQALWNACEKLPKANHNNIRYLIKFLSKLSEYQDVNKMTPSNMAIVLGPN 209
Cdd:cd04372    81 YFRDLPIPVITYDTYPKFIDAAKISNPDERLEAVHEALMLLPPAHYETLRYLMEHLKRVTLHEKDNKMNAENLGIVFGPT 160

                         170       180       190
                  ....*....|....*....|....*....|....*.
gi 1007377271 210 LLWPqAEGNITEMMTTVSLQIVgIIEPIIQHADWFF 245
Cdd:cd04372   161 LMRP-PEDSALTTLNDMRYQIL-IVQLLITNEDVLF 194

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 1007377271  83 GMQEEGLFRVAPSASKLKKLKAALDCCVVDVQEYSADPHAIAGALKSYLRELPEPLMTFELYDEWIQASNVQEQDKKLQA 162
Cdd:cd04407    30 GLYTEGIYRKSGSANRMKELHQLLQADPENVKLENYPIHAITGLLKQWLRELPEPLMTFAQYNDFLRAVELPEKQEQLQA 109

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1007377271 163 LWNACEKLPKANHNNIRYLIKFLSKLSEYQDVNKMTPSNMAIVLGPNLL-WPQAEGNITEM 222
Cdd:cd04407   110 IYRVLEQLPTANHNTLERLIFHLVKVALEEDVNRMSPNALAIVFAPCLLrCPDSSDPLTSM 170

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 1007377271  72 IEACVTMLLECGMQEEGLFRVAPSASKLKKLKaaldcCVVDVQEYSA-------DPHAIAGALKSYLRELPEPLMTFELY 144
Cdd:cd04403    20 VRLCIEAVEKRGLDVDGIYRVSGNLAVIQKLR-----FAVDHDEKLDlddskweDIHVITGALKLFFRELPEPLFPYSLF 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1007377271 145 DEWIQASNVQEQDKKLQALWNACEKLPKANHNNIRYLIKFLSKLSEYQDVNKMTPSNMAIVLGPNLLWPQAE-GNITEMM 223
Cdd:cd04403    95 NDFVAAIKLSDYEQRVSAVKDLIKSLPKPNHDTLKMLFRHLCRVIEHGEKNRMTTQNLAIVFGPTLLRPEQEtGNIAVHM 174

                         170
                  ....*....|.
gi 1007377271 224 TTVSlQIVGII 234
Cdd:cd04403   175 VYQN-QIVELI 184

RhoGAP_fBEM3: RhoGAP (GTPase-activator [GAP] protein for Rho-like small GTPases) domain of fungal BEM3-like proteins. Bem3 is a GAP protein of Cdc42, and is specifically involved in the control of the initial assembly of the septin ring in yeast bud formation. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1007377271  53 FGKPLEEHLTIS-----GREIAFPIEACVTMLLECG-MQEEGLFRVAPSASKLKKLKAALDCCV-VDVQEYSA--DPHAI 123
Cdd:cd04400     2 FGSPLEEAVELSshkynGRDLPSVVYRCIEYLDKNRaIYEEGIFRLSGSASVIKQLKERFNTEYdVDLFSSSLypDVHTV 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1007377271 124 AGALKSYLRELPEPLMTFELYDEWIQASNVQEQD-KKLQALWNACEKLPKANHNNIRYLIKFLSKLSEYQDVNKMTPSNM 202
Cdd:cd04400    82 AGLLKLYLRELPTLILGGELHNDFKRLVEENHDRsQRALELKDLVSQLPQANYDLLYVLFSFLRKIIEHSDVNKMNLRNV 161

                  ....*...
gi 1007377271 203 AIVLGPNL 210
Cdd:cd04400   162 CIVFSPTL 169

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 1007377271  61 LTISGRE---IAFPIEACVTMLLECGMQEEGLFRVAPSASKLKKLKAALDCCVVDVQEY--SADPHAIAGALKSYLRELP 135
Cdd:cd04387     6 STVTKRErskVPYIVRQCVEEVERRGMEEVGIYRISGVATDIQALKAAFDTNNKDVSVMlsEMDVNAIAGTLKLYFRELP 85

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1007377271 136 EPLMTFELYDEWIQASNVQEQDKKLQALWNACEKLPKANHNNIRYLIKFLSKLSEYQDVNKMTPSNMAIVLGPNLLWP 213
Cdd:cd04387    86 EPLFTDELYPNFAEGIALSDPVAKESCMLNLLLSLPDPNLVTFLFLLHHLKRVAEREEVNKMSLHNLATVFGPTLLRP 163

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 1007377271  53 FGKPLE----EHLTISGREIAFPIEACVTmlLECGMQEEGLFRVAPSASKLKKLKAALD---CCVvdvqeYSADPHAIAG 125
Cdd:cd04394     2 FGVPLHslphSTVPEYGNVPKFLVDACTF--LLDHLSTEGLFRKSGSVVRQKELKAKLEggeACL-----SSALPCDVAG 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1007377271 126 ALKSYLRELPEPLMTFELYDEWIQASNVQEQDKKLQALWNACEKLPKANHNNIRYLIKFLSKLSEYQDVNKMTPSNMAIV 205
Cdd:cd04394    75 LLKQFFRELPEPLLPYDLHEALLKAQELPTDEERKSATLLLTCLLPDEHVNTLRYFFSFLYDVAQRCSENKMDSSNLAVI 154

                  ....*.
gi 1007377271 206 LGPNLL 211
Cdd:cd04394   155 FAPNLF 160

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1007377271   1 MYSFVAKEIDYANYFQTLIEVQAEYHRKSLTLLQAVLPQIKAQQEAWVEKPSFGKPLEEH 60
Cdd:cd07595   185 MYEFLAKEAEIASYLIDLIEAQREYHRTALSVLEAVLPELQEQIEQSPSKPVFGQPLEEH 244

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 1007377271  53 FGKPLEEHLTISGREIAFPIEACVTMLLECGMQEEGLFRVAPSASKLKKLKAAL---DCCVVDVQEYSaDPHAIAGALKS 129
Cdd:cd04383     3 FNGSLEEYIQDSGQAIPLVVESCIRFINLYGLQHQGIFRVSGSQVEVNDIKNAFergEDPLADDQNDH-DINSVAGVLKL 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1007377271 130 YLRELPEPLMTFELYD---EWIQASNVQEQDKKLQALwnaCEKLPKANHNNIRYLIKFLSKLSEYQDVNKMTPSNMAIVL 206
Cdd:cd04383    82 YFRGLENPLFPKERFEdlmSCVKLENPTERVHQIREI---LSTLPRSVIIVMRYLFAFLNHLSQFSDENMMDPYNLAICF 158

                  ....*
gi 1007377271 207 GPNLL 211
Cdd:cd04383   159 GPTLM 163

RhoGAP_fLRG1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of fungal LRG1-like proteins. Yeast Lrg1p is required for efficient cell fusion, and mother-daughter cell separation, possibly through acting as a RhoGAP specifically regulating 1,3-beta-glucan synthesis. 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 1007377271  53 FGKPLE---------EHLTISGREIAFP--IEACVTMLLECGMQEEGLFRVAPSASKLKKLKAALDCCVVDVQEYSAD-P 120
Cdd:cd04397     1 FGVPLEilvekfgadSTLGVGPGKLRIPalIDDIISAMRQMDMSVEGVFRKNGNIRRLKELTEEIDKNPTEVPDLSKEnP 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1007377271 121 HAIAGALKSYLRELPEPLMTFELYDEWIQASNVQEQDKKLQALWNACEKLPKANHNNIRYLIKFLSKLSEYQDV-----N 195
Cdd:cd04397    81 VQLAALLKKFLRELPDPLLTFKLYRLWISSQKIEDEEERKRVLHLVYCLLPKYHRDTMEVLFSFLKWVSSFSHIdeetgS 160

                         170       180
                  ....*....|....*....|...
gi 1007377271 196 KMTPSNMAIVLGPNLLWPQAEGN 218
Cdd:cd04397   161 KMDIHNLATVITPNILYSKTDNP 183

RhoGAP_PARG1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of PARG1 (PTPL1-associated RhoGAP1). PARG1 was originally cloned as an interaction partner of PTPL1, an intracellular protein-tyrosine phosphatase. PARG1 interacts with Rap2, also a member of the Ras small GTPase superfamily whose exact function is unknown, and shows strong preference for Rho. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1007377271  53 FGKPLEEHLTISGREIAFPIEACVTMLLECGMQEEGLFRVAPSASKLKKLKAALDCC--VVDVQEYSadPHAIAGALKSY 130
Cdd:cd04409     1 FGADFAQVAKKSPDGIPFIIKKCTSEIESRALCLKGIYRVNGAKSRVEKLCQAFENGkdLVELSELS--PHDISNVLKLY 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1007377271 131 LRELPEPLMTFELYDEWI----QASNVQEQD---KKLQALW-NAC--------------EKLPKANHNNIRYLIKFLSKL 188
Cdd:cd04409    79 LRQLPEPLILFRLYNEFIglakESQHVNETQeakKNSDKKWpNMCtelnrillkskdllRQLPAPNYNTLQFLIVHLHRV 158

                         170       180
                  ....*....|....*....|....*.
gi 1007377271 189 SEYQDVNKMTPSNMAIVLGPNLLWPQ 214
Cdd:cd04409   159 SEQAEENKMSASNLGIIFGPTLIRPR 184

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 1007377271  53 FGKPLEEHLTIS----GREIAFPIEACVTMLLECGMQEEGLFRVAPSASKLKKLKAALD---CcvVDVQEYsaDPHAIAG 125
Cdd:cd04381     1 FGASLSLAVERSrchdGIDLPLVFRECIDYVEKHGMKCEGIYKVSGIKSKVDELKAAYNrreS--PNLEEY--EPPTVAS 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1007377271 126 ALKSYLRELPEPLMTFEL---YDEWIQASNVQEQDKKLQALwnaCEKLPKANHNNIRYLIKFLSKLSEYQDVNKMTPSNM 202
Cdd:cd04381    77 LLKQYLRELPEPLLTKELmprFEEACGRPTEAEREQELQRL---LKELPECNRLLLAWLIVHMDHVIAQELETKMNIQNI 153

                  ....*...
gi 1007377271 203 AIVLGPNL 210
Cdd:cd04381   154 SIVLSPTV 161

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 1007377271  75 CVTMLLECGMQEEGLFRVAPSASKLKKL-------KAALDCCVVDVqeysadpHAIAGALKSYLRELPEPLMTFELYDEW 147
Cdd:cd04382    24 CVNEIEARGLTEEGLYRVSGSEREVKALkekflrgKTVPNLSKVDI-------HVICGCLKDFLRSLKEPLITFALWKEF 96